Olfactory function declines during normal aging; however, accelerated olfactory decline is observed in neurodegenerative diseases, such as Alzheimer’s disease (AD). Moreover, olfactory deficits in pre-clinical AD are associated with future cognitive decline. Odor identification and memory deficits have been consistently reported in early stage AD indicating its potential sensitivity to AD pathophysiology in olfactory and limbic structures, yet few studies of olfaction have incorporated structural measures in a well-characterized cohort of older adults. In the current study we examined the association between odor identification impairment, cognition, and medial temporal lobe (MTL) sub-regions in cognitively unimpaired and impaired older adults.

We enrolled 140 participants (age=72.25±6.54, 56% female, years of education=16.30±2.63, 82% Caucasian, 15% Black/AA, 3% Multiracial) from the Penn Alzheimer’s Disease Research Center Clinical Cohort. Participants completed the Sniffin’ Sticks Odor Identification Test (SS-OIT), cognitive testing (NACC UDS2 or UDS3 and additional cognitive tests), and MRI scans (3T Siemens MAGNETOM Prisma MRI scanner). For the SS-OIT, participants were presented with 16 odorants using felt-tipped pen dispensers and asked to identify each odor from four multiple-choice options. Scores range from 0 to 16. Additionally, cognitive domains were created by averaging z-scores from tests within each domain: attention, memory, language, executive function, and visuospatial. This cohort was divided into participants with unimpaired cognition (n=96) and impaired cognition (MCI, dementia; n=44) using established normative data and consensus diagnosis. Linear regressions were performed to examine the association between SS-OIT score, each cognitive domain, and MTL measurements for unimpaired and impaired groups. For all analyses, we controlled for age, race, sex, education, smoking status, and hypertension and additionally for MOCA score and intracranial volume with MTL measurements.

In the unimpaired group, SS-OIT significantly associated with language (p<.05). In the impaired group, SS-OIT significantly associated with language and memory (p<.05). In the unimpaired group, SS-OIT significantly associated with right anterior hippocampal volume (p<.05). In the impaired group, significant associations were found between SS-OIT and right anterior hippocampal volume (p<.05) and left hippocampal mean thickness (p<.05). Additionally, SS-OIT significantly associated with left and right entorhinal cortex volume (p<.05) and mean thickness (p<.05).

This study reveals that lower odor identification performance is related to lower performance on measures of cognition and atrophy in MTL sub-regions in unimpaired and impaired older adults. Our findings support prior results demonstrating relationships between olfactory function, cognition, and MTL sub-regions. Specifically, olfactory function and episodic memory have been shown to follow similar patterns of decline in the course of AD, potentially reflecting AD pathology in shared regions of the MTL subserving episodic memory and olfactory function. Our findings demonstrate that reductions in both cortical thickness and grey matter volume of MTL regions are linked to olfactory deficits in individuals at risk for Alzheimer’s dementia. Future steps will include the analysis of longitudinal cognitive and imaging indices and the incorporation of fluid biomarker data.