User:Koala0090/失智症

失智症
同义词老人癡呆症[1]、重度神經認知障礙症(Major neurocognitive disorder)
1880年描繪失智症患者的版畫
症状思考及記憶功能減退、情緒障礙、語言功能受損、动机減退[2][3]
常見始發於漸發性[2]
病程長期[2]
肇因阿茲海默症血管性痴呆路易氏體失智症額顳葉型失智症英语frontotemporal dementia[4][3]
診斷方法認知功能測驗英语Cognitive testing簡短智能測驗[3][5]
相似疾病或共病譫妄[6]甲狀腺機能低下症
預防及早接受教育、避免高血壓、避免肥胖、戒菸或禁菸、社會參與[7]
治療支持性療法[2]
藥物乙醯膽鹼酯酶抑制劑英语Acetylcholinesterase inhibitor(效果有限)[8][9]
盛行率5000萬(2020年)[4]
死亡數240萬(2016年)[10]
分类和外部资源
醫學專科神經內科身心醫學
[编辑此条目的维基数据]
「Dementia」的各地常用譯名
中国大陸痴呆症
臺灣失智症
香港認知障礙症
澳門腦退化症

失智症(英語:dementia),是囊括許多腦部神經性疾病英语Neurological disorder的泛稱[11]。長期下來,患者的思考能力和記憶力會逐漸減弱、退化,並對其日常生活功能造成影響[4]。其他常見症狀有情緒問題、語言困難以及意志缺失英语Aboulia[2][3]。失智症並不屬於意識障礙,患者的意識通常不受影響[4][a]。若要診斷一個人得了失智症,患者必須要有心智功能減退,且其減退程度較正常老化嚴重[4][13]DSM-5將失智症歸類為一種重性神經認知失調病(major neurocognitive disorder)。失智症可能是因某些疾病或腦部損傷所致,其下包含許多病因所造成的不同亞型[14]。失智症也常會對患者及其照顧者之間的關係造成一定程度的衝擊[4]

最常見的失智症類型為阿茲海默症,約佔總患者數的五到七成[2][3]。其他常見的種類有血管性痴呆25%、路易氏體失智症15%,以及額顳葉型失智症英语frontotemporal dementia[3][2]。較少見的成因則有常壓型水腦症英语Normal_pressure_hydrocephalus帕金森氏症型失智症英语Parkinson's disease dementia梅毒人類免疫缺乏病毒型失智症英语HIV-associated_neurocognitive_disorder以及克雅二氏病[15]。一位患者可能同時罹患兩種(含)以上的失智症[2]。家族遺傳的患者所佔比例不多[16]。在精神疾病診斷與統計手冊第五版英语DSM-5中,將失智症視為一種認知障礙,並依其嚴重程度進行分類[14]。診斷失智症時,通常需根據患者的病史,輔以一系列的認知測驗英语Cognitive_test醫學影像血液檢查結果,來排除其他可能的病因[5]。例如簡短智能測驗,就是一種常見的認知測驗英语Cognitive_test工具[3]。預防失智症的方法為減少常見危險因子,如高血壓吸菸糖尿病以及肥胖症[2]。目前並不建議全面對一般民眾進行失智症篩檢[17]

目前尚無方法可治癒失智症[2]。臨床常用乙醯膽鹼酯酶抑制劑(AChEI)英语Acetylcholinesterase_inhibitor型藥物,例如多奈哌齊;此類藥物或許對輕至中度失智症有效[8][18][19],但藥效終歸有限[8][9]。對患者與其照護者而言,仍有不少方法能有助改善其生活品質,像是認知行為療法[2]。另外,對照護者提供衛教與情感支持也很重要[2]。運動有助於病患的日常生活活動,且有望改善預後[20]。此症帶來的行為問題,常以抗精神病藥治療,但一般而言不特別推薦,因療效有限且有副作用,可能會提高患者的死亡風險[21][22]

2015年,全球失智症患者約有4,600萬人[23]。終身盛行率約為10%,意即全球約有一成人口,終其一生有機會罹患此症[16]。失智症與老化顯然有其關聯[24],65到74歲的族群中,約有3%罹患失智症;75到84歲族群中則有 19%,而85歲以上者,幾乎一半以上是患者[25]。1990年,此症造成80萬人死亡,但是2013年,死亡人數升高至1,700萬[26]。隨著人類壽命延長,此症也更形普遍[24]。然而特定年齡層的盛行率卻可能反而是比較低的,至少已開發國家有這樣的傾向,是由於風險因子減少之故[24]。此症是老年族群中,最常見的身心障礙病因之一[3]。據信在美國一年會造成6,040億美元的經濟損失[2] 。失智症患者常因照護需要,其人身自由遭到物理性或化學約束英语Chemical restraint,引發了人權議題的爭論[2] ;患者也經常苦於因病遭遇汙名化[3]

症候及徵象 编辑

 
失智症女患者畫像
 
罹患老年性失智症的年長男子

失智症的症狀隨著不同的診斷的類型和階段而有所變異[27]。腦部最常被影響的區塊為記憶視覺空間感英语visual-spatial語言注意力,和解決問題的部分;多數失智症的類型多為緩慢漸進型式,當患者顯現相關症狀時,可能已持續經歷長期的失智症腦部進展。同一患者也可能同時得到兩種以上的失智症。約有10%失智症病人是混合型態的,通常會合併得到阿茲海默症和另一種失智症像是額顳葉型失智症英语frontotemporal dementia或是血管性失智症

失智症可能同時具備神經精神醫學英语neuropsychiatric的症狀,稱為失智之行為精神症狀(英語:Behavioural and psychological symptoms of dementia,簡稱為 BPSD),茲列如下[28]

  • 平衡感異常
  • 顫抖
  • 言語及語言異常
  • 飲食及吞嚥有困難
  • 記憶扭曲(相信某些不存在的記憶、把以前的記憶當成最近發生的事、混合兩段記憶或是弄錯記憶中的人物)
  • 遊走或躁動
  • 視知覺異常[29]

所有失智症類型患者皆可能出現的行為及心理症狀如下[30][31]

當失智症患者遇到超乎其所能掌控之情況,易導致情緒改變之反應,如大哭或暴怒,也就是所謂「災難性反應」(英語:catastrophic reaction[32]

失智症患者亦可能伴隨精神病(常為被害妄想)、躁動和攻擊行為[33]

期別 编辑

輕度認知功能障礙(MCI) 编辑

在失智症的第一階段,疾病的症狀和體徵可能不易察覺。初期的失智症症狀,常在確診後回溯過往徵兆時,才較為明朗。初期階段稱為輕度認知功能障礙英语mild cognitive impairment,診斷為此階段之患者中,近七成會進展為失智症[13]。雖然患者的腦部大多已有長期病變,然而尚未嚴重到影響患者的日常作息,其症狀也才正開始顯現;若症狀已影響到患者的日常作息,診斷結果多已為失智症。患者的簡短智能測驗(簡稱 MMSE)分數仍會落在正常區間,大約27~30之間。患者可能會有部份記憶問題或遺忘某些詞彙,但患者仍能解決日常生活所遇到的問題,也能妥善處理自己的生活起居[34]

早期階段 编辑

失智症早期階段,周遭親友開始可意識到患者的症狀。此外,患者症狀亦開始干擾日常活動。早期階段患者的簡短智能測驗,得分多介於20~25之間。階段症狀取決於失智症的類型。患者可能開始在從事較複雜家務或工作任務時遭遇困難。患者通常仍可照顧自己,但容易忘記服藥或洗衣服等事情,可能需要提示或提醒[35]

初期症狀症狀通常包括記憶障礙、喚詞困難(失語症)及計劃組織能力的功能性問題[36]。較有效地評估患者的退化情形,可透過詢問患者能否獨立處理自身財務,這也是患者首要常見的生活問題。其他常反映在生活中的現象,例如:在陌生區域迷路、重複行為或事件、性格改變、社交退縮和難以如常工作[37]

當評估對象是否罹患失智症時,須將其 5~10 年內的行為能力狀況,納入考量重點;然而在評估對象行為能力是否耗損時,亦須將其教育程度也納入考量。舉例來說:再也無法計算帳務達收支平衡的會計師,與高中輟學者或從未關心財務者相比,前者較後者需要更多關注[13]

阿茲海默症型失智症中,最顯著的早期症狀是記憶困難,其餘症狀包括喚詞困難(失語症)及容易迷路。其他種類如路易體失智症(Lewy bodies dementia)和額顳型失智症(fronto-temporal dementia)的早期病徵,常見是性格改變,及計劃組織能力的功能性問題。

中期階段 编辑

隨著失智症之病程進展,初期顯現症狀會漸趨惡化,其衰退速度因人而異。中期階段患者的簡短智能測驗,得分通常在6~17之間。舉例而言,此階段的阿茲海默症型失智症,在面對多數新接收資訊時,遺忘相當迅速。患者的解決問題能力可能會嚴重缺損,社交判斷力亦會受影響。患者離家出外時的行為能力不足,平均而言不建議讓患者單獨行動。患者或許能在家中處理簡單家務,但可能無法完成較複雜的任務。患者可能開始需要個人照護與衛生上的協助,而非簡單的提醒或提示[13]

晚期階段 编辑

晚期階段的失智症患者常見會漸趨內向,且需要大範圍或全職的個人照護,常需要全天候照護以確保其人身安全,並滿足其日常基本需求。若無人照料,患者容易在外迷路遊蕩或跌倒,亦可能無法辨認日常環境中的危險因子,像是滾燙的火爐。患者不一定能意識到自己需要如廁,或無法控制自己的膀胱及肛門機能(即失禁[34]

晚期失智症階段也常會影響患者飲食。照顧者為延長患者之生命,常會提供泥狀食物英语pureed diet和糊狀飲品,使患者增加體重、避免噎到,亦讓進食過程簡單化,並協助進食[38]。病患食慾可能下降至不願進食,亦可能不願下床,或需要他人全力協助才能下床。一般而言,患者在此階段不再能認出親友。患者在睡眠習慣上常有重大改變,亦或難以入眠[13]

病因 编辑

可逆的病因 编辑

有些類型的失智症在治療後可以輕易恢復,例如甲狀腺機能低下症維生素B12缺乏症萊姆病神經性梅毒。 所有出現記憶障礙的人,都應檢查甲狀腺功能並排除B12缺乏症。對萊姆病和神經梅毒,若患者具有患病的危險因子,也應進行測試。但是否具有危險因子常常難以確定[39],因此,對懷疑患有失智症者進行進行神經梅毒、萊姆病以及其他上述檢查,尚屬必需[13]:31–32聽覺障礙也可能與失智症相互關聯[40]。初步研究顯示配帶助聽器可能有幫助。

阿茲海默症 编辑

 
嚴重阿茲海默症(右)所造成的腦萎縮。

阿茲海默症佔失智症總病例的50%至70%[2][3]。阿茲海默症最常見的症狀是短期記憶喪失和單詞提取困難英语Anomic aphasia。患有阿茲海默症的人在視覺空間區域(例如,他們可能開始常常迷路),推理、判斷和洞察方面也存在問題。洞察力是指該人是否意識到自己存在記憶障礙。

阿茲海默症的常見早期症狀包括重複行為(repetition)、迷路、財務處理困難,尤其是在做新的或複雜的飯菜時出現烹飪問題,忘記服藥,或是單字回憶困難。

受阿茲海默症影響最大的大腦部分是海馬體,大腦顳葉頂葉也可能會出現萎縮情形[13]。這種頂顳型腦皮質萎縮很可能是阿茲海默症,但反之未必如此。阿茲海默症的大腦萎縮變化很大,單純腦部斷層掃描實際上無法做出診斷。麻醉與阿茲海默症病之間的關係尚不清楚[41]

血管性失智症 编辑

血管性失智症約佔失智症患者的20%以上,是常見病因中的第二名[42]。血管性失智是因為疾病或是創傷,影響腦部的血液供應,一般是因為幾次的輕微中風造成。血管性失智的症狀會依中風影響的腦部部位,以及堵塞血管的大小而不同[13],多重的受傷可能會造成隨時間惡化的失智症,而有關認知關鍵區域(例如海馬體,丘腦)的單次受傷可能會造成突然的認知衰退[42]

腦部斷層掃描可以看出腦部不同部位多次中風的證據。有血管性失智的人也常會有血管性疾病英语vascular disease的危險因子,例如吸菸高血壓心房顫動高膽固醇血症或,糖尿病,也可能有其他血管疾病的症狀,例如以往可能也曾有心肌梗死心绞痛

路易氏體失智症 编辑

路易氏體失智症的典型症狀為視幻覺及帕金森症候群。帕金森氏症候群是帕金森氏症的症狀集之一,症狀包含震顫、肌肉僵硬,以及面無表情等等。路易氏體失智症的視幻覺內容多半是生動的人或動物,經常發生於患者即將入睡或剛醒來時。其他較突出的症狀包含注意力不集中、組織企劃與解決能力產生問題、以及視覺空間功能出現障礙等[13]

在診斷路易氏體失智症時,只根據醫學影像不足以進行診斷,不過還是有些特殊的症狀。路易氏體失智大症患者在進行單光子電腦斷層掃描英语SPECT scan(SPECT)時,後枕骨部位會有低灌流英语hypoperfusion的情形,或是在正子斷層照影時,後枕骨會有低代謝的症狀。一般而言,路易氏體失智症會直接給予診斷,除非是較複雜的情形,不然多半不需要腦部影像[13]

額顳型失智症 编辑

額顳葉型失智症英语frontotemporal dementia(Frontotemporal Dementia,FTD)的特點是劇烈的性格變化以及語言的困難。所有的額顳型失智症都有較早期的社交退縮,早期也不容易查覺是此一病症。此病症的主要症狀不是記憶方面的問題[13][43]

額顳葉型失智症共有六型。第一型的主要症狀是在個性和行為上,稱為行為變異型FTD(behavioral variant FTD,bv-FTD),也是最常見的一種。其症狀包括個人衛生上的改變,思考的僵化,不過常常不會注意到這些症狀。患者會有社交退縮及食慾的大幅增加。患者有時會有在社交上不恰當的舉動,例如不恰當的性評論,或是開始公開的看色情的刊物或影片。其中最常見的症狀是冷漠(Apathy),對任何事物都不關心,不過其他種類的失智症也常會有冷漠的症狀[13]

Two types of FTD feature aphasia (language problems) as the main symptom. One type is called semantic variant primary progressive aphasia (SV-PPA). The main feature of this is the loss of the meaning of words. It may begin with difficulty naming things. The person eventually may lose the meaning of objects as well. For example, a drawing of a bird, dog, and an airplane in someone with FTD may all appear almost the same.[13] In a classic test for this, a patient is shown a picture of a pyramid and below it a picture of both a palm tree and a pine tree. The person is asked to say which one goes best with the pyramid. In SV-PPA the person cannot answer that question. The other type is called non-fluent agrammatic variant primary progressive aphasia (NFA-PPA). This is mainly a problem with producing speech. They have trouble finding the right words, but mostly they have a difficulty coordinating the muscles they need to speak. Eventually, someone with NFA-PPA only uses one-syllable words or may become totally mute.

額顳葉型失智症中有兩種的主要症狀都是失语症。一種稱為語義變異原發進行性失語症(semantic variant primary progressive aphasia、SV-PPA),主要特徵是忘記詞語的意思,一開始的症狀是會弄混東西的名稱,最後也會忘記東西的意思,例如此種失智症患者畫的鳥、狗及飛機可能會幾乎一模一樣[11]。在相關的經典測試中,會給病患看金字塔的圖片,其下方有棕櫚樹和松樹的圖片,問病患哪一種樹會適合在金字塔附近出現,SV-PPA的患者會無法回答。另一種稱為不流利語法變異原發進行性失語症(non-fluent agrammatic variant primary progressive aphasia、NFA-PPA),主要的症狀是在說話時出現,此疾病的病患不容易找到正確的字,不過大部份的困難是在無法控制說話時需要用到的肌肉。最後有些NFA-PPA的患者只會用單字節的字,有些則不再說話。

Progressive supranuclear palsy英语Progressive supranuclear palsy (PSP) is a form of FTD that is characterized by problems with eye movements. Generally the problems begin with difficulty moving the eyes up or down (vertical gaze palsy). Since difficulty moving the eyes upward can sometimes happen in normal aging, problems with downward eye movements are the key in PSP. Other key symptoms include falling backward, balance problems, slow movements, rigid muscles, irritability, apathy, social withdrawal and depression. The person may have certain "frontal lobe" signs such as perseveration, a grasp reflex and utilization behavior英语utilization behavior (the need to use an object once you see it). People with PSP often have progressive difficulty eating and swallowing, and eventually with talking. Because of the rigidity and slow movements, PSP is sometimes misdiagnosed as Parkinson's disease. On scans the midbrain of people with PSP is generally shrunken (atrophied), but no other common brain abnormalities are visible.

漸進性核上性麻痺英语Progressive supranuclear palsy(PSP)也是額顳葉型失智症中的一種,特徵是無法控制眼球的活動。一開始的問題多半是眼球上下移動的困難(垂直凝視麻痺),由於在一般的老化過程中,有時也會有眼球無法朝上動的問題,因此診斷PSP的關鍵是眼球無法往下移動。其他主要的症狀包括往後跌倒、平衡問題、動作緩慢、肌肉僵硬、煩躁、冷漠、社交退縮和抑鬱。此疾病的患者可能會有一些「額葉」症狀,例如持續動作(perseveration)、抓握反射及使用行為英语utilization behavior(看到物體後一定要用該物體)。PSP的患者會漸進性的難以進食及吞嚥,最後在說話上也有困難,因為PSP患者的肢體僵硬,而且動作緩慢,有時會誤診為帕金森氏症。在腦部掃描時會發現PSP患者的中腦萎縮,不過多半不會有其他的症狀。

Corticobasal degeneration英语Corticobasal degeneration (CBD) is a rare form of FTD that is characterized by many different types of neurological problems that progressively worsen. This is because the disorder affects the brain in many different places, but at different rates. One common sign is difficulty with using only one limb. One symptom that is rare in any other condition is the "alien limb". The alien limb is a limb that seems to have a mind of its own, it moves without conscious control of the person's brain. Other common symptoms include jerky movements of one or more limbs (myoclonus英语myoclonus), symptoms that are different in different limbs (asymmetric), difficulty with speech from inability to move the mouth muscles in a coordinated way, numbness and tingling of the limbs and neglecting one side of vision or senses. In neglect, a person ignores the opposite side of the body from the one that has the problem. For example, a person may not feel pain on one side, or may only draw half of a picture when asked. In addition, the person's affected limbs may be rigid or have muscle contractions causing dystonia (strange repetitive movements).[13] The brain area most often affected in corticobasal degeneration is the posterior frontal lobe and parietal lobe, although many other parts can be affected.[13]

皮質基底核退化症英语Corticobasal degeneration(Corticobasal degeneration,CBD)是罕見的額顳葉型失智症,特點是有幾許多不同種類的神經問題,而且都會漸漸惡化。這是因為疾病會影響大腦不同的部位,而影響的速度也各有不同。其中一個常見的症狀是只能活動一隻手或是一隻腳,另一種症狀在其他疾病中很少見,稱為「外星人肢體」(alien limb),是似乎有自己意志的肢體,會不受大腦控制,無意識的活動。另一個常見的症狀包括一個或多個肢體的抽搐運動(肌陣攣),兩側肢體的症狀不同(不對稱),因為無法以協調的方式控制嘴部肌肉運動,因此無法說話,肢體麻痺或是刺痛,失去某一側的視覺或是感覺。若有人無法感覺到身體的某一側,可能就有此問題。例如,患者可能會感受不到身體某一側的疼痛,或是在畫圖時只畫了某半邊的圖。另外,受影響的肢體可能會僵硬或肌肉收縮,因此有肌张力障碍(奇怪的重覆動作)[11]。最容易受到皮質基底核退化症影響的大腦部位為後額葉顶叶,不過其他部位也常會受到影響[11]。

最後,額顳葉型失智症(FTD)也可能伴隨著運動神經元疾病(Motor Neurone Disease),稱為FTD-MDD。此類患者會同時有額顳葉型失智症的症狀(行為、語言及活動問題,以及神經肌肉疾病的症狀(運動神經元的死亡)。

快速進展性失智症 编辑

Creutzfeldt–Jakob disease typically causes a dementia that worsens over weeks to months, and is caused by prions. The common causes of slowly progressive dementia also sometimes present with rapid progression: Alzheimer's disease, dementia with Lewy bodies, frontotemporal lobar degeneration英语frontotemporal lobar degeneration (including corticobasal degeneration英语corticobasal degeneration and progressive supranuclear palsy英语progressive supranuclear palsy).

庫賈氏病會造成的失智症多半會在幾週到數個月內惡化,是由朊毒體引起。一般緩慢進展的失智症有時也會以快速進展的方式出現: 阿茲海默症路易氏體失智症額顳葉退化英语frontotemporal lobar degeneration(包括皮質基底退化英语corticobasal degeneration進行性核上性麻痺英语progressive supranuclear palsy)。

Encephalopathy英语Encephalopathy or delirium may develop relatively slowly and resemble dementia. Possible causes include brain infection (viral encephalitis英语viral encephalitis, subacute sclerosing panencephalitis, Whipple's disease) or inflammation (limbic encephalitis英语limbic encephalitis, Hashimoto's encephalopathy英语Hashimoto's encephalopathy, cerebral vasculitis); tumors such as lymphoma英语Primary central nervous system lymphoma or glioma; drug toxicity (e.g., anticonvulsant英语anticonvulsant drugs[需要明確引用]); metabolic causes such as liver failure or kidney failure; chronic subdural hematoma; and repeated brain trauma (chronic traumatic encephalopathy, a condition associated with contact sports).

另一方面,腦病英语encephalopathy譫妄也可能發展的較慢,出現類似失智症的症狀。可能的原因還包括腦部感染(病毒性腦炎英语viral encephalitis亞急性硬化性全腦炎英语subacute sclerosing panencephalitiswhipple氏病英语Whipple's disease)或是發炎(邊緣性腦炎英语limbic encephalitis橋本腦病英语Hashimoto's encephalopathy腦血管炎),像是淋巴瘤神經膠質瘤等腫瘤,藥物毒性(例如抗驚厥藥英语anticonvulsant),或是代謝相關原因(例如肝性腦病、[]腎功能衰竭]]或慢性硬膜下血腫英语subdural hematoma)。

免疫相關的失智症 编辑

Chronic inflammatory conditions that may affect the brain and cognition include Behçet's disease, multiple sclerosis, sarcoidosis, Sjögren's syndrome, systemic lupus erythematosus, celiac disease, and non-celiac gluten sensitivity英语non-celiac gluten sensitivity.[44][45] These types of dementias can rapidly progress, but usually have a good response to early treatment. This consists of immunomodulators or steroid administration, or in certain cases, the elimination of the causative agent.[45] A 2019 review found no association between celiac disease and dementia overall but a potential association with vascular dementia.[46] A 2018 review found a link between celiac disease or non-celiac gluten sensitivity and cognitive impairment and that celiac disease may be associated with Alzheimer's disease, vascular dementia, and frontotemporal dementia.[47] A strict gluten-free diet started early may protect against dementia associated with gluten-related disorders英语gluten-related disorders.[46][47]

會影響到腦部和認知狀態的慢性發炎性疾病有貝賽特氏症多發性硬化症結節病乾燥綜合症全身性紅斑狼瘡乳糜瀉非乳糜瀉的麩質敏感英语non-celiac gluten sensitivity[42][43]。這些型態的失智症可以進展快速,但通常早期治療的效果很好。治療種類有免疫治療類固醇,或在特殊狀況下,可以移除影響的物質[43]。一篇2019的回顧性文章發現乳糜瀉和失智症沒有任何關聯,但可能跟血管性癡呆有一點關聯性[44]。一篇2018的回顧性文章發現乳糜瀉或是非乳糜瀉的麩質敏感跟認知功能受損有一點相關,也就是乳糜瀉有可能跟阿茲海默症、血管性癡呆以及額顳葉型失智症英语frontotemporal dementia有相關性[45]。盡早開始嚴格的無麩質飲食對於與麩質相關病症英语gluten-related disorders有關聯的失智症可能會有改善[44][45]。

其他疾病 编辑

Many other medical and neurological conditions include dementia only late in the illness. For example, a proportion of patients with Parkinson's disease develop dementia, though widely varying figures are quoted for this proportion.[48] When dementia occurs in Parkinson's disease, the underlying cause may be dementia with Lewy bodies or Alzheimer's disease, or both.[49] Cognitive impairment also occurs in the Parkinson-plus syndromes of progressive supranuclear palsy英语progressive supranuclear palsy and corticobasal degeneration英语corticobasal degeneration (and the same underlying pathology may cause the clinical syndromes of frontotemporal lobar degeneration英语frontotemporal lobar degeneration). Although the acute porphyrias may cause episodes of confusion and psychiatric disturbance, dementia is a rare feature of these rare diseases. Limbic-predominant age-related TDP-43 encephalopathy英语Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a type of dementia that primarily affects people in their 80s or 90s and in which TDP-43英语TDP-43 protein deposits in the limbic portion of the brain.[50]

有許多疾病和神經疾病在後期會有失智症的症狀。例如帕金森氏症的患者中,有些會出現失智症,程度度各有不同[46]。若帕金森氏症伴隨著失智症,根本病因可能是路易氏體失智症阿茲海默症,也可能兩者都有[47]。認知障礙也可能出現在進行性核上性麻痺英语progressive supranuclear palsy皮質基底突變性英语corticobasal degeneration的病症中(和相同潛在病理可能導致額顳葉變性的臨床症狀)。急性紫質症會有精神錯亂及精神疾病的症狀,但很少會出現失智症的情形。邊緣性為主的年齡相關性TDP-43腦病英语Limbic-predominant age-related TDP-43 encephalopathy(LATE)也是失智症的一種,主要影響80至90歲的人,是腦部邊緣系統TDP-43英语TDP-43蛋白質沈積的病症[48]。

Aside from those mentioned above, heritable conditions that can cause dementia (alongside other symptoms) include:[51]

除了上述疾病外,以下遺傳性疾病也可能引起失智症[49]:

輕度認知障礙 编辑

Mild cognitive impairment英语Mild cognitive impairment means that the person exhibits memory or thinking difficulties, but those difficulties are not severe enough for a diagnosis of dementia.[52] They should score between 25–30 on the MMSE.[13] Around 70% of people with MCI go on to develop some form of dementia.[13] MCI is generally divided into two categories. The first is primarily memory loss (amnestic MCI). The second is anything else (non-amnestic MCI). People with primarily memory problems typically develop Alzheimer's disease. People with the other type of MCI may develop other types of dementia.

輕度認知障礙(MCI)是指患者雖然出現記憶力或思考困難的症狀,但程度尚未嚴重到可以被診斷為癡呆症的情形,[50]此類患者的MMSE測試得分會介於25-30之間[10],而約有70%的輕度認知障礙患者病情會持續演變成某些癡呆症。[10] 輕度認知障礙通常分為兩類,第一類是主要記憶喪失(健忘型MCI),第二類是其他記憶喪失(非健忘型MCI)。罹有健忘型MCI的人常常會演變成阿爾海默症,而罹有非健忘型的MCI的人則可能會演變為其他種類的癡呆症。

Diagnosis of MCI is often difficult, as cognitive testing may be normal. Often, more in-depth neuropsychological testing is necessary to make the diagnosis. The most commonly used criteria are called the Peterson criteria and include:

  • Memory or other cognitive (thought-processing) complaint by the person or a person who knows the patient well.
  • A memory or other cognitive problem as compared to a person of the same age and level of education.
  • Symptoms not severe enough to affect daily function.
  • Absence of dementia.

要診斷輕度認知障礙並不容易,因為患者的認知功能測試結果可能與正常人無異,因此經常需要進行更深入的神經心理學測試才能確診。目前最常使用的標準稱為彼得森標準,內容包括:

  • 患者自己或與患者熟識的人對患者的記憶力或其他認知(思維處理)功能的抱怨或投訴狀況。
  • 與相同年齡及教育水平的人相比之下,患者的記憶力或其他認知功能有無出現特別問題。
  • 患者雖有出現症狀,但不至於嚴重到影響日常生活。
  • 尚未有失智症的症狀。

固定型認知障礙 编辑

Various types of brain injury may cause irreversible cognitive impairment that remains stable over time. Traumatic brain injury英语Traumatic brain injury may cause generalized damage to the white matter of the brain (diffuse axonal injury英语diffuse axonal injury), or more localized damage (as may also accompany neurosurgery). A temporary reduction in the brain's blood supply or oxygen may lead to hypoxic-ischemic injury英语cerebral hypoxia. Strokes (ischemic stroke, or intracerebral, subarachnoid, subdural or extradural hemorrhage) or infections (meningitis or encephalitis) affecting the brain, prolonged epileptic seizures, and acute hydrocephalus may also have long-term effects on cognition. Excessive alcohol use may cause alcohol dementia英语alcohol dementia, Wernicke's encephalopathy英语Wernicke's encephalopathy, or Korsakoff's psychosis英语Korsakoff's psychosis.

許多類型的腦部損傷可能會導致無法回復的認知障礙,情況並會隨著時間經過趨向固定。例如頭部外傷(Traumatic brain injury, TBI)可能會對腦白質造成整體性的傷害(瀰漫性軸索損傷英语diffuse axonal injury),或者造成特定的局部損害(或因此需進行神經外科手術)。而大腦的血液或氧氣供應若因故暫時減少,則可能會導致腦部產生缺氧或缺血性的傷害。再像是中風(例如缺血性中風、出血性中風、蛛網膜下腔出血、硬腦膜下出血或硬膜外出血等)及細菌或病毒感染(例如腦膜炎腦炎)也都會影響腦部功能。此外,長時間的癲癇發作和急性腦積水也可能會對認知功能產生長期性的影響。至於過量飲酒則可能會導致酒精性失智症英语alcohol dementia韋尼克式氏腦病變英语Wernicke's encephalopathy(Wernicke's encephalopathy)或是高沙可夫症候群(Korsakoff's syndrome,和前者一樣都是一種缺乏維生素B1引發的神經系統疾病)。

緩慢進展的失智症 编辑

Dementia that begins gradually and worsens over several years is usually caused by neurodegenerative disease—that is, by conditions that affect only or primarily brain neurons and cause gradual but irreversible loss of function. Less commonly, a non-degenerative condition may have secondary effects on brain cells, which may or may not be reversible if the condition is treated.

若失智症是慢慢出現,在幾年內惡化,一般是由神經退化障礙所造成的,也就是一些只影響腦神經(或是主要影響腦神經)的疾病,其機能會漸進式的喪失,但其影響是不可逆的。偶爾有些非退化性的疾病也會影響腦神經,若已治療該疾病,腦神經的影響有些可逆,有些不可逆。

Causes of dementia depend on the age when symptoms begin. In the elderly population, a large majority of dementia cases are caused by Alzheimer's disease, vascular dementia, or dementia with Lewy bodies.[53][54][55] Hypothyroidism sometimes causes slowly progressive cognitive impairment as the main symptom, which may be fully reversible with treatment. Normal pressure hydrocephalus英语Normal pressure hydrocephalus, though relatively rare, is important to recognize since treatment may prevent progression and improve other symptoms of the condition. However, significant cognitive improvement is unusual.

失智症的病因和症狀開始時的年齡有關。若是年齡較長的病患,大部份的失智症是因為阿茲海默症血管性失智症路易氏體失智症[51][52][53]。有時甲狀腺機能低下症也會有緩慢進展的認知障礙,在治療後,其認知障礙的影響是完全可逆的。常壓性水腦症英语Normal pressure hydrocephalus相當少見,但若治療,可以預防失智症的進展,也可乆改善此病症的其他症狀,只是不太容易有顯著的改善。

Dementia is much less common under 65 years of age. Alzheimer's disease is still the most frequent cause, but inherited forms of the disorder account for a higher proportion of cases in this age group. 額顳葉變性英语Frontotemporal lobar degeneration and Huntington's disease account for most of the remaining cases.[56] Vascular dementia also occurs, but this in turn may be due to underlying conditions (including antiphospholipid syndrome, CADASIL英语CADASIL, MELAS英语MELAS, homocystinuria, moyamoya英语moyamoya, and Binswanger's disease英语Binswanger's disease). People who receive frequent head trauma, such as boxers or football players, are at risk of chronic traumatic encephalopathy[57] (also called dementia pugilistica in boxers).

65歲以下的人罹患失智症的比例就少很多。阿茲海默症仍是最常見的病因,不過遺傳類的疾病也佔了相當的比例,最常見的是額顳葉變性英语Frontotemporal lobar degeneration亨丁頓舞蹈症[54]。也有血管性失智症的情形,火過也可能是因為其他潛藏的病因造成(例如抗磷脂症候群體顯性腦動脈血管病變合併皮質下腦梗塞及腦白質病變英语CADASIL乳酸血症及類中風症狀英语MELAS高胱胺酸尿症毛毛樣血管疾病英语moyamoya賓斯旺格病英语Binswanger's disease)。若是頭部常受創傷的人,例如拳擊手或是美式足球員,其患有慢性創傷性腦病變的風險較高[55]。對於拳擊手而言,也稱為拳擊手失智(dementia pugilistica)。

In young adults (up to 40 years of age) who were previously of normal intelligence, it is very rare to develop dementia without other features of neurological disease, or without features of disease elsewhere in the body. Most cases of progressive cognitive disturbance in this age group are caused by psychiatric illness, alcohol or other drugs, or metabolic disturbance. However, certain genetic disorders can cause true neurodegenerative dementia at this age. These include familial Alzheimer's disease英语Early-onset Alzheimer's disease, SCA17 (dominant inheritance); adrenoleukodystrophy (X-linked); Gaucher's disease type 3, metachromatic leukodystrophy, Niemann-Pick disease type C, pantothenate kinase-associated neurodegeneration英语pantothenate kinase-associated neurodegeneration, Tay–Sachs disease, and Wilson's disease (all recessive). Wilson's disease is particularly important since cognition can improve with treatment.

若發生失智症的是四十歲以下的青年,且之前的智力正常,絕大多數是因為其他神經疾病,或是身體其他部份的疾病所造成的。此年齡層會有漸進型認知障礙的主要原因是為精神疾病、使用酒精或是其他藥物、或是代謝性疾病。不過有些遺傳性疾病會在此年齡層產生真正的神經退化性失智,這些疾病包括早發性阿茲海默症英语Early-onset Alzheimer's disease小腦萎縮症(显性基因)、腎上腺腦白質失養症(X染色體的伴性遗传)、高雪氏症第三型、異染性腦白質退化症C型尼曼匹克氏症泛酸激酶相關的神經變性英语pantothenate kinase-associated neurodegenerationTay-sachs疾病,及肝豆狀核變性(都是隱性基因)。肝豆狀核變性特別值得注意,因為治療後認知會有一些改善。

At all ages, a substantial proportion of patients who complain of memory difficulty or other cognitive symptoms have depression rather than a neurodegenerative disease. Vitamin deficiencies and chronic infections may also occur at any age; they usually cause other symptoms before dementia occurs, but occasionally mimic degenerative dementia. These include deficiencies of vitamin B12, folate, or niacin, and infective causes including cryptococcal meningitis, AIDS英语AIDS dementia complex, Lyme disease, progressive multifocal leukoencephalopathy, subacute sclerosing panencephalitis, syphilis, and Whipple's disease.

不論是哪個年齡層,有記憶困難或是其他認知症狀的人當中,有一定比例是因為重性抑鬱疾患而造成此症狀。維生素不足及慢性感染在任何年齡層都可能出現,一般在出現失智症狀前,會有其他的症狀,不過偶爾也會有類似失智症的症狀。這類維生素不足疾病有维生素B12缺乏症葉酸缺乏症糙皮病,感染性疾病有[[隱球菌病、AIDS英语AIDS dementia complex莱姆病进行性多灶性白质脑病亚急性硬化性全脑炎梅毒鞭毛病英语Whipple's disease

邊緣性為主的年齡相關性TDP-43腦病 编辑

Limbic-predominant age-related TDP-43 encephalopathy英语Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a type of dementia similar to Alzheimer disease which was proposed in 2019.[58] Usually older people are affected.[58]

邊緣性為主的年齡相關性TDP-43腦病英语Limbic-predominant age-related TDP-43 encephalopathy(LATE)是類似阿茲海默症的失智症,在2019年發現的[54]。一般是較年長者容易患病[54]。

聽覺障礙 编辑

Hearing loss is linked with dementia with a greater degree of hearing loss tied to a higher risk.[40] One hypothesis is that as hearing loss increases, cognitive resources are redistributed to auditory perception to the detriment of other cognitive processes.[40] Another hypothesis is that hearing loss leads to social isolation which negatively affect the cognitive functions.[40]

聽覺障礙和失智症有關,聽覺障礙的程度越嚴重,失智症的風險越高[36]。有種假說認為在聽覺障礙變嚴重時,人體會將認知資源重新調整到听觉,因此造成其他認知功能的惡化[36]。另一種假說是聽覺障礙會造成社交孤立,對認知功能有負面影響[36]。

混合型失智症 编辑

失智症的患者中,約有10%的病人為混合型失智症(mixed dementia),多半是結合阿茲海默症和其他種類的失智症(如額顳葉型失智症英语frontotemporal dementia血管性失智症等)[59][60]

診斷 编辑

Symptoms are similar across dementia types and it is difficult to diagnose by symptoms alone. Diagnosis may be aided by brain scanning techniques. In many cases, the diagnosis requires a brain biopsy英语brain biopsy to become final, but this is rarely recommended (though it can be performed at autopsy). In those who are getting older, general screening for cognitive impairment英语cognitive impairment using cognitive testing or early diagnosis of dementia has not been shown to improve outcomes.[61] However, screening exams are useful in 65+ persons with memory complaints.[13]

不同的失智症的症狀表現往往相似,因此單純從症狀來診斷失智症是很困難的。診斷的方法可以納入神經成像的技術。在很多案例中,需要大腦活體組織切片英语brain biopsy才能確定診斷,但這個方法罕有人推薦(雖然可以驗屍)。在年紀增長的人們中,用認知檢測工具來篩檢認知功能衰退英语cognitive impairment者或是早期診斷失智症者並沒有顯示有改善預後[59]。然而,篩檢工具對於65歲以上並且有記憶問題的老年人們是有幫助的[10]。

Normally, symptoms must be present for at least six months to support a diagnosis.[62] Cognitive dysfunction of shorter duration is called delirium. Delirium can be easily confused with dementia due to similar symptoms. Delirium is characterized by a sudden onset, fluctuating course, a short duration (often lasting from hours to weeks), and is primarily related to a somatic (or medical) disturbance. In comparison, dementia has typically a long, slow onset (except in the cases of a stroke or trauma), slow decline of mental functioning, as well as a longer trajectory (from months to years).[63]

正常來說,要下診斷前症狀必須持續表現至少六個月[60]。短時間的認知功能缺損稱為譫妄。譫妄和失智症常常會因為相似的症狀而被混淆。譫妄通常是有一個快速的發作、高低起伏的過程、短的持續時間(多半是持續幾小時到幾周)和多跟身體混亂或醫療狀態有關。相比之下,失智症典型是有長的持續時間、緩慢的發作型態(除了中風或創傷造成的失智症以外)、心智功能緩慢的下降,和相對較長的過程(幾個月到幾年)[61]。

Some mental illnesses, including depression and psychosis, may produce symptoms that must be differentiated from both delirium and dementia.[64] Therefore, any dementia evaluation should include a depression screening such as the Neuropsychiatric Inventory or the Geriatric Depression Scale英语Geriatric Depression Scale.[13] Physicians used to think that people with memory complaints had depression and not dementia (because they thought that those with dementia are generally unaware of their memory problems). This is called pseudodementia英语pseudodementia. However, in recent years researchers have realized that many older people with memory complaints in fact have MCI, the earliest stage of dementia. Depression should always remain high on the list of possibilities, however, for an elderly person with memory trouble.

一些精神疾患包含抑鬱思覺失調可能會表現出一些類似的症狀,需要跟譫妄和失智症表現出的症狀做鑑別診斷[62]。因此,任何對失智症的評估都應該要包含一個對抑鬱症的篩檢,像是神經精神評估量表或是老年憂鬱量表英语Geriatric Depression Scale[10]。醫生們過去認為會提到自己有記憶問題的患者通常是患有抑鬱症而非失智症(因為醫生們認為患有失智症者多半會不知道自己有記憶問題)。這以往被叫做偽失智症英语pseudodementia。然而,在最近幾年,研究者發現到許多自訴有記憶問題的老年人實際上患有MCI,也就是最剛開始階段的失智症。雖說如此,但在有記憶問題的年長者身上還是不能太快排除抑鬱症的可能性。

Changes in thinking, hearing and vision are associated with normal ageing and can cause problems when diagnosing dementia due to the similarities.[65]

思考、聽力和視覺的改變可以是正常老化的影響,但相似於失智症的表現也就造成診斷失智症一定的困難[63]。

認知檢測 编辑

Sensitivity and specificity of common tests for dementia
Test Sensitivity Specificity Reference
MMSE 71%–92% 56%–96% [66]
3MS 83%–93.5% 85%–90% [67]
AMTS 73%–100% 71%–100% [67]

Various brief tests (5–15 minutes) have reasonable reliability to screen for dementia. While many tests have been studied,[68][69][70] presently the mini mental state examination (MMSE) is the best studied and most commonly used. The MMSE is a useful tool for helping to diagnose dementia if the results are interpreted along with an assessment of a person's personality, their ability to perform activities of daily living, and their behaviour.[71] Other cognitive tests include the abbreviated mental test score英语abbreviated mental test score (AMTS), the, Modified Mini-Mental State Examination (3MS),[72] the Cognitive Abilities Screening Instrument英语Cognitive Abilities Screening Instrument (CASI),[73] the Trail-making test英语Trail-making test,[74] and the clock drawing test.[75] The MoCA (Montreal Cognitive Assessment英语Montreal Cognitive Assessment) is a reliable screening test and is available online for free in 35 different languages.[13] The MoCA has also been shown somewhat better at detecting mild cognitive impairment than the MMSE.[76][77]Brief cognitive tests may be affected by factors such as age, education and ethnicity.[78]

常見失智症檢測的靈敏度和特異度
檢測 靈敏度 特異度 參考資料
MMSE 71%–92% 56%–96% [62]
3MS 83%–93.5% 85%–90% [63]
AMTS 73%–100% 71%–100% [63]

許多簡短(5至15分鐘)的檢測在篩檢失智症上有不錯的可靠度。已針對許多的檢測進行研究[64][65][66],其中簡短智能測驗(MMSE)是研究效果最好,也是最常使用的測驗。假如MMSE的結果可以配合個人的人格特質、進行日常行為的能力及行為評估來進行詮釋,MMSE是有效診斷失智症的工具。其他認知測驗的工具包括簡短智力檢測量表英语abbreviated mental test score(AMTS)、修正簡短心智量表英语Modified Mini-Mental State Examination(3MSE)[68]、認知篩檢測驗英语Cognitive Abilities Screening Instrument(CASI)[69]、路徑描繪測驗英语Trail-making test[70]以及畫時鐘測驗(clock drawing test)[71]。蒙特利爾認知評估英语Montreal Cognitive Assessment(MoCA)是可以篩檢失智症的可靠工具,已有35種語言的線上免費版本[10]。在檢測輕微的認知障礙時,MoCA某些方面的效果比MMSE要好[72][73]。簡短的認知測驗可能會受到年齡、教育或是民族等因素的影響[74]。

Another approach to screening for dementia is to ask an informant (relative or other supporter) to fill out a questionnaire about the person's everyday cognitive functioning. Informant questionnaires provide complementary information to brief cognitive tests. Probably the best known questionnaire of this sort is the Informant Questionnaire on Cognitive Decline in the Elderly英语Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE).[79] Evidence is insufficient to determine how accurate the IQCODE is for diagnosing or predicting dementia.[80] The Alzheimer's Disease Caregiver Questionnaire is another tool. It is about 90% accurate for Alzheimer's when by a caregiver.[13] The General Practitioner Assessment Of Cognition英语General Practitioner Assessment Of Cognition combines both a patient assessment and an informant interview. It was specifically designed for use in the primary care setting.

另一種篩檢失智症的方式是詢問可提供患者資訊的人(親友或是照顧者),來填寫患者日常認知功能的問卷。這類的問卷會補充簡短認知測驗的資訊。這類問卷中最好的可能是老年人認知能力下降的調查問卷英语Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE)[75]。在診斷或預測失智症上,目前還沒有足夠資訊確認IQCODE的準確性[76]。另一個工具是阿茲海默症照顧者問卷(Alzheimer's Disease Caregiver Questionnaire),若由照顧者填寫的話,偵測阿茲海默症約有90%的準確度[10]。全科醫生認知評估英语General Practitioner Assessment Of Cognition結合了病患評估以及和資訊提供者的會談。此問卷特別設計用在初級醫療的情境中。

Clinical neuropsychologists provide diagnostic consultation following administration of a full battery of cognitive testing, often lasting several hours, to determine functional patterns of decline associated with varying types of dementia. Tests of memory, executive function, processing speed, attention and language skills are relevant, as well as tests of emotional and psychological adjustment. These tests assist with ruling out other etiologies and determining relative cognitive decline over time or from estimates of prior cognitive abilities.

臨床神經心理學家會在診斷協談後進行一連串的認知測驗,來確認不同類型失智症的功能衰退模式,測驗大約需要幾個小時,內容包括相關的記憶力、執行功能、處理速度、注意力以及語言能力,也會有情緒及心理調整功能的測試。這些測試可以排除其他的病因,也可以確認其他隨時間進展的認知退化,及排除之前估計的認知異常。

Instead of using “mild or early stage”, “middle stage”, and “late stage” dementia as descriptors, numeric scales allow more detailed descriptions. These scales include: Global Deterioration Scale for Assessment of Primary Degenerative Dementia (GDS or Reisberg Scale),[81] Functional Assessment Staging Test (FAST),[82] and Clinical Dementia Rating英语Clinical Dementia Rating (CDR).

描述失智症時,可以用初期、中期、末期的敘述,使用數字的量表可以提供更多的資訊。這些量表包括評估原發性退化性失智症的整體惡化量表(Global Deterioration Scale for Assessment of Primary Degenerative Dementia,簡稱GDS)或稱為Reisberg量表[77]、功能評估分期測試(Functional Assessment Staging Test、簡稱FAST)[78]以及臨床失智症分級英语Clinical Dementia Rating(CDR)。

血液检查 编辑

Routine blood tests are usually performed to rule out treatable causes. These tests include vitamin B12, folic acid, thyroid-stimulating hormone (TSH), C-reactive protein, full blood count, electrolytes, calcium, renal function, and liver enzymes. Abnormalities may suggest vitamin deficiency, infection, or other problems that commonly cause confusion or disorientation in the elderly.[來源請求]

可以用常規的 血液检查來排除一些可以治療的病例,這些測試包括維生素B12叶酸促甲状腺激素 (TSH)、 C反應蛋白全血细胞計數电解质鈣質腎功能肝功能測試。異常可能是因為维生素缺乏症感染、或是其他常見造成年長者混亂或方向感障礙的症狀[來源請求]

醫學影像檢測 编辑

A CT scan or magnetic resonance imaging (MRI scan) is commonly performed, although these tests do not pick up diffuse metabolic changes associated with dementia in a person who shows no gross neurological problems (such as paralysis or weakness) on a neurological exam.[來源請求] CT or MRI may suggest normal pressure hydrocephalus英语normal pressure hydrocephalus, a potentially reversible cause of dementia, and can yield information relevant to other types of dementia, such as infarction (stroke) that would point at a vascular type of dementia.

診斷失智症時,常會進行斷層掃描核磁共振成像,雖然這兩項醫學測試若針對在神經系統檢查中正常,沒有神經系統問題(例如麻痺或虛弱)的人,無法檢查出和失智病有關有關的彌散性代謝變化[來源請求]。斷層掃描與核磁共振成像建議用於常壓性水腦症英语normal pressure hydrocephalus,此症狀可能會導致可逆性的失智症。同時斷層掃描與核磁共振成像也可提供其他類型的失智症影像證據,例如血管梗塞(中風)可能會造成血管性失智症。

The functional neuroimaging英语functional neuroimaging modalities of SPECT英语SPECT and PET are more useful in assessing long-standing cognitive dysfunction, since they have shown similar ability to diagnose dementia as a clinical exam and cognitive testing.[83] The ability of SPECT to differentiate the vascular cause (i.e., multi-infarct dementia) from Alzheimer's disease dementias, appears superior to differentiation by clinical exam.[84]

單光子發射計算機斷層成像術英语SPECT(SPECT)及正子斷層照影(PET)的功能性神經影像學英语functional neuroimaging在診斷失智症上的效果和臨床測試以及認知測試的效果相近,在評估長期的認知功能障礙時更加有效[79]。SPECT在區分血管性失智症(例如多發性梗塞性失智)以及阿茲海默症時,可以比臨床測試更早區分這二種病症[80]。

Recent research has established the value of PET imaging using carbon-11 Pittsburgh Compound B英语Pittsburgh compound B as a radiotracer (PIB-PET) in predictive diagnosis, particularly Alzheimer's disease. Studies reported that PIB-PET was 86% accurate in predicting which patients with mild cognitive impairment would develop Alzheimer's disease within two years. In another study, carried out using 66 patients, PET studies using either PIB or another radiotracer, carbon-11 dihydrotetrabenazine英语dihydrotetrabenazine (DTBZ), led to more accurate diagnosis for more than one-fourth of patients with mild cognitive impairment or mild dementia.[85]

最近的研究發現利用碳-11匹茲堡化合物B英语Pittsburgh Compound B的正子斷層照影(PIB-PET)在預測性診斷上的價值,特別是針對阿茲海默症。研究指出若是預測輕微認知障礙的患者在二年內出現阿茲海默症的機率,用 PIB-PET有86%的準確度。另一個研究針對66位患者的PET研究,使用PIB以及碳-11的dihydrotetrabenazine英语二氫丁苯那嗪(DTBZ)比較,結果在輕微認知障礙或是輕微失智的診斷上,準確度要高25%[81]。

預防 编辑

Various factors can decrease the risk of dementia.[86] As a group they may be able to prevent a third of cases. The group includes early education, treating high blood pressure, preventing obesity, preventing hearing loss, treating depression, physical activity, preventing diabetes, not smoking, and social connection.[86][87] The decreased risk with a healthy lifestyle is seen even in those with a high genetic risk.[88] A 2018 review however concluded that no medications have good evidence of a preventive effect, including blood pressure medications.[89]

許多方式都可以降低失智症的風險[5],若一起使用,可能可以減少三分之一的病例。這些方式包括早期教育、治療高血壓、避免肥胖、糖尿病及听觉障碍、治療抑鬱症、增加身體活動量、不要吸烟,以及增加和其他人的 社交連結[5][82]。較健康的生活方式可以減少風險,就算是遺傳風險較高的人也可以看到效果[83]。不過2018年的回顧研究指出,沒有哪一種醫療的預防效果有良好的文獻支持,包括控制血壓在內[84]。

Among otherwise healthy older people, computerized cognitive training英语cognitive training may improve memory. However it is not known whether it prevents dementia.[90][91] Exercise has poor evidence of preventing dementia.[92][93] In those with normal mental function evidence for medications is poor.[94] The same applies to supplements.[95]

針對沒有失智症症狀的年長者,電腦化的認知訓練英语cognitive training可以提昇記憶力,但不確定是否可以預防失智症[85][86]。找不到運動可以預防失智症的證據[87][88]。針對心智正常的年長者,有關藥物預防失智的效果,缺乏足支支持的證據[89],營養補充品的情形也類似[90]。

The early introduction of a strict gluten-free diet in people with celiac disease or non-celiac gluten sensitivity英语non-celiac gluten sensitivity before cognitive impairment begins potentially has a protective effect.[46]

若是有乳糜泻或是非乳糜瀉的麩質敏感英语non-celiac gluten sensitivity的人,在其出現認知障礙之前提早採用嚴格的无麸质饮食,可能會有保護作用,使其比較不容易罹患失智症[42]。

治療 编辑

Except for the treatable types listed above, no cure has been developed. Cholinesterase inhibitors英语Acetylcholinesterase inhibitor are often used early in the disorder course; however, benefit is generally small.[9][96] Treatments other than medication appear to be better for agitation and aggression than medication.[97] Cognitive and behavioral interventions may be appropriate. Some evidence suggests that education and support for the person with dementia, as well as caregivers and family members, improves outcomes.[98] Exercise programs are beneficial with respect to activities of daily living and potentially improve dementia.[20]

除了上述所列可治療類型的失智症外,其餘失智症則尚未發現任何治癒方式。乙酰膽鹼酯酶抑製劑(Acetylcholinesterase inhibitor)通常會用於治療早期症狀,但大多只有輕微療效[7][91]。對於患者出現的燥動不安和侵略性行為,藥物以外的治療方式似乎較為有效[92]。視情形有時也需要適當的介入以控制患者的認知和行為。某些證據顯示,同時提供癡呆症患者、照顧者及家屬相關的衛教及各種支援將有助於患者的病況[93]。制定運動菜單對患者的日常活動會有助益,且有潛力改善症狀[17]。

心理治療 编辑

Psychological therapies for dementia include some limited evidence for reminiscence therapy英语reminiscence therapy (namely, some positive effects in the areas of quality of life, cognition, communication and mood – the first three particularly in care home settings),[99] some benefit for cognitive reframing英语cognitive reframing for caretakers,[100] unclear evidence for validation therapy英语validation therapy[101] and tentative evidence for mental exercise英语mental exercises, such as cognitive stimulation programs for people with mild to moderate dementia.[102] Reminiscence therapy can improve quality of life, cognition, communication and possibly mood in people with dementia in some circumstances, although all of these benefits may be small.[99]

失智症的心理治療包括證據還不太足份的懷舊療法英语reminiscence therapy(以其名稱來看,是一些在生活品質、認知、溝通以及情緒上的一些正面效果,在家庭護理環境中,格外重視前三項)[94],可能有些幫助,針對照顧者的認知重新框架英语cognitive reframing[95],還沒有清楚證據的確認療法英语validation therapy[96],以及有初步證據的心智鍛煉英语mental exercise,像是針對輕微到中度失智症的認知刺激計劃[97]。懷舊療法可以提昇失智症在一些環境下的生活品質、認知、溝通,也可能對情緒有幫助,不過這些的效果都很小[94]。

Adult daycare英语Adult daycare centers as well as special care units in nursing homes often provide specialized care for dementia patients. Adult daycare centers offer supervision, recreation, meals, and limited health care to participants, as well as providing respite for caregivers. In addition, home care can provide one-on-one support and care in the home allowing for more individualized attention that is needed as the disorder progresses. Psychiatric nurses can make a distinctive contribution to people's mental health.[103]

成人日托英语Adult daycare中心以及療養院中的特殊護理單位可以提到失智症患者的特殊照顧。成人日托中心可以提供監督,娛樂,進餐和一定程度的醫療保健,也是給照顧者的喘息機會。而且居家照護可以在家中提到一對一的支持以及照顧,隨著病情的進展,可以有更多個人化的個性化護理。精神科的護理師可以對病患的心理健康作出獨特的貢獻[98]。

Since dementia impairs normal communication due to changes in receptive and expressive language, as well as the ability to plan and problem solve, agitated behaviour is often a form of communication for the person with dementia. Actively searching for a potential cause, such as pain, physical illness, or overstimulation can be helpful in reducing agitation.[104] Additionally, using an "ABC analysis of behaviour" can be a useful tool for understanding behavior in people with dementia. It involves looking at the antecedents (A), behavior (B), and consequences (C) associated with an event to help define the problem and prevent further incidents that may arise if the person's needs are misunderstood.[105] The strongest evidence for non-pharmacological therapies for the management of changed behaviours in dementia is for using such approaches.[106] Low quality evidence suggests that regular (at least five sessions of) music therapy may help institutionalized residents. It may reduce depressive symptoms and improve overall behaviour. It may also supply a beneficial effect on emotional well-being and quality of life, as well as reduce anxiety.[107] In 2003, The Alzheimer’s Society英语Alzheimer’s Society established 'Singing for the Brain' (SftB) a project based on pilot studies which suggested that the activity encouraged participation and facilitated the learning of new songs. The sessions combine aspects of reminiscence therapy and music. [108]

由於失智症患者接收語言及表達的能力改變,其日常溝通的能力退化,而計劃及解決問題的能力也受到影響,躁動行動常常是失智症患者的一種溝通方式。主動的找尋其潛在原因(可能是疼痛、身體疾病或是過度刺激)可能可以減輕其躁動情形[99]。另外,「ABC行為分析」(ABC analysis of behaviour)是分析失智症患者行為的有效工具,其作法是分析一個事件有關的前因(antecedents,A)、行為(behavior, B)及結果(consequences,C),有助於定義其問題,並且可避免在患者需求被誤解時,可能衍生的問題[100]。目前在針對失智症行為調整的非藥物治療中,具有最有力證據的就是使用此方式的研究[101]。有研究指出規律性(至少五次)的音樂治療可能會對住院病患有幫助,可以減少憂鬱症狀,並提昇整體行為,也對於情緒健康以及生活品質有正面的影響,也可以降低焦慮。不過證據品質不高[102]。阿茲海默症學會英语Alzheimer’s Society在2003年推動了Singing for the Brain(SftB)的前導研究計劃,建議在活動中鼓勵參與者學習新歌。此治療方式結合了懷舊療法以及音樂治療[103]。

Some London hospitals found that using color, designs, pictures and lights helped people with dementia adjust to being at the hospital. These adjustments to the layout of the dementia wings at these hospitals helped patients by preventing confusion.[109]

有一些英國的醫院發現改造病床與環境風格可以幫助失智症住院患者適應,包含配色、設計、海報圖片與光線等方式。而利用舊照片、舊電影、舊傢俱等復古裝飾有助於減少失智症患者的困惑與焦慮。[102]<nowiki>

藥物治療 编辑

 
多奈哌齊

No medications have been shown to prevent or cure dementia.[110] Medications may be used to treat the behavioural and cognitive symptoms, but have no effect on the underlying disease process.[13][111]

沒有藥物能夠預防或治療失智症[101]。雖然藥物可以用於治療行為和認知上的症狀,不過對潛在的疾病進程沒有影響[11][102]。

Acetylcholinesterase inhibitor英语Acetylcholinesterase inhibitors, such as donepezil, may be useful for Alzheimer disease[112] and dementia in Parkinson's, DLB, or vascular dementia.[111] The quality of the evidence is poor[113] and the benefit is small.[9] No difference has been shown between the agents in this family.[18] In a minority of people side effects include a slow heart rate and fainting.[114]

乙酰膽鹼酯酶抑製劑英语Acetylcholinesterase inhibitors(例如多奈哌齊),可能對阿茲海默症[103]、帕金森氏症、路易氏體失智症和血管性失智症有所幫助[102]。然而該證據的質量並不是那麼好[104],效益也不大[8]。在少數群體中副作用包含心跳過緩以及昏厥[105]。

As assessment for an underlying cause of the behavior is needed before prescribing antipsychotic medication for symptoms of dementia.[115] Antipsychotic drugs should be used to treat dementia only if non-drug therapies have not worked, and the person's actions threaten themselves or others.[116][117][118][119] Aggressive behavior changes are sometimes the result of other solvable problems, that could make treatment with antipsychotics unnecessary.[116] Because people with dementia can be aggressive, resistant to their treatment, and otherwise disruptive, sometimes antipsychotic drugs are considered as a therapy in response.[116] These drugs have risky adverse effects, including increasing the person's chance of stroke and death.[116] Given these adverse events and small benefit antipsychotics should be avoided whenever possible.[106] Generally, stopping antipsychotics for people with dementia does not cause problems, even in those who have been on them a long time.[120]

在開立抗精神病藥物治療失智症症狀前,需評估造成症狀的病因[106]。只有在非藥物治療對失智症患者無效,而且其行為威脅到自身或他人時,才能用抗精神病藥物進行治療[107][108][109][110]。激烈的行為改變,也有可能是其他可治療疾病所造成,若是這樣,其實不用抗精神病藥物治療[107]。由於有些失智症患者可能有攻擊性,有破壞力,而且會抗拒治療,有時會將抗精神病藥物視為治療方式之一[107]。抗精神病藥物有危險性的不良反應,會增加中風及死亡的機率[107]。考慮抗精神病藥物的不良反應及較小的益處,若可能的話,盡量避免使用這類藥物[99]。一般而言,服用抗精神病藥物的失智症病患停藥不會有副作用,就算是長期服藥的患者也是如此[111]。

N-methyl-D-aspartate (NMDA) receptor blockers such as memantine英语memantine may be of benefit but the evidence is less conclusive than for AChEIs.[121] Due to their differing mechanisms of action memantine and acetylcholinesterase inhibitors can be used in combination however the benefit is slight.[122][123]

N-甲基-D-天門冬胺酸受體阻抗劑(像是美金剛英语mematine)對失智症可能有效,但其證據效果沒有AChEI要好[112]。由於這兩種藥物的作用機制不同,因此可以同時使用,不過助益不大[113][114]。

While depression is frequently associated with dementia, selective serotonin reuptake inhibitors (SSRIs) do not appear to affect outcomes.[124][125] The SSRIs sertraline and citalopram have been demonstrated to reduce symptoms of agitation, compared to placebo.[126]

雖然重度抑郁症常伴隨失智症一起出現,但治療重度抑鬱症的选择性5-羟色胺再摄取抑制剂(SSRI)對失智症的症狀改善不大[115][116]。SSRI中的舍曲林(sertraline)和西肽普蘭(citalopram)已確認可以降低躁動的症狀,效果比安慰劑要好[117]。

The use of medications to alleviate sleep disturbances that people with dementia often experience has not been well researched, even for medications that are commonly prescribed.[127] In 2012 the American Geriatrics Society英语American Geriatrics Society recommended that benzodiazepines such as diazepam, and non-benzodiazepine hypnotics, be avoided for people with dementia due to the risks of increased cognitive impairment and falls.[128] Additionally, little evidence supports the effectiveness of benzodiazepines in this population.[127][129] No clear evidence shows that melatonin or ramelteon英语ramelteon improves sleep for people with dementia due to Alzheimer's.[127] Limited evidence suggests that a low dose of trazodone may improve sleep, however more research is needed.[127]

關於使用藥物改善失智症患者睡眠品質的策略,即使是常用的藥物,目前也尚無足夠研究[118]。2012年美國老年醫學會建議苯二氮䓬类(BZD)安眠藥物,如地西泮(Diazepam)等,應避免使用,因為這些藥物可能會增加認知功能損傷的風險[119]。此外,目前也尚無足夠實證支持此類藥物對於此類患者的療效[118][120]。目前尚無足夠實證證明褪黑素柔速瑞(ramelteon)能改善阿茲海默症的睡眠品質[118]。有薄弱證據顯示曲唑酮可能可以改善睡眠症狀,但仍需進一步研究[118]。

No solid evidence indicates that folate or vitamin B12 improves outcomes in those with cognitive problems.[130] Statins have no benefit in dementia.[131] Medications for other health conditions may need to be managed differently for a person who has a dementia diagnosis. It is unclear whether blood pressure medication and dementia are linked. People may experience an increase in cardiovascular-related events if these medications are withdrawn.[132]

目前尚無足夠實證支持葉酸維生素B12能改善認知問題[121]。他汀類藥物(Statins)對於失智症也沒有效益。失智症患者若同時患有其他疾病,必須斟酌調整藥物。目前失智症與血壓藥之間的關聯性尚不清楚。但目前認為停掉這些藥物可能會增加心血管疾病的風險[123]。

The Medication Appropriateness Tool for Comorbid Health Conditions in Dementia英语MATCH-D (MATCH-D) criteria can help identify ways that a diagnosis of dementia changes medication management for other health conditions.[133] These criteria were developed because people with dementia live with an average of five other chronic diseases, which are often managed with medications.

平均每位失智症患者都罹患有其他五種慢性疾病,因此常併用其他藥物。失智症患者共病藥物使用適當性英语Medication Appropriateness Tool for Comorbid Health Conditions in Dementia(MATCH-D)可以協助醫事人員在處理失智症患者的共病時,可如何調整藥物[124]。

疼痛 编辑

As people age, they experience more health problems, and most health problems associated with aging carry a substantial burden of pain; therefore, between 25% and 50% of older adults experience persistent pain. Seniors with dementia experience the same prevalence of conditions likely to cause pain as seniors without dementia.[134] Pain is often overlooked in older adults and, when screened for, is often poorly assessed, especially among those with dementia, since they become incapable of informing others of their pain.[134][135] Beyond the issue of humane care, unrelieved pain has functional implications. Persistent pain can lead to decreased ambulation, depressed mood, sleep disturbances, impaired appetite, and exacerbation of cognitive impairment[135] and pain-related interference with activity is a factor contributing to falls in the elderly.[134][136]

隨著年齡增長,成年人會遇到愈來愈多的健康問題,而且大部分的問題都會導致相當程度的疼痛;因此,有25%至50%的年長者平時會不斷感到疼痛。而老年癡呆症患者出現疼痛情形的機率也與正常人一樣[129] [129] [130]。老年人的疼痛問題常常被忽略,就算有進行監測,但疼痛評估的品質也往往不佳。對於癡呆症的患者的疼痛評估品質尤其低下,因為他們已無法告訴其他人他們的疼痛狀況如何[129] [130]。除了人道關懷問題之外,持續無法緩解的疼痛更會為患者日常生活帶來實際影響,造成包括活動力下降、情緒低落、睡眠障礙、食慾不振以及認知障礙惡化等問題[130],且因為疼痛造成的肢體活動不順也是導致老年人跌倒的因素之一[129] [131]。

Although persistent pain in people with dementia is difficult to communicate, diagnose, and treat, failure to address persistent pain has profound functional, psychosocial英语psychosocial and quality of life implications for this vulnerable population. Health professionals often lack the skills and usually lack the time needed to recognize, accurately assess and adequately monitor pain in people with dementia.[134][137] Family members and friends can make a valuable contribution to the care of a person with dementia by learning to recognize and assess their pain. Educational resources (such as the Understand Pain and Dementia tutorial) and observational assessment tools are available.[134][138][139]

儘管癡呆症患者的持續性疼痛難以傳達、診斷和治療,但若不去解決,將對已經是弱勢的他們造成更嚴重的身心及生活品質上的影響。醫護專業人員通常沒時間,也缺乏技巧去識別、準確評估和充分監測癡呆症患者遭受的疼痛,[129] [132],但家人和朋友則可以藉由學習如何識別及評估患者的痛苦,從而為照顧患者做出寶貴貢獻;目前也已有提供相關教育資源(例如“了解疼痛與癡呆症”課程)及觀察評估工具可使學習及使用[129] [133] [134]。

進食困難 编辑

Persons with dementia may have difficulty eating. Whenever it is available as an option, the recommended response to eating problems is having a caretaker assist them英语assisted feeding.[116] A secondary option for people who cannot swallow effectively is to consider gastrostomy英语Percutaneous endoscopic gastrostomy feeding tube英语feeding tube placement as a way to give nutrition. However, in bringing comfort and maintaining functional status while lowering risk of aspiration pneumonia and death, assistance with oral feeding is at least as good as tube feeding.[116][140] Tube-feeding is associated with agitation, increased use of physical and chemical restraints and worsening pressure ulcers. Tube feedings may cause fluid overload, diarrhea, abdominal pain, local complications, less human interaction and may increase the risk of aspiration.[141][142]

失智症的患者可能會有進食困難的問題,若在可行的情形下,比較建議針對進食困難的患者,有照顧者可以協助進食英语assisted feeding[111]。針對無法有效吞嚥的患者,另一個可行的作法是用胃造口灌食英语feeding tube來供給營養。不過若在吸入性肺炎及死亡風險較低的情形下,考慮患者的舒適以及維持其機能狀態,協助進食的效果至少和胃造口灌食的效果相當[111][135]。胃管灌食比較容易出現躁動,需要比較多的物理性及化學性約束,也比較容易讓褥疮惡化。灌食比較容易造成流體過載、腹瀉、腹痛、局部併發症、人際互動減少以及增加誤吸入肺部的風險[136][137]

Benefits in those with advanced dementia has not been shown.[143] The risks of using tube feeding include agitation, rejection by the person (pulling out the tube, or otherwise physical or chemical immobilization to prevent them from doing this), or developing pressure ulcers.[116] The procedure is directly related to a 1% fatality rate[144] with a 3% major complication rate.[145] The percentage of people at end of life with dementia using feeding tubes in the US has dropped from 12% in 2000 to 6% as of 2014.[146][147]

針對晚度失智症的患者,還不確定這些作法是否有助益[138]。胃管灌食的風險是容易躁動、患者會拒絕(將管子拔出,會需要用其他物理或化學的限制方式讓患者不去拔管子)、也會造成褥疮[111]。此程序和1%的死亡率[139]以及3%的的併發重症比較有關[140]。在美國失智症患者在臨終時仍使用胃管灌食的比例,從2000年的12%降到2014年的6%[141][142]。

飲食 编辑

In those with celiac disease or non-celiac gluten sensitivity英语non-celiac gluten sensitivity, a strict gluten-free diet may relieve the symptoms given a mild cognitive impairment.[46][47] Once dementia is advanced no evidence suggests that a gluten free diet is useful.[46]

針對乳糜泻或是非乳糜泻麸质敏感英语non-celiac gluten sensitivity的輕度認知失調的患者,无麸质饮食可能可以緩解其症狀[42][43]。若發展到失智症,目前還沒有證據支持无麸质饮食的效果[42]。

替代療法 编辑

Aromatherapy and massage have unclear evidence.[148][149] Studies support the efficacy and safety of cannabinoids in relieving behavioral and psychological symptoms of dementia.[150]

芳香療法按摩在失智症上的療效,相關的證據還不清楚[143][144]。研究支持用大麻素緩解失智症行為及心理症狀的效果及安全性[145]。

Omega-3 fatty acid supplements from plants or fish sources do not appear to benefit or harm people with mild to moderate Alzheimer's disease. It is unclear whether taking omega-3 fatty acid supplements can improve other types of dementia.[151]

對於輕度到中度的阿茲海默症患者,來自植物或是魚的Ω-3脂肪酸補充品似乎對患者沒有幫助,不過也沒有損害。目前還不清楚Ω-3脂肪酸補充品對其他種類的失智症是否有幫助[146]。

和緩治療 编辑

Given the progressive and terminal nature of dementia, palliative care can be helpful to patients and their caregivers by helping people with the disorder and their caregivers understand what to expect, deal with loss of physical and mental abilities, support the person's wishes and goals including surrogate decision making, and discuss wishes for or against CPR and life support英语life support.[152][153] Because the decline can be rapid, and because most people prefer to allow the person with dementia to make their own decisions, palliative care involvement before the late stages of dementia is recommended.[154][155] Further research is required to determine the appropriate palliative care interventions and how well they help people with advanced dementia.[156]

由於失智症病程進展以及終末不可逆的特質,和缓医疗可以幫助患者以及照顧者,讓他們理解接下來可能發生事,處理生理以及心智機能的喪失、支持患者的期望以及目標(包括一些妥協性的決策),以及討論在有生命危急時,希不希望進行CPR生命支持英语life support[147][148]。因為失智症的機能退化很快,大部份的人都希望患者是自己進行這個決定,因此和缓医疗建議在失智症的最後一個病程之前就要進行[149][150]。有關如何決定適當的和缓医疗方式,以及針對末期病患的助益如何,都還需要更多的資料支持[157]。 (by Wolfch)

Person-centered care英语Person-centered care helps maintain the dignity of people with dementia.[158]

患者中心醫療英语Person-centered care可以讓失智症的患者仍可以維持其尊嚴[152]。(by Wolfch)

流行病學 编辑

 
2012年因為失智症死亡的人數。(單位:百萬人)
  0–4
  5–8
  9–10
  11–13
  14–17
  18–24
  25–45
  46–114
  115–375
  376–1266
 
Disability-adjusted life year for Alzheimer and other dementias per 100,000 inhabitants in 2004.

The number of cases of dementia worldwide in 2010 was estimated at 35.6 million.[159] In 2015, 46.8 million people live with dementia, with 58% living in low and middle income countries.[160] The prevalence of dementia differs in different world regions, ranging from 4.7% in Central Europe to 8.7% in North Africa/Middle East; the prevalence in other regions is estimated to be between 5.6 and 7.6%.[160] The number of people living with dementia is estimated to double every 20 years. In 2013 dementia resulted in about 1.7 million deaths, up from 0.8 million in 1990.[26] Around two-thirds of individuals with dementia live in low- and middle-income countries, where the sharpest increases in numbers were predicted in a 2009 study.[159]

2010年,世界上的失智症患者計約3560萬人[149]。到2015年,患有失智症的人數約有4680萬,其中 58% 的患者生活於中低收入國家[150]。失智症的盛行率隨世界及區域而有所不同,中歐約4.7%,北非和中東則約8.7%[150]。失智症的案例數約每20年會翻倍。到2013年,失智症導致的死亡案例已從1990年的80萬上升到約170萬例[23]。其中三分之二的案例居住於中低收入戶國家,且這些區域的案例數增長幅度也最為劇烈[149]。

The annual incidence of dementia diagnosis is over 9.9 million worldwide. Almost half of new dementia cases occur in Asia, followed by Europe (25%), the Americas (18%) and Africa (8%). The incidence of dementia increases exponentially with age, doubling with every 6.3 year increase in age.[160] Dementia affects 5% of the population older than 65 and 20–40% of those older than 85.[161] Rates are slightly higher in women than men at ages 65 and greater.[161]

全球每年約會增加990萬例。其中約有一半的新診斷案例位於亞洲,其餘多到少分別為歐洲(25%)、美洲(18%),和非洲(8%)。失智症的發生率會隨年齡呈指數性是增長,約每6.3年即會上升一倍[150]。65以上的年長者約有5%人口為失智症所苦,85歲以上的長者則高達20-40%[151]。其中在65歲以上的年長者中,女性發生比率較男性略高[151]。

(這邊incidence 不用發生率一詞是因為該句呈現的並非一個比率)

Dementia impacts not only individuals with dementia, but also their carers and the wider society. Among people aged 60 years and over, dementia is ranked the 9th most burdensome condition according to the 2010 Global Burden of Disease英语Disease burden (GBD) estimates. The global costs of dementia was around US$818 billion in 2015, a 35.4% increase from US$604 billion in 2010.[160]

失智症除了影響患者本身之外,對於照護者和整個社會也會造成負擔。根據2010年全球疾病負擔研究(Global Burden of Disease,GBD)顯示,對於60歲以上的長者而言,失智症在所有疾病中造成的負擔為第九名。2010年,失智症約耗費全球6040億美金,2015年這個數字則上升至8180億,上升了35.4%[150]。

歷史 编辑

Until the end of the 19th century, dementia was a much broader clinical concept. It included mental illness and any type of psychosocial incapacity, including reversible conditions.[162] Dementia at this time simply referred to anyone who had lost the ability to reason, and was applied equally to psychosis, "organic" diseases like syphilis that destroy the brain, and to the dementia associated with old age, which was attributed to "hardening of the arteries".

在十九世紀之前,在醫學臨床上,失智是範圍較廣的概念,包括了心理疾病,也包括了社會心理機能喪失的症狀,(可逆的症狀也包括在內)[157]。這個時期「失智」指的就是失去理解能力的人,以及精神病,或是一些會破壞大腦的生理疾病(例如梅毒),其中也包括了老年時會產生的失智,當時認為的原因是「動脈硬化」。

Dementia has been referred to in medical texts since antiquity. One of the earliest known allusions to dementia is attributed to the 7th-century BC Greek philosopher Pythagoras, who divided the human lifespan into six distinct phases: 0–6 (infancy), 7–21 (adolescence), 22–49 (young adulthood), 50–62 (middle age), 63–79 (old age), and 80–death (advanced age). The last two he described as the "senium", a period of mental and physical decay, and that the final phase was when "the scene of mortal existence closes after a great length of time that very fortunately, few of the human species arrive at, where the mind is reduced to the imbecility of the first epoch of infancy".[163] In 550 BC, the Athenian statesman and poet Solon argued that the terms of a man's will might be invalidated if he exhibited loss of judgement due to advanced age. Chinese medical texts made allusions to the condition as well, and the characters for "dementia" translate literally to "foolish old person".[來源請求]

古代史開始,醫學文獻中就有失智症的記載。目前有關失智症最早的典故是出自西元前第七世紀古希腊哲学毕达哥拉斯,他將人生分為六個不同的階段:0-6歲(兒童)、7-21歲(青少年)、22-49歲(青壯年)、50-62歲(中年)、63-79歲(老年)以及80歲以後(advanced age)。他將最後二段描述為「衰老期」,是心智以及身體都退化的階段,最後一段則是「生命在一段長久的時間後會走到盡頭,屆時心智也會退化到如初生時的失能狀態。幸運的是,只有極少數的人會活到這麼久。」[158]。在西元前550年時,雅典的政治家及詩人梭伦就認為,若一個人因為年老而失去判斷能力,則他的遺囑條款應該要失效。中医学也有描述類似失智的症狀[來源請求]。而以往也曾用「老年癡呆症」來作為Dementia的翻譯。

Athenians Aristotle and Plato spoke of the mental decay of advanced age, apparently viewing it as an inevitable process that affected all old men, and which nothing could prevent. Plato stated that the elderly were unsuited for any position of responsibility because, "There is not much acumen of the mind that once carried them in their youth, those characteristics one would call judgement, imagination, power of reasoning, and memory. They see them gradually blunted by deterioration and can hardly fulfill their function."[來源請求]

雅典的亚里士多德柏拉图曾提到老年時的心智衰退,將這些症狀視為是會影響所有老年人,不可逆的過程。柏拉圖曾認為老年人不適合擔任任何職務,因為「年輕時曾有的敏銳頭腦,判斷力、想像力、理解力及記憶力,在年老時已所剩無幾。這些機能慢慢的退化及惡化,很難再發揮作用。」[來源請求]

For comparison, the Roman statesman Cicero held a view much more in line with modern-day medical wisdom that loss of mental function was not inevitable in the elderly and "affected only those old men who were weak-willed". He spoke of how those who remained mentally active and eager to learn new things could stave off dementia. However, Cicero's views on aging, although progressive, were largely ignored in a world that would be dominated for centuries by Aristotle's medical writings. Physicians during the Roman Empire, such as Galen and Celsus, simply repeated the beliefs of Aristotle while adding few new contributions to medical knowledge.

比較起來,羅馬政治家西塞罗的觀點比較接近現代醫學的觀點,認為老年人的心智退化是可逆的,而且「只影響那些意志薄弱的老年人」h。他提出精神仍然活躍而且熱切學習新事物的人不容易患有失智症。不過西塞罗有關老年的理論雖然先進,但當時是以亚里士多德的醫學思想為主,因此西塞罗的理論被忽視了。羅馬帝國時的醫學家,例如盖伦克理索主要是重覆亚里士多德的理論,偶爾才會加入新的醫學知識。

Byzantine physicians sometimes wrote of dementia. It is recorded that at least seven emperors whose lifespans exceeded 70 years displayed signs of cognitive decline. In Constantinople, special hospitals housed those diagnosed with dementia or insanity, but these did not apply to the emperors, who were above the law and whose health conditions could not be publicly acknowledged.

拜占庭帝国的醫師曾寫到失智症。有記錄提到至少有七位70歲以上的皇帝出現認知衰退的情形。君士坦丁堡有特殊的醫院診斷失智症或是精神錯亂,但這不適用於皇帝,其地位比法律還要高,而其健康狀態也不會公開,

Otherwise, little is recorded about dementia in Western medical texts for nearly 1700 years. One of the few references was the 13th-century friar Roger Bacon, who viewed old age as divine punishment for original sin. Although he repeated existing Aristotelian beliefs that dementia was inevitable, he did make the progressive assertion that the brain was the center of memory and thought rather than the heart.

此外,在西方的醫學文獻中,有長達1700年的時間只有少許有關失智症的記錄。其中一個資料是來自13世紀的男修道士罗吉尔·培根,他認為老年因為原罪而有的懲罰。雖然他重覆亚里士多德失智症不可逆的論點,不過提出了一個進步的想法,認為心不是記憶的中心,大腦才是。

Poets, playwrights, and other writers made frequent allusions to the loss of mental function in old age. William Shakespeare notably mentions it in plays such as Hamlet and King Lear.

詩人、劇作家以及其他作家常會描述到老年時的心智功能退化。像威廉·莎士比亚的《哈姆雷特》及《李爾王》中都有描述。

During the 19th century, doctors generally came to believe that elderly dementia was the result of cerebral atherosclerosis英语cerebral atherosclerosis, although opinions fluctuated between the idea that it was due to blockage of the major arteries supplying the brain or small strokes within the vessels of the cerebral cortex.

在十九世紀時,醫師普遍認為老年的失智是因為腦動脈粥樣硬化英语cerebral atherosclerosis的結果,不過是因為腦中大動脈的阻塞,或因為大脑皮质中小血管造成的小型中風,則沒有定論。

In 1907 Alzheimer's disease was described. This was associated with particular microscopic changes in the brain, but was seen as a rare disease of middle age because the first person diagnosed with it was a 50-year-old woman英语Auguste Deter. By 1913–20, schizophrenia had been well-defined in a way similar to later times.

1907年時開始有阿茲海默症的描述,其症狀和大腦特別的微觀變化有關,不過因為一開始是在五十歲的女性身上發現,被視為是罕見的中年疾病。大約在1913年至1920年時,也開始有精神分裂症的定義,定義方式和現在的差不多。

This viewpoint remained conventional medical wisdom through the first half of the 20th century, but by the 1960s it was increasingly challenged as the link between neurodegenerative diseases and age-related cognitive decline was established. By the 1970s, the medical community maintained that vascular dementia was rarer than previously thought and Alzheimer's disease caused the vast majority of old age mental impairments. More recently however, it is believed that dementia is often a mixture of conditions.

在20世紀的前半段時,有關失智的觀點仍停留在傳統的醫學智慧。1960年代開始建立神經退化障礙以及老年認知退化之間的關聯,傳統的醫學智慧也開始受到挑戰。1970年代時,醫學界認為血管型失智比以往認為的比例要少,老年心智退化主要是因為阿茲海默症的影響。之後又慢慢有新的觀點,認為失智症是幾種病症所混合而成。

In 1976, neurologist Robert Katzmann英语Robert Katzmann suggested a link between senile dementia and Alzheimer's disease.[164] Katzmann suggested that much of the senile dementia occurring (by definition) after the age of 65, was pathologically identical with Alzheimer's disease occurring in people under age 65 and therefore should not be treated differently.[165] Katzmann thus suggested that Alzheimer's disease, if taken to occur over age 65, is actually common, not rare, and was the fourth- or 5th-leading cause of death, even though rarely reported on death certificates in 1976.

神經學家羅伯特·卡茲曼英语Robert Katzmann在1976年提出老年失智症和阿茲海默症的關聯性[159],卡茲曼認為(依照其定義)發生在65歲以上的老年失智症,和許多65歲以下發生的阿茲海默症,在病理上是相同的,因此需視為同一種疾病[160]。因此卡茲曼推測:若將阿茲海默症的條件放寬到65歲以上,此疾病其實相當常見,是死因中的第四名到第五名,只是很少出現在1976年的死因鑑定書。

A helpful finding was that although the incidence of Alzheimer's disease increased with age (from 5–10% of 75-year-olds to as many as 40–50% of 90-year-olds), no threshold was found by which age all persons developed it. This is shown by documented supercentenarians (people living to 110 or more) who experienced no substantial cognitive impairment. Some evidence suggests that dementia is most likely to develop between ages 80 and 84 and individuals who pass that point without being affected have a lower chance of developing it. Women account for a larger percentage of dementia cases than men, although this can be attributed to their longer overall lifespan and greater odds of attaining an age where the condition is likely to occur.[來源請求]

另一個對診斷有幫助的發現是:雖然阿茲海默症的發生率會隨年齡增加而提高(從75歲的5-10%到90歲的40-50%),但沒有證據顯示超過某一年齡就一定會罹患阿茲海默症,例如有資料記錄超過110歲的人瑞,沒有出現明顯的認知退化。有些證據支持發生阿茲海默症的年齡主要是在80至84歲,超過此一階段後,發生率會下降。女性罹患失智症的比例比男性要高,不過不確定是不是因為女性平均壽命較高,會活到容易罹患阿茲海默症的年齡有關[來源請求]

Much like other diseases associated with aging, dementia was comparatively rare before the 20th century, because few people lived past 80. Conversely, syphilitic dementia was widespread in the developed world until it was largely eradicated by the use of penicillin after World War II. With significant increases in life expectancy thereafter, the number of people over 65 started rapidly climbing. While elderly persons constituted an average of 3–5% of the population prior to 1945, by 2010 many countries reached 10–14% and in Germany and Japan, this figure exceeded 20%. Public awareness of Alzheimer's Disease greatly increased in 1994 when former US president Ronald Reagan announced that he had been diagnosed with the condition.

失智症和其他和老年有關的疾病類似,在20世紀之前很少出現,因為當時很少人可以活到80歲。以前梅毒失智症在已開發國家很普遍,後來因為青霉素的使用,此病症在第二次世界大战後已經絕跡。隨著預期生命的顯著增加,65歲以上的人口也快速增加。在1945年以前,老年人約佔總人口的3-5%,在2010年時會佔約10-14%,若是德國及日本,會佔到20%以上。1994年時前美國總統罗纳德·里根宣佈他罹患阿茲海默症,也提昇大眾對阿茲海默症的認識。

In the 21st century, other types of dementia were differentiated from Alzheimer's disease and vascular dementias (the most common types). This differentiation is on the basis of pathological examination of brain tissues, by symptomatology, and by different patterns of brain metabolic activity in nuclear medical imaging tests such as SPECT英语SPECT and PETscans of the brain. The various forms have differing prognoses and differing epidemiologic risk factors. The causal etiology of many of them, including Alzheimer's disease, remains unclear.[來源請求]

21世紀時,除了阿茲海默症及血管型失智症外,也分別出Frontotemporal dementia,其差異以在腦部組織的病理學檢查、症狀學為基礎,而在核醫學成像測試(例如SPECT英语SPECT正子斷層照影)下,大腦代謝活動的模式也有所不同。這些差異造成了不同的預後,以及不同的流行病學危險因素。失智症中有許多種的確切原因還不清楚,其中也包括了阿茲海默症[來源請求]


辭彙 编辑

Dementia in the elderly was once called senile dementia or senility, and viewed as a normal and somewhat inevitable aspect of growing old. This terminology is no longer standard.[166][167]

老年時的失智症曾被稱為是「老年失智症」(senile dementia),視為是年老時正常的現象,在一定程度上是無法避免的。此詞語已不是醫學標準的用法[161][162]。

By 1913–20 the term dementia praecox英语dementia praecox was introduced to suggest the development of senile-type dementia at a younger age. Eventually the two terms fused, so that until 1952 physicians used the terms dementia praecox (precocious dementia) and schizophrenia interchangeably. The term precocious dementia for a mental illness suggested that a type of mental illness like schizophrenia (including paranoia and decreased cognitive capacity) could be expected to arrive normally in all persons with greater age (see paraphrenia英语paraphrenia). After about 1920, the beginning use of dementia for what is now understood as schizophrenia and senile dementia helped limit the word's meaning to "permanent, irreversible mental deterioration". This began the change to the later use of the term.

在1913年至1920年間,出現了早發型失智症英语dementia praecox詞語,說明老年型失智症在較年輕時的情形。最後二個詞融合了,在1952年之前,醫生會將「早發型失智症」及「思覺失調症」(schizophrenia)視為是同義詞,彼此替換使用。精神疾病上的「早發型失智症」意味著有一種類似思覺失調症(包括偏執以及認知能力減退)的症狀,只要年齡夠大,都自然而然會出現。在1920年後,開始使用「失智症」來描述後來認為是「思覺失調症」的症狀,而「老年失智症」是專指永久性、不可逆的心智退化。這是此一詞語後來意義變化的開始。

The view that dementia must always be the result of a particular disease process led for a time to the proposed diagnosis of "senile dementia of the Alzheimer's type" (SDAT) in persons over the age of 65, with "Alzheimer's disease" diagnosed in persons younger than 65 who had the same pathology. Eventually, however, it was agreed that the age limit was artificial, and that Alzheimer's disease was the appropriate term for persons with that particular brain pathology, regardless of age.

以往認為失智症一定是某一種特別疾病所導致的後果,這也造成了有一段時間會將65歲以上的患者診斷為「阿茲海默型老年性失智」(SDAT),將65歲以下有相關症狀的患者診斷為「阿茲海默症」。後來專家們同意年齡的限制是人為不必要的,針對這種腦部病變,不論年齡為何,最適合的診斷即為「阿茲海默症」。

After 1952 mental illnesses including schizophrenia were removed from the category of organic brain syndrome英语organic brain syndromes, and thus (by definition) removed from possible causes of "dementing illnesses" (dementias). At the same, however, the traditional cause of senile dementia – "hardening of the arteries" – now returned as a set of dementias of vascular cause (small strokes). These were now termed multi-infarct dementias or vascular dementias.

在1952年後,包括思覺失調症在內的精神疾病已不再列在器質性腦症候群英语organic brain syndrome的分類中,因此(依照定義),思覺失調症也就不再是失智症的可能病因。同時,老年型失智症的傳統原因「血管硬化」變成一種血管型的失智症(小型中風),現在會稱為「多發性梗塞型失智症」或是「血管型失智症」。

社會及文化 编辑

The societal cost of dementia is high, especially for family caregivers.[168]

 
Old woman from 埃塞俄比亚的老年女性

失智症的社會成本很高,尤其會影響家庭中的照顧者[163]。

Many countries consider the care of people living with dementia a national priority and invest in resources and education to better inform health and social service workers, unpaid caregivers, relatives and members of the wider community. Several countries have authored national plans or strategies.[169][170] These plans recognize that people can live reasonably with dementia for years, as long as the right support and timely access to a diagnosis are available. Former British Prime Minister David Cameron described dementia as a "national crisis", affecting 800,000 people in the United Kingdom.[171]

許多國家將照顧失智症患者列為國家優先事務,投入資源以及教育,讓醫療人員、社會服務工作者、無薪看護者、親屬以及社會大眾對失智症有更多的了解。不少國家有訂定國家級的計劃或是戰略[164][165]。這些計劃認知到,只要提供正確的支援,並且有及時的診斷,人可以在有失智症的情形下生活相當一段時間。前英國首相戴维·卡梅伦稱失智症是「國家危機」,在英國影響超過80萬人[166]。

There, as with all mental disorders, people with dementia could potentially be a danger to themselves or others, they can be detained under the Mental Health Act 1983英语Mental Health Act 1983 for assessment, care and treatment. This is a last resort, and is usually avoided by people with family or friends who can ensure care.

不過如同所有的精神疾病一樣,失智症患者有可能會傷害自身,也可能會傷害他人。依照Mental Health Act 1983英语1983年精神健康法可以拘留,以進行評估、照料及治療。這是最後的手段,只有在失智症患者沒有可以照顧他的家人或是朋友時,才會使用此方式處理。

Some hospitals in Britain work to provide enriched and friendlier care. To make the hospital wards calmer and less overwhelming to residents, staff replaced the usual nurses' station with a collection of smaller desks, similar to a reception area. The incorporation of bright lighting helps increase positive mood and allow residents to see more easily.[172]

有些英國的醫院會提供較豐富以及較友善的照護。為了讓病房更安靜,對住院患者的壓力較小,工作人員將一般的護理站換成許多較小的桌子,類似接待區。其中也整合了較明亮的燈光讓住院患者有較積極的情緒,也讓患者可以看的比較清楚[167]。

Driving with dementia can lead to injury or death. Doctors should advise appropriate testing on when to quit driving.[173] The United Kingdom DVLA英语DVLA (Driver & Vehicle Licensing Agency) states that people with dementia who specifically have poor short term memory, disorientation, or lack of insight or judgment are not allowed to drive, and in these instances the DVLA must be informed so that the driving licence can be revoked. They acknowledge that in low-severity cases and those with an early diagnosis, drivers may be permitted to continue driving.

失智症患者駕駛有可能會造成受傷甚至死亡。醫師應該針對患者何時要停止駕駛進行相關的測驗[168]。英國的DVLA英语DVLA(車輛及駕駛執照機構)提出失智者患者若短期記憶力不佳、失去方向感或判斷能力,都不允許駕駛,這些情形都需要知會DVLA,以作廢對應的執照。他們也同意針對症狀輕或是早期診斷的駕駛,可以繼續開車。

Many support networks are available to people with dementia and their families and caregivers. Charitable organisations aim to raise awareness and campaign for the rights of people living with dementia. Support and guidance are available on assessing testamentary capacity in people with dementia.[174]

已針對失智症患者、家庭以及照顧者有許多的支持網路。慈善機構計劃開展活動,提昇大眾對失智症的認知,並且爭取和失智症同住者的權益。針對評估失智症遺囑的效力上,已有相關的支持以及指引[169]。

In 2015, Atlantic Philanthropies announced a $177 million gift aimed at understanding and reducing dementia. The recipient was Global Brain Health Institute, a program co-led by the University of California, San Francisco and Trinity College Dublin. This donation is the largest non-capital grant Atlantic has ever made, and the biggest philanthropic donation in Irish history.[175]

2015年時,大西洋慈善基金会(Atlantic Philanthropies)為了要瞭解及減少失智症,捐贈了1.77兆美金。得主是全球脑健康研究所(Global Brain Health Institute),是由加利福尼亚大学旧金山分校以及都柏林三一學院合作的計劃。此捐贈是大西洋慈善基金会進行過最大筆的非資金捐贈,也是愛爾蘭歷史上最大規模的的慈善捐贈[169]。

口腔衛生 编辑

目前,並沒有足夠的研究結果能夠證明,不佳的口腔健康狀況和認知能力的下降有明確的關係。然而,錯誤的刷牙習慣和常態性的牙齦紅腫,已被證實可作為失智症的罹病風險指標[176]

口腔病原菌 编辑

阿茲海默症和牙周炎的關聯因素是口腔菌群英语Oral microbiology[177]。口腔中的細菌種類有齒齦假單胞菌英语Porphyromonas gingivalisP. gingivalis)、具核梭桿菌英语Fusobacterium nucleatumF. nucleatum)、中間普氏菌英语Prevotella intermediaP. intermedia)及福賽斯坦納菌英语Tannerella forsythiaT. forsythia)。在阿茲海默症患者腦部有發現六種口腔密螺旋體Trepomena[178]。螺旋體為嗜神經性(neurotropic)病原體,會傷害神經及造成發炎。炎症性病原體是阿茲海默症的指標,在阿茲海默症患者的腦部有發現和牙周炎有關的細菌[178]。這些細菌會入侵腦部的神經、增加血腦屏障的通透性,促使阿茲海默症的發作。若患者有過多的牙菌斑,有認知能力下降的風險[179]。口腔衛生不良會對語言和營養有不良影響,使得整體健康及認知的衰退。

口腔中的病毒 编辑

50歲或是更年長的族群中,有超過70%會檢測到單純疱疹病毒(HSV)。單純疱疹病毒會持續的維持在周圍神經系統,可能因為壓力、疾病或疲勞而引發[178]。含有澱粉樣蛋白的斑塊或是神經原纖維纏結(NFT)中和病毒相關蛋白的比例很高,因此證實了HSV-1參與了阿茲海默症的病理。神經原纖維纏結是阿茲海默症的主要標記物,HSV-1產生了NFT中的主要成份[180]

參考文獻 编辑

  1. ^ Dementia. MedlinePlus. U.S. National Library of Medicine. 14 May 2015 [6 August 2018]. (原始内容存档于12 May 2015). Dementia Also called: Senility 
  2. ^ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 引证错误:没有为名为WHO2014的参考文献提供内容
  3. ^ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 Burns A, Iliffe S. Dementia. BMJ. February 2009, 338: b75. PMID 19196746. S2CID 220101432. doi:10.1136/bmj.b75. 
  4. ^ 4.0 4.1 4.2 4.3 4.4 4.5 Dementia. www.who.int. [7 November 2020] (英语). 
  5. ^ 5.0 5.1 Dementia diagnosis and assessment (PDF). pathways.nice.org.uk. [2014-11-30]. (原始内容 (PDF)存档于2014-12-05). 
  6. ^ Hales, Robert E. The American Psychiatric Publishing Textbook of Psychiatry. American Psychiatric Pub. 2008: 311. ISBN 978-1-58562-257-3. (原始内容存档于2017-09-08). 
  7. ^ 引证错误:没有为名为Lancet2020的参考文献提供内容
  8. ^ 8.0 8.1 8.2 Kavirajan H, Schneider LS. Efficacy and adverse effects of cholinesterase inhibitors and memantine in vascular dementia: a meta-analysis of randomised controlled trials. The Lancet. Neurology. September 2007, 6 (9): 782–92. PMID 17689146. doi:10.1016/s1474-4422(07)70195-3. 
  9. ^ 9.0 9.1 9.2 9.3 Commission de la transparence. Drugs for Alzheimer's disease: best avoided. No therapeutic advantage [Drugs for Alzheimer's disease: best avoided. No therapeutic advantage]. Prescrire International. June 2012, 21 (128): 150. PMID 22822592. 
  10. ^ Global, regional, and national burden of Alzheimer's disease and other dementias, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. January 2019, 18 (1): 88–106. PMC 6291454 . PMID 30497964. doi:10.1016/S1474-4422(18)30403-4. 
  11. ^ Normal ageing vs dementia. Alzheimer's Society. [22 November 2020] (英语). 
  12. ^ McKeith IG, Ferman TJ, Thomas AJ, et al. Research criteria for the diagnosis of prodromal dementia with Lewy bodies. Neurology (Review). April 2020, 94 (17): 743–55. PMC 7274845 . PMID 32241955. doi:10.1212/WNL.0000000000009323. 
  13. ^ 13.00 13.01 13.02 13.03 13.04 13.05 13.06 13.07 13.08 13.09 13.10 13.11 13.12 13.13 13.14 13.15 13.16 13.17 13.18 13.19 13.20 13.21 Budson A, Solomon P. Memory loss : a practical guide for clinicians. [Edinburgh?]: Elsevier Saunders. 2011. ISBN 978-1-4160-3597-8. 
  14. ^ 14.0 14.1 Association, American Psychiatric. Diagnostic and statistical manual of mental disorders : DSM-5. 5th. Washington, DC: American Psychiatric Association. 2013: 591–603. ISBN 978-0-89042-554-1. 
  15. ^ Gauthier S. Clinical diagnosis and management of Alzheimer's disease 3rd. Abingdon, Oxon: Informa Healthcare. 2006: 53–54. ISBN 978-0-203-93171-4. (原始内容存档于2016-05-03). 
  16. ^ 16.0 16.1 Loy CT, Schofield PR, Turner AM, Kwok JB. Genetics of dementia. Lancet. March 2014, 383 (9919): 828–40. PMID 23927914. doi:10.1016/s0140-6736(13)60630-3. 
  17. ^ Dementia overview (PDF). pathways.nice.org.uk. [2014-11-30]. (原始内容存档 (PDF)于2014-12-05). 
  18. ^ 18.0 18.1 Birks J. Cholinesterase inhibitors for Alzheimer's disease. The Cochrane Database of Systematic Reviews. January 2006, (1): CD005593. PMID 16437532. doi:10.1002/14651858.CD005593. 
  19. ^ Rolinski M, Fox C, Maidment I, McShane R. Cholinesterase inhibitors for dementia with Lewy bodies, Parkinson's disease dementia and cognitive impairment in Parkinson's disease (PDF). The Cochrane Database of Systematic Reviews. March 2012, 3 (3): CD006504. PMID 22419314. doi:10.1002/14651858.CD006504.pub2. 
  20. ^ 20.0 20.1 Forbes D, Forbes SC, Blake CM, Thiessen EJ, Forbes S. Exercise programs for people with dementia. The Cochrane Database of Systematic Reviews (Submitted manuscript). April 2015, 132 (4): 195–96. PMID 25874613. doi:10.1002/14651858.CD006489.pub4. 
  21. ^ Information for Healthcare Professionals: Conventional Antipsychotics. fda.gov. 2008-06-16 [2014-11-29]. (原始内容存档于2014-11-29). 
  22. ^ National Institute for Health and Clinical Excellence. Low-dose antipsychotics in people with dementia. nice.org.uk. [2014-11-29]. (原始内容存档于2014-12-05). 
  23. ^ GBD 2015 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. October 2016, 388 (10053): 1545–1602. PMC 5055577 . PMID 27733282. doi:10.1016/S0140-6736(16)31678-6. 
  24. ^ 24.0 24.1 24.2 Larson EB, Yaffe K, Langa KM. New insights into the dementia epidemic. The New England Journal of Medicine. December 2013, 369 (24): 2275–77. PMC 4130738 . PMID 24283198. doi:10.1056/nejmp1311405. 
  25. ^ Umphred, Darcy. Neurological rehabilitation 6th. St. Louis, MO: Elsevier Mosby. 2012: 838. ISBN 978-0-323-07586-2. (原始内容存档于2016-04-22). 
  26. ^ 26.0 26.1 GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. January 2015, 385 (9963): 117–71. PMC 4340604 . PMID 25530442. doi:10.1016/S0140-6736(14)61682-2. 
  27. ^ Dementia – Signs and Symptoms. American Speech Language Hearing Association. 
  28. ^ Şahin Cankurtaran, E. Management of Behavioral and Psychological Symptoms of Dementia.. Noro Psikiyatri Arsivi. December 2014, 51 (4): 303–12. PMC 5353163 . PMID 28360647. doi:10.5152/npa.2014.7405. 
  29. ^ Sight, perception and hallucinations in dementia (PDF). Alzheimer's Society. October 2015 [2015-11-04]. (原始内容 (PDF)存档于2017-08-13). 
  30. ^ Cerejeira J, Lagarto L, Mukaetova-Ladinska EB. Behavioral and psychological symptoms of dementia. Frontiers in Neurology. 2012, 3: 73. PMC 3345875 . PMID 22586419. doi:10.3389/fneur.2012.00073. 
  31. ^ Calleo J, Stanley M. Anxiety Disorders in Later Life Differentiated Diagnosis and Treatment Strategies. Psychiatric Times. 2008, 25 (8). (原始内容存档于2009-09-04). 
  32. ^ Geddes J, Gelder MG, Mayou R. Psychiatry. Oxford [Oxfordshire]: Oxford University Press. 2005: 141. ISBN 978-0-19-852863-0. OCLC 56348037. 
  33. ^ Shub D, Kunik ME. Psychiatric Comorbidity in Persons With Dementia: Assessment and Treatment Strategies. Psychiatric Times. 2009-04-16, 26 (4). (原始内容存档于2009-04-27). 
  34. ^ 34.0 34.1 Hugo J, Ganguli M. Dementia and cognitive impairment: epidemiology, diagnosis, and treatment. Clinics in Geriatric Medicine. August 2014, 30 (3): 421–42. PMC 4104432 . PMID 25037289. doi:10.1016/j.cger.2014.04.001. 
  35. ^ Jenkins, Catharine. Dementia care at a glance. Ginesi, Laura; Keenan, Bernie. Chichester, West Sussex. 2016-01-26. ISBN 978-1-118-85998-8. OCLC 905089525. 
  36. ^ Rohrer JD, Knight WD, Warren JE, Fox NC, Rossor MN, Warren JD. Word-finding difficulty: a clinical analysis of the progressive aphasias. Brain. January 2008, 131 (Pt 1): 8–38. PMC 2373641 . PMID 17947337. doi:10.1093/brain/awm251. 
  37. ^ Islam, Maheen; Mazumder, Mridul; Schwabe-Warf, Derek; Stephan, Yannick; Sutin, Angelina R.; Terracciano, Antonio. Personality Changes With Dementia From the Informant Perspective: New Data and Meta-Analysis. Journal of the American Medical Directors Association. 2019-02-01, 20 (2): 131–137. ISSN 1525-8610. PMID 30630729. doi:10.1016/j.jamda.2018.11.004 (英语). 
  38. ^ Erickson K. How We Die Now: Intimacy and the Work of Dying. Temple University Press. 2013-09-27: 109–11. ISBN 978-1-4399-0823-5. (原始内容存档于2016-12-23). 
  39. ^ Dawes, P. Hearing interventions to prevent dementia.. HNO. March 2019, 67 (3): 165–171. PMC 6399173 . PMID 30767054. doi:10.1007/s00106-019-0617-7. 
  40. ^ 40.0 40.1 40.2 40.3 Thomson, RS; Auduong, P; Miller, AT; Gurgel, RK. Hearing loss as a risk factor for dementia: A systematic review.. Laryngoscope Investigative Otolaryngology. April 2017, 2 (2): 69–79. PMC 5527366 . PMID 28894825. doi:10.1002/lio2.65. 
  41. ^ Hussain M, Berger M, Eckenhoff RG, Seitz DP. General anesthetic and the risk of dementia in elderly patients: current insights. Clinical Interventions in Aging. 2014, 9: 1619–28. PMC 4181446 . PMID 25284995. doi:10.2147/CIA.S49680. 
  42. ^ 42.0 42.1 Iadecola C. The pathobiology of vascular dementia. Neuron. November 2013, 80 (4): 844–66. PMC 3842016 . PMID 24267647. doi:10.1016/j.neuron.2013.10.008. 
  43. ^ Finger, Elizabeth C. Frontotemporal Dementias. Continuum (Minneapolis, Minn.). April 2016, 22 (2 Dementia): 464–489. ISSN 1538-6899. PMC 5390934 . PMID 27042904. doi:10.1212/CON.0000000000000300. 
  44. ^ Schofield P. Dementia associated with toxic causes and autoimmune disease. International Psychogeriatrics (Review). 2005,. 17 Suppl 1: S129–47. PMID 16240488. doi:10.1017/s1041610205001997. 
  45. ^ 45.0 45.1 Rosenbloom MH, Smith S, Akdal G, Geschwind MD. Immunologically mediated dementias. Current Neurology and Neuroscience Reports (Review). September 2009, 9 (5): 359–67. PMC 2832614 . PMID 19664365. doi:10.1007/s11910-009-0053-2. 
  46. ^ 46.0 46.1 46.2 46.3 46.4 Zis P, Hadjivassiliou M. Treatment of Neurological Manifestations of Gluten Sensitivity and Coeliac Disease.. Curr Treat Options Neurol (Review). 2019-02-26, 21 (3): 10. PMID 30806821. doi:10.1007/s11940-019-0552-7. 
  47. ^ 47.0 47.1 47.2 Makhlouf S, Messelmani M, Zaouali J, Mrissa R. Cognitive impairment in celiac disease and non-celiac gluten sensitivity: review of literature on the main cognitive impairments, the imaging and the effect of gluten free diet.. Acta Neurol Belg (Review). 2018, 118 (1): 21–27. PMID 29247390. doi:10.1007/s13760-017-0870-z. 
  48. ^ Aarsland D, Kurz MW. The epidemiology of dementia associated with Parkinson disease. Journal of the Neurological Sciences (Review). February 2010, 289 (1–2): 18–22. PMID 19733364. doi:10.1016/j.jns.2009.08.034. 
  49. ^ Galvin JE, Pollack J, Morris JC. Clinical phenotype of Parkinson disease dementia. Neurology. November 2006, 67 (9): 1605–11. PMID 17101891. doi:10.1212/01.wnl.0000242630.52203.8f. 
  50. ^ Abbasi, Jennifer. Debate Sparks Over LATE, a Recently Recognized Dementia. JAMA. 2019-08-21, 322 (10): 914. doi:10.1001/jama.2019.12232. 
  51. ^ Lamont P. Cognitive Decline in a Young Adult with Pre-Existent Developmental Delay – What the Adult Neurologist Needs to Know. Practical Neurology. 2004, 4 (2): 70–87. doi:10.1111/j.1474-7766.2004.02-206.x. (原始内容存档于2008-10-07). 
  52. ^ Langa KM, Levine DA. The diagnosis and management of mild cognitive impairment: a clinical review. JAMA. December 2014, 312 (23): 2551–61. PMC 4269302 . PMID 25514304. doi:10.1001/jama.2014.13806. 
  53. ^ Neuropathology Group. Medical Research Council Cognitive Function and Aging Study. Pathological correlates of late-onset dementia in a multicentre, community-based population in England and Wales. Neuropathology Group of the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS). Lancet. January 2001, 357 (9251): 169–75. PMID 11213093. doi:10.1016/S0140-6736(00)03589-3. 
  54. ^ Wakisaka Y, Furuta A, Tanizaki Y, Kiyohara Y, Iida M, Iwaki T. Age-associated prevalence and risk factors of Lewy body pathology in a general population: the Hisayama study. Acta Neuropathologica. October 2003, 106 (4): 374–82. PMID 12904992. doi:10.1007/s00401-003-0750-x. 
  55. ^ White L, Petrovitch H, Hardman J, Nelson J, Davis DG, Ross GW, et al. Cerebrovascular pathology and dementia in autopsied Honolulu-Asia Aging Study participants. Annals of the New York Academy of Sciences. November 2002, 977 (9): 9–23. Bibcode:2002NYASA.977....9W. PMID 12480729. doi:10.1111/j.1749-6632.2002.tb04794.x. 
  56. ^ Ratnavalli E, Brayne C, Dawson K, Hodges JR. The prevalence of frontotemporal dementia. Neurology. June 2002, 58 (11): 1615–21. PMID 12058088. doi:10.1212/WNL.58.11.1615. 
  57. ^ McKee AC, Cantu RC, Nowinski CJ, Hedley-Whyte ET, Gavett BE, Budson AE, Santini VE, Lee HS, Kubilus CA, Stern RA. Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury. Journal of Neuropathology and Experimental Neurology. July 2009, 68 (7): 709–35. PMC 2945234 . PMID 19535999. doi:10.1097/NEN.0b013e3181a9d503. 
  58. ^ 58.0 58.1 Nelson PT, Dickson DW, Trojanowski JQ, Jack CR, Boyle PA, Arfanakis K, et al. Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report. Brain. April 2019, 142 (6): 1503–1527. PMC 6536849 . PMID 31039256. doi:10.1093/brain/awz099. 
  59. ^ What is vascular dementia? 互联网档案馆存檔,存档日期2013-10-19. Alzheimer's Society.
  60. ^ Lee AY. Vascular dementia. Chonnam Medical Journal. August 2011, 47 (2): 66–71. PMC 3214877 . PMID 22111063. doi:10.4068/cmj.2011.47.2.66. 
  61. ^ Lin JS, O'Connor E, Rossom RC, Perdue LA, Eckstrom E. Screening for cognitive impairment in older adults: A systematic review for the U.S. Preventive Services Task Force. Annals of Internal Medicine. November 2013, 159 (9): 601–12. PMID 24145578. doi:10.7326/0003-4819-159-9-201311050-00730. 
  62. ^ Dementia definition. MDGuidelines. Reed Group. [2009-06-04]. (原始内容存档于2009-06-29). 
  63. ^ Caplan JP, Rabinowitz T. An approach to the patient with cognitive impairment: delirium and dementia. The Medical Clinics of North America. November 2010, 94 (6): 1103–16, ix. PMID 20951272. doi:10.1016/j.mcna.2010.08.004. 
  64. ^ Gleason OC. Delirium. American Family Physician. March 2003, 67 (5): 1027–34. PMID 12643363. (原始内容存档于2007-09-29). 
  65. ^ Worrall L, Hickson LM. Implications for theory, practice, and policy. Worrall LE, Hickson LM (编). Communication disability in aging: from prevention to intervention. Clifton Park, NY: Delmar Learning. 2003: 297–98. ISBN 978-0-7693-0015-3. 
  66. ^ Boustani M, Peterson B, Hanson L, Harris R, Lohr KN. Screening for dementia in primary care: a summary of the evidence for the U.S. Preventive Services Task Force. Annals of Internal Medicine. June 2003, 138 (11): 927–37. PMID 12779304. doi:10.7326/0003-4819-138-11-200306030-00015. 
  67. ^ 67.0 67.1 Cullen B, O'Neill B, Evans JJ, Coen RF, Lawlor BA. A review of screening tests for cognitive impairment. Journal of Neurology, Neurosurgery, and Psychiatry. August 2007, 78 (8): 790–99. PMC 2117747 . PMID 17178826. doi:10.1136/jnnp.2006.095414. 
  68. ^ Sager MA, Hermann BP, La Rue A, Woodard JL. Screening for dementia in community-based memory clinics (PDF). WMJ. October 2006, 105 (7): 25–29. PMID 17163083. (原始内容 (PDF)存档于2010-06-26). 
  69. ^ Fleisher AS, Sowell BB, Taylor C, Gamst AC, Petersen RC, Thal LJ. Clinical predictors of progression to Alzheimer disease in amnestic mild cognitive impairment. Neurology. May 2007, 68 (19): 1588–95. PMID 17287448. doi:10.1212/01.wnl.0000258542.58725.4c. 
  70. ^ Karlawish JH, Clark CM. Diagnostic evaluation of elderly patients with mild memory problems. Annals of Internal Medicine. March 2003, 138 (5): 411–19. PMID 12614094. doi:10.7326/0003-4819-138-5-200303040-00011. 
  71. ^ Creavin ST, Wisniewski S, Noel-Storr AH, Trevelyan CM, Hampton T, Rayment D, et al. Mini-Mental State Examination (MMSE) for the detection of dementia in clinically unevaluated people aged 65 and over in community and primary care populations. The Cochrane Database of Systematic Reviews. January 2016, (1): CD011145. PMID 26760674. doi:10.1002/14651858.CD011145.pub2. hdl:1983/00876aeb-2061-43f5-b7e1-938c666030ab. 
  72. ^ Teng EL, Chui HC. The Modified Mini-Mental State (3MS) examination. The Journal of Clinical Psychiatry. August 1987, 48 (8): 314–8. PMID 3611032. 
  73. ^ Teng EL, Hasegawa K, Homma A, Imai Y, Larson E, Graves A, et al. The Cognitive Abilities Screening Instrument (CASI): a practical test for cross-cultural epidemiological studies of dementia. International Psychogeriatrics. 1994, 6 (1): 45–58; discussion 62. PMID 8054493. doi:10.1017/S1041610294001602. 
  74. ^ Tombaugh TN. Trail Making Test A and B: normative data stratified by age and education. Archives of Clinical Neuropsychology. March 2004, 19 (2): 203–14. PMID 15010086. doi:10.1016/S0887-6177(03)00039-8. 
  75. ^ Royall DR, Cordes JA, Polk M. CLOX: an executive clock drawing task. Journal of Neurology, Neurosurgery, and Psychiatry. May 1998, 64 (5): 588–94. PMC 2170069 . PMID 9598672. doi:10.1136/jnnp.64.5.588. 
  76. ^ Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. Journal of the American Geriatrics Society. April 2005, 53 (4): 695–99. PMID 15817019. doi:10.1111/j.1532-5415.2005.53221.x. 
  77. ^ Breton, Alexandre; Casey, Daniel; Arnaoutoglou, Nikitas A. Cognitive tests for the detection of mild cognitive impairment (MCI), the prodromal stage of dementia: Meta-analysis of diagnostic accuracy studies. International Journal of Geriatric Psychiatry. 2019, 34 (2): 233–242. ISSN 1099-1166. PMID 30370616. doi:10.1002/gps.5016 (英语). 
  78. ^ Ranson JM, Kuźma E, Hamilton W, Muniz-Terrera G, Langa KM, Llewellyn D. Predictors of dementia misclassification when using brief cognitive assessments. Neurology: Clinical Practice. 2018-11-28, 9 (2): 109–117. PMC 6461420 . PMID 31041124. doi:10.1212/CPJ.0000000000000566. 
  79. ^ Jorm AF. The Informant Questionnaire on cognitive decline in the elderly (IQCODE): a review. International Psychogeriatrics. September 2004, 16 (3): 275–93. PMID 15559753. doi:10.1017/S1041610204000390. 
  80. ^ Harrison JK, Stott DJ, McShane R, Noel-Storr AH, Swann-Price RS, Quinn TJ. Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the early diagnosis of dementia across a variety of healthcare settings. The Cochrane Database of Systematic Reviews. November 2016, 11: CD011333. PMC 6477966 . PMID 27869298. doi:10.1002/14651858.cd011333.pub2. 
  81. ^ Reisberg B, Ferris SH, de Leon MJ, Crook T. The Global Deterioration Scale for assessment of primary degenerative dementia. Am J Psychiatry. 1982 Sep;139(9):1136-9. PMID 7114305
  82. ^ Sclan SG, Reisberg B. Functional assessment staging (FAST) in Alzheimer's disease: reliability, validity, and ordinality. Int Psychogeriatr. 1992;4 Suppl 1:55-69. PMID 1504288
  83. ^ Bonte FJ, Harris TS, Hynan LS, Bigio EH, White CL. Tc-99m HMPAO SPECT in the differential diagnosis of the dementias with histopathologic confirmation. Clinical Nuclear Medicine. July 2006, 31 (7): 376–78. PMID 16785801. doi:10.1097/01.rlu.0000222736.81365.63. 
  84. ^ Dougall NJ, Bruggink S, Ebmeier KP. Systematic review of the diagnostic accuracy of 99mTc-HMPAO-SPECT in dementia. The American Journal of Geriatric Psychiatry. 2004, 12 (6): 554–70. PMID 15545324. doi:10.1176/appi.ajgp.12.6.554. 
  85. ^ Abella HA. Report from SNM: PET imaging of brain chemistry bolsters characterization of dementias. Diagnostic Imaging. 2009-06-16. [永久失效連結]
  86. ^ 86.0 86.1 Livingston G, Sommerlad A, Orgeta V, Costafreda SG, Huntley J, Ames D, et al. Dementia prevention, intervention, and care. Lancet (Submitted manuscript). December 2017, 390 (10113): 2673–2734. PMID 28735855. doi:10.1016/S0140-6736(17)31363-6. 
  87. ^ Ding, Jie; Davis-Plourde, Kendra L; Sedaghat, Sanaz; Tully, Phillip J; Wang, Wanmei; Phillips, Caroline; Pase, Matthew P; Himali, Jayandra J; Gwen Windham, B; Griswold, Michael; Gottesman, Rebecca; Mosley, Thomas H; White, Lon; Guðnason, Vilmundur; Debette, Stéphanie; Beiser, Alexa S; Seshadri, Sudha; Arfan Ikram, M; Meirelles, Osorio; Tzourio, Christophe; Launer, Lenore J. Antihypertensive medications and risk for incident dementia and Alzheimer's disease: a meta-analysis of individual participant data from prospective cohort studies. The Lancet Neurology. November 2019. PMID 31706889. doi:10.1016/S1474-4422(19)30393-X. 
  88. ^ Llewellyn, David J.; Kuźma, Elżbieta; Hyppönen, Elina; Langa, Kenneth M.; Littlejohns, Thomas J.; Hannon, Eilis; Lourida, Ilianna. Association of Lifestyle and Genetic Risk With Incidence of Dementia. JAMA. 2019-07-14, 322 (5): 430. PMC 6628594 . PMID 31302669. doi:10.1001/jama.2019.9879 (英语). 
  89. ^ Fink HA, Jutkowitz E, McCarten JR, Hemmy LS, Butler M, Davila H, et al. Pharmacologic Interventions to Prevent Cognitive Decline, Mild Cognitive Impairment, and Clinical Alzheimer-Type Dementia: A Systematic Review. Annals of Internal Medicine. January 2018, 168 (1): 39–51. PMID 29255847. doi:10.7326/M17-1529. 
  90. ^ Butler M, McCreedy E, Nelson VA, Desai P, Ratner E, Fink HA, Hemmy LS, McCarten JR, Barclay TR, Brasure M, Davila H, Kane RL. Does Cognitive Training Prevent Cognitive Decline?: A Systematic Review. Annals of Internal Medicine. January 2018, 168 (1): 63–68. PMID 29255842. doi:10.7326/M17-1531. 
  91. ^ Lampit A, Hallock H, Valenzuela M. Computerized cognitive training in cognitively healthy older adults: a systematic review and meta-analysis of effect modifiers. PLoS Medicine. November 2014, 11 (11): e1001756. PMC 4236015 . PMID 25405755. doi:10.1371/journal.pmed.1001756. 
  92. ^ Brasure M, Desai P, Davila H, Nelson VA, Calvert C, Jutkowitz E, Butler M, Fink HA, Ratner E, Hemmy LS, McCarten JR, Barclay TR, Kane RL. Physical Activity Interventions in Preventing Cognitive Decline and Alzheimer-Type Dementia: A Systematic Review. Annals of Internal Medicine. January 2018, 168 (1): 30–38. PMID 29255839. doi:10.7326/M17-1528. 
  93. ^ Kivimäki M, Singh-Manoux A, Pentti J, Sabia S, Nyberg ST, Alfredsson L, et al. Physical inactivity, cardiometabolic disease, and risk of dementia: an individual-participant meta-analysis. BMJ. April 2019, 365: l1495. PMC 6468884 . PMID 30995986. doi:10.1136/bmj.l1495. 
  94. ^ Fink HA, Jutkowitz E, McCarten JR, Hemmy LS, Butler M, Davila H, Ratner E, Calvert C, Barclay TR, Brasure M, Nelson VA, Kane RL. Pharmacologic Interventions to Prevent Cognitive Decline, Mild Cognitive Impairment, and Clinical Alzheimer-Type Dementia: A Systematic Review. Annals of Internal Medicine. January 2018, 168 (1): 39–51. PMID 29255847. doi:10.7326/M17-1529. 
  95. ^ Butler M, Nelson VA, Davila H, Ratner E, Fink HA, Hemmy LS, McCarten JR, Barclay TR, Brasure M, Kane RL. Over-the-Counter Supplement Interventions to Prevent Cognitive Decline, Mild Cognitive Impairment, and Clinical Alzheimer-Type Dementia: A Systematic Review. Annals of Internal Medicine. January 2018, 168 (1): 52–62. PMID 29255909. doi:10.7326/M17-1530. 
  96. ^ Schneider LS, Mangialasche F, Andreasen N, Feldman H, Giacobini E, Jones R, Mantua V, Mecocci P, Pani L, Winblad B, Kivipelto M. Clinical trials and late-stage drug development for Alzheimer's disease: an appraisal from 1984 to 2014. Journal of Internal Medicine. March 2014, 275 (3): 251–83. PMC 3956752 . PMID 24605808. doi:10.1111/joim.12191. 
  97. ^ Watt, Jennifer A.; Goodarzi, Zahra; Veroniki, Areti Angeliki; Nincic, Vera; Khan, Paul A.; Ghassemi, Marco; Thompson, Yuan; Tricco, Andrea C.; Straus, Sharon E. Comparative Efficacy of Interventions for Aggressive and Agitated Behaviors in Dementia. Annals of Internal Medicine. 2019-10-15, 171 (9): 633. doi:10.7326/M19-0993. 
  98. ^ Vandepitte S, Van Den Noortgate N, Putman K, Verhaeghe S, Verdonck C, Annemans L. Effectiveness of respite care in supporting informal caregivers of persons with dementia: a systematic review. International Journal of Geriatric Psychiatry. December 2016, 31 (12): 1277–88. PMID 27245986. doi:10.1002/gps.4504. 
  99. ^ 99.0 99.1 Woods B, O'Philbin L, Farrell EM, Spector AE, Orrell M. Reminiscence therapy for dementia. The Cochrane Database of Systematic Reviews. March 2018, 3: CD001120. PMC 6494367 . PMID 29493789. doi:10.1002/14651858.CD001120.pub3. 
  100. ^ Vernooij-Dassen M, Draskovic I, McCleery J, Downs M. Cognitive reframing for carers of people with dementia. The Cochrane Database of Systematic Reviews. November 2011, (11): CD005318. PMID 22071821. arXiv:0706.4406 . doi:10.1002/14651858.CD005318.pub2. hdl:2066/97731. 
  101. ^ Neal M, Barton Wright P. Validation therapy for dementia. The Cochrane Database of Systematic Reviews. 2003, (3): CD001394. PMID 12917907. doi:10.1002/14651858.CD001394. 
  102. ^ Woods B, Aguirre E, Spector AE, Orrell M. Cognitive stimulation to improve cognitive functioning in people with dementia. The Cochrane Database of Systematic Reviews. February 2012, 2 (2): CD005562. PMID 22336813. doi:10.1002/14651858.CD005562.pub2. 
  103. ^ Barker P. Psychiatric and mental health nursing: the craft of caring. London: Arnold. 2003. ISBN 978-0-340-81026-2. OCLC 53373798. 
  104. ^ Weitzel T, Robinson S, Barnes MR, Berry TA, Holmes JM, Mercer S, et al. The special needs of the hospitalized patient with dementia. Medsurg Nursing. 2011, 20 (1): 13–18; quiz 19. PMID 21446290. 
  105. ^ Cunningham C. Understanding challenging behaviour in patients with dementia. Nursing Standard. 2006, 20 (47): 42–45. PMID 16913375. doi:10.7748/ns2006.08.20.47.42.c4477. 
  106. ^ 106.0 106.1 Dyer SM, Harrison SL, Laver K, Whitehead C, Crotty M. An overview of systematic reviews of pharmacological and non-pharmacological interventions for the treatment of behavioral and psychological symptoms of dementia. International Psychogeriatrics. March 2018, 30 (3): 295–309. PMID 29143695. doi:10.1017/S1041610217002344. 
  107. ^ van der Steen JT, Smaling HJ, van der Wouden JC, Bruinsma MS, Scholten RJ, Vink AC. Music-based therapeutic interventions for people with dementia. The Cochrane Database of Systematic Reviews. July 2018, 7: CD003477. PMC 6513122 . PMID 30033623. doi:10.1002/14651858.CD003477.pub4. hdl:1874/350441. 
  108. ^ Eldirdiry Osman, Sara; Tischler, Victoria; Schneider, Justine. ‘Singing for the Brain’: A qualitative study exploring the health and well-being benefits of singing for people with dementia and their carers. Dementia. 2014-11-24, 15 (6): 1328 [2020-02-04]. PMID 25425445. doi:10.1177/1471301214556291. 
  109. ^ British hospitals are having a dementia-friendly makeover. The Economist. [2018-09-19]. 
  110. ^ Rafii MS, Aisen PS. Recent developments in Alzheimer's disease therapeutics. BMC Medicine. February 2009, 7: 7. PMC 2649159 . PMID 19228370. doi:10.1186/1741-7015-7-7. 
  111. ^ 111.0 111.1 Lleó A, Greenberg SM, Growdon JH. Current pharmacotherapy for Alzheimer's disease. Annual Review of Medicine. 2006, 57 (1): 513–33. PMID 16409164. doi:10.1146/annurev.med.57.121304.131442. 
  112. ^ Bond M, Rogers G, Peters J, Anderson R, Hoyle M, Miners A, Moxham T, Davis S, Thokala P, Wailoo A, Jeffreys M, Hyde C. The effectiveness and cost-effectiveness of donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer's disease (review of Technology Appraisal No. 111): a systematic review and economic model. Health Technology Assessment. 2012, 16 (21): 1–470. PMC 4780923 . PMID 22541366. doi:10.3310/hta16210. 
  113. ^ Rodda J, Morgan S, Walker Z. Are cholinesterase inhibitors effective in the management of the behavioral and psychological symptoms of dementia in Alzheimer's disease? A systematic review of randomized, placebo-controlled trials of donepezil, rivastigmine and galantamine. International Psychogeriatrics. October 2009, 21 (5): 813–24. PMID 19538824. doi:10.1017/S1041610209990354. 
  114. ^ Gill SS, Anderson GM, Fischer HD, Bell CM, Li P, Normand SL, Rochon PA. Syncope and its consequences in patients with dementia receiving cholinesterase inhibitors: a population-based cohort study. Archives of Internal Medicine. May 2009, 169 (9): 867–73. PMID 19433698. doi:10.1001/archinternmed.2009.43. 
  115. ^ AMDA – The Society for Post-Acute and Long-Term Care Medicine, Ten Things Physicians and Patients Should Question, Choosing Wisely英语Choosing Wisely: an initiative of the ABIM Foundation英语ABIM Foundation (AMDA – The Society for Post-Acute and Long-Term Care Medicine), February 2014 [2015-04-20], (原始内容存档于2015-04-12) 
  116. ^ 116.0 116.1 116.2 116.3 116.4 116.5 116.6 American Geriatrics Society. Five Things Physicians and Patients Should Question. Choosing Wisely: An Initiative of the ABIM Foundation. [2013-08-01]. (原始内容存档于2013-09-01). 
  117. ^ American Psychiatric Association, Five Things Physicians and Patients Should Question, Choosing Wisely英语Choosing Wisely: an initiative of the ABIM Foundation英语ABIM Foundation (American Psychiatric Association), September 2013 [2013-12-30], (原始内容存档于2013-12-03) 
  118. ^ Dementia: assessment, management and support for people living with dementia and their carers | Guidance and guidelines | NICE. NICE. [2018-12-18]. 
  119. ^ Dyer SM, Laver K, Pond CD, Cumming RG, Whitehead C, Crotty M. Clinical practice guidelines and principles of care for people with dementia in Australia. Australian Family Physician. December 2016, 45 (12): 884–889. PMID 27903038. 
  120. ^ Declercq T, Petrovic M, Azermai M, Vander Stichele R, De Sutter AI, van Driel ML, Christiaens T. Withdrawal versus continuation of chronic antipsychotic drugs for behavioural and psychological symptoms in older people with dementia (PDF). The Cochrane Database of Systematic Reviews. March 2013, 3 (3): CD007726. PMID 23543555. doi:10.1002/14651858.CD007726.pub2. hdl:1854/LU-3109108. 
  121. ^ Bond M, Rogers G, Peters J, Anderson R, Hoyle M, Miners A, Moxham T, Davis S, Thokala P, Wailoo A, Jeffreys M, Hyde C. The effectiveness and cost-effectiveness of donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer's disease (review of Technology Appraisal No. 111): a systematic review and economic model. Health Technology Assessment. 2012, 16 (21): 1–470. PMC 4780923 . PMID 22541366. doi:10.3310/hta16210. 
  122. ^ Raina P, Santaguida P, Ismaila A, Patterson C, Cowan D, Levine M, et al. Effectiveness of cholinesterase inhibitors and memantine for treating dementia: evidence review for a clinical practice guideline. Annals of Internal Medicine. March 2008, 148 (5): 379–97. PMID 18316756. doi:10.7326/0003-4819-148-5-200803040-00009. 
  123. ^ Atri A, Shaughnessy LW, Locascio JJ, Growdon JH. Long-term course and effectiveness of combination therapy in Alzheimer disease. Alzheimer Disease and Associated Disorders. 2008, 22 (3): 209–21. PMC 2718545 . PMID 18580597. doi:10.1097/WAD.0b013e31816653bc. 
  124. ^ Jones HE, Joshi A, Shenkin S, Mead GE. The effect of treatment with selective serotonin reuptake inhibitors in comparison to placebo in the progression of dementia: a systematic review and meta-analysis. Age and Ageing. July 2016, 45 (4): 448–56. PMID 27055878. doi:10.1093/ageing/afw053. 
  125. ^ Dudas, Robert; Malouf, Reem; McCleery, Jenny; Dening, Tom. Cochrane Dementia and Cognitive Improvement Group , 编. Antidepressants for treating depression in dementia. Cochrane Database of Systematic Reviews. 2018-08-31, 8: CD003944. PMC 6513376 . PMID 30168578. doi:10.1002/14651858.CD003944.pub2 (英语). 
  126. ^ Seitz DP, Adunuri N, Gill SS, Gruneir A, Herrmann N, Rochon P. Antidepressants for agitation and psychosis in dementia. The Cochrane Database of Systematic Reviews. February 2011, (2): CD008191. PMID 21328305. doi:10.1002/14651858.CD008191.pub2. 
  127. ^ 127.0 127.1 127.2 127.3 McCleery J, Cohen DA, Sharpley AL. Pharmacotherapies for sleep disturbances in dementia. The Cochrane Database of Systematic Reviews. November 2016, 11 (11): CD009178. PMC 6464889 . PMID 27851868. doi:10.1002/14651858.CD009178.pub3. 
  128. ^ American Geriatrics Society 2012 Beers Criteria Update Expert Panel. American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults. Journal of the American Geriatrics Society. April 2012, 60 (4): 616–31. PMC 3571677 . PMID 22376048. doi:10.1111/j.1532-5415.2012.03923.x. 
  129. ^ Lolk A, Gulmann NC. [Psychopharmacological treatment of behavioral and psychological symptoms in dementia]. Ugeskrift for Laeger. October 2006, 168 (40): 3429–32. PMID 17032610 (丹麦语). 
  130. ^ Malouf R, Grimley Evans J. Folic acid with or without vitamin B12 for the prevention and treatment of healthy elderly and demented people. The Cochrane Database of Systematic Reviews. October 2008, (4): CD004514. PMID 18843658. doi:10.1002/14651858.CD004514.pub2. 
  131. ^ McGuinness B, Craig D, Bullock R, Malouf R, Passmore P. Statins for the treatment of dementia (PDF). The Cochrane Database of Systematic Reviews. July 2014, 7 (7): CD007514 [2019-09-03]. PMID 25004278. doi:10.1002/14651858.CD007514.pub3. (原始内容 (PDF)存档于2019-09-03). 
  132. ^ Jongstra S, Harrison JK, Quinn TJ, Richard E. Antihypertensive withdrawal for the prevention of cognitive decline. The Cochrane Database of Systematic Reviews. November 2016, 11: CD011971. PMC 6465000 . PMID 27802359. doi:10.1002/14651858.CD011971.pub2. 
  133. ^ Page AT, Potter K, Clifford R, McLachlan AJ, Etherton-Beer C. Medication appropriateness tool for co-morbid health conditions in dementia: consensus recommendations from a multidisciplinary expert panel. Internal Medicine Journal. October 2016, 46 (10): 1189–1197. PMC 5129475 . PMID 27527376. doi:10.1111/imj.13215. 
  134. ^ 134.0 134.1 134.2 134.3 134.4 Hadjistavropoulos T, Herr K, Turk DC, Fine PG, Dworkin RH, Helme R, Jackson K, Parmelee PA, Rudy TE, Lynn Beattie B, Chibnall JT, Craig KD, Ferrell B, Ferrell B, Fillingim RB, Gagliese L, Gallagher R, Gibson SJ, Harrison EL, Katz B, Keefe FJ, Lieber SJ, Lussier D, Schmader KE, Tait RC, Weiner DK, Williams J. An interdisciplinary expert consensus statement on assessment of pain in older persons. The Clinical Journal of Pain. January 2007, 23 (1 Suppl): S1–43. PMID 17179836. doi:10.1097/AJP.0b013e31802be869. 
  135. ^ 135.0 135.1 Shega J, Emanuel L, Vargish L, Levine SK, Bursch H, Herr K, Karp JF, Weiner DK. Pain in persons with dementia: complex, common, and challenging. The Journal of Pain. May 2007, 8 (5): 373–78. PMID 17485039. doi:10.1016/j.jpain.2007.03.003. 
  136. ^ Blyth FM, Cumming R, Mitchell P, Wang JJ. Pain and falls in older people. European Journal of Pain. July 2007, 11 (5): 564–71. PMID 17015026. doi:10.1016/j.ejpain.2006.08.001. 
  137. ^ Brown, C. Pain, aging and dementia: The crisis is looming, but are we ready?. British Journal of Occupational Therapy. 2009, 72 (8): 371–75. doi:10.1177/030802260907200808. 
  138. ^ Herr K, Bjoro K, Decker S. Tools for assessment of pain in nonverbal older adults with dementia: a state-of-the-science review. Journal of Pain and Symptom Management. February 2006, 31 (2): 170–92. PMID 16488350. doi:10.1016/j.jpainsymman.2005.07.001. 
  139. ^ Stolee P, Hillier LM, Esbaugh J, Bol N, McKellar L, Gauthier N. Instruments for the assessment of pain in older persons with cognitive impairment. Journal of the American Geriatrics Society. February 2005, 53 (2): 319–26. PMID 15673359. doi:10.1111/j.1532-5415.2005.53121.x. 
  140. ^ AMDA – The Society for Post-Acute and Long-Term Care Medicine, Five Things Physicians and Patients Should Question, Choosing Wisely英语Choosing Wisely: an initiative of the ABIM Foundation英语ABIM Foundation (AMDA – The Society for Post-Acute and Long-Term Care Medicine), February 2014 [2013-02-10], (原始内容存档于2014-09-13) 
  141. ^ AMDA – The Society for Post-Acute and Long-Term Care Medicine, Five Things Physicians and Patients Should Question, Choosing Wisely英语Choosing Wisely: an initiative of the ABIM Foundation英语ABIM Foundation (AMDA – The Society for Post-Acute and Long-Term Care Medicine), February 2014 [2013-02-10], (原始内容存档于2014-09-13) , which cites:
  142. ^ Mitchell SL, Kiely DK, Lipsitz LA. The risk factors and impact on survival of feeding tube placement in nursing home residents with severe cognitive impairment. Archives of Internal Medicine. February 1997, 157 (3): 327–32. PMID 9040301. doi:10.1001/archinte.1997.00440240091014. 
  143. ^ Sampson EL, Candy B, Jones L. Enteral tube feeding for older people with advanced dementia. The Cochrane Database of Systematic Reviews. April 2009, (2): CD007209. PMID 19370678. doi:10.1002/14651858.CD007209.pub2. 
  144. ^ Lockett MA, Templeton ML, Byrne TK, Norcross ED. Percutaneous endoscopic gastrostomy complications in a tertiary-care center. The American Surgeon. February 2002, 68 (2): 117–20. PMID 11842953. 
  145. ^ Finocchiaro C, Galletti R, Rovera G, Ferrari A, Todros L, Vuolo A, Balzola F. Percutaneous endoscopic gastrostomy: a long-term follow-up. Nutrition. June 1997, 13 (6): 520–3. PMID 9263232. doi:10.1016/S0899-9007(97)00030-0. 
  146. ^ Mitchell SL, Mor V, Gozalo PL, Servadio JL, Teno JM. Tube Feeding in US Nursing Home Residents With Advanced Dementia, 2000–2014 (PDF). JAMA. August 2016, 316 (7): 769–70. PMC 4991625 . PMID 27533163. doi:10.1001/jama.2016.9374. (原始内容存档 (PDF)于2017-09-21). 
  147. ^ Span P. The Decline of Tube Feeding for Dementia Patients. New York Times. 2016-08-29 [2016-08-31]. (原始内容存档于2016-09-03). 
  148. ^ Viggo Hansen N, Jørgensen T, Ørtenblad L. Massage and touch for dementia. The Cochrane Database of Systematic Reviews. October 2006, (4): CD004989. PMC 6823223 . PMID 17054228. doi:10.1002/14651858.CD004989.pub2. 
  149. ^ Forrester LT, Maayan N, Orrell M, Spector AE, Buchan LD, Soares-Weiser K. Aromatherapy for dementia. The Cochrane Database of Systematic Reviews. February 2014, 2 (2): CD003150. PMID 24569873. doi:10.1002/14651858.CD003150.pub2. 
  150. ^ van den Elsen GA, Ahmed AI, Lammers M, Kramers C, Verkes RJ, van der Marck MA, Rikkert MG. Efficacy and safety of medical cannabinoids in older subjects: a systematic review. Ageing Research Reviews. March 2014, 14: 56–64. PMID 24509411. doi:10.1016/j.arr.2014.01.007. 
  151. ^ Burckhardt M, Herke M, Wustmann T, Watzke S, Langer G, Fink A. Omega-3 fatty acids for the treatment of dementia. The Cochrane Database of Systematic Reviews. April 2016, 4: CD009002. PMID 27063583. doi:10.1002/14651858.CD009002.pub3. 
  152. ^ Sampson EL, Ritchie CW, Lai R, Raven PW, Blanchard MR. A systematic review of the scientific evidence for the efficacy of a palliative care approach in advanced dementia. International Psychogeriatrics. March 2005, 17 (1): 31–40. PMID 15945590. doi:10.1017/S1041610205001018. 
  153. ^ Van den Block L. The need for integrating palliative care in ageing and dementia policies. European Journal of Public Health. October 2014, 24 (5): 705–06. PMID 24997202. doi:10.1093/eurpub/cku084. 
  154. ^ Van Der Steen, Jenny T.; Radbruch, Lukas; Hertogh, Cees MPM; De Boer, Marike E.; Hughes, Julian C.; Larkin, Philip; Francke, Anneke L.; Jünger, Saskia; Gove, Dianne; Firth, Pam; Koopmans, Raymond TCM; Volicer, Ladislav; European Association for Palliative Care (EAPC). White paper defining optimal palliative care in older people with dementia: A Delphi study and recommendations from the European Association for Palliative Care. Palliative Medicine. 2014-03-11, 28 (3): 197–209. PMID 23828874. doi:10.1177/0269216313493685. 
  155. ^ Birch D, Draper J. A critical literature review exploring the challenges of delivering effective palliative care to older people with dementia (PDF). Journal of Clinical Nursing. May 2008, 17 (9): 1144–63. PMID 18416791. doi:10.1111/j.1365-2702.2007.02220.x. 
  156. ^ Murphy E, Froggatt K, Connolly S, O'Shea E, Sampson EL, Casey D, Devane D. Palliative care interventions in advanced dementia. The Cochrane Database of Systematic Reviews. December 2016, 12: CD011513. PMC 6463843 . PMID 27911489. doi:10.1002/14651858.CD011513.pub2. 
  157. ^ Murphy E, Froggatt K, Connolly S, O'Shea E, Sampson EL, Casey D, Devane D. Palliative care interventions in advanced dementia. The Cochrane Database of Systematic Reviews. December 2016, 12: CD011513. PMC 6463843 . PMID 27911489. doi:10.1002/14651858.CD011513.pub2. 
  158. ^ Mitchell G, Agnelli J. Person-centred care for people with dementia: Kitwood reconsidered. Nursing Standard. October 2015, 30 (7): 46–50. PMID 26463810. doi:10.7748/ns.30.7.46.s47. 
  159. ^ 159.0 159.1 Prince M, Jackson J. World Alzheimer Report 2009. Alzheimer's Disease International. 2009: 38 [2012-03-11]. (原始内容存档于2012-03-11). 
  160. ^ 160.0 160.1 160.2 160.3 Alzheimer's Disease International. World Alzheimer Report 2015 (PDF). Sep 2015 [2018-10-30]. 
  161. ^ 161.0 161.1 Sadock BJ, Sadock VA. Delirium, Dementia, and Amnestic and Other Cobnitive Disorders and Mental Disorders Due to a General Medical Condition. Kaplan & Sadock's concise textbook of clinical psychiatry 3rd. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins. 2008: 52. ISBN 978-0-7817-8746-8. 
  162. ^ Berrios GE. Dementia during the seventeenth and eighteenth centuries: a conceptual history. Psychological Medicine. November 1987, 17 (4): 829–37. PMID 3324141. doi:10.1017/S0033291700000623. 
  163. ^ Berchtold, N.C. and Cotman, C.W. (1998) Evolution in the conceptu-alization of dementia and Alzheimer's disease: Greco-Roman period to the 1960s. Neurobiol Aging 19, 173–89
  164. ^ Kolata G. Drug Trials Test Bold Plan to Slow Alzheimer's. The New York Times. 2010-06-17 [2010-06-17]. (原始内容存档于2012-04-09). 
  165. ^ Katzman R. Editorial: The prevalence and malignancy of Alzheimer disease. A major killer. Archives of Neurology. April 1976, 33 (4): 217–18. PMID 1259639. doi:10.1001/archneur.1976.00500040001001. 
  166. ^ What is dementia?. Alzheimer's Association. [2018-08-06]. Dementia is often incorrectly referred to as "senility" or "senile dementia," which reflects the formerly widespread but incorrect belief that serious mental decline is a normal part of aging. 
  167. ^ Taylor, Danette C. Dementia. MedicineNet. [2018-08-06]. Senile dementia ("senility") is a term that was once used to describe all dementias; this term is no longer used as a diagnosis. 
  168. ^ Brodaty H, Donkin M. Family caregivers of people with dementia. Dialogues in Clinical Neuroscience. 2017-04-29, 11 (2): 217–28. PMC 3181916 . PMID 19585957. 
  169. ^ National Alzheimer and Dementia Plans Planned Policies and Activities (PDF) (PDF). London: Alzheimer's Disease International. April 2012. (原始内容存档 (PDF)于2012-05-18). 
  170. ^ Addressing Alzheimer's and Other Types of Dementia:Israeli National Strategy Summary Document of the Interdisciplinary, Inter-Organizational Group of Experts » Brookdale. Brookdale. [2018-06-04]. 
  171. ^ Boseley S. Dementia research funding to more than double to £66m by 2015. The Guardian (London). 2012-03-26 [2012-04-27]. ISSN 0261-3077. OCLC 60623878. (原始内容存档于2013-10-20). 
  172. ^ British hospitals are having a dementia-friendly makeover. The Economist. [2018-09-17]. 
  173. ^ Drivers with dementia a growing problem, MDs warn. CBC News, Canada. 2007-09-19. (原始内容存档于2007-10-02). 
  174. ^ Thompson SB. Testamentary capacity and cognitive rehabilitation: implications for head-injured and neurologically impaired individuals. Journal of Cognitive Rehabilitation. 2009, 27: 11–13. 
  175. ^ Tackling dementia. Philanthropy magazine. Winter 2016. (原始内容存档于2016-02-11). 
  176. ^ Daly B, Thompsell A, Sharpling J, Rooney YM, Hillman L, Wanyonyi KL, White S, Gallagher JE. Evidence summary: the relationship between oral health and dementia. British Dental Journal. January 2018, 223 (11): 846–53. PMID 29192686. doi:10.1038/sj.bdj.2017.992. 
  177. ^ Miklossy, J. Historic evidence to support a causal relationship between spirochetal infections and Alzheimer's disease.. Frontiers in Aging Neuroscience. 2015, 7: 46. PMC 4399390 . PMID 25932012. doi:10.3389/fnagi.2015.00046. 
  178. ^ 178.0 178.1 178.2 Olsen I, Singhrao SK. Can oral infection be a risk factor for Alzheimer's disease?. Journal of Oral Microbiology. 2015-09-17, 7: 29143. PMC 4575419 . PMID 26385886. doi:10.3402/jom.v7.29143. 
  179. ^ Can poor oral health lead to dementia?. British Dental Journal. December 2017, 223 (11): 840. PMID 29243693. doi:10.1038/sj.bdj.2017.1064. 
  180. ^ Carter CJ. Alzheimer's disease plaques and tangles: cemeteries of a pyrrhic victory of the immune defence network against herpes simplex infection at the expense of complement and inflammation-mediated neuronal destruction. Neurochemistry International. February 2011, 58 (3): 301–20. PMID 21167244. doi:10.1016/j.neuint.2010.12.003. 

外部連結 编辑

  维基共享资源上的相關多媒體資源:Koala0090/失智症


引证错误:页面中存在<ref group="lower-alpha">标签或{{efn}}模板,但没有找到相应的<references group="lower-alpha" />标签或{{notelist}}模板