Association between apolipoprotein E4 and cognitive decline in elderly adults.
OBJECTIVE
To determine the influence of apolipoprotein E on cognitive decline in a cohort of elderly men and women.


METHODS
Prospective study.


METHODS
Scotland, Ireland, and the Netherlands.


METHODS
Five thousand eight hundred four subjects aged 70 to 82 from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER).


METHODS
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.


CONCLUSIONS
Findings in PROSPER indicate that E(4) is associated with more-rapid cognitive decline and may, therefore, predispose to dementia.
Packard
Chris J
CJ
Department of Vascular Biochemistry, University of Glasgow, Glasgow, Scotland. chris.packard@clinmed.gla.ac.uk
Westendorp
Rudi G J
RG
Stott
David J
DJ
Caslake
Muriel J
MJ
Murray
Heather M
HM
Shepherd
James
J
Blauw
Gerard J
GJ
Murphy
Michael B
MB
Bollen
Edward L E M
EL
Buckley
Brendan M
BM
Cobbe
Stuart M
SM
Ford
Ian
I
Gaw
Allan
A
Hyland
Michael
M
Jukema
J Wouter
JW
Kamper
Adriaan M
AM
Macfarlane
Peter W
PW
Jolles
Jellemer
J
Perry
Ivan J
IJ
Sweeney
Brian J
BJ
Twomey
Cillian
C
D000203:Activities of Daily Living / Q000145:classification; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D053327:Apolipoprotein E4 / Q000235:genetics*; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D003072:Cognition Disorders / Q000097:blood / Q000235:genetics*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D015140:Dementia, Vascular / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006580:Genetic Carrier Screening; D006720:Homozygote; D006801:Humans; D007494:Ireland; D008297:Male; D008609:Mental Status Schedule; D009426:Netherlands; D009483:Neuropsychological Tests; D010641:Phenotype; D017035:Pravastatin / Q000627:therapeutic use; D012307:Risk Factors; D012606:Scotland; D013223:Statistics as Topic; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D053327:Apolipoprotein E4; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides; D002784:Cholesterol; D017035:Pravastatin