Appendix 2 Table 3: Results for Placebo-Controlled Studies by Outcome

Blood Pressure (mmHg) / Cognitive function / ADL / Adverse Outcomes
Baseline / End / Baseline Mean (SD) / End/Change from Baseline
Morich / All groups:
200-100/
50-114 / Not reported / MMSE / ADAS / ADAS(c) / CGI(GI) / CGI(s) / GERRI / MMSE / GDS / BSR / Not reported / No difference in drop-outs.
6 deaths (in treatment group); 2 likely related to Nimodipine
Pooled data / Placebo / 18.0 (3.4) / 4.28 / 3.03 / 4.45 / 0.19 / 0.14 / -1.97 / 0.19 / -1.85
Nimodipine 90mg / 18.0 (3.4) / 3.82 / 2.59 / 4.51 / 0.19 / 0.11 / -1.68 / 0.18 / -0.80
Nimodipine 180mg / 18.2 (3.4) / 3.46 / 2.58 / 4.38 / 0.18 / 0.11 / -1.37 / 0.16 / -0.83
P value / p=0.11 / p=0.25 / p=0.22 / p=0.73 / p=0.2 / p=0.004 / p=0.35 / p=0.109
Stratum I / Placebo / 5.65 / 3.98 / 4.64 / 0.24 / 0.16 / -2.93 / 0.23 / -3.28
Nimodipine 180mg / 3.78 / 2.81 / 4.55 / 0.18 / 0.11 / -2.11 / 0.21 / -2.29
P value / p=0.01 / p=0.03 / p=0.11 / p=0.14 / p=0.18 / p=0.006 / p=0.777 / p=0.26
Pantoni / SCAG / MMSE / SCAG / MMSE / Set Test / Digit Span / Lexical Production / Not reported / Drop-outs higher in placebo group:
Cardiovascular
RR: 2.26
CI: 1.11-4.6
Cerebrovascular RR: 3.88
CI: 1.49-10.2
Nimodipine / 144/83 / 143/82 / 43.7 (13.0) / 20.0 (3.0) / 48.6 (16.4) / 19.2 (4.6) / 25.6 (11.2) / 2.2 (1.3) / 8.3 (5.6)
Placebo / 145/82 / 144/82 / 45.0 (12.6) / 20.5 (3.2) / 47.9 (16.1) / 19.1 (5.5) / 24.9 (11.7) / 2.6 (1.4) / 8.1 (6.9)
Difference from baseline / p=0.27 / p=0.60 / p=0.07 / p=0.15 / p<0.01
ITT / p=0.36 / p=0.10 / p=0.13 / p=0.43 / p<0.01
WR / p=0.15 / p<0.01 / p<0.01 / p=0.27 / p<0.001
PROGRESS / Mean diff / MMSE / Cognitive Decline
Placebo / Values not reported / vs placebo / 29
Med IQR: 27-30 / No apparent effect on 964 with baseline cognitive impairment
RRR: -5% (95% CI: -42% to 22%; p=0.7) / Not reported / Drop-out rates 23% active treatment vs. 21% placebo group
p=0.02
Single therapy / 12/5 (0.5/0.3) / For all active treatment 29 Med IQR: 27-30
Double therapy / 5/3 (0.6/0.3)
P value / <0.001
Sze / Values not reported for either group / No difference in mean BP change between groups p=0.2 / MMSE / FOME / MMSE / No difference in Barthel Score mean score change p=0.6 / No difference in drop-out (p=0.3) or death rates (p=1.0)
GROUP A / Nimodipine / 28.91 +/- 0.31 / FOME results not stratified by Group
Nimodipine: 12-wk FOME score higher than baseline; 9.23 +/-0.25
Placebo: 12-wk FOME score lower than baseline; 8.46 +/-0.48
Mean score change p=0.03
Change of time N vs. C p=0.002 / 29.86 +/- 0.07
Control / 28.64 +/- 0.32 / 29.63 +/- 0.16
Mean change in score p=0.84
Change in time p=0.7
GROUP B / Nimodipine / 21.48 +/- 0.95 / 25.11 +/- 1.09
Control / 18.47 +/- 0.33
No FOME values given / 19.00 +/- 2.43
Mean change in score p=0.53
Change in time p=0.04

Key

ADAS: Alzheimer’s Disease Assessment Scale; ADAS (c): Alzheimer’s Disease Assessment Scale (Cognitive); ADAS J Cog: Alzheimer’s Disease Assessment Scale (Cognitive Subscale, Japanese version); ADL: Activities of Daily Living; BSR: Buschke Selective Reminding (test); CGI (GI): Clinical Global Impressions Scale; CGI (s): Clinical Global Impressions Scale (Severity); CI: confidence interval; Dias: Diastolic BP; FOME: Fuld Object-Memory Evaluation; GERRI: Geriatric Evaluation by Relative’s Rating Instrument; GDS: Global Deterioration Scale; MED IQR: Median Inter-quartile Range; MMSE: Mini Mental State Examination; Morich Stratum I: MMSE 12-18; N vs C: Nimodipine vs. control; RMBPC: Revised Memory and Behaviour Problems Checklist; RRR= relative risk reduction; Sze Group A: Barthel>25 and MMSE 24; Sze Group B: Barthel 25 or MMSE <24; Sys: Systolic BP; WR: Worst Rank

Appendix 2 Table 4: Results for Comparative Studies by Outcome

Blood Pressure
(mmHg) / Cognitive function / ADL / Adverse Outcomes
Baseline / End / Baseline / End/Change from baseline
Mean (SD) / Mean (SD) (+/-SE) / Mean (SD) (+/-SE) / Mean (SD) (+/-SE) / Mean (SD) / Number (%)
Kume / Amlodipine:
Telmisartan: / 153/82 (9/7)
150/81(12/10) / 134/74 (11/6)
136/72 (11/8) / MMSE / ADASJCOG / WMSR / MMSE / ADASJCOG / WMSR / Not reported / Not reported
22.4 (3.6) / 15(5.6) / 4.4(3.3) / 21.6(4.5) / 17.8(6.7) / 3.9(4.3)
21.1 (2.5) / 18.1(4.5) / 5.4(3.7) / 21.6(2.2) / 16.7(5.1) / 6.9(2.8)
Difference between Groups / Systolic p<0.05
Diastolic p<0.01 / p<0.05
Ohrui / Systolic only / MMSE (SE) / Mean 1yr-decline in MMSE / Not reported / Not reported
Group A / All participants had to have BP >140/90 at entry / 132 (+/-4) / 19.3 (+/-0.5) / 0.6 (+/-0.1)
Group B / 133 (+/-2) / 20.7 (+/-0.4) / 4.6 (+/-0.3) p=0.0023
Group C / 130 (+/-3) / 20.5 (+/-0.4) / 4.9 (+/-0.3) p<0.001

Key

ADAS J COG: Alzheimer’s Disease Assessment Scale (Cognitive Subscale, Japanese version); IDDD: Interview for Deterioration of Daily Activities in Dementia; MMSE: Mini Mental State Examination; Ohrui Group A: Perindopril or Captopril; Ohrui Group B: Enalapril or Imidapril; Ohrui Group C: Nifedipine or Nivaldipine; WMSR: Wechsler Memory Scale