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Apolipoprotein E ε4 and impaired episodic memory in community-dwelling elderly people: a marked sex difference. The Hordaland Health Study
  1. D J Lehmann1,
  2. H Refsum1,2,3,
  3. E Nurk1,2,
  4. D R Warden1,
  5. G S Tell4,
  6. S E Vollset4,
  7. K Engedal5,
  8. H A Nygaard4,
  9. A D Smith1
  1. 1OPTIMA, Oxford Centre for Gene Function, University Laboratory of Physiology, Oxford, UK
  2. 2Institute of Basic Medical Science, Department of Nutrition, University of Oslo, Oslo, Norway
  3. 3Institute of Medicine, Section of Pharmacology, University of Bergen, Bergen, Norway
  4. 4Department of Public Health and Primary Health Care, University of Bergen, Bergen
  5. 5Department of Geriatric Medicine, Norwegian Centre for Dementia Research, Ullevål University Hospital, Oslo
  1. Correspondence to:
 D J Lehmann
 OPTIMA, Oxford Centre for Gene Function, University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK; donald.lehmann{at}


Background: Among elderly people without dementia, the apolipoprotein E ε4 allele (APOE4) has been associated with cognitive deficit, particularly in episodic memory, but few reports are available on whether this association differs by sex.

Methods: In a community-dwelling Norwegian cohort of 2181 elderly people (55% women), aged 70–74 years, episodic memory was examined in relation to sex and APOE4 zygosity, with the Kendrick Object Learning Test (KOLT).

Results: Possession of at least one APOE4 allele had a modest, detrimental effect on episodic memory in women, whereas in men, heterozygotes were unaffected and homozygotes had markedly lower scores across the distribution of KOLT scores. This sex difference was found consistently in all analyses: on comparing means and medians, examining trends across quintiles, and studying the distribution of scores and the risk of cognitive impairment. Results were broadly similar when adjusted for known determinants of cognition and also when severely impaired participants were excluded. The adjusted odds ratio (OR) of cognitive impairment in women was shown to be 1.8 (95% confidence interval (CI): 1.1 to 2.8) for heterozygotes and 1.1 (0.3 to 3.7) for homozygotes; the adjusted OR in men was observed to be 1.1 (0.6 to 2.1) for heterozygotes and 10.7 (4.7 to 24) for homozygotes.

Conclusions: Although the harmful effect of APOE4 on episodic memory was modest in women, the risk was found to occur in about 30%. APOE4 was observed to have a dramatic effect on episodic memory in men, but only in homozygotes, who comprised about 3% of men: the whole male homozygous group showed a marked shift to lower memory scores.

  • APOE4, apolipoprotein E ε4 allele
  • CI, confidence interval
  • HDL, high-density lipoprotein
  • HUSK, Hordaland Health Study
  • KOLT, Kendrick Object Learning Test
  • OR, odds ratio

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  • Published Online First 4 April 2006

  • Competing interests: None.

  • Ethical approval: The Regional Committee for Medical Research Ethics of western Norway approved the study protocol.

    Data collection was conducted as part of the Hordaland Health Study (HUSK) 1997–9, as a collaboration between the University of Bergen, the Norwegian National Health Screening Service (now the Norwegian Institute of Public Health) and local health services. The project was partially financed with support from the Research Council of Norway. Dr EN held a Blaschko Visiting Research Scholarship at the University of Oxford.