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Association between apolipoprotein E4 and cognitive decline in elderly adults.

Packard CJ, Westendorp RG, Stott DJ, Caslake MJ, Murray HM, Shepherd J, Blauw GJ, Murphy MB, Bollen EL, Buckley BM, Cobbe SM, Ford I, Gaw A, Hyland M, Jukema JW, Kamper AM, Macfarlane PW, Jolles J, Perry IJ, Sweeney BJ, Twomey C,

Department of Vascular Biochemistry, University of Glasgow, Glasgow, Scotland. chris.packard@clinmed.gla.ac.uk

OBJECTIVE: To determine the influence of apolipoprotein E on cognitive decline in a cohort of elderly men and women. DESIGN: Prospective study. SETTING: Scotland, Ireland, and the Netherlands. PARTICIPANTS: Five thousand eight hundred four subjects aged 70 to 82 from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). MEASUREMENTS: Subjects were assessed at baseline and over a mean 3.2-year (range 0.7-4.2) follow-up for memory (Picture-Word Recall), speed of information processing (Stroop and Letter-Digit Coding), global cognitive function (Mini-Mental State Examination), and activities of daily living. RESULTS: At baseline, subjects with apolipoprotein E(4) versus those without E(4) had poorer memory performance (mean score difference -0.20 (95% confidence interval (CI)=-0.31 to -0.09) for immediate recall and -0.32 (95% CI=-0.48 to -0.16) for delayed recall and slower information processing (difference in Stroop, 2.79 seconds, (95% CI=1.20-4.28); Letter-Digit score, -0.36, (95% CI=-0.77-0.05). Subjects with apolipoprotein E(4) showed a greater decline in immediate (-0.22, 95% CI=-0.33 to -0.11) and delayed (-0.30, 95% CI=-0.46 to -0.15) memory scores but no significant change in speed of information processing (Stroop, P=.17; Letter-Digit, P=.06). Memory scores decreased 2.5% from baseline in those without E(4), 4.3% in E(4) heterozygotes (P=.01 for immediate and P=.03 for delayed, vs no E(4)) and 8.9% to 13.8% in E(4) homozygotes (P=.04 for immediate and P=.004 for delayed, vs heterozygotes). Apolipoprotein E(4) was associated with greater decline in instrumental activities of daily living (P<.001). Cognitive decline was not associated with lipoprotein levels. CONCLUSION: Findings in PROSPER indicate that E(4) is associated with more-rapid cognitive decline and may, therefore, predispose to dementia.

Published 5 November 2007 in J Am Geriatr Soc, 55(11): 1777-85.
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