Stronger Effect of Amyloid Load Than APOE Genotype on Cognitive Decline in Healthy Older Adults

Neurology. 2012 Oct 16;79(16):1645-1652.

Stronger effect of amyloid load than APOE genotype on cognitive decline in healthy older adults.

Lim YYEllis KAPietrzak RHAmes DDarby DHarrington KMartins RNMasters CLRowe CSavage GSzoeke CVillemagne VL,Maruff PFor the AIBL Research Group.

Source

From the Mental Health Research Institute (Y.Y.L., K.A.E., D.D., K.H., C.L.M., V.L.V., P.M.), Department of Psychiatry (Y.Y.L.), and Academic Unit for Psychiatry of Old Age, Department of Psychiatry (K.A.E., D.A.), The University of Melbourne, Parkville, Australia; National Ageing Research Institute (K.A.E., D.A., C.S.), Parkville, Australia; Department of Psychiatry (R.H.P.), Yale University School of Medicine, New Haven, CT; Florey Neuroscience Institutes (D.D.), The University of Melbourne, Carlton South, Australia; Centre of Excellence for Alzheimer’s Disease Research and Care, School of Exercise, Biomedical and Health Sciences (R.N.M.), Edith Cowan University, Perth, Australia; Department of Nuclear Medicine and Centre for PET (C.R., V.L.V.) and Department of Medicine (C.R.), Austin Health, The University of Melbourne, Heidelberg, Australia; Department of Psychology and ARC Centre of Excellence in Cognition and Its Disorders (G.S.), Macquarie University, Sydney, Australia; and CogState Ltd. (P.M.), Melbourne, Australia.

Abstract

OBJECTIVE:

Although the APOE ε4 allele is associated with more rapid decline in memory in healthy older adults, the significance of elevated cerebral β-amyloid (Aβ) load for longitudinal changes in cognition is unclear.

METHODS:

Healthy and cognitively normal older adults (n = 141; mean age 76 years) underwent PET neuroimaging for cerebral Aβ, APOE genotyping, and cognitive assessment as part of their baseline assessment in the Australian Imaging Biomarkers and Lifestyle study. Cognitive function was reassessed 18 months later.

RESULTS:

Linear mixed-model analyses adjusted for baseline cognitive function indicated that, relative to individuals with low cerebral Aβ, individuals with high cerebral Aβ showed significantly greater decline in working memory and verbal and visual episodic memory at 18 months. Compared with noncarriers, APOE ε4 carriers showed a greater decline in visual memory at the 18-month assessment. No interaction between APOE ε4 and cerebral Aβ load was observed for any measure of cognitive function.

CONCLUSIONS:

In this prospective study of healthy older adults, high cerebral Aβ load was associated with greater decline in episodic and working memory over 18 months. The APOE ε4 genotype was also associated with a decline in visual memory, although the effect was less than that observed for cerebral Aβ load.

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