1. Dementia with Lewy bodies
DLB

2. Dementia with Lewy bodies
Int J Geriatr Psychiatry 2001; 16: S12±S18.
DLBはAlzheimer病に次いで最も多い認知症の原因
認知症の20%を占める.
発症年齢は75[50-83]歳, 男性が多く女性の1.2-3.0倍程度.
発症は慢性, 急性, 突如発症 どのタイプもあり得る.
急性の認知症, 入院後の急速なADL低下もあり得るため,
誰しも知っておかねばならない疾患の1つ.

3. DLBは変動性の認知機能低下, 視覚幻覚,
パーキンソニズムの3つを特徴とする.
他にはNeuroleptic sensitivity, 転倒, 他の精神症状,
幻聴, 失神, めまいなど認められる.
Lewy bodyは視床下部, 前帯状回, 後頭葉, 辺縁系,
そして脊髄交感神経に沈着.
前帯状回, 交感神経への沈着 ⇒ 全身性の自律神経障害
後頭葉 ⇒ 幻視
視床下部, 深部覚 ⇒ Parkinsonism を呈する.
自律神経障害; 嘔吐, イレウス, 便秘, 体重減少, 失神等.
>> DLBは全身症状を来す疾患であることに注意

4. Int J Geriatr Psychiatry 2001; 16: S12±S18.
変動する認識障害; 数分∼数日にかけて変動.
50-75%の患者で認められる.
意識レベルや注意力が変動することが多い.
幻視; 80%で認められる.
幻視は細かく, 色も多彩な幻視.
子供や動物であることが多い.
判別能の低下と合併することが多い.
他には幻聴は20%, Paranoid delusionは65%で認める.

5. Int J Geriatr Psychiatry 2001; 16: S12±S18.
Parkinsonism; 初診時, DLBの∼50%で認めるとの報告あり
必発ではなく, 25%はパーキンソン症状を認めない.
特に多い症状はBradykinesiaと固縮で, 安静時振戦は少ない.
繰り返す転倒はDLBの1/3で認められる.

6. DLBとADの症状
Australian and New Zealand Journal of Psychiatry 1999; 33:800–808
DLB DLB AD AD
症状
@来院時 ＠全期間 @来院時 @全期間
認知症 82[40-100] 100 100 100
変動 58[8-85] 75[45-90] 6[3-11] 12[5-19]
幻視 33[11-64] 46[13-80] 13[3-19] 20[11-28]
幻聴 19[13-30] 19[0-45] 1[0-3] 4[0-13]
抑うつ 29[7-75] 38[12-89] 16[9-38] 16[12-21]
パーキンソニズム 43[10-78] 77[50-100] 12[5-30] 23[19-30]
転倒 28[10-38] 37[22-50] 9[5-14] 18[11-24]
Neuroleptic sensitivity 61[0-100] 15[0-29]

7. 早期のDLB, ADの症状比較;
Table 2. Presenting symptoms of DLB and AD
DLB (n = 61) AD (n = 109) DLB and abnormal p value1
DAT scan (n = 26)
Memory impairment 35 (57.4) 108 (99.1) 11 (42.3) 0.000
Visual hallucinations 27 (44.3) 3 (2.8) 11 (42.3) 0.000
Depression 21 (34.4 ) 26 (23.9) 10 (38.4) 0.045
Problem-solving difficulties 20 (32.8) 31 (28.4) 8 (30.8) 0.018
Gait problems 17 (27.9) 9 (8.3) 7 (26.9) 0.000
Tremor and/or stiffness 15 (24.6) 4 (3.7) 10 (38.4) 0.000
Language problems 10 (16.4) 19 (17.4) 2 (7.7) 0.001
Tendency to fall 8 (13.1) 4 (3.7) 4 (15.4) 0.000
Values are presented as patient numbers (%). 1 DLB (n = 61) and AD (n = 109) compared. More than one
symptom can be reported.
DLBは認知症はADよりも進行が遅い
Table 3. Symptoms prior to the dementia stage
一方, 幻覚や抑うつ, 歩行障害, パーキンソニズムを認め,
DLB (n = 61) AD (n = 109) p value
ADL低下に関与する.
Visual hallucinations 47 (77.0) 7 (6.4) 0.000
Gait problems, problems with balance or falling 40 (65.6) 21 (19.3) 0.000
Tremor or stiffness 36 (59.0) 11 (10.1) 0.000
Delirium/fluctuations of consciousness 26 (42.6) 15 (13.8) 0.000
Dement Geriatr Cogn Disord 2011;32:202–208

8. Values are presented as patient numbers (%). 1 DLB (n = 61) and AD (n = 109) compared. More than one
symptom can be reported.
認知症出現前に認める症状の比較
Table 3. Symptoms prior to the dementia stage
DLB (n = 61) AD (n = 109) p value
Visual hallucinations 47 (77.0) 7 (6.4) 0.000
Gait problems, problems with balance or falling 40 (65.6) 21 (19.3) 0.000
Tremor or stiffness 36 (59.0) 11 (10.1) 0.000
Delirium/fluctuations of consciousness 26 (42.6) 15 (13.8) 0.000
Values are presented as patient numbers (%).
ptoms, followed by depression (38%) and Discussion
ess (38%).
nalyzed the distribution of presenting symp- Caregivers reported memory impairment (57%), visu-
e and female DLB patients separately, and al hallucinations (44%), depression (34%), and problem
no differences between genders (data not solving difficulties (33%) as the most common presenting
symptoms in DLB. Among the core features, visual hal-
ows the frequency of core features which oc- lucinations (77%) were the most common symptom prior
to diagnosis. In DLB, visual hallucinations to the first assessment, followed by parkinsonism (ϳ60%)
77% of the patients, gait problems/problems and delirium/fluctuating cognition (43%). Very few pre-
or falling in 66%, tremor/stiffness in 59%, vious studies have attempted to determine the presenting
m/attentional fluctuations in 43%. In con- symptoms of a relatively large groupDisord 2011;32:202–208
Dement Geriatr Cogn of DLB patients. In

9. Pathology
Int J Geriatr Psychiatry 2001; 16: S12±S18.
Lewy body; α-synuclein, ubiquitin陽性の封入体.
Parkinson病では, 皮質下のLB沈着が主であり,
錐体外路症状に関連しているとされる.
DLBでは, 皮質下, 辺縁系, 神経皮質への沈着が多い.
辺縁系, 皮質へのLBの沈着 ⇒ 認知機能, 神経精神症状に関連
脊髄交感神経への沈着 ⇒ 自律神経障害に関連
迷走神経背側核への沈着 ⇒ 嚥下障害に関連

10. Int J Geriatr Psychiatry 2001; 16: S12±S18.
Neurochemicalの異常としては,
Choline acetyltrasferase(ChAt)の減少を認める.
ADと比較してもAChの活動性は低下している.
ADもDLBも前脳基底核からのACh投射は低下しているが,
DLBでは脳幹からのACh投射も低下している.

11. DLBの画像
Int J Geriatr Psychiatry 2001; 16: S12±S18.
ADと比較して, DLBでは側頭葉内側,
特に海馬は保たれていることが多い.
SPECTや他の所見はADと類似している.

12. MIBG心筋シンチ
Neurology 2006;66:1850-54
• PD, DLBにて取り込みの低下を認める
と, 言われているが, その他疾患でも取り込みは低下する
– PDに対するSn 87.7%, Sp 37.4%
(J Neurol Neurosurg Psychiatry 2005;76:249-51)
診断 感度 診断 感度
PD Hohen-Yahr I 38.9% 多系統委縮 21.4%
PD Hohen-Yahr II 85.2% DLB 100%
PD Hohen-Yahr III 100% PSP 85.7%
PD Hohen-Yahr IV 100% Alzheimer type 80%
PD Hohen-Yahr V 100% 脳血管障害 64.3%
– DLBとADとの鑑別にはheart-to-mediastinum(H/M)が有用
• Cut-off 1.68とした時, Sn/Sp 100/100%でDLBを示唆する
• Washout rateではSn/Sp 84/83%と診断能は低下する

13. 804
DLBの診断Criteria DEMENTIA WITH LEWY BODIES
Table 4. Consensus criteria for the clinical diagnosis of probable and possible dementia with
Lewy bodies (DLB)
Criteria
1. The central feature required for a diagnosis of DLB is progressive cognitive decline of sufficient magnitude to interfere
with normal social or occupational function. Prominent or persistent memory impairment may not necessarily occur in the
early stages but is usually evident with progression. Deficits on tests of attention and of frontal-subcortical skills and visu-
ospatial ability may be especially prominent.
2. Two of the following core features are essential for a diagnosis of probable DLB, one is essential for possible DLB:
(a) fluctuating cognition with pronounced variations in attention and alterness;
(b) recurrent visual hallucinations which are typically well formed and detailed;
(c) spontaneous motor features of parkinsonism.
3. Features supportive of the diagnosis are:
(a) repeated falls;
(b) syncope;
(c) transient loss of consciousness;
(d) neuroleptic sensitivity;
(e) systematised delusions;
(f) hallucinations in other modalities.
4. A diagnosis of DLB is less likely in the presence of:
(a) stroke disease, evident as focal neurological signs or on brain imaging;
(b) evidence on physical examination and investigation of any physical illness, or other brain disorder, sufficient to account
for the clinical picture.
From McKeith et al. [10].
Australian and New Zealand Journal of Psychiatry 1999; 33:800–808

14. DLBの治療
Int J Geriatr Psychiatry 2001; 16: S12±S18.
DLBに特異的な治療は現時点では無し.
認知障害に対するD2-R antagonismではParkinson症状の増悪のリス
クがあり, Neurolepticを使用すればNeuroleptic sensitivityと呼ばれる
致死的な副作用が出現するリスクが高い.
PDに対する薬剤は精神症状を増悪させるため,
減量, 中止を考慮すべき;
抗コリン薬, アマンタジン, Selegeline, Dopamine agonist, Levodopa
抗PD薬中止しても精神症状が改善しない場合,
抗精神病薬の使用を考慮すべき.

15. 抗精神病薬を使用する場合
Neuroleptic sensitivityのリスクがあるため, Low-doseで使用
リスペリドン <1mg, オランザピン 2.5-7.5mg,
クエチアピン 12.5-150mg が推奨される.
幻覚や焦燥感の改善を狙う.
コリンエステラーゼ阻害薬; Rivastigmine
イクセロンパッチ®, リバスタッチパッチ® 4.5~18mg
ADに対する貼付薬だが, DLBの認知機能,
精神症状改善効果も期待可能.
無為や不安, せん妄, 幻覚の軽減効果もあり.

16. Drugs most frequently discontinued after baseline were
those acting on the nervous system (discontinued in 24
patients) and on the cardiovascular system (11); no major
differences between groups emerged in this respect.
RivastigmineのRCT
92 patients completed the 20 weeks’ treatment (figure
1) and were available for the observed-cases analysis. A
total of 28 patients (18 rivastigmine, ten placebo)
discontinued the study Lancet 2000; 356: 2031–36
prematurely. Reasons for
discontinuation were similar in both groups, apart from
120名のDLB患者のDB-RCT;
withdrawal of consent, which arose more often in the
rivastigmine group than in those on placebo. There were
117 patients available for the last observation carried
forward data set efficacy analysis, and a total of 89
Rivastigmine 12mg vs Placeboに割り付け, 20wk継続. その後3wk休薬
患者群のBaseline; Treatment group
Rivastigmine (n=59) Placebo (n=61)
Age (years)
Mean 73·9 73·9
SD 6·5 6·4
イクセロンパッチ®, range
р65*
57–87
6 (10·2%)
62–85
8 (13·1%)
66–75* 26 (44·1%) 26 (42·6%)
リバスタッチパッチ® 4.5~18mg 76–85*
>85*
26 (44·1%)
1 (1·7%)
27 (44·3%)
0
お値段 337円∼427円/日 Sex
Male* 31 (52·5%) 37 (60·7%)
Female* 28 (47·5%) 24 (39·3%)
MMSE
Mean 17·9 17·8
SD 4·7 4·4
Range 10–29 11–26
*n (%) shown.
Table 1: Baseline characteristics of patients

17. Number of Baseline Mean change Comparison
patients mean (SD) from baseline
Between-group p
at week 20
difference
mean (SD)
(95% CI)
アウトカム; NPI-4
ITT
Rivastigmine 59 12·2 (8·2) 2·5 (8·4)
1·7 (Ϫ1·1 to 4·6) 0·088
Placebo 61 11·7 (8·6) 0·8 (7·3)
LOCF
神経精神症状 Rivastigmine
Placebo
47
53
12·1 (7·9)
11·2 (8·4)
3·1 (9·1)
0·8 (7·4)
2·3 (Ϫ0·9 to 5·7) 0·045
Scoreは有意差ないが, OC
Rivastigmine 41 12·0 (7·9) 4·1 (8·3)
3·4 (0·06 to 6·6) 0·010
Placebo 51 11·3 (8·6) 0·7 (7·4)
≥30%の改善を示した例は NPI-10
LOCF
Rivastigmine 47 23·2 (15·0) 5·0 (16·2)
3·8 (Ϫ1·6 to 9·2) 0·048
有意にrivastigmine群で多い. Placebo 53 20·2 (14·2) 1·2 (10·7)
OC
Rivastigmine 41 22·7 (15·0) 7·3 (13·7)
6·4 (1·4 to 11·5) 0·005
Placebo 51 20·1 (14·4) 0·9 (10·4)
p=0·030 p=0·005 p=0·001
NPI-4=four item neuropsychiatric inventory sub-score; ITT=intent to treat dataset;
70 63·4 LOCF=last observation carried forward dataset; OC=observed cases dataset;
60 57·4 NPI-10=ten item neuropsychiatric inventory sub-score.
Percentage of patients
Table 2: Mean changes from baseline for NPI-4 and NPI-10
improving by ୑30%
47·5 Rivastigmine
50
Placebo NPI-4; four item neuropsychiatric inventory sub-score
40 Efficacy
30·2 30·0 NPI-10; Ten item neuropsychiatric inventory sub-score
30 27·9 The mean change from baseline on NPI-4 at week 20
favoured rivastigmine for all three data sets (table 2). The
20 difference between rivastigmine and placebo for analyses of
10 the last observation carried forward and the observed cases
was significant at week 20. For the computerised cognitive
0 assessment system speed score, difference between
ITT LOCF OC rivastigmine and placebo was significant in all three data
Figure 3: Percentage of patients showing ୑30% improvement sets at week 12 (intent to treat p=0·010; last observation
from baseline on NPI-4 by week 20 carried forward p=0·005; observed cases p=0·002) and at
ITT=intent to treat dataset; LOCF=last observation carried forward week 20 (intent to treat p=0·048; last observation carried
dataset; OC=observed cases dataset. forward p=0·046; observed Lancet 2000; 356: 2031–36The
cases p=0·017) (figure 2).

18. sets at week 12 (intent to treat p=0·010; last observation (p=0·085) for rivastigmine was seen in patient showing
Mean change from baseline (week
Improvemen
–2·00
carried
–5000 forward p=0·005; observed cases p=0·002) and at CGC-plus improvement at week 20 (good, moderate, and
–1·50
week 20 (intent to treat p=0·048; last observation carried
–4000 Rivastigmine minimum) in the observed dataset cases. No significant
Improvement
forward p=0·046; observed cases p=0·017) (figure 2). The
Placebo –1·00 difference between rivastigmine and placebo was seen in
–3000
proportion of patients who improved significantly at week –0·50 mean CGC-plus score. Changes in MMSE scores at week
–2000
20—ie, showed at least a 30% reduction from baseline on 0
–1000
認知機能もRivastigmineで改善する傾向. 20 favoured rivastigmine for all three data sets, although the
Deterioration
their NPI-4 scores—was significantly greater in the 0·50
differences between treatment groups were not significant.
ms
0
rivastigmine group for all three data sets (figure 3). The observed cases analysis showed a mean improvement
Deterioration
1000 1·00
For the NPI-10 score, difference between treatments, of 1·5 points for patients on rivastigmine, whereas patients
2000
with respect to mean change from baseline at week 20, was 1·50 on placebo declined by 0·1 points (p=0·072). All other
significant for both the last observation carried forward and
3000 2·00
observed cases data sets (table 2). The percentage of
4000
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Figure 2: Computerised cognitive assessment system speed
Ab
pe
–1·50
–4000
Ap
score: mean change (95%Rivastigmine
CIs) from baseline
Mean values (rivastigmine 1084 and 1318 ms; placebo Ϫ2503 and
Improvement
–3000 Placebo
Ϫ991 ms) and 95% CIs in observed cases dataset at weeks 12 and 20 Figure 4: Mean changes–1·00CIs) of individual NPI items—
(95%
were close to those shown for follow-up. observed-cases analysis
–0·50
–2000
Mean change from
–1000 0
Deterioration
2034 THE LANCET • Vol 356 • December 16, 2000
0·50
ms
0 Copyright © 2000 All Rights Reserved
Deterioration
神経精神症状を細かく比較;
1000 1·00
For personal use only. Not to be reproduced without1·50
2000 permission of The Lancet.
せん妄, 幻覚, 不安, 無為は
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Figure 2: Computerised cognitive assessment system speed
Ab
pe
Ap
score: mean change (95% CIs) from baseline
Mean values (rivastigmine 1084 and 1318 ms; placebo Ϫ2503 and
Ϫ991 ms) and 95% CIs in observed cases dataset at weeks 12 and 20 Figure 4: Mean changes (95% CIs) of individual NPI items—
were close to those shown for follow-up. observed-cases analysis
Lancet 2000; 356: 2031–36