Cognitive Performance and Cerebrospinal Fluid Markers in Preclinical Alzheimer’s Disease: Results from the Gothenburg H70 Birth Cohort Studies

Article type: Research Article

Authors: Rådestig, Maya Arvidsson^{a; c; *} | Skoog, Johan^{a; b; c} | Zetterberg, Henrik^{c; d; e; f} | Kern, Jürgen^{a; c} | Zettergren, Anna^{a; c} | Sacuiu, Simona^{a; c} | Waern, Margda^{a; c} | Wetterberg, Hanna^{a; c} | Blennow, Kaj^{c; d} | Skoog, Ingmar^{a; c; 1} | Kern, Silke^{a; c; 1}

Affiliations: [a] Center for Ageing and Health (AgeCap) at the University of Gothenburg, Mölndal, Sweden | [b] Department of Psychology, University of Gothenburg, Gothenburg, Sweden | [c] Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden | [d] Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden | [e] UCL Institute of Neurology (H.Z.), Queen Square, London, United Kingdom | [f] The UK Dementia Research Institute at UCL, London, United Kingdom

Correspondence: [*] Correspondence to:Maya Arvidsson Rådestig, MSc, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Wallinsgatan 6, SE 431 41 Mölndal, Sweden. Tel.: +46 031 342 21; Fax: +46 031 828163; E-mail: [email protected].

Note: [1] These authors share last authorship.

Abstract: Background:We have previously shown that older adults with preclinical Alzheimer’s disease (AD) pathology in cerebrospinal fluid (CSF) had slightly worse performance in Mini-Mental State Examination (MMSE) than participants without preclinical AD pathology. Objective:We therefore aimed to compare performance on neurocognitive tests in a population-based sample of 70-year-olds with and without CSF AD pathology. Methods:The sample was derived from the population-based Gothenburg H70 Birth Cohort Studies in Sweden. Participants (n = 316, 70 years old) underwent comprehensive cognitive examinations, and CSF Aβ-42, Aβ-40, T-tau, and P-tau concentrations were measured. Participants were classified according to the ATN system, and according to their Clinical Dementia Rating (CDR) score. Cognitive performance was examined in the CSF amyloid, tau, and neurodegeneration (ATN) categories. Results:Among participants with CDR 0 (n = 259), those with amyloid (A+) and/or tau pathology (T+, N+) showed similar performance on most cognitive tests compared to participants with A-T-N-. Participants with A-T-N+ performed worse in memory (Supra span (p = 0.003), object Delayed (p = 0.042) and Immediate recall (p = 0.033)). Among participants with CDR 0.5 (n = 57), those with amyloid pathology (A+) scored worse in category fluency (p = 0.003). Conclusion:Cognitively normal participants with amyloid and/or tau pathology performed similarly to those without any biomarker evidence of preclinical AD in most cognitive domains, with the exception of slightly poorer memory performance in A-T-N+. Our study suggests that preclinical AD biomarkers are altered before cognitive decline.

Keywords: Biomarkers in early Alzheimer’s disease, cerebrospinal fluid, cognition, population-based

DOI: 10.3233/JAD-200751

Journal: Journal of Alzheimer's Disease, vol. 79, no. 1, pp. 225-235, 2021