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

Ageing Research Unit, Centre for Mental Health Research, Australian National University, Canberra ACT, Australia.
The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry (Impact Factor: 4.24). 06/2008; 16(5):343-54. DOI: 10.1097/JGP.0b013e31816b72d4
Source: PubMed


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.

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    • "Kivipelto et al. [23] found that obesity was a significant risk factor for dementia over a 20 year follow-up period, whereas Barnes et al. [24] found that low body mass index (BMI) was a risk factor for the development of dementia over 6 years. As pointed out by Anstey et al. [27] [28], high cholesterol and high BMI in mid-life are both significant risk factors for AD, but neither is a risk factor when it appears in late-life. Thus, the time frame over which the risk factor is assessed may be an important factor. "
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    • "Cholesterol is a risk factor for vascular disease which is, in turn, an important risk factor for cognitive decline and dementia. The relationship between total cholesterol (T-C) and cognition in the elderly is however, currently a matter of debate; a higher prevalence of mild cognitive impairment and cognitive decline being associated with both low and high T-C, or showing no significant association (Anstey et al., 2008; Shepardson et al., 2011). Inconsistencies could result from heterogeneity in study design, sample characteristics, and lack of examination of cholesterol components, lowand high density lipoprotein cholesterol (LDL-C and HDL-C) being inversely associated with vascular disease. "
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    ABSTRACT: The aim of this study was to examine the associations between serum lipid levels and cognitive function in a community-based sample of non-demented subjects aged 65 years and over. Participants were 2737 men and 4118 women from a population-based cohort recruited from three French cities. Visual memory, verbal fluency, psychomotor speed, and executive abilities were evaluated at baseline, and after 2, 4, and 7 years of follow-up. Lipid levels were evaluated at baseline. Multiadjusted Cox models stratified by gender were adjusted for sociodemographic and lifestyle characteristics, mental and physical health, and genetic vulnerability to dyslipidemia (apolipoprotein E and A, and cholesteryl ester transfer protein) and taking into account baseline vascular pathologies. In men, a hypercholesterolemic pattern in late-life (high total cholesterol (T-C), low HDL-C, high LDL-C levels) was associated with a 25 to 50% increased risk of decline over 7 years in psychomotor speed, executive abilities, and verbal fluency. Specific associations with low T-C and low LDL-C levels were also observed which may depend on genetic vulnerability to dyslipidemia (related to apolipoprotein A5 and cholesteryl exchange transfer protein). In contrast, in women, a 30% higher rate of decline was found in psychomotor speed with high HDL-C levels and in executive abilities with low levels of LDL-C and triglycerides, in interaction with hormonal treatment. For men and women, vascular pathologies only slightly outweighed the risk related to lipids. This suggests a complex gender-specific pattern of cognitive decline involving genetic vulnerability in men and hormonal status in women.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 07/2014; 24(7). DOI:10.1016/j.euroneuro.2014.02.003 · 4.37 Impact Factor
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    • "A high-fat diet (HFD) is a well-known risk factor for cardiovascular disease and is one of many factors responsible for chronic liver disorders, dementia and cognitive decline.[1],[2] Whether HFD is directly associated with depression and depressive behavior remains unknown. "
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    ABSTRACT: BackgroundA high-fat diet (HFD) is a well-known risk factor for cardio-cerebrovascular disease but the relationship between a HFD and depressive symptoms remains unknown.ObjectiveCompare changes in behavioral and measures of brain glucose metabolism in rats fed a HFD to those of rats fed a standard diet.MethodsTwenty male Sprague-Dawley rats were randomly assigned to a study group (n=10) that received a high fat diet for 9 weeks or a control group (n=10) that received a standard diet for 9 weeks. At baseline and at the end of the 9-week trial assessments included body weight, serum lipids (total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol), the sucrose preference test, and the open field test. The rate of brain glucose metabolism in different brain regions (assessed using micro-positron emission tomography) at the end of the trial was also compared between the two groups of rats.ResultsNine weeks of a HFD in rats resulted in the expected increase in weight and changes in serum lipid levels, but it was also associated with a decreased preference for sucrose (which may be due to a loss of interest in pleasurable activities), increased weight-adjusted water intake, and a significant deactivation of the right thalamus and right striatum (based on decreased rates of glucose metabolism). In the HFD group the magnitude of the drop in the sucrose preference was strongly correlated to the magnitude of the deactivation of the right thalamus (r=0.78) and the right striatum (r=0.81).ConclusionsThese findings support hypotheses about the role of a HFD in the causal pathway for depressive symptoms. Further work is needed to clarify the underling mechanism, but it appears that the interaction between the content of the diet and the limbic system-striatum-thalamus circuit plays a role in both eating behavior and depressive symptoms.
    Shanghai Archives of Psychiatry 06/2014; 26(3):129-137. DOI:10.3969/j.issn.1002-0829.2014.03.004
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