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Apolipoprotein E4 is only a weak predictor of dementia and cognitive decline in the general population
  1. A G Yip1,2,
  2. C Brayne1,
  3. D Easton3,
  4. D C Rubinsztein2,
  5. The Medical Research Council Cognitive Function Ageing Study (MRC CFAS)
  1. 1Department of Public Health and Primary Care, University Forvie Site, Robinson Way, Cambridge CB2 2SR, UK
  2. 2Department of Medical Genetics, Cambridge Institute for Medical Research, Wellcome/MRC Building, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 2XY, UK
  3. 3CRC Genetic Epidemiology Unit, Cambridge University Department of Public Health and Primary Care, Strangeways Research Laboratory, Worts’ Causeway, Cambridge CB1 8RN, UK
  1. Correspondence to:
 Dr D C Rubinsztein, Department of Medical Genetics, Cambridge Institute for Medical Research, Wellcome/MRC Building, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 2XY, UK;
 dcr1000{at}cus.cam.ac.uk

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 ε4 allele conferred increased risk for dementia (OR=1.5, 95% CI=1.1 to 2.2) compared to ε3 in the MRC CFAS sample. Compared with APOE ε3/ε3 subjects, those with the ε3/ε4 genotypes were not at significantly higher risk for dementia (OR=1.1, 95% CI=0.6 to 1.9), although ε4/ε4 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 ε4 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 ε4 effect on AD risk (and therefore dementia) has started to decline.

  • apolipoprotein E
  • association study
  • cognitive decline
  • dementia
  • APOE, apolipoprotein E
  • AD, Alzheimer’s disease
  • MRC CFAS, Medical Research Council Cognitive Function and Ageing Study
  • VaD, vascular dementia
  • LDL, low density lipoprotein
  • MMSE, Mini Mental State Examination
  • AGECAT, Automated Geriatric Examination for Computer Based Taxonomy
  • OR, odds ratio

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