Open Access Research article

The association of APOE genotype and cognitive decline in interaction with risk factors in a 65–69 year old community sample

Helen Christensen1*, Philip J Batterham1, Andrew J Mackinnon12, Anthony F Jorm2, Holly A Mack1, Karen A Mather1, Kaarin J Anstey1, Perminder S Sachdev34 and Simon Easteal1

Author Affiliations

1 The Australian National University, Canberra, Australia

2 The University of Melbourne, Melbourne, Australia

3 School of Psychiatry, University of New South Wales, Sydney, Australia

4 Neuropsychiatric Institute, the Prince of Wales Hospital, Sydney, Australia

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BMC Geriatrics 2008, 8:14  doi:10.1186/1471-2318-8-14

Published: 14 July 2008



While the evidence of an association between the apolipoprotein E (APOE) *E4 allele and Alzheimer's disease is very strong, the effect of the *E4 allele on cognitive decline in the general population is more equivocal. A cross-sectional study on the lifespan effects of the *E4 allele [1] failed to find any effect of the *E4 allele on cognitive performance at ages 20–24, 40–44 or 60–64 years.


In this four year follow-up study, we reexamine the effect of *E4 in the sample of 2,021 individuals, now aged 65–69 years.


Performance on the Mini-Mental State Examination (MMSE) was significantly poorer for *E4 homozygotes than heterozygotes or non-carriers. The effects of the *E4 genotype on cognitive decline over four years were found on the MMSE and Symbol-Digit Modalities test but only when controlling for risk factors such as head injury and education. Analyses were repeated with the exclusion of participants diagnosed with a mild cognitive disorder, with little change.


It is possible that *E4 carriers become vulnerable to greater cognitive decline in the presence of other risk factors at 65–69 years of age.