Olfactory Function and Markers of Brain Pathology in Non-Demented Individuals with Autosomal Dominant Alzheimer’s Disease

Article type: Research Article

Authors: Ramirez-Gomez, Liliana^a | Albers, Mark W.^a | Baena, Ana^b | Vila-Castelar, Clara^c | Fox-Fuller, Joshua T.^{c; d} | Sanchez, Justin^a | Jain, Felipe^c | Albers, Alefiya D.^{a; e} | Lopera, Francisco^b | Quiroz, Yakeel T.^{a; b; c; *}

Affiliations: [a] Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA | [b] Grupo de Neurociencias, Universidad de Antioquia, Medellin, Colombia | [c] Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA | [d] Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA | [e] Department of Psychology, Endicott College, Beverly, MA, USA

Correspondence: [*] Correspondence to: Yakeel T. Quiroz, PhD, Associate Professor, Harvard Medical School, Departments of Psychiatry and Neurology, Massachusetts General Hospital, 39 First Ave, Suite 101, Charlestown, MA 02129, USA. Tel.: +1 617 643 5944; E-mail: [email protected]

Abstract: Background:Olfactory dysfunction is one of the earliest signs of Alzheimer’s disease (AD), highlighting its potential use as a biomarker for early detection. It has also been linked to progression from mild cognitive impairment (MCI) to dementia. Objective:To study olfactory function and its associations with markers of AD brain pathology in non-demented mutation carriers of an autosomal dominant AD (ADAD) mutation and non-carrier family members. Methods:We analyzed cross-sectional data from 16 non-demented carriers of the Presenilin1 E280A ADAD mutation (mean age [SD]: 40.1 [5.3], and 19 non-carrier family members (mean age [SD]: 36.0 [5.5]) from Colombia, who completed olfactory and cognitive testing and underwent amyloid and tau positron emission tomography (PET) imaging. Results:Worse olfactory identification performance was associated with greater age in mutation carriers (r = –0.52 p = 0.037). In carriers, worse olfactory identification performance was related to worse MMSE scores (r = 0.55, p = 0.024) and CERAD delayed recall (r = 0.63, p = 0.007) and greater cortical amyloid-β (r = –0.53, p = 0.042) and tau pathology burden (entorhinal: r = –0.59, p = 0.016; inferior temporal: r = –0.52, p = 0.038). Conclusion:Worse performance on olfactory identification tasks was associated with greater age, a proxy for disease progression in this genetically vulnerable ADAD cohort. In addition, this is the first study to report olfactory dysfunction in ADAD mutation carriers with diagnosis of MCI and its correlation with abnormal accumulation of tau pathology in the entorhinal region. Taken together, our findings suggest that olfactory dysfunction has promise as an early marker of brain pathology and future risk for dementia.

Keywords: Alzheimer’s disease, autosomal dominant Alzheimer’s disease, mild cognitive impairment, olfactory function

DOI: 10.3233/JAD-220075

Journal: Journal of Alzheimer's Disease, vol. 88, no. 2, pp. 721-729, 2022