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

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

1. Yen Ying Lim, MPsych,
2. Kathryn A. Ellis, PhD,
3. Robert H. Pietrzak, PhD, MPH,
4. David Ames, MD,
5. David Darby, MBBS, PhD, FRACP,
6. Karra Harrington, BA,
7. Ralph N. Martins, PhD,
8. Colin L. Masters, MD,
9. Christopher Rowe, MD,
10. Greg Savage, PhD,
11. Cassandra Szoeke, PhD,
12. Victor L. Villemagne, MD,
13. Paul Maruff, PhD and
14. For the AIBL Research Group

+ Author Affiliations

1. 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.

1. Melbourne, biomarkers analysis

1. Melbourne, neuropsychology

1. Melbourne, member of management group

1. Melbourne, member of biomarkers leadership group

1. Perth, research assistant involved in physical activity assessments

1. Sydney, biomarkers analysis

1. Melbourne, blood processing and analysis

1. Melbourne, neuropsychological assessment

1. Perth, clinician involved in cognitive testing of AIBL participants

1. Melbourne, neuropsychological assessment

1. Melbourne, neuroimaging analysis

1. Melbourne, neuroimaging analysis

1. Melbourne, neuroimaging data acquisition

1. Perth, research fellow involved in handling the AIBL plasma samples

1. Melbourne, neuropsychological assessment

1. Brisbane, neuroimaging analysis

1. Melbourne, blood processing and analysis

1. Melbourne, consumer representation

1. Melbourne, clinician involved in recruitment and review of cohort

1. Perth, research associate involved in brain imaging of AIBL participants

1. Melbourne, neuroimaging analysis

1. Melbourne, clinician involved in recruitment and review of cohort

1. Melbourne, biomarkers analysis

1. Melbourne, administration

1. Brisbane, neuroimaging analysis

1. Brisbane, neuroimaging analysis

1. Melbourne, neuroimaging analysis

1. Brisbane, neuroimaging analysis

1. Melbourne, biomarkers analysis

1. Perth, research assistant involved in neuropsychiatric testing

1. Melbourne, blood processing and analysis

1. Perth, clinician involved in AIBL participants recruitment

1. Perth, research fellow involved in analysing and revising the manuscript

1. Brisbane, data management

1. Perth, research assistant involved in neuropsychiatric testing

1. Melbourne, genetics analysis

1. Perth, research assistant involved in dietary assessments of AIBL participants

1. Brisbane, neuroimaging analysis.

1. Correspondence & reprintrequests to Dr: Lim: y.lim@mhri.edu.au

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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.

Footnotes

• AIBL Research Group Coinvestigators are listed on the Neurology® Web site at www.neurology.org.