Table 2.

Characteristics and efficacy results of clinical trials included in this study

StudyDesignStudy populationTherapy: study arm / control armNumber of patients (n)Efficacy results, N (SD)p-value
Simons et al18Randomised, double-blind, placebo-controlled, clinical trial; phase IIIPatients with diagnosis of probable AD, with MMSE 12–26Simvastatin 40 mg/24 h orally for 4 weeks followed by 80 mg/24 h until 26 weeks/placebo/24 h orally for 22 weeks44 (simvastatin, 24; placebo, 20) ADAS-Cog
MMSE		Simvastatin 4.1 (6.5)
–0.6 (0.2)		Placebo 3.4 (7.0)
–2.7 (0.7)		 ns
<0.02
Change from baseline levels (pmol/L):
MMSE 12–20
Aβ40 (CSF)–2.8 (10.3)4.3 (14.2)ns
Aβ42 (CSF)2.3 (15.2)4.0 (9.0)ns
24S-hydroxycholesterol (CSF) –7.8 (13.5) 1.7 (10.1)ns
MMSE 20–26
Aβ40 (CSF)–5.7 (6.5)6.8 (13.2)<0.05b
Aβ42 (CSF)–5.6 (9.5)–0.9 (9.7)ns
24S-hydroxycholesterol (CSF)–15.2 (12.6)6.2 (16.3)<0.01b
Sjogren et al19Open-label clinical trialPatients with AD; 64–84-years old; MMSE 12–26Simvastatin 20 mg/24 h orally for 12 weeks19Levels (pmol/L)
α-SAPP (CSF)		Before
2264 (543)		After
1986 (557)		 
<0.001b
β-SAPP (CSF)945 (133)830 (83)<0.001b
Total tau (CSF)658 (352)638 (306)ns
Phosphorylated tau (CSF)95 (43)92 (37)ns
Aβ42 (CSF)460 (172)472 (160)ns
Aβ42 (plasma)75 (80)80 (88)ns
ADAS-Cog16.6 (7.8)19.3 (8.0)<0.05b
Sparks et al20 ADCLT studyRandomised, double-blind, placebo-controlled, clinical trial, phase IIPatients with mild to moderate AD; MMSE 12–28Atorvastatin 80 mg/24 h orally for 1 year/placebo 24 h orally for 1 year63 (atorvastatin, 32; placebo, 31)AtorvastatinPlacebo
ADAS-Cog0.5 (5.9)–3.7 (6.7)0.019b
MMSE–0.77 (2.7)–2.42 (3.2)0.009b
CGIC0.40 (1.81)a0.037
NPI6.99 (6.85)2.69 (6.68)0.120
Serrano-Pozo et al21Open-label clinical trialPatients with probable AD or amnestic mild cognitive impairment; TC: 170–240 mg/dLSimvastatin 20 mg/24 h orally for 6 weeks followed by 40 mg/24 h for 6 weeks12Levels (pmol/L)
24S-hydroxycholesterol (plasma)		Before
52.3 (11.8)		After
47.8 (12.5)		 0.0368
24S-hydroxycholesterol (CSF)2.459 (1.966)2.485 (1.805)0.8225
Aβ40 (plasma)81.4 (22.0)85.3 (17.3)0.3700
Aβ40 (CSF)1573.1 (501.4)1542.8 (531.0)0.3016
Aβ42 (CSF)61.2 (29.9)59.1 (26.2)0.2624
Total tau (CSF)690.2 (312.2)699.0 (322.4)0.6072
Phosphorylated tau (CSF)87.1 (57.4)90.0 (60.9)0.1705
Feldman et al22 LEADe studyRandomised, double-blind, placebo-controlled, multicentre and parallel clinical trialPatients with mild to moderate probable AD; older than 50 years; taking donepezil 10 mg/24 h >3 months before screening; MMSE 13–25; LDL 95–195 mg/dLAtorvastatin 80 mg/24 h orally for 72 weeks followed by 8-week withdrawal of treatment/placebo 24 h for 72 weeks followed by 8-week withdrawal of treatment640 (atorvastatin,314; placebo, 326)AtorvastatinPlacebo
ADAS-Cog2.77 (9.00)3.3 (10.00)0.73
MMSE–0.87 (2.9)–1.11 (2.8)ns
CGIC–0.02 (2.43)a0.26
Sano et al7Randomised, double-blind, placebo-controlled, multicentre clinical trial, phase IIIPatients with probable AD and normal lipid levels; older than 50 years; MMSE 12–26Simvastatin 20 mg/24 h orally for 6 weeks followed by 40 mg/24 h until 18 months; placebo/24 h orally for 18 months406 (simvastatin, 204; placebo, 202)SimvastatinPlacebo
ADAS-Cog9.51 (9.48)8.18 (8.70)ns
MMSE–4.23 (4.77)–3.75 (4.38)ns
NPI3.21 (12.71)3.78 (10.73)ns

  • ↵aMean difference data were calculated as statin–placebo results;

  • *Significant values after regression analysis.

  • AD = Alzheimer's Disease; ADAS-Cog = Alzheimer's Disease Assessment Scale-cognitive; CGIC = Clinical Global Impressions of Change; CSF = cerebrospinal fluid; MMSE = Mini-Mental State Examination; NPI = Neuropsychiatric Inventory; OR = odds ratio; RR = relative risk