Estimates of age-related memory decline are inflated by unrecognized Alzheimer's disease

Karra D Harrington; Adrian Schembri; Yen Ying Lim; Christa Dang; David Ames; Jason Hassenstab; Simon M Laws; Stephanie Rainey-Smith; Joanne Robertson; Christopher C Rowe; Hamid R Sohrabi; Olivier Salvado; Michael Weinborn; Victor L Villemagne; Colin L Masters; Paul Maruff; AIBL Research Group

doi:10.1016/j.neurobiolaging.2018.06.005

Estimates of age-related memory decline are inflated by unrecognized Alzheimer's disease

Neurobiol Aging. 2018 Oct:70:170-179. doi: 10.1016/j.neurobiolaging.2018.06.005. Epub 2018 Jun 11.

Authors

Karra D Harrington¹, Adrian Schembri², Yen Ying Lim³, Christa Dang⁴, David Ames⁵, Jason Hassenstab⁶, Simon M Laws⁷, Stephanie Rainey-Smith⁸, Joanne Robertson³, Christopher C Rowe⁹, Hamid R Sohrabi¹⁰, Olivier Salvado¹¹, Michael Weinborn¹², Victor L Villemagne¹³, Colin L Masters³, Paul Maruff¹⁴; AIBL Research Group

Affiliations

¹ The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia; Cooperative Research Centre for Mental Health, Carlton, Victoria, Australia. Electronic address: karra.harrington@florey.edu.au.
² CogState Ltd., Melbourne, Victoria, Australia.
³ The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.
⁴ Department of Obstetrics and Gynaecology, Melbourne Medical School, The University of Melbourne, Parkville, Victoria, Australia.
⁵ Department of Psychiatry, Academic Unit for Psychiatry of Old Age, The University of Melbourne, Parkville, Victoria, Australia; National Ageing Research Institute, Parkville, Victoria, Australia.
⁶ Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA; Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA; Department of Psychological & Brain Sciences, Washington University, St. Louis, MO, USA.
⁷ Cooperative Research Centre for Mental Health, Carlton, Victoria, Australia; Collaborative Genomics Group, Centre of Excellence for Alzheimer's Disease Research and Care, School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Perth, Western Australia, Australia; School of Biomedical Sciences, Faculty of Health Sciences, Curtin Health Innovation Research Institute, Curtin University, Western Australia, Australia.
⁸ Centre of Excellence for Alzheimer's Disease Research and Care, School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Perth, Western Australia, Australia; Australian Alzheimer's Disease Research Unit, Hollywood Private Hospital, Perth, Western Australia, Australia.
⁹ Department of Molecular Imaging & Therapy, Austin Health, Melbourne, Victoria, Australia; Department of Medicine, Austin Health, The University of Melbourne, Melbourne, Victoria, Australia.
¹⁰ Centre of Excellence for Alzheimer's Disease Research and Care, School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Perth, Western Australia, Australia; School of Psychiatry and Clinical Neurosciences, University of Western Australia, Nedlands, Western Australia, Australia.
¹¹ CSIRO Health and Biosecurity, The Australian eHealth Research Centre, Brisbane, Queensland, Australia.
¹² Centre of Excellence for Alzheimer's Disease Research and Care, School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Perth, Western Australia, Australia; Australian Alzheimer's Disease Research Unit, Hollywood Private Hospital, Perth, Western Australia, Australia; School of Psychological Science, University of Western Australia, Crawley, Western Australia, Australia.
¹³ The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia; Department of Molecular Imaging & Therapy, Austin Health, Melbourne, Victoria, Australia; Department of Medicine, Austin Health, The University of Melbourne, Melbourne, Victoria, Australia.
¹⁴ The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia; CogState Ltd., Melbourne, Victoria, Australia.

PMID: 30015036
DOI: 10.1016/j.neurobiolaging.2018.06.005

Abstract

Cognitive decline is considered an inevitable consequence of aging; however, estimates of cognitive aging may be influenced negatively by undetected preclinical Alzheimer's disease (AD). This study aimed to determine the extent to which estimates of cognitive aging were biased by preclinical AD. Cognitively normal older adults (n = 494) with amyloid-β status determined from positron emission tomography neuroimaging underwent serial neuropsychological assessment at 18-month intervals over 72 months. Estimates of the effects of age on verbal memory, working memory, executive function, and processing speed were derived using linear mixed models. The presence of preclinical AD and clinical progression to mild cognitive impairment or dementia during the study were then added to these models as covariates. Initially, age was associated with decline across all 4 cognitive domains. With the effects of elevated amyloid-β and clinical progression controlled, age was no longer associated with decline in verbal or working memory. However, the magnitude of decline was reduced only slightly for executive function and was unchanged for processing speed. Thus, considered together, the results of the study indicate that undetected preclinical AD negatively biases estimates of age-related cognitive decline for verbal and working memory.

Keywords: Aging; Alzheimer; Amyloid-β; Cognition; Preclinical.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Alzheimer Disease / complications
Alzheimer Disease / psychology*
Amyloid beta-Peptides / analysis
Cognitive Aging*
Cognitive Dysfunction / complications
Cognitive Dysfunction / psychology
Disease Progression
Executive Function
Female
Humans
Male
Memory*
Neuropsychological Tests
Prodromal Symptoms
Prospective Studies

Substances

Amyloid beta-Peptides