Relation of odor identification with Alzheimer's disease markers in cerebrospinal fluid and cognition

Background: Impaired olfactory function is an early characteristic of Alzheimer's disease (AD), but it remains unclear if odor identification also relates to early markers of AD in cerebrospinal fluid (CSF). Objective: To investigate the association between odor identification and amyloid-β 1-42 (Aβ₄₂) and total tau (t-Tau) concentrations in CSF. In addition, to examine the relation between odor identification and cognitive function at baseline and at follow-up, and whether these associations are moderated by CSF Aβ₄₂ and t-Tau and apolipoprotein E (APOE) genotype. Methods: We included 160 individuals (40 with normal cognition, 45 with mild cognitive impairment (MCI), 42 with ADtype dementia, and 26 individuals with non-AD dementia) from the EDAR study. Individuals were recruited from six memory clinics across Europe. Odor identification was tested with the brief University of Pennsylvania Smell Identification Test. CSF A-42 and t-Tau were assessed with INNO-BIA AlzBio3 Luminex assay. Neuropsychological assessment included tests for verbal memory, verbal fluency, attention, executive function, and visuoconstruction. Follow-up was performed within 3 years after baseline. Results: Lower odor identification scores correlated with increased CSF t-Tau concentrations and with lower scores on all cognitive measures at baseline independent of diagnostic group. Lower odor identification scores predicted decline on the MMSE in the total group, and decline on wordlist learning and delayed recall in APOE β4 carriers and in individuals with abnormal Aβ₄₂. Conclusion: Odor identification impairment may be an indicator of neuronal injury rather than amyloid pathology.