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Cholesterol as a Risk Factor for Dementia and Cognitive Decline: A Systematic Review of Prospective Studies With Meta-Analysis

From the Ageing Research Unit, Centre for Mental Health Research, Australian National University, Canberra ACT, Australia (KJA, DML); and Primary Dementia Collaborative Research Centre, University of New South Wales, Sydney NSW, Australia (L-FL).

The relationships between total serum cholesterol (TC) and dementia and between TC and cognitive decline were investigated in a systematic review of 18 prospective studies. Follow-ups ranged from 3 to 29 years, and included a total of 14,331 participants evaluated for Alzheimer disease (AD), 9,458 participants evaluated for Vascular dementia (VaD), 1,893 participants evaluated for cognitive decline, and 4,793 participants evaluated for cognitive impairment. Compatible results were pooled using meta-analysis. Consistent associations between high midlife TC and increased risk of AD, and high midlife TC and increased risk of any dementia were found. There was no evidence supporting an association between late-life TC and AD, or between late-life TC and any dementia. No study reported a significant association between TC (measured in midlife or late-life) and VaD. An association between high midlife TC and cognitive impairment was found but there was only weak evidence for an association between TC and cognitive decline. Two of seven studies reporting data on the interaction between TC and apolipoprotein e4-allele had significant effects. Results suggest the effect of TC on dementia risk occurs in midlife but not late-life, and that there may be different cardiovascular risk factor profiles for AD and VaD. Results from additional studies involving long-term follow-up of midlife samples will allow for clarification of the association between age, TC and risk of specific types of dementia. These data are required to inform recommendations of modulation of cholesterol to reduce or delay dementia risk.

Key Words: Alzheimer disease • vascular dementia • mild cognitive impairment • lipoprotein • APOE • systematic review