The Neuroanatomic Correlates of Olfactory Identification Impairment in Healthy Older Adults and in Persons with Mild Cognitive Impairment

Article type: Research Article

Authors: Kamath, Vidyulata^{a; *} | Senjem, Matthew L.^{b; c} | Spychalla, Anthony J.^b | Chen, Honglei^d | Palta, Priya^e | Mosley, Thomas H.^f | Windham, B. Gwen^f | Griswold, Michael^f | Knopman, David S.^g | Gottesman, Rebecca F.^h | Jack Jr, Clifford R.^b | Sharrett, A. Richeyⁱ | Schneider, Andrea L.C.^j

Affiliations: [a] Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA | [b] Department of Radiology, Mayo Clinic, Rochester, MN, USA | [c] Department of Information Technology, Mayo Clinic, Rochester, MN, USA | [d] Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, USA | [e] Division of General Medicine, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA | [f] The MIND Center, Department of Medicine, The University of Mississippi School of Medicine, Jackson, MI, USA | [g] Department of Neurology, Mayo Clinic, Rochester, MN, USA | [h] National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA | [i] Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA | [j] Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

Correspondence: [*] Correspondence to: Vidyulata Kamath, PhD, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Meyer 218, Baltimore, MD 21287, USA. Tel.: +1 410 614 6342; Fax: +1 410 955 0504; E-mail: vkamath@jhmi.edu.

Abstract: Background:Olfactory identification (OI) impairment appears early in the course of Alzheimer’s disease dementia (AD), prior to detectable cognitive impairment. However, the neuroanatomical correlates of impaired OI in cognitively normal older adults (CN) and persons with mild cognitive impairment (MCI) are not fully understood. Objective:We examined the neuroanatomic correlates of OI impairment in older adults from the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS). Methods:Our sample included 1,600 older adults without dementia who completed clinical assessment and structural brain imaging from 2011 to 2013. We characterized OI impairment using the 12-item Sniffin’ Sticks odor identification test (score ≤6). We used voxel-based morphometry (VBM) and region of interest (ROI) analyses to examine the neuroanatomic correlates of impaired OI in CN and MCI, after adjusting for potential confounders. Analyses were also separately stratified by race and sex. Results:In CN, OI impairment was associated with smaller amygdala gray matter (GM) volume (p < 0.05). In MCI, OI impairment was associated with smaller GM volumes of the olfactory cortex, amygdala, entorhinal cortex, hippocampus, and insula (ps < 0.05). Differential associations were observed by sex in MCI; OI impairment was associated with lower insular GM volumes among men but not among women (p-interaction = 0.04). There were no meaningful interactions by race. Conclusion:The brain regions associated with OI impairment in individuals without dementia are specifically those regions known to be the primary targets of AD pathogenic processes. These findings highlight the potential utility of olfactory assessment in the identification and stratification of older adults at risk for AD.

Keywords: Alzheimer’s disease, chemosensory, hyposmia, olfaction, smell

DOI: 10.3233/JAD-220228

Journal: Journal of Alzheimer's Disease, vol. 89, no. 1, pp. 233-245, 2022