Regional Differences in Effects of APOE epsilon 4 on Cognitive Impairment in Non-Demented Subjects

J. Norberg*, C. Graff, Ove Almkvist, M. Ewers, Giovanni B. Frisoni, Lutz Froelich, H. Hampel, Roy W. Jones, P.G. Kehoe, H. Lenoir, L. Minthon, F. Nobili, Marcel Olde Rikkert, A.S. Rigaud, P. Scheltens, H. Soininen, L. Spiru, M. Tsolaki, L.O. Wahlund, B. VellasG. Wilcock, L. S. Elias-Sonnenschein, F. R. J. Verhey, P. J. Visser

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Background: The APOE epsilon 4 allele is a risk factor for Alzheimer's disease (AD). APOE epsilon 4 is common in non-demented subjects with cognitive impairment. In both healthy people and people with AD, its prevalence has a north-south gradient across Europe. In the present study, we investigated whether the relation between the APOE epsilon 4 allele and cognitive impairment varied across Northern, Middle and Southern Europe. We also investigated whether a north-south gradient existed in subjects with subjective cognitive impairment (SCI), amnestic mild cognitive impairment (MCI) and non-amnestic MCI. Methods: Data from 16 centers across Europe were analyzed. Results: A north-south gradient in APOE epsilon 4 prevalence existed in the total sample (62.7% for APOE epsilon 4 carriers in the northern region, 42.1% in the middle region, and 31.5% in the southern region) and in subjects with SCI and amnestic MCI separately. Only in Middle Europe was the APOE epsilon 4 allele significantly associated with poor performance on tests of delayed recall and learning, as well as with the amnestic subtype of MCI. Conclusion: The APOE epsilon 4 allele frequencies in subjects with SCI and amnestic MCI have a north-south gradient. The relation between the APOE epsilon 4 allele and cognition is region dependent.
Original languageEnglish
Pages (from-to)135-142
JournalDementia and Geriatric Cognitive Disorders
Issue number2
Publication statusPublished - Oct 2011


  • Alzheimer's disease
  • APOE epsilon 4 allele
  • Europe
  • Gradient

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