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Apolipoprotein E4 is only a weak predictor of dementia and cognitive decline in the general population.

ABSTRACT: BACKGROUND: Apolipoprotein E (APOE) polymorphisms are unequivocally associated with risk for Alzheimer's disease (AD). It is crucial to understand how this genetic factor affects dementia risk in the general population, as well as in narrowly diagnosed, selected, patient groups. METHODS: We assessed the cross sectional association between APOE genotype and dementia status in a community based sample, the MRC Cognitive Function and Ageing Study (MRC CFAS). In addition, we tested the effects of APOE genotypes on the differences in MMSE scores between the first and third assessment waves (about six years apart), an index of cognitive decline. RESULTS: The APOE epsilon4 allele conferred increased risk for dementia (OR=1.5, 95% CI=1.1 to 2.2) compared to epsilon3 in the MRC CFAS sample. Compared with APOE epsilon3/epsilon 3 subjects, those with the epsilon3/epsilon4 genotypes were not at significantly higher risk for dementia (OR=1.1, 95% CI=0.6 to 1.9), although epsilon4/epsilon4 subjects were (OR= 3.8, 95% CI=1.0 to 14.0). Risk estimates were not different between men and women. Notably, our risk estimates for dementia were significantly lower than those reported for a diagnosis of Alzheimer's disease. MMSE scores at wave 3 and the difference in MMSE between baseline and at the third assessment wave were not different across APOE genotypes. INTERPRETATION: The APOE epsilon4 allele is a weaker predictor for dementia in the general population than for AD. This may be because dementia can be caused by non-AD pathological processes and because most prevalent dementia occurs at an age when the APOE epsilon4 effect on AD risk (and therefore dementia) has started to decline.

SUBMITTER: Yip AG

PROVIDER: S-EPMC1735244 | biostudies-other | 2002 Sep

REPOSITORIES: biostudies-other

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Apolipoprotein E4 is only a weak predictor of dementia and cognitive decline in the general population.

Yip A G AG Brayne C C Easton D D Rubinsztein D C DC

Journal of medical genetics 20020901 9

<h4>Background</h4>Apolipoprotein E (APOE) polymorphisms are unequivocally associated with risk for Alzheimer's disease (AD). It is crucial to understand how this genetic factor affects dementia risk in the general population, as well as in narrowly diagnosed, selected, patient groups.<h4>Methods</h4>We assessed the cross sectional association between APOE genotype and dementia status in a community based sample, the MRC Cognitive Function and Ageing Study (MRC CFAS). In addition, we tested the ...[more]

PMID: 12205106

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Project description:Preclinical prediction of Alzheimer disease (AD) is important and critical to effective intervention. Plasma levels of amyloid-? (A?) peptides have been a principal focus of the growing literature on blood-based biomarkers, but studies to date have varied in design, assay methods, and sample size, making it difficult to readily interpret the overall data.To conduct a systematic review and meta-analysis of relevant prospective studies to determine whether plasma amyloid-? levels may predict development of dementia, AD, and cognitive decline.We searched prospective studies published between 1995 and 2011 indexed in the MEDLINE, EMBASE, and PsycINFO databases. Selected studies included those measuring at least 1 relevant plasma amyloid-? species (A?(40), A?(42), or A?(42):A?(40) ratio) and reporting an effect estimate for dementia, AD, or cognitive change.Using a standardized extraction form, appropriate study parameters on subject information, exposure, and outcome were extracted. Random effects models were used to generate summary risk ratios and 95% confidence intervals comparing the bottom vs top quantiles for each plasma measure.Thirteen studies with a total of 10 303 subjects met inclusion criteria for meta-analysis. Lower A?(42):A?(40) ratios were significantly associated with development of AD (summary risk ratio, 1.60; 95% CI, 1.04-2.46; P = .03) and dementia (risk ratio, 1.67; 95% CI, 1.02-2.75; P = .04). Significant heterogeneity was found for both summary estimates, which could not be explained by participants' age, sex distribution, the study's follow-up time, or year of publication. Plasma levels of A?(40) and A?(42) alone were not significantly associated with either outcome.Overall, the literature indicates that plasma A?(42):A?(40) ratios predict development of AD and dementia. However, significant heterogeneity in the meta-analysis underlines the need for substantial further investigation of plasma amyloid-? levels as a preclinical biomarker.

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Apolipoprotein E4 is only a weak predictor of dementia and cognitive decline in the general population.

Publications

Apolipoprotein E4 is only a weak predictor of dementia and cognitive decline in the general population.

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