Cost-effective, noninvasive screening methods for preclinical Alzheimer's disease (AD) and other neurocognitive disorders remain an unmet need. The olfactory neural circuits develop AD pathological changes prior to symptom onset. To probe these vulnerable circuits, we developed the digital remote AROMHA Brain Health Test (ABHT), an at-home odor identification, discrimination, memory, and intensity assessment. The ABHT was self-administered among cognitively normal (CN) English and Spanish speakers (n=127), participants with subjective cognitive complaints (SCC; n=34), and mild cognitive impairment (MCI; n=19). Self-administered tests took place remotely at home under unobserved (among interested CN participants) and observed modalities (CN, SCC, and MCI), as well as in-person with a research assistant present (CN, SCC, and MCI). Olfactory performance was similar across observed and unobserved remote self-administration and between English and Spanish speakers. Odor memory, identification, and discrimination scores decreased with age, and olfactory identification and discrimination were lower in the MCI group compared to CN and SCC groups, independent of age, sex, and education. The ABHT revealed age-related olfactory decline, and discriminated CN older adults from those with cognitive impairment. Replication of our results in other populations would support the use of the ABHT to identify and monitor individuals at risk for developing dementia. Keywords: Remote assessment, screening, Alzheimer's disease, Mild cognitive impairment, olfaction.

S.R. and M.W.A. are co-founders and own shares in Aromha, Inc. C.M. and A.D.A. are consultants for Aromha, Inc. M.W.A. and A.D.A.'s participation in this research was reviewed by the MGB Office of Industrial Interactions. M.W.A is a consultant for Sudo Bioscience Limited, Transposon Therapeutics, and has received in kind donations from IFF and from Eli Lilly. He has received speaking fees from Biohaven and Incyte.

NCT05881239

https://clinicaltrials.gov/study/NCT05881239?term=NCT05881239&rank=1

BJ is supported by scholarships from the Canadian Institutes of Health Research, the Fonds de Recherche Québec Santé, the Québec Bio-Imaging Network, the Université du Québec â Trois-Rivières, and MITACS. The study was funded by NIH R41AG062130 and NIHR42AG 062130 (awarded to S.R.), and U01DC019579 (awarded to M.W.A.).

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The research protocol was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of Partners Health.

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