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Statins for the treatment of dementia.
Cochrane Database Syst Rev 2014; (7):CD007514CD

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.

Authors+Show Affiliations

Department of Geriatric Medicine, Belfast Health and Social Care Trust, Lisburn Road, Belfast, Co Antrim, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Meta-Analysis
Review
Systematic Review

Language

eng

PubMed ID

25004278

Citation

McGuinness, Bernadette, et al. "Statins for the Treatment of Dementia." The Cochrane Database of Systematic Reviews, 2014, p. CD007514.
McGuinness B, Craig D, Bullock R, et al. Statins for the treatment of dementia. Cochrane Database Syst Rev. 2014.
McGuinness, B., Craig, D., Bullock, R., Malouf, R., & Passmore, P. (2014). Statins for the treatment of dementia. The Cochrane Database of Systematic Reviews, (7), p. CD007514. doi:10.1002/14651858.CD007514.pub3.
McGuinness B, et al. Statins for the Treatment of Dementia. Cochrane Database Syst Rev. 2014 Jul 8;(7)CD007514. PubMed PMID: 25004278.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Statins for the treatment of dementia. AU - McGuinness,Bernadette, AU - Craig,David, AU - Bullock,Roger, AU - Malouf,Reem, AU - Passmore,Peter, Y1 - 2014/07/08/ PY - 2014/7/9/entrez PY - 2014/7/9/pubmed PY - 2015/1/13/medline SP - CD007514 EP - CD007514 JF - The Cochrane database of systematic reviews JO - Cochrane Database Syst Rev IS - 7 N2 - 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. SN - 1469-493X UR - https://www.unboundmedicine.com/medline/citation/25004278/Statins_for_the_treatment_of_dementia_ L2 - https://doi.org/10.1002/14651858.CD007514.pub3 DB - PRIME DP - Unbound Medicine ER -