Memory Correlates of Alzheimer’s Disease Cerebrospinal Fluid Markers: A Longitudinal Cohort Study

Article type: Research Article

Authors: Reijs, Babette L.R.^{a; *} | Ramakers, Inez H.G.B.^a | Köhler, Sebastian^a | Teunissen, Charlotte E.^b | Koel-Simmelink, Marleen^b | Nathan, Pradeep J.^{c; d} | Tsolaki, Magda^e | Wahlund, Lars-Olof^f | Waldemar, Gunhild^g | Hausner, Lucrezia^h | Vandenberghe, Rikⁱ | Johannsen, Peter^g | Blackwell, Andrew^j | Vanderstichele, Hugo^k | Verhey, Frans^a | Visser, Pieter Jelle^{a; l; *}

Affiliations: [a] Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands | [b] Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Neuroscience Campus Amsterdam, VU University Medical Center Amsterdam, The Netherlands | [c] Department of Psychiatry, University of Cambridge, UK | [d] School of Psychological Sciences, Monash University, Melbourne, Australia | [e] Aristotle University of Thessaloniki, Thessaloniki, Greece | [f] Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden | [g] Danish Dementia Research Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark | [h] Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty of Mannheim, Heidelberg University, Germany | [i] University Hospital Leuven, Leuven, Belgium | [j] Cambridge Cognition, Cambridge, UK | [k] ADx NeuroSciences, Gent, Belgium | [l] Department of Neurology and Alzheimer Center, VU University Medical Center, 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 Center Limburg, P.O. Box 616, 6200 MD Maastricht,the Netherlands. Tel.: +31 0 43 38 81841; Fax: +31 0 43 38 84092; E-mails: [email protected] (B.L.R. Reijs), [email protected] (P. J. Visser).

Abstract: Background:Performance on episodic, semantic, and working memory tests is impaired in Alzheimer’s disease (AD)-type dementia, but it is unclear which type of memory test is most strongly associated with early AD biomarkers in cerebrospinal fluid (CSF), and most useful for monitoring disease progression. Objective:To examine the association between amyloid-β 1-42 (Aβ42) and tau in CSF with performance on different memory domains at baseline, and how these CSF markers are related with memory decline. Methods:We included 263 individuals with normal cognition, mild cognitive impairment, AD-type dementia, and non-AD dementia from the European EDAR study. Assessment included CSF Aβ42 and t-tau analyses with INNO-BIA AlzBio3 Luminex assay, the CERAD wordlist learning and delayed recall, animal fluency test, and the CANTAB Paired Associates Learning (PAL) and Spatial Working Memory tasks. Follow-up assessments were performed within 3 years after baseline. Results:At baseline, decreased CSF Aβ42 correlated most strongly with the PAL total errors adjusted and the wordlist delayed recall and increased CSF t-tau with the wordlist delayed recall. Over time, decreased CSF Aβ42 was associated with decline on the wordlist learning, whereas increased CSF t-tau were associated with decline in scores on the wordlist learning, wordlist delayed recall, and animal fluency. Associations were independent of baseline diagnosis. Conclusion:Tests assessing episodic verbal and visuospatial memory are most useful for detection of AD pathology. Tests for episodic verbal memory and semantic memory are most useful for tracking memory decline.

Keywords: Alzheimer’s disease, amyloid-β, biomarkers, cerebrospinal fluid, episodic memory, spatial memory, working memory

DOI: 10.3233/JAD-160766

Journal: Journal of Alzheimer's Disease, vol. 60, no. 3, pp. 1119-1128, 2017