CLINICAL BOTTOM LINE
There is good evidence that the taking of statins later in life by people at risk of vascular disease has no more impact on preventing cognitive decline or dementia than a placebo. A healthy lifestyle is considered important for reducing dementia risk but more research is needed to clarify the relationship between cholesterol and development of dementia in other populations.
Dementia is a significant healthcare concern and advising people of effective prevention strategies is part of your nursing role. You have heard that cardiovascular risk factors such as high cholesterol are also risk factors for developing dementia and wonder if people at risk of dementia because of their age should be encouraged to take cholesterol-lowering medication such as statins. You decide to review the evidence.
Do statins taken by people late in life prevent dementia, compared with no treatment or placebos?
PubMed- Clinical Queries (Therapy/Narrow): dementia AND statins
McGuinness B, Craig D, Bullock R & Passmore P, Statins for the prevention of dementia, Cochrane Database Syst Rev 2016 (1), 10.1002/14651858.CD003160.pub3
A Cochrane systematic review evaluating the efficacy and safety of statins for the prevention of dementia in people at risk of dementia due to their age and to determine whether the efficacy and safety of statins for this purpose depends on cholesterol level, apolipoprotein E (ApoE) genotype or cognitive level. Inclusion criteria were:
Type of study: Randomised, double-blind, placebo-controlled trials in which a statin was given for at least 12 months.
Participants: People with normal cognitive function and of sufficient age to be at risk of Alzheimer’s disease (AD) (mean age 65 years or over) including those with evidence of, or at high risk of vascular disease.
Intervention: Any statin given within the licensed dose range compared with a placebo.
Primary outcomes: Objective diagnosis of dementia, AD, or vascular dementia; change in accepted objective and standardised tests of cognitive performance; and the incidence and severity of adverse effects.
Secondary outcomes: Change in cognitive status accounting for prior cholesterol level, ApoE genotype and cognitive level; quality of life; change in ADLs; and change in behaviour.
Search strategy: The authors sought eligible studies via ALOIS (the specialised register of the Cochrane Dementia and Cognitive Improvement Group), the Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS, trial registers and sources of grey (unpublished) literature until 11 November 2015.
Review process: Two authors independently searched and screened potentially relevant studies for eligibility. Disagreements were resolved by discussion amongst four authors. A standardised form guided data extraction.
Quality assessment: Included studies were assessed for risk of bias using the following criteria: random sequence generation, allocation concealment, blinding of participants, personnel and outcome assessment, incomplete outcome data and selective reporting.
Overall validity: A high-quality review involving two randomised, controlled trials (RCTs) at low risk of bias.
After removal of duplicates, 288 articles were screened for eligibility. Full text of 36 articles were assessed, from which two RCTs involving 26,340 participants were included in this review. Participants were between 40 and 82 years old with 44 per cent (11,610 participants) 70 years or older. On study entry, participants’ mean total cholesterol was 5.9 mmol/L (standard deviation (SD) 1.0) in one study and 5.7 mmol/L (SD 0.9) in the other.
Mean follow-up was 3.2 years in one study and five years in the other. There was no difference in the incidence of dementia between those given statins and those given placebo (one study), the quality of this evidence was graded as moderate because of wide confidence intervals (refer table).
Both studies assessed cognitive function and found no significant differences between those who took statins and those in the placebo group for the five different cognitive function tests involved (high-quality evidence). Results were not suitable for meta-analysis. Adverse events were low in both the statin and placebo groups. There was no difference between groups in the risk of withdrawal from the trial due to adverse events (refer table).
- These results are an example of an intervention that is biologically plausible and appeared promising based on results from observational studies but testing via randomised controlled trials has failed to identify any benefit.
Participants were at moderate to high risk of vascular events and the results may not be generalisable to people of low vascular risk.
- Risk factors for dementia are complex and no single factor has been identified as the cause of dementia.
- Limitations within the primary studies means there is still much to know about the relationship between cholesterol and development of dementia, including the benefit of starting statins at an earlier age and in those with a family history of AD. In the meantime, Alzheimers New Zealand 1 recommends lifestyle changes to reduce the risk of developing dementia in later life that include following a healthy diet.
Reviewer: Cynthia Wensley RN, MHSc. Honorary Professional Teaching Fellow, University of Auckland and PhD candidate, Deakin University, Melbourne. firstname.lastname@example.org.
1. Alzheimers New Zealand. Reduce the risk of developing dementia. Available from www.alzheimers.org.nz/about-dementia/reducing-the-risk.