To assess odor identification (OI) as an indicator of presymptomatic Alzheimer disease (AD) pathogenesis in cognitively normal aging individuals at increased risk of AD dementia.
In 274 members of the PREVENT-AD cohort of healthy aging persons with a parental or multiple-sibling history of AD dementia, we assessed the cross-sectional association of OI with potential indicators of presymptomatic AD. Some 101 participants donated CSF, thus enabling assessment of AD pathology with the biomarkers total tau (t-tau), phospho-tau (P 181-tau), and their ratios with β-amyloid (Aβ 1-42). Adjusted analyses considered age, cognition, APOE ε4 status, education, and sex as covariates. We measured OI using the University of Pennsylvania Smell Identification Test and cognitive performance using the Repeatable Battery for Assessment of Neuropsychological Status. Standard kits provided assays of the AD biomarkers. Analyses used robust-fit linear regression models.
Reduced OI was associated with lower cognitive score and older age, as well as increased ratios of CSF t-tau and P 181-tau to Aβ 1-42 (all p < 0.02). However, the observed associations of OI with age and cognition were unapparent in adjusted models that restricted observations to CSF donors and included AD biomarkers. OI showed little association with CSF Aβ 1-42 alone except in APOE ε4 carriers having lowest-quartile Aβ 1-42 levels.
These findings from healthy high-risk older individuals suggest that OI reflects degree of preclinical AD pathology, while its relationships with age and cognition result from the association of these latter variables with such pathology. Diminished OI may be a practical and affordable biomarker of AD pathology.
(1) FRSQ, 35271, principal applicant, 2014-2018 (2) CIHR, 363444, co-applicant, 2016-2019 (3) CIHR, 366009, co-applicant, 2016-2020 (4) CIHR, 201312CNA-322265-CNA-CFAF-32054, co- investigator, 2014-2019
(1) Merck, Sharpe & Dohme Corporation/McGill Faculty of Medicine Grant for Translational Research
(1) Weston Brain Institute (2) Alzheimer's Association (3) Brain Canada CQDM
(1) Mayo Clinic Studies on Aging, Scientific Advisory Board (NIH-funded program) (2) Data and Safety Monitoring Board, SPRINT-MIND clinical trial (NIA / NHLBI sponsor) (3) Consultant to Cerespir Pharmaceuticals
Alzheimer's Disease and Associated Disorders, Editorial Board, 2003 - present; PLOS-One, Academics, 2009 - present; Alzheimer's and Dementia, Editorial Board, 2007 - present;
Fast Facts - Dementia. Second Edition. Health Press, 2009 (no royalties received in over two years)
(2) Research support from the Douglas Hospital Research Centre and the Douglas Hospital Foundation.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. The Article Processing charge was funded by McGill University.
Coinvestigators are listed at Neurology.org.
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