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Alzheimer’s Environmental and Genetic Risk Scores are Differentially Associated With General Cognitive Ability and Dementia Severity

Andrews, Shea J., PhD*,†; McFall, G. Peggy, PhD‡,§; Dixon, Roger A., PhD‡,§; Cherbuin, Nicolas, PhD*; Eramudugolla, Ranmalee, PhD; Anstey, Kaarin J., PhD*,∥,¶

Alzheimer Disease & Associated Disorders: April-June 2019 - Volume 33 - Issue 2 - p 95–103
doi: 10.1097/WAD.0000000000000292
Original Articles

Purpose: We investigated the association of the Australian National University Alzheimer’s Disease Risk Index (ANU-ADRI) and an Alzheimer disease (AD) genetic risk score (GRS) with cognitive performance.

Methods: The ANU-ADRI (composed of 12 risk factors for AD) and GRS (composed of 25 AD risk loci) were computed in 1061 community-dwelling older adults. Participants were assessed on 11 cognitive tests and activities of daily living. Structural equation modeling was used to evaluate the association of the ANU-ADRI and GRS with: (1) general cognitive ability (g), (2) dementia-related variance in cognitive performance (δ), and (3) verbal ability (VA), episodic memory (EM), executive function (EF), and processing speed (PS).

Results: A worse ANU-ADRI score was associated with poorer performance in “g” [β (SE)=−0.40 (0.02), P<0.001], δ [−0.40 (0.04), P<0.001], and each cognitive domain [VA=−0.29 (0.04), P<0.001; EM=−0.34 (0.03), P<0.001; EF=−0.38 (0.03), P<0.001; and PS=−0.40 (0.03), P<0.001]. A worse GRS was associated with poorer performance in δ [−0.08 (0.03), P=0.041] and EM [−0.10 (0.03), P=0.035].

Conclusions: The ANU-ADRI was broadly associated with worse cognitive performance, including general ability and dementia severity, validating its further use in early dementia risk assessment.

*Centre for Research on Ageing, Health and Wellbeing, Australian National University, Canberra, Australian Capital Territory

School of Psychology, University of New South Wales

Lifecourse Ageing Research Centre, Neuroscience Research Australia, Sydney, NSW, Australia

Department of Neuroscience, Icahn School of Medicine at Mount Sinai, NY

Neuroscience and Mental Health Institute

§Department of Psychology, University of Alberta, Edmonton, AB, Canada

Supported by the National Health and Medical Research Council (NHMRC) grants 179805 and 1002160 and the NHMRC Dementia Collaborative Research Centre Early Diagnosis and Prevention. S.J.A. is funded by the ARC Centre of Excellence in Population Ageing Research, ARC grant CE1101029. K.J.A. is funded by NHMRC Research Fellowship number 1002560. R.A.D. and G.P.M. are funded by the National Institutes of Health (National Institute on Aging, R01 AG008235) and the Canadian Consortium on Neurodegeneration in Aging (with funding from the Canadian Institutes of Health Research and partners).

The authors declare no conflicts of interest.

Reprints: Shea J. Andrews, PhD, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave., New York, NY 10029 (e-mail:

Received August 8, 2018

Accepted December 1, 2018

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