Affiliations: [a]
Taub Institute, Columbia University Irving Medical Center, New York, NY, USA
| [b]
Mailman School of Public Health, Columbia University Irving Medical Center, New York, NY, USA
| [c]
Weill Cornell Medical College, New York, NY, USA
| [d]
Gertrude H. Sergievsky Center, Columbia University Irving Medical Center, New York, NY, USA
| [e]
The Research Foundation for Mental Hygiene, Inc, New York, NY, USA
Correspondence:
[*]
Correspondence to: William C. Kreisl, MD, 622 West 168th Street, PH 19, New York, NY 10032, USA. Tel.: +1 212 305 9079; E-mail: wck2107@cumc.columbia.edu.
Abstract: Background:Olfactory impairment is evident in Alzheimer’s disease (AD); however, its precise relationships with clinical biomarker measures of tau pathology and neuroinflammation are not well understood. Objective:To determine if odor identification performance measured with the University of Pennsylvania Smell Identification Test (UPSIT) is related to in vivo measures of tau pathology and neuroinflammation. Methods:Cognitively normal and cognitively impaired participants were selected from an established research cohort of adults aged 50 and older who underwent neuropsychological testing, brain MRI, and amyloid PET. Fifty-four participants were administered the UPSIT. Forty-one underwent 18F-MK-6240 PET (measuring tau pathology) and fifty-three underwent 11C-PBR28 PET (measuring TSPO, present in activated microglia). Twenty-three participants had lumbar puncture to measure CSF concentrations of total tau (t-tau), phosphorylated tau (p-tau), and amyloid-β (Aβ42). Results:Low UPSIT performance was associated with greater18F-MK-6240 binding in medial temporal cortex, hippocampus, middle/inferior temporal gyri, inferior parietal cortex, and posterior cingulate cortex (p < 0.05). Similar relationships were seen for 11C-PBR28. These relationships were primarily driven by amyloid-positive participants. Lower UPSIT performance was associated with greater CSF concentrations of t-tau and p-tau (p < 0.05). Amyloid status and cognitive status exhibited independent effects on UPSIT performance (p < 0.01). Conclusion:Olfactory identification deficits are related to extent of tau pathology and neuroinflammation, particularly in those with amyloid pathophysiology. The independent association of amyloid-positivity and cognitive impairment with odor identification suggests that low UPSIT performance may be a marker for AD pathophysiology in cognitive normal individuals, although impaired odor identification is associated with both AD and non-AD related neurodegeneration.NCT Registration Numbers: NCT03373604; NCT02831283
Keywords: Alzheimer’s disease, anosmia, microglia, olfaction, tau proteins
