Rapid olfactory decline during aging predicts dementia and GMV loss in AD brain regions.

Introduction: Longitudinal multivariable analyses are needed to determine if the rate of olfactory decline during normal cognition predicts subsequent Alzheimer's disease (AD) diagnoses and brain dysmorphology. Methods: Older adults (n = 515) were assessed annually for odor identification, cognitive function and dementia clinical diagnosis (max follow‐up 18 years). Regional gray matter volumes (GMV) were quantified (3T MRI) in a cross‐sectional subsample (n = 121). Regression models were adjusted for APOE‐ε4 genotype, dementia risk factors and demographics. Results: Faster olfactory decline during periods of normal cognition predicted higher incidence of subsequent MCI or dementia (OR 1.89, 95% CI: 1.26, 2.90, p < 0.01; comparable to carrying an APOE‐ε4 allele) and smaller GMV in AD and olfactory regions (β = −0.11, 95% CI −0.21, −0.00). Discussion: Rapid olfactory decline during normal cognition, using repeated olfactory measurement, predicted subsequent cognitive impairment, dementia, and smaller GMVs, highlighting its potential as a simple biomarker for early AD detection. Highlights: Rate of olfactory decline was calculated from olfactory testing over ≥3 time points.Rapid olfactory decline predicted impaired cognition and higher risk of dementia.Neurodegeneration on 3T magnetic resonance imaging was identical in those with olfactory decline and Alzheimer's disease. [ABSTRACT FROM AUTHOR]