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Joint effect of stroke and APOE 4 on dementia risk

The Canadian Study of Health and Aging

From the Department of Clinical Neurological Sciences, London Health Sciences Centre and University of Western Ontario, London, Ontario, Canada (Y.P.J., S.D.L., V.H.); Department of Community and Family Medicine, Duke University, Durham, NC (T.O.); Department of Family Medicine, Canadian Task Force on Preventive Health Care and University of Western Ontario, London, Ontario, Canada (J.W.F.); and Stroke Unit, Department of Neurosciences, Università Tor Vergata, Rome, Italy (S.D.L.).

Address correspondence and reprint requests to Dr Jin, Department of Clinical Neurological Sciences, London Health Sciences Centre and University of Western Ontario, 339 Windermere Rd., London, Ontario, Canada N6A 5A5 yaping.jin{at}utoronto.ca.

Background: Although stroke and APOE 4 are independent risk factors for dementia, their combined effect remains uncertain. We assessed their joint effect on dementia risk.

Methods: Subjects participated in Phases 1 and 2 of the Canadian Study of Health and Aging (CSHA). Dementia was diagnosed by consensus, and stroke was diagnosed by history or clinical examination. Analyses were first conducted among clinical participants only, and then rerun with the screening sample included as well.

Results: Analyses included 949 participants from CSHA-1 and 1,413 from CSHA-2. During a median 4.6-year follow-up, 740 were included in the CSHA-1 to -2 incidence study. Among clinical participants, the highest prevalence (40.6% for CSHA-1 and 57.6% for CSHA-2) and incidence (8.4 per 100 person-years) of dementia occurred in elderly having both stroke and APOE 4; the lowest prevalence (19.8% for CSHA-1 and 23.3% for CSHA-2) and incidence (4.3 per 100 person-years) were among persons having neither. These findings held true when the screening sample was included. The adjusted hazard ratios of incident dementia, relative to elderly with neither stroke nor APOE 4, were 1.33 (95% CI 0.73 to 2.43) for stroke alone, 2.06 (95% CI 1.42 to 2.99) for APOE 4 alone, and 2.57 (95% CI 1.11 to 5.94) for both. No interaction on additive or multiplicative scales was suggested.

Conclusions: The joint presence of stroke and APOE 4 was associated with a greater risk of dementia compared with absence of these two factors. The effect of stroke on dementia does not seem to be modified by APOE 4.

Abbreviations: 3MS = Modified Mini-Mental State Examination; CIHR = Canadian Institutes of Health Research; CIND = cognitive impairment no dementia; CSHA = Canadian Study of Health and Aging; HSFC = Heart and Stroke Foundation of Canada; HR = hazard ratio; OR = odds ratio; NHRDP = National Health Research and Development Program; SBP = systolic blood pressure.

e-Pub ahead of print on October 31, 2007, at www.neurology.org.

The data reported in this article were collected as part of the Canadian Study of Health and Aging (CSHA). The core funding for Phases 1 and 2 of the CSHA was provided by the Seniors' Independence Research Program, through Health Canada's National Health Research and Development Program (NHRDP). Funding for analysis of the caregiver component was provided by the Medical Research Council. Additional funding was provided by Pfizer Canada Inc., through the Medical Research Council/Pharmaceutical Manufacturers Association of Canada, through NHRDP, by Bayer Inc., and by the British Columbia Health Research Foundation. Core funding for Phase 3 was provided by the Canadian Institutes of Health Research (CIHR). Supplementary funding for the caregiver component was obtained from CIHR. Additional funding was provided by Merck-Frosst and by Janssen-Ortho. CSHA was coordinated through the University of Ottawa and Health Canada. Dr. Jin is supported by a research fellowship award from the Heart and Stroke Foundation of Canada (HSFC) under the fourth International Conference on Preventive Cardiology (ICPC)/Canadian Cardiovascular Society fellowship.

Disclosure: The authors report no conflicts of interest.

Supplemental data at www.neurology.org

Editorial, see page 5

See also page 17

Received October 27, 2006. Accepted in final form March 6, 2007.

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