Olfactory deficits predict cognitive decline and Alzheimer dementia in an urban community

To determine the predictive utility of baseline odor identification deficits for future cognitive decline and the diagnosis of Alzheimer disease (AD) dementia.

In a multiethnic community cohort in North Manhattan, NY, 1,037 participants without dementia were evaluated with the 40-item University of Pennsylvania Smell Identification Test (UPSIT). In 757 participants, follow-up occurred at 2 years and 4 years.

In logistic regression analyses, lower baseline UPSIT scores were associated with cognitive decline (relative risk 1.067 per point interval; 95% confidence interval [CI] 1.040, 1.095; p < 0.0001), and remained significant (relative risk 1.065 per point interval; 95% CI 1.034, 1.095; p < 0.0001) after including covariates. UPSIT, but not Selective Reminding Test-total immediate recall, predicted cognitive decline in participants without baseline cognitive impairment. During follow-up, 101 participants transitioned to AD dementia. In discrete time survival analyses, lower baseline UPSIT scores were associated with transition to AD dementia (hazard ratio 1.099 per point interval; 95% CI 1.067, 1.131; p < 0.0001), and remained highly significant (hazard ratio 1.072 per point interval; 95% CI 1.036, 1.109; p < 0.0001) after including demographic, cognitive, and functional covariates.

Impairment in odor identification was superior to deficits in verbal episodic memory in predicting cognitive decline in cognitively intact participants. The findings support the cross-cultural use of a relatively inexpensive odor identification test as an early biomarker of cognitive decline and AD dementia. Such testing may have the potential to select/stratify patients in treatment trials of cognitively impaired patients or prevention trials in cognitively intact individuals.