Alzheimer's & Dementia: The Journal of the Alzheimer's Association
Volume 6, Issue 5 , Pages 412-419, September 2010

Influence of apolipoprotein E ɛ4 on rates of cognitive and functional decline in mild cognitive impairment

  • Danielle C. Whitehair

      Affiliations

    • Department of Neurosciences, University of California, San Diego, CA, USA
    • ,
  • Abdullah Sherzai

      Affiliations

    • Loma Linda University Medical Center, Riverside, CA, USA
    • ,
  • Jennifer Emond

      Affiliations

    • Department of Family and Preventive Medicine, University of California, San Diego, CA, USA
    • ,
  • Rema Raman

      Affiliations

    • Department of Neurosciences, University of California, San Diego, CA, USA
    • Department of Family and Preventive Medicine, University of California, San Diego, CA, USA
    • ,
  • Paul S. Aisen

      Affiliations

    • Department of Neurosciences, University of California, San Diego, CA, USA
    • ,
  • Ronald C. Petersen

      Affiliations

    • Neurology, Mayo Clinic College of Medicine, Rochester, MN, USA
    • ,
  • Adam S. Fleisher

      Affiliations

    • Banner Alzheimer's Institute, Phoenix, AZ, USA
    • Corresponding Author InformationCorresponding author. Tel.: 602 239-6979; Fax: 602 239-6499.
    • ,
  • Alzheimer's Disease Cooperative Study

Abstract 

Background

Apolipoprotein E ɛ4 (APOE ɛ4) allele carrier status has been well established as a risk factor for developing Alzheimer's disease. However, the specific influence of APOE ɛ4 allele status on cognitive and functional rates of decline in mild cognitive impairment (MCI) is poorly understood. We examine the prospective association of APOE ɛ4 allele status on measures of cognitive and functional decline in subjects with amnestic MCI (aMCI).

Methods

A total of 516 aMCI participants aged 55–90 years who received placebo or vitamin E from the Alzheimer's Disease Cooperative Study's MCI treatment trial were evaluated. During the 36-month study period, neurocognitive and functional measures were collected. These measures were assessed over time for change and association with APOE ɛ4 status. Generalized Estimating Equations were performed to model each outcome measure over the study period.

Results

APOE ɛ4 status had a significant impact on cognitive and functional decline on multiple measures; those who were APOE ɛ4 positive had significantly more rapid decline in performance on all cognitive and functional measures except Number Cancellation and Maze tracing (P < .05). The greatest decline was seen in global measures of cognition and function including the Clinical Diagnostic Rating scale, followed by the Mini-Mental State Examination, Global Deterioration scale, and the Alzheimer's Disease Assessment Scale-Cognitive Subscale.

Conclusions

These findings demonstrate that APOE ɛ4 genotype is predictive of increased general rates of decline with global measures of cognition and function most affected. With accelerated declines in common clinical trial primary efficacy measures, APOE ɛ4 status needs to be accounted for in treatment trials of MCI.

Keywords: All cognitive disorders/dementia, MCI (mild cognitive impairment), Alzheimer's disease, Risk factors in epidemiology, All genetics

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 For all authors there are no disclosures to be made of any financial support from, or equity positions in, manufacturers of drugs or products mentioned in the manuscript. These authors and the Alzheimer's Disease Cooperative study had full publication rights without influence or restrictions from the Institute for the Study of Aging, Pfizer Inc., or Eisai Inc. All authors have agreed to conditions noted on the Author Disclosure Form. All of the authors have been instrumental in the interpretation and presentation of data in this paper. This manuscript has not been simultaneously submitted for publication to any other journal.

 Financial disclosure: Danielle C. Whitehair, Jennifer Emond, Rema Raman, Adam S. Fleisher: none. Abdullah Sherzai is a speaker for Novartis (Exelon patch); Paul S. Aisen consults with pharmaceutical companies regarding AD drug development, including Elan, Wyeth, Eisai, Neurochem, Schering-Plough, Bristol Myers Squibb, Lilly, Neurophage, Merck, Roche, Amgen, Genentech, Abbott, Pfizer, Novartis and Medivation; Ronald C. Petersen consults with pharmaceutical companies regarding AD drug development, including Elan, GE Healthcare and Wyeth. He also is a speaker for Eisai, Janssen, Novartis and Pfizer.

PII: S1552-5260(10)00002-6

doi:10.1016/j.jalz.2009.12.003

Alzheimer's & Dementia: The Journal of the Alzheimer's Association
Volume 6, Issue 5 , Pages 412-419, September 2010

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