認知症総論

精神科

認知症

アルツハイマー型認知症(Alzheimer dementia)・脳血管性認知症(cerebrovascular dementia)・レビー小体型認知症(dementia with Lewy bodies)を「三大認知症」と呼び、この3つに前頭側頭葉型認知症(Frontotemporal dementia:FTD)を加えたものを「四大認知症」と呼ぶ。

Alzheimer型認知症が最も多く約68%、そして脳血管性認知症が約20%、Lewy小体型認知症が約4%、前頭側頭型認知症が約1%を占めるというように続く。

認知症の症状には中核症状と周辺症状がある。

中核症状とは脳の損傷を受けて直接現れる症状を指し、記憶障害・見当識障害・失語、失認、失行・遂行機能障害がある。中核症状は程度や時期の差はあるものの、全ての認知症患者に必ず出現する症状である。

老化現象による「物忘れ」と認知症による「物忘れ」の違いに関して、老化現象による「物忘れ」は記憶を再生する(思い出す)能力の障害によるものであり、認知症による「物忘れ」は記憶自体をする能力の障害によるものである。このため、老化現象による「物忘れ」の場合は約束したこと自体は覚えているが約束した内容を思い出すことができないというような形となり、ヒントがあれば思い出すことができることもある。一方で、認知症による「物忘れ」の場合は約束したこと自体を覚えていないので、ヒントを与えられても全く身に覚えがないという形となる。老化現象による「物忘れ」と認知症による「物忘れ」の同じ点は、昔の記憶は比較的保たれるが最近の出来事に関する記憶が障害されるという点である。

一方、周辺症状は中核症状と周囲の環境やその人の性格などが相互に影響して二次的に生じる症状を指す。周辺症状には、幻覚・妄想・せん妄などの精神症状と徘徊・暴力・過食などの行動症状がある。

Alzheimer型認知症

細胞毒性のあるAβ蛋白と過リン酸化タウ蛋白が側頭葉内側面に存在する海馬や頭頂葉に徐々に蓄積することで神経細胞死が生じて、海馬と頭頂葉が萎縮して緩徐進行性の認知機能障害が起こる疾患である。

Alzheimer型認知症の症状

Alzheimer型認知症における初発症状は海馬によって形成される「個人が経験した出来事に関する記憶」である「エピソード記憶(陳述記憶)」の障害である。例えば、Alzheimer型認知症の患者は会話の内容や昨日の夕食で食べた物を忘れてしまう。また、Alzheimer型認知症で見られるのは記銘力(新しいことを覚える力)の低下なので、誕生日・現住所・卒業した大学名・自宅の電話番号などの昔の記憶は保たれている。

後頭葉から送られてくる視覚情報を統合して「空間認識」を行う頭頂葉が障害されると「身体と衣服を空間的に把握できず一人で衣服を着用できなくなる」着衣失行や「場所が分からなくなって迷子になる」見当識障害や「障害側と反対側の視空間を無視する状態になる」半側空間無視といった症状が出る。ただし、Alzheimer型認知症で典型的な半側空間無視が起こることは少ない。

「物事を順序立てて行うことができなくなる」遂行機能障害が認められる。例えば、Alzheimer型認知症における遂行機能障害は「今までは料理が得意であったのに、最近は献立の種類が減り簡単なものしか作ることができなくなった」というような形で表現されることが多い。

被害妄想の一つである物盗られ妄想がAlzheimer型認知症ではみられ特徴的である。

Alzheimer型認知症の脳病理所見

①神経原線維変化・・・過リン酸化タウ蛋白の神経細胞内への蓄積は神経原線維の変性を引き起こし、神経原線維変化はこれを指す。

タウ蛋白…細胞骨格を形成する微小管を支えるタンパク質の一つ

神経原線維…細胞の骨格を支えたり、細胞内の物質の移動に役立っている神経線維

②老人斑・・・βセクレターゼとγセクレターゼによって形成される神経細胞毒性の強いAβ蛋白(アミロイドβタンパク)が神経細胞外に沈着したものが「老人斑」である。

神経原線維変化と老人斑に伴って神経細胞死が起きて、海馬や頭頂葉における神経細胞が脱落する。これによって側頭葉内側面に存在する海馬と頭頂葉は萎縮する。

海馬と頭頂葉ではアセチルコリンが神経伝達物質として使われており、海馬と頭頂葉におけるアセチルコリン産生神経細胞が脱落してアセチルコリンが減少することで海馬と頭頂葉の機能障害が生じるのである。

Alzheimer型認知症の検査

脳SPECT…脳の血流状態を画像にしてみることができる脳SPECTで側頭葉と頭頂葉に早期から血流低下を認める。

頭部単純MRI…海馬の萎縮によって側脳室下角の拡大を認めることになる。

Alzheimer型認知症の治療

アセチルコリンエステラーゼ阻害薬であるドネペジル塩酸塩が有効である。

脳血管性認知症(Vascular dementia)

脳梗塞や脳出血などによって生じる認知症である。

脳血管性認知症の特徴

①脳血管性認知症は階段状に進行するという症状の出現様式が特徴的である。

症状が突発的に出現したり、落ち着いていると思うと急に悪化することを繰り返したりして変動したりすることがしばしば見られる。

このため、正常な認知機能が保たれている状態と認知症による認知機能低下の状態が混在することになり「まだら認知症」と呼ばれる。

②このほか、些細なことで急に怒りだしたり泣きだすというように感情のコントロールが難しくなる「情動失禁」が見られるのが特徴である。

Lewy小体型認知症(dementia in Lewy disease=dementia with Lewy bodies)

Lewy小体型認知症はα-シヌクレインを主体とするLewy小体が大脳皮質や脳幹にもびまん性にみられるようになって発症する。

Lewy小体型認知症の検査

脳血流SPECT

Lewy小体型認知症では脳血流SPECTにおいてアルツハイマー型認知症と同様に頭頂葉と側頭葉に血流低下がみられることに加えて、後頭葉の血流低下もみられることが特徴とされる。しかし、Lewy小体型認知症における大脳皮質のレビー小体は頭頂葉と側頭葉に多く認められるが後頭葉には稀である。これは、Lewy小体型認知症における後頭葉の血流低下は神経細胞死による病理学的変化というよりも、大脳基底核の下にある前脳基底部や脳幹のアセチルコリン起始細胞の脱落によってアセチルコリンが後頭葉で不足して機能低下を引き起こすという説の根拠となっている。

ドパミントランスポーターシンチグラフィ

MIBG心筋シンチグラフィ

Lewy小体型認知症の症状

視覚認知の中枢である後頭葉が血流低下によって障害された結果として、Lewy小体型認知症に特徴的な症状である幻視が起こる。

幻視では実際にはその場にいない小動物や人などが本人にははっきりと見える。

幻視に伴う被害妄想が生じることもある。

注意や覚醒レベルによって顕著に変動する動揺性の認知機能がみられる。

パーキンソン病とLewy小体型認知症はLewy小体病という同じスペクトラム上(連続上)にあるので、Lewy小体型認知症ではパーキンソニズムを認める。

リスペリドンなどの抗精神病薬を使用するとパーキンソニズム(錐体外路症状)が憎悪して筋強剛(筋固縮)を認めるという「抗精神病薬に対する感受性の亢進」がみられる。

Lewy小体型認知症は初期から中期にかけては記憶障害が目立たない場合も多く、アルツハイマー型認知症のような一般的な認知症だとは認識されにくい面があるが、進行するにつれて記憶障害はみられるようになる。

Lewy小体型認知症の治療

アセチルコリン不足を改善するためにアセチルコリンエステラーゼ阻害薬が有効となる。

パーキンソニズムに対してはパーキンソン病の治療薬が有効である。

前頭側頭型認知症:Frontotemporal Dementia(Pick病)

細胞毒性のあるPick小体(Pick球)が側頭葉前方や前頭葉に徐々に蓄積することで神経細胞死が生じて、側頭葉前方と前頭葉が萎縮して緩徐進行性の認知機能障害が起こる疾患である。

前頭側頭型認知症の症状

「行動を開始したり、行動を抑制する機能」を司るのが前頭葉である。

前頭葉の「行動を開始する機能」が障害されると、自発性の減退や無関心が見られて「何もしない状態が続く」ようになる。

前頭葉の「行動を抑制する機能」が障害されると、「衝動的な行動をしてしまう」脱抑制状態になってしまうことで「自己中心的な振る舞いや無礼な行動をするといった人格変化(性格変化)と異常行動」が認められる。

また、「同じ行動を繰り返す」常同行動が特徴的であり、常同行動の例としては「会話の内容に関係ない言葉を繰り返す」滞続言語や「毎食同じ食事を摂取する」といったようなことが挙げられる。

「物事を順序立てて行うことができなくなる」遂行機能障害が認められるのも重要である。

性格変化や行動異常が主な症状で物忘れなどの症状は出にくいので、単に性格が変わっただけだと思われて病気の発見が遅れやすい。

前頭側頭型認知症の脳病理所見

神経細胞内にPick球(Pick小体)と呼ばれる異常リン酸化タウ蛋白を主とする好酸性【染色色素エオシンを取り込む組織学的切片に見られる細胞および構造の外観を表す】で丸い形の封入体【異常な物質の集積により形成される細胞内の異染色領域であり能動的機能を有しない小体】が認められる。

前頭側頭型認知症の検査

脳血流SPECTの所見は前頭葉から側頭葉にかけての血流低下が特徴的である。

参考文献

認知症の行動・心理症状(BPSD)と効果的介入:https://www.jstage.jst.go.jp/article/rousha/34/1/34_29/_pdf/-char/ja

認知症の要因と予防:https://www.nuas.ac.jp/IHN/report/pdf/07/02.pdf

アルツハイマー型認知症の診断と治療:https://journal.jspn.or.jp/jspn/openpdf/1100070577.pdf

認知症診療ガイドライン 2017:https://journal.jspn.or.jp/jspn/openpdf/1100070577.pdf

Lewy小体型認知症の治療:https://www.jstage.jst.go.jp/article/jsnt/37/1/37_32/_pdf

レビー小体病の症候と病態:http://www.rouninken.jp/member/pdf/21_pdf/vol.21_03-21-01.pdf

レビー小体型認知症の病態と、早期診断のコツ:https://www.jstage.jst.go.jp/article/ninchishinkeikagaku/18/3+4/18_162/_pdf/-char/ja

高齢者の脳血管性認知症:https://www.jstage.jst.go.jp/article/geriatrics/54/4/54_54.519/_pdf

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