Babette L R Reijs1, Inez H G B Ramakers1, Lyzel Elias-Sonnenschein1, Charlotte E Teunissen2, Marleen Koel-Simmelink2, Magda Tsolaki3, Lars-Olof Wahlund4, Gunhild Waldemar5, Lucrezia Hausner6, Peter Johannsen5, Hugo Vanderstichele7, Frans Verhey1, D P Devanand8, Pieter Jelle Visser1,9. 1. Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, Maastricht, The Netherlands. 2. Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Neuroscience Campus Amsterdam, VU University Medical Centre Amsterdam, The Netherlands. 3. Aristotle University of Thessaloniki, Thessaloniki, Greece. 4. Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden. 5. Danish Dementia Research Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 6. Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty of Mannheim, Heidelberg University, Germany. 7. ADx NeuroSciences, Gent, Belgium. 8. Division of Geriatric Psychiatry, New York State Psychiatric Institute and Columbia University Medical Center, New York, NY, USA. 9. Department of Neurology and Alzheimer Centre, VU University Medical Centre, Amsterdam, The Netherlands.
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.
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.
Authors: Isabelle Bos; Stephanie Vos; Rik Vandenberghe; Philip Scheltens; Sebastiaan Engelborghs; Giovanni Frisoni; José Luis Molinuevo; Anders Wallin; Alberto Lleó; Julius Popp; Pablo Martinez-Lage; Alison Baird; Richard Dobson; Cristina Legido-Quigley; Kristel Sleegers; Christine Van Broeckhoven; Lars Bertram; Mara Ten Kate; Frederik Barkhof; Henrik Zetterberg; Simon Lovestone; Johannes Streffer; Pieter Jelle Visser Journal: Alzheimers Res Ther Date: 2018-07-06 Impact factor: 6.982
Authors: Isabelle Bos; Stephanie J B Vos; Willemijn J Jansen; Rik Vandenberghe; Silvy Gabel; Ainara Estanga; Mirian Ecay-Torres; Jori Tomassen; Anouk den Braber; Alberto Lleó; Isabel Sala; Anders Wallin; Petronella Kettunen; José L Molinuevo; Lorena Rami; Gaël Chetelat; Vincent de la Sayette; Magda Tsolaki; Yvonne Freund-Levi; Peter Johannsen; Gerald P Novak; Inez Ramakers; Frans R Verhey; Pieter Jelle Visser Journal: Front Aging Neurosci Date: 2018-06-25 Impact factor: 5.750
Authors: Maryam Yahiaoui-Doktor; Tobias Luck; Steffi G Riedel-Heller; Markus Loeffler; Kerstin Wirkner; Christoph Engel Journal: Alzheimers Res Ther Date: 2019-05-10 Impact factor: 6.982
Authors: Sarah Westwood; Alison L Baird; Sneha N Anand; Alejo J Nevado-Holgado; Andrey Kormilitzin; Liu Shi; Abdul Hye; Nicholas J Ashton; Angharad R Morgan; Isabelle Bos; Stephanie J B Vos; Susan Baker; Noel J Buckley; Mara Ten Kate; Philip Scheltens; Charlotte E Teunissen; Rik Vandenberghe; Silvy Gabel; Karen Meersmans; Sebastiaan Engelborghs; Ellen E De Roeck; Kristel Sleegers; Giovanni B Frisoni; Olivier Blin; Jill C Richardson; Régis Bordet; José L Molinuevo; Lorena Rami; Anders Wallin; Petronella Kettunen; Magda Tsolaki; Frans Verhey; Alberto Lléo; Isabel Sala; Julius Popp; Gwendoline Peyratout; Pablo Martinez-Lage; Mikel Tainta; Peter Johannsen; Yvonne Freund-Levi; Lutz Frölich; Valerija Dobricic; Cristina Legido-Quigley; Lars Bertram; Frederik Barkhof; Henrik Zetterberg; B Paul Morgan; Johannes Streffer; Pieter Jelle Visser; Simon Lovestone Journal: J Alzheimers Dis Date: 2020 Impact factor: 4.472