User login
Do statins alter the risk or progression of dementia?
EVIDENCE SUMMARY
A 2016 Cochrane systematic review identified 2 double-blind RCTs that evaluated statins for preventing cognitive decline and dementia in patients with either risk factors or a history of vascular disease.1 The authors couldn’t perform a meta-analysis because of heterogeneity.
Statins don’t prevent dementia
The first RCT found that 5804 patients (70-82 years old with pre-existing vascular disease or increased risk because of smoking, hypertension, or diabetes) manifested equivalent cognitive decline at 3.5 years after random assignment to pravastatin 40 mg/d or placebo.2 Investigators measured cognition with the Mini-Mental State Exam (MMSE), which scores cognitive function on a scale of 0 to 30, with higher numbers indicating better function (mean difference [MD] at follow-up=0.06 points; 95% confidence interval [CI], −0.04 to 0.16).
A second RCT evaluated simvastatin 40 mg/d or placebo for as long as 5 years in 20,536 patients 40 to 80 years of age with a history of coronary artery disease or diabetes.3 The study excluded patients with dementia at baseline. The odds of developing dementia didn’t differ between groups (odds ratio=1.0; 95% CI, 0.61-1.65).
Both studies were originally designed to measure cardiovascular outcomes. The authors rated both as high quality with a low risk of bias.
A contrast to earlier, lower-quality studies
These results contrast with an earlier meta-analysis based on one of the previously described RCTs and lower-quality evidence (16 cohort studies and 3 case-control studies) that found using statins to be associated with lower relative risk (RR) of dementia than not using a statin (all-type dementia RR=0.82; 95% CI, 0.69-0.97; Alzheimer’s disease RR=0.70; 95% CI, 0.60-0.83).3,4
The total patient population was more than 2 million and varied widely. Duration of statin use and type of statin (simvastatin, atorvastatin, fluvastatin, pravastatin, rosuvastatin) also varied. The authors noted potential bias in results for 2 reasons: Cross-sectional studies included patients with impaired cognition who were less likely to be prescribed statins, and statin use was determined by patient self-report.
Statins don’t treat dementia
A Cochrane review that included 4 RCTs with 1154 patients, 50 to 90 years old, assessed the effect of ≥6 months of statin therapy (atorvastatin 80 mg/d or simvastatin 40-80 mg/d) on the course of Alzheimer’s disease and vascular dementia.5 Most patients had mild to moderate dementia and most were also taking an anticholinesterase inhibitor.
Continue to: All studies reported...
All studies reported outcomes using the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), scored 0 to 70, with lower numbers indicating better function, and the MMSE. Results of statin use were equivalent to placebo (ADAS-Cog MD= −0.26; 95% CI, −1.05 to 0.52; MMSE MD= −0.32; 95% CI, −0.71 to 0.06).
But do they slow its progression?
In contrast, a case-control study of 6431 patients with mild-to-moderate Alzheimer’s disease concluded that statin use was associated with slower progression of AD.6 Using cholinesterase inhibitor discontinuation as a proxy for worsening dementia, researchers noted that patients with early statin exposure (719 patients) had a lower rate of cholinesterase discontinuation than patients who didn’t receive early statin therapy (RR=0.85; 95% CI, 0.76-0.95).
A 2016 systematic review attempted to identify randomized clinical trials evaluating the effects of statin withdrawal in dementia.7 None were found.
RECOMMENDATIONS
Based primarily on post-marketing surveillance data, the US Food and Drug Administration (FDA) has warned that memory loss and confusion are occasionally associated with statin use from within one day to several years of initiation.8 The FDA indicated that such symptoms are rare, not associated with dementia or clinically significant cognitive decline, and resolve with discontinuation of the medication.
1. McGuinness B, Craig D, Bullock R, et al. Statins for the prevention of dementia. Cochrane Database Syst Rev. 2016;(1):CD003160.
2. Trompet S, van Vliet P, de Craen AJ, et al. Pravastatin and cognitive function in the elderly. Results of the PROSPER study. J Neurol. 2010;257:85-90.
3. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:7-22.
4. Wong WB, Lin VW, Boudreau D, et al. Statins in the prevention of dementia and Alzheimer’s disease: a meta-analysis of observational studies and an assessment of confounding. Pharmacoepidemiol Drug Saf. 2013;22:345-358.
5. McGuinness B, Craig D, Bullock R, et al. Statins for the treatment of dementia. Cochrane Database Syst Rev. 2014;(7):CD007514.
6. Lin FC, Chuang YS, Hsieh HM, et al. Early statin use and the progression of Alzheimer disease: a total population-based case-control study. Medicine. 2015;94:e2143.
7. McGuinness B, Cardwell CR, Passmore P. Statin withdrawal in people with dementia. Cochrane Database Syst Rev. 2016;(9):CD012050.
8. US Food and Drug Administration. FDA Drug Safety Communication: Important safety label changes to cholesterol-lowering statin drugs. Available at: www.fda.gov/Drugs/DrugSafety/ucm293101.htm. Accessed August 24, 2018.
EVIDENCE SUMMARY
A 2016 Cochrane systematic review identified 2 double-blind RCTs that evaluated statins for preventing cognitive decline and dementia in patients with either risk factors or a history of vascular disease.1 The authors couldn’t perform a meta-analysis because of heterogeneity.
Statins don’t prevent dementia
The first RCT found that 5804 patients (70-82 years old with pre-existing vascular disease or increased risk because of smoking, hypertension, or diabetes) manifested equivalent cognitive decline at 3.5 years after random assignment to pravastatin 40 mg/d or placebo.2 Investigators measured cognition with the Mini-Mental State Exam (MMSE), which scores cognitive function on a scale of 0 to 30, with higher numbers indicating better function (mean difference [MD] at follow-up=0.06 points; 95% confidence interval [CI], −0.04 to 0.16).
A second RCT evaluated simvastatin 40 mg/d or placebo for as long as 5 years in 20,536 patients 40 to 80 years of age with a history of coronary artery disease or diabetes.3 The study excluded patients with dementia at baseline. The odds of developing dementia didn’t differ between groups (odds ratio=1.0; 95% CI, 0.61-1.65).
Both studies were originally designed to measure cardiovascular outcomes. The authors rated both as high quality with a low risk of bias.
A contrast to earlier, lower-quality studies
These results contrast with an earlier meta-analysis based on one of the previously described RCTs and lower-quality evidence (16 cohort studies and 3 case-control studies) that found using statins to be associated with lower relative risk (RR) of dementia than not using a statin (all-type dementia RR=0.82; 95% CI, 0.69-0.97; Alzheimer’s disease RR=0.70; 95% CI, 0.60-0.83).3,4
The total patient population was more than 2 million and varied widely. Duration of statin use and type of statin (simvastatin, atorvastatin, fluvastatin, pravastatin, rosuvastatin) also varied. The authors noted potential bias in results for 2 reasons: Cross-sectional studies included patients with impaired cognition who were less likely to be prescribed statins, and statin use was determined by patient self-report.
Statins don’t treat dementia
A Cochrane review that included 4 RCTs with 1154 patients, 50 to 90 years old, assessed the effect of ≥6 months of statin therapy (atorvastatin 80 mg/d or simvastatin 40-80 mg/d) on the course of Alzheimer’s disease and vascular dementia.5 Most patients had mild to moderate dementia and most were also taking an anticholinesterase inhibitor.
Continue to: All studies reported...
All studies reported outcomes using the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), scored 0 to 70, with lower numbers indicating better function, and the MMSE. Results of statin use were equivalent to placebo (ADAS-Cog MD= −0.26; 95% CI, −1.05 to 0.52; MMSE MD= −0.32; 95% CI, −0.71 to 0.06).
But do they slow its progression?
In contrast, a case-control study of 6431 patients with mild-to-moderate Alzheimer’s disease concluded that statin use was associated with slower progression of AD.6 Using cholinesterase inhibitor discontinuation as a proxy for worsening dementia, researchers noted that patients with early statin exposure (719 patients) had a lower rate of cholinesterase discontinuation than patients who didn’t receive early statin therapy (RR=0.85; 95% CI, 0.76-0.95).
A 2016 systematic review attempted to identify randomized clinical trials evaluating the effects of statin withdrawal in dementia.7 None were found.
RECOMMENDATIONS
Based primarily on post-marketing surveillance data, the US Food and Drug Administration (FDA) has warned that memory loss and confusion are occasionally associated with statin use from within one day to several years of initiation.8 The FDA indicated that such symptoms are rare, not associated with dementia or clinically significant cognitive decline, and resolve with discontinuation of the medication.
EVIDENCE SUMMARY
A 2016 Cochrane systematic review identified 2 double-blind RCTs that evaluated statins for preventing cognitive decline and dementia in patients with either risk factors or a history of vascular disease.1 The authors couldn’t perform a meta-analysis because of heterogeneity.
Statins don’t prevent dementia
The first RCT found that 5804 patients (70-82 years old with pre-existing vascular disease or increased risk because of smoking, hypertension, or diabetes) manifested equivalent cognitive decline at 3.5 years after random assignment to pravastatin 40 mg/d or placebo.2 Investigators measured cognition with the Mini-Mental State Exam (MMSE), which scores cognitive function on a scale of 0 to 30, with higher numbers indicating better function (mean difference [MD] at follow-up=0.06 points; 95% confidence interval [CI], −0.04 to 0.16).
A second RCT evaluated simvastatin 40 mg/d or placebo for as long as 5 years in 20,536 patients 40 to 80 years of age with a history of coronary artery disease or diabetes.3 The study excluded patients with dementia at baseline. The odds of developing dementia didn’t differ between groups (odds ratio=1.0; 95% CI, 0.61-1.65).
Both studies were originally designed to measure cardiovascular outcomes. The authors rated both as high quality with a low risk of bias.
A contrast to earlier, lower-quality studies
These results contrast with an earlier meta-analysis based on one of the previously described RCTs and lower-quality evidence (16 cohort studies and 3 case-control studies) that found using statins to be associated with lower relative risk (RR) of dementia than not using a statin (all-type dementia RR=0.82; 95% CI, 0.69-0.97; Alzheimer’s disease RR=0.70; 95% CI, 0.60-0.83).3,4
The total patient population was more than 2 million and varied widely. Duration of statin use and type of statin (simvastatin, atorvastatin, fluvastatin, pravastatin, rosuvastatin) also varied. The authors noted potential bias in results for 2 reasons: Cross-sectional studies included patients with impaired cognition who were less likely to be prescribed statins, and statin use was determined by patient self-report.
Statins don’t treat dementia
A Cochrane review that included 4 RCTs with 1154 patients, 50 to 90 years old, assessed the effect of ≥6 months of statin therapy (atorvastatin 80 mg/d or simvastatin 40-80 mg/d) on the course of Alzheimer’s disease and vascular dementia.5 Most patients had mild to moderate dementia and most were also taking an anticholinesterase inhibitor.
Continue to: All studies reported...
All studies reported outcomes using the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), scored 0 to 70, with lower numbers indicating better function, and the MMSE. Results of statin use were equivalent to placebo (ADAS-Cog MD= −0.26; 95% CI, −1.05 to 0.52; MMSE MD= −0.32; 95% CI, −0.71 to 0.06).
But do they slow its progression?
In contrast, a case-control study of 6431 patients with mild-to-moderate Alzheimer’s disease concluded that statin use was associated with slower progression of AD.6 Using cholinesterase inhibitor discontinuation as a proxy for worsening dementia, researchers noted that patients with early statin exposure (719 patients) had a lower rate of cholinesterase discontinuation than patients who didn’t receive early statin therapy (RR=0.85; 95% CI, 0.76-0.95).
A 2016 systematic review attempted to identify randomized clinical trials evaluating the effects of statin withdrawal in dementia.7 None were found.
RECOMMENDATIONS
Based primarily on post-marketing surveillance data, the US Food and Drug Administration (FDA) has warned that memory loss and confusion are occasionally associated with statin use from within one day to several years of initiation.8 The FDA indicated that such symptoms are rare, not associated with dementia or clinically significant cognitive decline, and resolve with discontinuation of the medication.
1. McGuinness B, Craig D, Bullock R, et al. Statins for the prevention of dementia. Cochrane Database Syst Rev. 2016;(1):CD003160.
2. Trompet S, van Vliet P, de Craen AJ, et al. Pravastatin and cognitive function in the elderly. Results of the PROSPER study. J Neurol. 2010;257:85-90.
3. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:7-22.
4. Wong WB, Lin VW, Boudreau D, et al. Statins in the prevention of dementia and Alzheimer’s disease: a meta-analysis of observational studies and an assessment of confounding. Pharmacoepidemiol Drug Saf. 2013;22:345-358.
5. McGuinness B, Craig D, Bullock R, et al. Statins for the treatment of dementia. Cochrane Database Syst Rev. 2014;(7):CD007514.
6. Lin FC, Chuang YS, Hsieh HM, et al. Early statin use and the progression of Alzheimer disease: a total population-based case-control study. Medicine. 2015;94:e2143.
7. McGuinness B, Cardwell CR, Passmore P. Statin withdrawal in people with dementia. Cochrane Database Syst Rev. 2016;(9):CD012050.
8. US Food and Drug Administration. FDA Drug Safety Communication: Important safety label changes to cholesterol-lowering statin drugs. Available at: www.fda.gov/Drugs/DrugSafety/ucm293101.htm. Accessed August 24, 2018.
1. McGuinness B, Craig D, Bullock R, et al. Statins for the prevention of dementia. Cochrane Database Syst Rev. 2016;(1):CD003160.
2. Trompet S, van Vliet P, de Craen AJ, et al. Pravastatin and cognitive function in the elderly. Results of the PROSPER study. J Neurol. 2010;257:85-90.
3. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:7-22.
4. Wong WB, Lin VW, Boudreau D, et al. Statins in the prevention of dementia and Alzheimer’s disease: a meta-analysis of observational studies and an assessment of confounding. Pharmacoepidemiol Drug Saf. 2013;22:345-358.
5. McGuinness B, Craig D, Bullock R, et al. Statins for the treatment of dementia. Cochrane Database Syst Rev. 2014;(7):CD007514.
6. Lin FC, Chuang YS, Hsieh HM, et al. Early statin use and the progression of Alzheimer disease: a total population-based case-control study. Medicine. 2015;94:e2143.
7. McGuinness B, Cardwell CR, Passmore P. Statin withdrawal in people with dementia. Cochrane Database Syst Rev. 2016;(9):CD012050.
8. US Food and Drug Administration. FDA Drug Safety Communication: Important safety label changes to cholesterol-lowering statin drugs. Available at: www.fda.gov/Drugs/DrugSafety/ucm293101.htm. Accessed August 24, 2018.
EVIDENCE-BASED SUMMARY:
Neither moderate- nor high-intensity statin therapy (with simvastatin or atorvastatin, respectively) improves existing mild to moderately severe Alzheimer’s or vascular dementia (SOR: A, RCTs).
Although statin use is associated with a mild, rare, reversible delirium, it isn’t linked to permanent cognitive decline (SOR: C, expert opinion).
