Relation of Odor Identification with Alzheimer’s Disease Markers in Cerebrospinal Fluid and Cognition

Article type: Research Article

Authors: Reijs, Babette L.R.^{a; *} | Ramakers, Inez H.G.B.^a | Elias-Sonnenschein, Lyzel^a | Teunissen, Charlotte E.^b | Koel-Simmelink, Marleen^b | Tsolaki, Magda^c | Wahlund, Lars-Olof^d | Waldemar, Gunhild^e | Hausner, Lucrezia^f | Johannsen, Peter^e | Vanderstichele, Hugo^g | Verhey, Frans^a | Devanand, D.P.^h | Visser, Pieter Jelle^{a; i; *}

Affiliations: [a] Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, Maastricht, The Netherlands | [b] Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Neuroscience Campus Amsterdam, VU University Medical Centre Amsterdam, The Netherlands | [c] Aristotle University of Thessaloniki, Thessaloniki, Greece | [d] Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden | [e] Danish Dementia Research Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark | [f] Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty of Mannheim, Heidelberg University, Germany | [g] ADx NeuroSciences, Gent, Belgium | [h] Division of Geriatric Psychiatry, New York State Psychiatric Institute and Columbia University Medical Center, New York, NY, USA | [i] Department of Neurology and Alzheimer Centre, VU University Medical Centre, Amsterdam, The Netherlands

Correspondence: [*] Correspondence to: Babette L.R. Reijs and Pieter Jelle Visser, Department of Psychiatry and Neuropsychology, Maastricht University, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, P.O. Box 616, 6200 MDMaastricht, The Netherlands. Tel.: +31 43 38 81841; Fax: +31 43 38 84092; E-mails: [email protected]; [email protected].

Abstract: 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 AD-type 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 Aβ42 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 ɛ4 carriers and in individuals with abnormal Aβ42. Conclusion:Odor identification impairment may be an indicator of neuronal injury rather than amyloid pathology.

Keywords: Alzheimer’s disease, amyloid-β (1–42), cerebrospinal fluid, mild cognitive impairment, olfaction

DOI: 10.3233/JAD-170564

Journal: Journal of Alzheimer's Disease, vol. 60, no. 3, pp. 1025-1034, 2017