{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T17:52:17Z","timestamp":1777917137142,"version":"3.51.4"},"posted":{"date-parts":[[2026,4,28]]},"group-title":"Neurology","reference-count":39,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Importance<\/jats:title>\n                  <jats:p>Decline in olfactory function may be used as a predictor of cognitive decline, to enhance early detection models, improve risk stratification, and enable early intervention.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To assess the longitudinal association between olfactory decline, cognitive decline, and postmortem neuropathology.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Design, setting and participants<\/jats:title>\n                  <jats:p>Retrospective longitudinal analysis with clinicopathological correlations of a prospective population-based cohort study using data from the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND) and its Brain and Body Donation Program. Participants included cognitively unimpaired individuals without parkinsonism that converted to mild cognitive impairment (MCI) and\/or dementia or remained cognitively stable.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Main Outcomes and Measures<\/jats:title>\n                  <jats:p>longitudinal change in olfaction, neuropsychiatric symptoms, motor function and memory, conversion to MCI\/dementia, postmortem neuropathology<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Over a mean follow-up period of 7.7 \u00b1 5.4 years, out of 922 participants who were cognitively unimpaired at the first cognitive conference, 643 remained cognitively unimpaired, 279 converted to MCI, and 82 developed dementia. Of these, 633 individuals had at least 2 olfactory tests.<\/jats:p>\n                  <jats:p>Converters showed reduced olfactory function (t=-12.6, p &lt;0.0001), faster progression in neuropsychiatric symptom burden (t=3.42, p &lt; 0.001), and faster decline in memory (t= -7.33, p &lt;0.0001) prior to conversion while no significant differences were observed in motor scores between converters and non-converters. Using ROC analysis, olfactory decline, increased neuropsychiatric symptom burden, as well as motor and memory decline predicted conversion to MCI with a consistent accuracy of \u223c 70% up to 5 years before conversion, while UPSIT alone had an accuracy of \u223c 60%. Longitudinal decline in olfaction was associated with a higher burden of a-synuclein (t= -8.21, p &lt;0.0005), tau tangle (t= -2.66, p &lt; 0.01) and amyloid plaque burden (t= -2.85, p &lt; 0.005) and a faster decline over time was associated with a higher burden of tau (t=5.66, p&lt;0.0001).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions and Relevance<\/jats:title>\n                  <jats:p>A reduction in olfactory identification ability is observed up to a decade prior to conversion to MCI and is associated with underlying burden of neuropathology markers, underscoring the value of incorporating olfactory testing in cognitively unimpaired individuals to identify those at-risk of future cognitive decline.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.04.27.26351817","type":"posted-content","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T22:10:44Z","timestamp":1777414244000},"source":"Crossref","is-referenced-by-count":0,"title":["Olfactory decline in aging: longitudinal trajectories and associations with cognitive decline and postmortem neuropathology"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8460-7421","authenticated-orcid":false,"given":"Cecilia","family":"Tremblay","sequence":"first","affiliation":[{"name":"Cerebral Imaging Centre, Douglas Mental Health University Institute, Montr\u00e9al, Qu\u00e9bec, Canada, H4H 1R3"},{"name":"Department of Psychiatry, McGill University, Montr\u00e9al, Qu\u00e9bec, Canada, H4H 1R3"},{"name":"Department of Neuropathology, Banner Sun Health Research Institute, Sun City, Arizona, 85351, 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Neuropathology, Banner Sun Health Research Institute, Sun City, Arizona, 85351, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holly A.","family":"Shill","sequence":"additional","affiliation":[{"name":"Department of Neurology, Barrow Neurological Institute, Phoenix, Arizona, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shyamal","family":"Mehta","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale, Arizona, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Ho","sequence":"additional","affiliation":[{"name":"Cleo Roberts Center, Banner Sun Health Research Institute, Sun City, Arizona, 85351, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seyed-Mohammad","family":"Fereshtehnejad","sequence":"additional","affiliation":[{"name":"Pacific Parkinson\u2019s Research Centre (PPRC), Djavad Mowafaghian Centre 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