Serum cholesterol and risk of Alzheimer disease

Li, Gail; Shofer, Jane B.; Kukull, Walter A.; Peskind, Elaine R.; Tsuang, Debby W.; Breitner, John C.S.; McCormick, Wayne C.; Bowen, James D.; Teri, Linda; Schellenberg, G. D.; Larson, Eric B.

doi:10.1212/01.wnl.0000178989.87072.11

Cited by 148 publications

(126 citation statements)

References 46 publications

(66 reference statements)

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“…Similar results were reported recently in a study that found no association between cholesterol or HDL-C and risk of dementia in a community-based study of cognitively intact elderly subjects. 26 In conclusion, this large-scale cognition study embedded in a clinical trial revealed that, over an average 3.2-year period, the presence of the apolipoprotein E 4 isoform was associated with greater decline in memory performance without apparently affecting attention or processing ability. The apolipoprotein E4 isoform was linked also to morepronounced deterioration in indices of ADLs and IADLs.…”

Section: Discussionmentioning

confidence: 70%

“…22 The nature of the association between lipid and lipoprotein levels and cognitive impairment is largely unknown, with conflicting results being reported. [23][24][25][26] Recently, low highdensity lipoprotein cholesterol (HDL-C) levels have been linked to poorer cognitive function, independent of an effect on cardiovascular disease in the oldest old, 23 whereas no association between total plasma cholesterol or HDL-C and risk of Alzheimer's disease was observed in another study. 26 The Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) was a trial of statin use for the prevention of cardiovascular and cerebrovascular disease in 5,804 men and women aged 70 to 82.…”

mentioning

confidence: 99%

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Association Between Apolipoprotein E₄ and Cognitive Decline in Elderly Adults

Packard

Westendorp

Stott

et al. 2007

J American Geriatrics Society

115

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OBJECTIVE:To determine the influence of apolipoprotein E on cognitive decline in a cohort of elderly men and women. DESIGN: Prospective study. SETTING: Scotland, Ireland, and the Netherlands. PARTICIPANTS: Five thousand eight hundred four subjects aged 70 to 82 from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). MEASUREMENTS: Subjects were assessed at baseline and over a mean 3.2-year (range 0.7-4.2) follow-up for memory (Picture-Word Recall), speed of information processing (Stroop and Letter-Digit Coding), global cognitive function (Mini-Mental State Examination), and activities of daily living. RESULTS: At baseline, subjects with apolipoprotein E 4 versus those without E 4 had poorer memory performance (mean score difference À 0.20 (95% confidence interval (CI) 5 À 0.31 to À 0.09) for immediate recall and À 0.32 (95% CI 5 À 0.48 to À 0.16) for delayed recall and slower information processing (difference in Stroop, 2.79 seconds, (95% CI 5 1.20-4.28); Letter-Digit score, À 0.36, (95% CI 5 À 0.77-0.05). Subjects with apolipoprotein E 4 showed a greater decline in immediate ( À 0.22, 95% CI 5 À 0.33 to À 0.11) and delayed ( À 0.30, 95% CI 5 À 0.46 to À 0.15) memory scores but no significant change in speed of information processing (Stroop, P 5.17; Letter-Digit, P 5.06). Memory scores decreased 2.5% from baseline in those without E 4 , 4.3% in E 4 heterozygotes (P 5.01 for immediate and P 5.03 for delayed, vs no E 4 ) and 8.9% to 13.8% in E 4 homozygotes (P 5.04 for immediate and P 5.004 for delayed, vs heterozygotes). Apolipoprotein E 4 was associated with greater decline in instrumental activities of daily living (Po.001). Cognitive decline was not associated with lipoprotein levels. CONCLUSION: Findings in PROSPER indicate that E 4 is associated with more-rapid cognitive decline and may, therefore, predispose to dementia. J Am Geriatr Soc 55:1777-1785, 2007. Key words: memory; dementia; trial; statin A major challenge in the quest to promote healthy aging is to uncover the determinants of cognitive decline in the general population and the risk factors that lead to the development of frank dementia. Although age is the main predictor of cognitive function, investigators have also reported that a history of hypertension, diabetes mellitus, stroke, depression, and lack of physical activity are factors. [1][2][3][4][5][6] The apolipoprotein E phenotype (apolipoprotein E is coded by a gene (e) that exhibits allelic variants e 2 , e 3 , and e 4 ) has been linked consistently and strongly to the appearance of Alzheimer's disease and to some aspects of cognitive decline in elderly cohorts. 1,2,[5][6][7][8][9] Inheritance of E 4 (the product of e 4 ) especially in the homozygous form, has been associated in cross-sectional studies with risk of Alzheimer's disease and poorer global cognitive function, episodic memory, and executive function, although the magnitude of the effect is modest. 10,11 Longitudinal data also show good evidence of an association between E 4 and risk of Alzheimer's diseas...

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Section: Discussionmentioning

confidence: 70%

mentioning

confidence: 99%

Association Between Apolipoprotein E₄ and Cognitive Decline in Elderly Adults

Packard

Westendorp

Stott

et al. 2007

J American Geriatrics Society

115

View full text Add to dashboard Cite

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“…Based on previous studies, HDL-C does not seem to associate with dementia or AD (Li et al 2005;Reitz et al 2010;Arntzen et al 2011) albeit the association is Total cholesterol, HDL cholesterol, systolic blood pressure, body mass index, apolipoprotein A-I, apolipoprotein B, and apolipoprotein B/A ratio were log-transformed before multivariate analysis a Model is not adjusted for total cholesterol apo A-I apolipoprotein A-I, HDL-C high density lipoprotein cholesterol, apo B apolipoprotein B, apo B/A ratio ratio between apo B and apo A-I seen in cross-sectional studies (Merched et al 2000). These findings are in line with our results where death is considered as a competing risk for dementia and AD, and statistically significant association is seen in CIF but not in Cox regression model between HDL-C and AD.…”

Section: Discussionmentioning

confidence: 91%

“…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). Apolipoprotein A-I (apo A-I) is the major surface protein of HDL-C, which is associated with lower risk for cardiovascular diseases (CVD).…”

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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“…However, several recent studies have not supported the idea of a link between cholesterol levels and risk of Alzheimer 654,655,656 disease.…”

Section: Genewatch Uk January 2006mentioning

confidence: 98%