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Journal of the American Geriatrics Society

Association Between Apolipoprotein E4 and Cognitive Decline in Elderly Adults

Authors

  • Chris J. Packard DSc,

    1. From the aDepartment of Vascular Biochemistry, bDivision of Cardiovascular and Medical Sciences, and cRobertson Centre for Biostatistics, University of Glasgow, Glasgow, ScotlanddSection of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands; Departments of ePsychiatryfNeuropsychology, Maastricht University, Maastricht, The Netherlands; Departments of gPharmacology and Therapeutics, hGeriatric Medicine, iEpidemiology and Public Health, and jNeurology, Cork University Hospital, Cork, IrelandkNorth Glasgow Operating Division, National Health Service Greater Glasgow and Clyde, Glasgow, Scotland; and Departments of lNeurologymCardiology, Leiden University Medical Centre, Leiden, The Netherlands
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  • Rudi G.J. Westendorp MD,

    1. From the aDepartment of Vascular Biochemistry, bDivision of Cardiovascular and Medical Sciences, and cRobertson Centre for Biostatistics, University of Glasgow, Glasgow, ScotlanddSection of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands; Departments of ePsychiatryfNeuropsychology, Maastricht University, Maastricht, The Netherlands; Departments of gPharmacology and Therapeutics, hGeriatric Medicine, iEpidemiology and Public Health, and jNeurology, Cork University Hospital, Cork, IrelandkNorth Glasgow Operating Division, National Health Service Greater Glasgow and Clyde, Glasgow, Scotland; and Departments of lNeurologymCardiology, Leiden University Medical Centre, Leiden, The Netherlands
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  • David J. Stott MD,

    1. From the aDepartment of Vascular Biochemistry, bDivision of Cardiovascular and Medical Sciences, and cRobertson Centre for Biostatistics, University of Glasgow, Glasgow, ScotlanddSection of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands; Departments of ePsychiatryfNeuropsychology, Maastricht University, Maastricht, The Netherlands; Departments of gPharmacology and Therapeutics, hGeriatric Medicine, iEpidemiology and Public Health, and jNeurology, Cork University Hospital, Cork, IrelandkNorth Glasgow Operating Division, National Health Service Greater Glasgow and Clyde, Glasgow, Scotland; and Departments of lNeurologymCardiology, Leiden University Medical Centre, Leiden, The Netherlands
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  • Muriel J. Caslake PhD,

    1. From the aDepartment of Vascular Biochemistry, bDivision of Cardiovascular and Medical Sciences, and cRobertson Centre for Biostatistics, University of Glasgow, Glasgow, ScotlanddSection of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands; Departments of ePsychiatryfNeuropsychology, Maastricht University, Maastricht, The Netherlands; Departments of gPharmacology and Therapeutics, hGeriatric Medicine, iEpidemiology and Public Health, and jNeurology, Cork University Hospital, Cork, IrelandkNorth Glasgow Operating Division, National Health Service Greater Glasgow and Clyde, Glasgow, Scotland; and Departments of lNeurologymCardiology, Leiden University Medical Centre, Leiden, The Netherlands
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  • Heather M. Murray MSc,

    1. From the aDepartment of Vascular Biochemistry, bDivision of Cardiovascular and Medical Sciences, and cRobertson Centre for Biostatistics, University of Glasgow, Glasgow, ScotlanddSection of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands; Departments of ePsychiatryfNeuropsychology, Maastricht University, Maastricht, The Netherlands; Departments of gPharmacology and Therapeutics, hGeriatric Medicine, iEpidemiology and Public Health, and jNeurology, Cork University Hospital, Cork, IrelandkNorth Glasgow Operating Division, National Health Service Greater Glasgow and Clyde, Glasgow, Scotland; and Departments of lNeurologymCardiology, Leiden University Medical Centre, Leiden, The Netherlands
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  • James Shepherd MD,

    1. From the aDepartment of Vascular Biochemistry, bDivision of Cardiovascular and Medical Sciences, and cRobertson Centre for Biostatistics, University of Glasgow, Glasgow, ScotlanddSection of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands; Departments of ePsychiatryfNeuropsychology, Maastricht University, Maastricht, The Netherlands; Departments of gPharmacology and Therapeutics, hGeriatric Medicine, iEpidemiology and Public Health, and jNeurology, Cork University Hospital, Cork, IrelandkNorth Glasgow Operating Division, National Health Service Greater Glasgow and Clyde, Glasgow, Scotland; and Departments of lNeurologymCardiology, Leiden University Medical Centre, Leiden, The Netherlands
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  • Gerard J. Blauw MD,

    1. From the aDepartment of Vascular Biochemistry, bDivision of Cardiovascular and Medical Sciences, and cRobertson Centre for Biostatistics, University of Glasgow, Glasgow, ScotlanddSection of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands; Departments of ePsychiatryfNeuropsychology, Maastricht University, Maastricht, The Netherlands; Departments of gPharmacology and Therapeutics, hGeriatric Medicine, iEpidemiology and Public Health, and jNeurology, Cork University Hospital, Cork, IrelandkNorth Glasgow Operating Division, National Health Service Greater Glasgow and Clyde, Glasgow, Scotland; and Departments of lNeurologymCardiology, Leiden University Medical Centre, Leiden, The Netherlands
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  • Michael B. Murphy MD,

    1. From the aDepartment of Vascular Biochemistry, bDivision of Cardiovascular and Medical Sciences, and cRobertson Centre for Biostatistics, University of Glasgow, Glasgow, ScotlanddSection of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands; Departments of ePsychiatryfNeuropsychology, Maastricht University, Maastricht, The Netherlands; Departments of gPharmacology and Therapeutics, hGeriatric Medicine, iEpidemiology and Public Health, and jNeurology, Cork University Hospital, Cork, IrelandkNorth Glasgow Operating Division, National Health Service Greater Glasgow and Clyde, Glasgow, Scotland; and Departments of lNeurologymCardiology, Leiden University Medical Centre, Leiden, The Netherlands
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  • Edward L.E.M. Bollen MD,

    1. From the aDepartment of Vascular Biochemistry, bDivision of Cardiovascular and Medical Sciences, and cRobertson Centre for Biostatistics, University of Glasgow, Glasgow, ScotlanddSection of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands; Departments of ePsychiatryfNeuropsychology, Maastricht University, Maastricht, The Netherlands; Departments of gPharmacology and Therapeutics, hGeriatric Medicine, iEpidemiology and Public Health, and jNeurology, Cork University Hospital, Cork, IrelandkNorth Glasgow Operating Division, National Health Service Greater Glasgow and Clyde, Glasgow, Scotland; and Departments of lNeurologymCardiology, Leiden University Medical Centre, Leiden, The Netherlands
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  • Brendan M. Buckley,

    1. From the aDepartment of Vascular Biochemistry, bDivision of Cardiovascular and Medical Sciences, and cRobertson Centre for Biostatistics, University of Glasgow, Glasgow, ScotlanddSection of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands; Departments of ePsychiatryfNeuropsychology, Maastricht University, Maastricht, The Netherlands; Departments of gPharmacology and Therapeutics, hGeriatric Medicine, iEpidemiology and Public Health, and jNeurology, Cork University Hospital, Cork, IrelandkNorth Glasgow Operating Division, National Health Service Greater Glasgow and Clyde, Glasgow, Scotland; and Departments of lNeurologymCardiology, Leiden University Medical Centre, Leiden, The Netherlands
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  • Stuart M. Cobbe MD,

    1. From the aDepartment of Vascular Biochemistry, bDivision of Cardiovascular and Medical Sciences, and cRobertson Centre for Biostatistics, University of Glasgow, Glasgow, ScotlanddSection of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands; Departments of ePsychiatryfNeuropsychology, Maastricht University, Maastricht, The Netherlands; Departments of gPharmacology and Therapeutics, hGeriatric Medicine, iEpidemiology and Public Health, and jNeurology, Cork University Hospital, Cork, IrelandkNorth Glasgow Operating Division, National Health Service Greater Glasgow and Clyde, Glasgow, Scotland; and Departments of lNeurologymCardiology, Leiden University Medical Centre, Leiden, The Netherlands
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  • Ian Ford PhD,

    1. From the aDepartment of Vascular Biochemistry, bDivision of Cardiovascular and Medical Sciences, and cRobertson Centre for Biostatistics, University of Glasgow, Glasgow, ScotlanddSection of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands; Departments of ePsychiatryfNeuropsychology, Maastricht University, Maastricht, The Netherlands; Departments of gPharmacology and Therapeutics, hGeriatric Medicine, iEpidemiology and Public Health, and jNeurology, Cork University Hospital, Cork, IrelandkNorth Glasgow Operating Division, National Health Service Greater Glasgow and Clyde, Glasgow, Scotland; and Departments of lNeurologymCardiology, Leiden University Medical Centre, Leiden, The Netherlands
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  • Allan Gaw MD,

    1. From the aDepartment of Vascular Biochemistry, bDivision of Cardiovascular and Medical Sciences, and cRobertson Centre for Biostatistics, University of Glasgow, Glasgow, ScotlanddSection of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands; Departments of ePsychiatryfNeuropsychology, Maastricht University, Maastricht, The Netherlands; Departments of gPharmacology and Therapeutics, hGeriatric Medicine, iEpidemiology and Public Health, and jNeurology, Cork University Hospital, Cork, IrelandkNorth Glasgow Operating Division, National Health Service Greater Glasgow and Clyde, Glasgow, Scotland; and Departments of lNeurologymCardiology, Leiden University Medical Centre, Leiden, The Netherlands
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  • Michael Hyland MD,

    1. From the aDepartment of Vascular Biochemistry, bDivision of Cardiovascular and Medical Sciences, and cRobertson Centre for Biostatistics, University of Glasgow, Glasgow, ScotlanddSection of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands; Departments of ePsychiatryfNeuropsychology, Maastricht University, Maastricht, The Netherlands; Departments of gPharmacology and Therapeutics, hGeriatric Medicine, iEpidemiology and Public Health, and jNeurology, Cork University Hospital, Cork, IrelandkNorth Glasgow Operating Division, National Health Service Greater Glasgow and Clyde, Glasgow, Scotland; and Departments of lNeurologymCardiology, Leiden University Medical Centre, Leiden, The Netherlands
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  • J. Wouter Jukema MD,

    1. From the aDepartment of Vascular Biochemistry, bDivision of Cardiovascular and Medical Sciences, and cRobertson Centre for Biostatistics, University of Glasgow, Glasgow, ScotlanddSection of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands; Departments of ePsychiatryfNeuropsychology, Maastricht University, Maastricht, The Netherlands; Departments of gPharmacology and Therapeutics, hGeriatric Medicine, iEpidemiology and Public Health, and jNeurology, Cork University Hospital, Cork, IrelandkNorth Glasgow Operating Division, National Health Service Greater Glasgow and Clyde, Glasgow, Scotland; and Departments of lNeurologymCardiology, Leiden University Medical Centre, Leiden, The Netherlands
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  • Adriaan M. Kamper MD,

    1. From the aDepartment of Vascular Biochemistry, bDivision of Cardiovascular and Medical Sciences, and cRobertson Centre for Biostatistics, University of Glasgow, Glasgow, ScotlanddSection of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands; Departments of ePsychiatryfNeuropsychology, Maastricht University, Maastricht, The Netherlands; Departments of gPharmacology and Therapeutics, hGeriatric Medicine, iEpidemiology and Public Health, and jNeurology, Cork University Hospital, Cork, IrelandkNorth Glasgow Operating Division, National Health Service Greater Glasgow and Clyde, Glasgow, Scotland; and Departments of lNeurologymCardiology, Leiden University Medical Centre, Leiden, The Netherlands
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  • Peter W. Macfarlane DSc,

    1. From the aDepartment of Vascular Biochemistry, bDivision of Cardiovascular and Medical Sciences, and cRobertson Centre for Biostatistics, University of Glasgow, Glasgow, ScotlanddSection of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands; Departments of ePsychiatryfNeuropsychology, Maastricht University, Maastricht, The Netherlands; Departments of gPharmacology and Therapeutics, hGeriatric Medicine, iEpidemiology and Public Health, and jNeurology, Cork University Hospital, Cork, IrelandkNorth Glasgow Operating Division, National Health Service Greater Glasgow and Clyde, Glasgow, Scotland; and Departments of lNeurologymCardiology, Leiden University Medical Centre, Leiden, The Netherlands
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  • Jellemer Jolles MD,

    1. From the aDepartment of Vascular Biochemistry, bDivision of Cardiovascular and Medical Sciences, and cRobertson Centre for Biostatistics, University of Glasgow, Glasgow, ScotlanddSection of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands; Departments of ePsychiatryfNeuropsychology, Maastricht University, Maastricht, The Netherlands; Departments of gPharmacology and Therapeutics, hGeriatric Medicine, iEpidemiology and Public Health, and jNeurology, Cork University Hospital, Cork, IrelandkNorth Glasgow Operating Division, National Health Service Greater Glasgow and Clyde, Glasgow, Scotland; and Departments of lNeurologymCardiology, Leiden University Medical Centre, Leiden, The Netherlands
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  • Ivan J. Perry MD,

    1. From the aDepartment of Vascular Biochemistry, bDivision of Cardiovascular and Medical Sciences, and cRobertson Centre for Biostatistics, University of Glasgow, Glasgow, ScotlanddSection of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands; Departments of ePsychiatryfNeuropsychology, Maastricht University, Maastricht, The Netherlands; Departments of gPharmacology and Therapeutics, hGeriatric Medicine, iEpidemiology and Public Health, and jNeurology, Cork University Hospital, Cork, IrelandkNorth Glasgow Operating Division, National Health Service Greater Glasgow and Clyde, Glasgow, Scotland; and Departments of lNeurologymCardiology, Leiden University Medical Centre, Leiden, The Netherlands
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  • Brian J. Sweeney,

    1. From the aDepartment of Vascular Biochemistry, bDivision of Cardiovascular and Medical Sciences, and cRobertson Centre for Biostatistics, University of Glasgow, Glasgow, ScotlanddSection of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands; Departments of ePsychiatryfNeuropsychology, Maastricht University, Maastricht, The Netherlands; Departments of gPharmacology and Therapeutics, hGeriatric Medicine, iEpidemiology and Public Health, and jNeurology, Cork University Hospital, Cork, IrelandkNorth Glasgow Operating Division, National Health Service Greater Glasgow and Clyde, Glasgow, Scotland; and Departments of lNeurologymCardiology, Leiden University Medical Centre, Leiden, The Netherlands
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  • Cillian Twomey MD,

    1. From the aDepartment of Vascular Biochemistry, bDivision of Cardiovascular and Medical Sciences, and cRobertson Centre for Biostatistics, University of Glasgow, Glasgow, ScotlanddSection of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands; Departments of ePsychiatryfNeuropsychology, Maastricht University, Maastricht, The Netherlands; Departments of gPharmacology and Therapeutics, hGeriatric Medicine, iEpidemiology and Public Health, and jNeurology, Cork University Hospital, Cork, IrelandkNorth Glasgow Operating Division, National Health Service Greater Glasgow and Clyde, Glasgow, Scotland; and Departments of lNeurologymCardiology, Leiden University Medical Centre, Leiden, The Netherlands
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  • for the Prospective Study of Pravastatin in the Elderly at Risk Group

    1. From the aDepartment of Vascular Biochemistry, bDivision of Cardiovascular and Medical Sciences, and cRobertson Centre for Biostatistics, University of Glasgow, Glasgow, ScotlanddSection of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands; Departments of ePsychiatryfNeuropsychology, Maastricht University, Maastricht, The Netherlands; Departments of gPharmacology and Therapeutics, hGeriatric Medicine, iEpidemiology and Public Health, and jNeurology, Cork University Hospital, Cork, IrelandkNorth Glasgow Operating Division, National Health Service Greater Glasgow and Clyde, Glasgow, Scotland; and Departments of lNeurologymCardiology, Leiden University Medical Centre, Leiden, The Netherlands
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Address correspondence to Professor Chris J. Packard, Department of Vascular Biochemistry, 4th Floor University Block, Glasgow Royal Infirmary, Glasgow G31 2ER. E-mail: chris.packard@clinmed.gla.ac.uk

Abstract

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 E4 versus those without E4 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 E4 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 E4, 4.3% in E4 heterozygotes (P=.01 for immediate and P=.03 for delayed, vs no E4) and 8.9% to 13.8% in E4 homozygotes (P=.04 for immediate and P=.004 for delayed, vs heterozygotes). Apolipoprotein E4 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 E4 is associated with more-rapid cognitive decline and may, therefore, predispose to dementia.

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