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-epsilon 4 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-epsilon 4 allele) and smaller GMV in AD and olfactory regions (beta = -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.

Automated summary

Rapid olfactory decline during normal cognition predicts subsequent cognitive impairment, dementia, and smaller gray matter volumes in the brain. This measurement has the potential to be a simple biomarker for early detection of AD.