High total cholesterol levels in late life associated with a reduced risk of dementia

Mielke, Michelle M.; Zandi, Peter P.; Sjögren, Magnus; Gustafson, Deb; Östling, Svante; Steen, Bertil; Skoog, Ingmar

doi:10.1212/01.wnl.0000161870.78572.a5

Cited by 367 publications

(316 citation statements)

References 44 publications

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“…This is in general agreement with previous epidemiological reports which show elevated mid-life cholesterol levels and decreased levels in later life in AD cases (Stewart et al, 2007). Some studies have also indicated that there may be an association between low plasma cholesterol and AD (Mielke et al, 2005), although these are not universal findings.…”

Section: Discussionsupporting

confidence: 92%

A functional polymorphism in the HMGCR promoter affects transcriptional activity but not the risk for Alzheimer disease in Swedish populations

et al. 2010

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Pages: 25 Pages including 2 tables Abstract:2 Variations in genes associated with cholesterol homeostasis have been reported to modify the risk of developing Alzheimer disease (AD). To date there have been few investigations into variations in genes directly involved in cholesterol biosynthesis and AD. We investigated the influence of the -911C>A polymorphism (rs3761740) in the hydroxy-methyl-glutaryl CoA reductase (HMGCR) gene promoter on basal and regulated transcription, plasma cholesterol levels and the association with AD. Under in vitro conditions the A allele was found to be significantly more responsive to SREBP-2 mediated regulation than the C allele. In an age and sex matched case-control study, the genotype distribution and allele frequency of this polymorphism were not associated with AD (OR=1.03; 95% CI=0.72-1.48). However, we did find evidence supporting an interaction between the HMGCR A allele, the APOE E4 allele and an altered risk of AD (OR=2.41; 95% CI=0.93-6.22).

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Section: Discussionsupporting

confidence: 92%

A functional polymorphism in the HMGCR promoter affects transcriptional activity but not the risk for Alzheimer disease in Swedish populations

et al. 2010

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“…Cardiovascular risk factors are known to predict the risk of dementia (Kivipelto et al 2006;Kaffashian et al 2013). Higher total serum cholesterol (TC) in midlife is associated with higher risk of AD (Kivipelto et al 2001;Li et al 2005;Solomon et al 2007) but the association of TC and dementia risk is reversed in later life (Mielke et al 2005). Low levels of high density lipoprotein cholesterol (HDL-C) also associate with adverse cerebral white matter changes (Gouw et al 2008;Crisby et al 2010), but no clear association of HDL with the risk of dementia or AD has been found in prospective studies (Li et al 2005;Reitz et al 2005;Reitz et al 2010;Arntzen et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Apolipoproteins and HDL cholesterol do not associate with the risk of future dementia and Alzheimer’s disease: the National Finnish population study (FINRISK)

Tynkkynen

Hernesniemi

Laatikainen

et al. 2016

AGE

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Data on associations of apolipoproteins A-I and B (apo A-I, apo B) and HDL cholesterol (HDL-C) with dementia and Alzheimer's disease (AD) are conflicting. Our aim was to examine, whether apo B, apoA-I, their ratio, or HDL-C are significant, independent predictors of incident dementia and AD in the general population free of dementia at baseline. We analyzed the results from two Finnish prospective population-based cohort studies in a total of 13,275 subjects aged 25 to 74 years with mainly Caucasian ethnicity. The followup time for both cohorts was 10 years. We used Cox proportional hazards regression to evaluate hazard ratios (HR) for incident dementia (including AD) (n = 220) and for AD (n = 154). Cumulative incidence function (CIF) analysis was also performed to adjust the results for competing risks of death. Adjusted for multiple dementia and AD risk factors, log-transformed apo A-I, log HDL-C, log apo B, and log apo B/A-I ratio were not associated with incident dementia or AD. HDL-C was inversely associated with AD risk when adjusted for competing risks but no other statistically significant associations were observed in the CIF analyses. Apo A-I, HDL-C, apo B, or apo B/A-I ratio were not associated with future dementia or AD. HDL-C was inversely

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“…Lipids and lipid peroxidation products have important roles in central nervous system homeostasis; lipid transport genes and peripheral dyslipidemia are associated with an increased risk of AD [21]. While laboratory and animal studies suggest hypercholesterolemia is a key factor in AD [29,30], epidemiological studies are conflicting [19,22,32]. Other lipids, such as sphingomyelins (SM) or ceramides, may be better indicators of AD progression by reflecting ongoing neurodegeneration.…”

Section: Introductionmentioning

confidence: 99%

Serum sphingomyelins and ceramides are early predictors of memory impairment

Mielke¹,

Bandaru²,

Haughey³

et al. 2010

Neurobiology of Aging

165

172

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A blood-based biomarker of Alzheimer's disease (AD) progression could be instrumental in targeting asymptomatic individuals for treatment early in the disease process. Given the direct connection between sphingomyelins (SM), ceramides, and apoptosis, these lipids may be indicators of neurodegeneration and AD progression. Baseline serum SM and ceramides from 100 women enrolled in a longitudinal population-based study were examined as predictors of cognitive impairment. Participants were followed up to 6 visits over 9 years. Baseline lipids, in tertiles, were examined in relation to cross-sectional and incident impairment (<1.5 SD below standard norms) on HVLTimmediate and -delayed memory recall and Trails A and B. SM and ceramides varied in relation to the timing of HVLT-delayed impairment: low levels were associated with cross-sectional impairment; high levels predicted incident impairment in asymptomatic individuals. Lipids were not associated with loss-to-follow-up. Results suggest serum SM and ceramides vary according to the timing of the onset of memory impairment and may be good pre-clinical predictors, or biomarkers, of memory impairment: a deficit observed early in AD pathogenesis.

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High total cholesterol levels in late life associated with a reduced risk of dementia

Cited by 367 publications

References 44 publications

A functional polymorphism in the HMGCR promoter affects transcriptional activity but not the risk for Alzheimer disease in Swedish populations

A functional polymorphism in the HMGCR promoter affects transcriptional activity but not the risk for Alzheimer disease in Swedish populations

Apolipoproteins and HDL cholesterol do not associate with the risk of future dementia and Alzheimer’s disease: the National Finnish population study (FINRISK)

Serum sphingomyelins and ceramides are early predictors of memory impairment

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