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Meta-Analysis
. 2014 Jul 8;2014(7):CD007514.
doi: 10.1002/14651858.CD007514.pub3.

Statins for the treatment of dementia

Bernadette McGuinness  1 , David Craig, Roger Bullock, Reem Malouf, Peter Passmore
Affiliations
Meta-Analysis

Statins for the treatment of dementia

Bernadette McGuinness et al. Cochrane Database Syst Rev. .

Abstract

Background: The use of statin therapy in established Alzheimer's disease (AD) or vascular dementia (VaD) is a relatively unexplored area. In AD, β-amyloid protein (Aβ) is deposited in the form of extracellular plaques and previous studies have determined Aβ generation is cholesterol dependent. Hypercholesterolaemia has also been implicated in the pathogenesis of VaD. Due to the role of statins in cholesterol reduction, it is biologically plausible they may be efficacious in the treatment of AD and VaD.

Objectives: To assess the clinical efficacy and safety of statins in the treatment of AD and VaD. To evaluate if the efficacy of statins in the treatment of AD and VaD depends on cholesterol level, ApoE genotype or cognitive level.

Search methods: We searched ALOIS, the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group, The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS, as well as many trials registries and grey literature sources (20 January 2014).

Selection criteria: Double-blind, randomised controlled trials of statins given for at least six months in people with a diagnosis of dementia.

Data collection and analysis: Two independent authors extracted and assessed data against the inclusion criteria. We pooled data where appropriate and entered them into a meta-analysis. We used standard methodological procedures expected by The Cochrane Collaboration.

Main results: We identified four studies (1154 participants, age range 50 to 90 years). All participants had a diagnosis of probable or possible AD according to standard criteria and most participants were established on a cholinesterase inhibitor. The primary outcome in all studies was change in Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-Cog) from baseline. When we pooled data, there was no significant benefit from statin (mean difference -0.26, 95% confidence interval (CI) -1.05 to 0.52, P value = 0.51). All studies provided change in Mini Mental State Examination (MMSE) from baseline. There was no significant benefit from statins in MMSE when we pooled the data (mean difference -0.32, 95% CI -0.71 to 0.06, P value = 0.10). Three studies reported treatment-related adverse effects. When we pooled data, there was no significant difference between statins and placebo (odds ratio 1.09, 95% CI 0.58 to 2.06, P value = 0.78). There was no significant difference in behaviour, global function or activities of daily living in the statin and placebo groups. We assessed risk of bias as low for all studies. We found no studies assessing role of statins in treatment of VaD.

Authors' conclusions: Analyses from the studies available, including two large randomised controlled trials, indicate that statins have no benefit on the primary outcome measures of ADAS-Cog or MMSE.

PubMed Disclaimer

Conflict of interest statement

Peter Passmore: investigator in LEADe study received grants from Pfizer, MSD, BMS and Novartis and honoraria from Pfizer, MSD, Novartis and Astra Zeneca.

Figures

1
1
Study flow diagram initial review.
2
2
Study flow diagram update 2013 search.
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
4
4
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
5
5
Forest plot of comparison: 1 Cognitive change (Alzheimer's Disease Assessment Scale ‐ cognitive subscale (ADAS‐Cog)) from baseline, outcome: 1.1 ADAS‐Cog change from baseline.
6
6
Forest plot of comparison: 1 Cognitive change (Alzheimer's Disease Assessment Scale ‐ cognitive subscale (ADAS‐Cog)) from baseline, outcome: 1.2 ADAS‐Cog change from baseline (using random‐effects model).
7
7
Forest plot of comparison: 2 Mini Mental State Examination (MMSE) change from baseline, outcome: 2.1 MMSE change from baseline.
8
8
Forest plot of comparison: 3 Clinical Global Impression of Change (CGIC), outcome: 3.1 CGIC change.
9
9
Forest plot of comparison: 4 Incidence of adverse effects, outcome: 4.1 Treatment‐related adverse effects requiring discontinuation of treatment.
10
10
Forest plot of comparison: 5 Neuropsychiatric Inventory (NPI), outcome: 5.2 NPI change from baseline at 1 year.
1.1
1.1. Analysis
Comparison 1 Cognitive change (Alzheimer's Disease Assessment Scale ‐ cognitive subscale (ADAS‐Cog)) from baseline, Outcome 1 ADAS‐Cog change from baseline.
1.2
1.2. Analysis
Comparison 1 Cognitive change (Alzheimer's Disease Assessment Scale ‐ cognitive subscale (ADAS‐Cog)) from baseline, Outcome 2 ADAS‐Cog change from baseline (using random‐effects model).
1.3
1.3. Analysis
Comparison 1 Cognitive change (Alzheimer's Disease Assessment Scale ‐ cognitive subscale (ADAS‐Cog)) from baseline, Outcome 3 ADAS‐Cog change at 3 months.
1.4
1.4. Analysis
Comparison 1 Cognitive change (Alzheimer's Disease Assessment Scale ‐ cognitive subscale (ADAS‐Cog)) from baseline, Outcome 4 ADAS‐Cog change at 6 months.
1.5
1.5. Analysis
Comparison 1 Cognitive change (Alzheimer's Disease Assessment Scale ‐ cognitive subscale (ADAS‐Cog)) from baseline, Outcome 5 ADAS‐Cog change at 12 months.
1.6
1.6. Analysis
Comparison 1 Cognitive change (Alzheimer's Disease Assessment Scale ‐ cognitive subscale (ADAS‐Cog)) from baseline, Outcome 6 ADAS‐Cog change at 18 months.
1.7
1.7. Analysis
Comparison 1 Cognitive change (Alzheimer's Disease Assessment Scale ‐ cognitive subscale (ADAS‐Cog)) from baseline, Outcome 7 ADAS‐Cog change to 18 months (last observation carried forward).
1.8
1.8. Analysis
Comparison 1 Cognitive change (Alzheimer's Disease Assessment Scale ‐ cognitive subscale (ADAS‐Cog)) from baseline, Outcome 8 Modified ADAS‐Cog.
2.1
2.1. Analysis
Comparison 2 Mini Mental State Examination (MMSE) change from baseline, Outcome 1 MMSE change from baseline.
2.2
2.2. Analysis
Comparison 2 Mini Mental State Examination (MMSE) change from baseline, Outcome 2 MMSE change from baseline using random‐effects model.
2.3
2.3. Analysis
Comparison 2 Mini Mental State Examination (MMSE) change from baseline, Outcome 3 MMSE change at 3 months.
2.4
2.4. Analysis
Comparison 2 Mini Mental State Examination (MMSE) change from baseline, Outcome 4 MMSE change at 6 months.
2.5
2.5. Analysis
Comparison 2 Mini Mental State Examination (MMSE) change from baseline, Outcome 5 MMSE change at 12 months.
2.6
2.6. Analysis
Comparison 2 Mini Mental State Examination (MMSE) change from baseline, Outcome 6 MMSE change at 18 months.
3.1
3.1. Analysis
Comparison 3 Clinical Global Impression of Change (CGIC), Outcome 1 CGIC change.
3.2
3.2. Analysis
Comparison 3 Clinical Global Impression of Change (CGIC), Outcome 2 CGIC change at 3 months.
3.3
3.3. Analysis
Comparison 3 Clinical Global Impression of Change (CGIC), Outcome 3 CGIC change at 6 months.
3.4
3.4. Analysis
Comparison 3 Clinical Global Impression of Change (CGIC), Outcome 4 CGIC change at 9 months.
3.5
3.5. Analysis
Comparison 3 Clinical Global Impression of Change (CGIC), Outcome 5 CGIC change at 12 months.
3.6
3.6. Analysis
Comparison 3 Clinical Global Impression of Change (CGIC), Outcome 6 CGIC change at 15 months.
3.7
3.7. Analysis
Comparison 3 Clinical Global Impression of Change (CGIC), Outcome 7 CGIC change at 18 months.
3.8
3.8. Analysis
Comparison 3 Clinical Global Impression of Change (CGIC), Outcome 8 CGIC (last observation carried forward).
4.1
4.1. Analysis
Comparison 4 Incidence of adverse effects, Outcome 1 Treatment‐related adverse effects requiring discontinuation of treatment.
5.1
5.1. Analysis
Comparison 5 Neuropsychiatric Inventory (NPI), Outcome 1 NPI change from baseline at 6 months.
5.2
5.2. Analysis
Comparison 5 Neuropsychiatric Inventory (NPI), Outcome 2 NPI change from baseline at 1 year.
5.3
5.3. Analysis
Comparison 5 Neuropsychiatric Inventory (NPI), Outcome 3 NPI change from baseline at 1 year (using random‐effects model).
6.1
6.1. Analysis
Comparison 6 Alzheimer's Disease Functional Assessment and Change Scale (ADFACS), Outcome 1 ADFACS change from baseline at 6 months.
6.2
6.2. Analysis
Comparison 6 Alzheimer's Disease Functional Assessment and Change Scale (ADFACS), Outcome 2 ADFACS change from baseline at 12 months.
6.3
6.3. Analysis
Comparison 6 Alzheimer's Disease Functional Assessment and Change Scale (ADFACS), Outcome 3 ADFACS change from baseline at 18 months.
6.4
6.4. Analysis
Comparison 6 Alzheimer's Disease Functional Assessment and Change Scale (ADFACS), Outcome 4 ADFACS overall (0‐18) months.
6.5
6.5. Analysis
Comparison 6 Alzheimer's Disease Functional Assessment and Change Scale (ADFACS), Outcome 5 ADFACS (last observation carried forward).
7.1
7.1. Analysis
Comparison 7 Alzheimer's Disease Cooperative Study‐Activities of Daily Living (ADCS‐ADL), Outcome 1 ADCS‐ADL change from baseline at 3 months.
7.2
7.2. Analysis
Comparison 7 Alzheimer's Disease Cooperative Study‐Activities of Daily Living (ADCS‐ADL), Outcome 2 ADCS‐ADL change from baseline at 6 months.
7.3
7.3. Analysis
Comparison 7 Alzheimer's Disease Cooperative Study‐Activities of Daily Living (ADCS‐ADL), Outcome 3 ADCS‐ADL change from baseline at 12 months.
7.4
7.4. Analysis
Comparison 7 Alzheimer's Disease Cooperative Study‐Activities of Daily Living (ADCS‐ADL), Outcome 4 ADCS‐ADL change from baseline at 18 months.
See this image and copyright information in PMC

Update of

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