Biomarkers and Functional Decline in Prodromal Alzheimer’s Disease

Article type: Research Article

Authors: Robb, Catherine^{a; 1} | Udeh-Momoh, Chinedu^{a; b; 1} | Wagenpfeil, Stefan^c | Schöpe, Jakob^c | Alexopoulos, Panagiotis^{d; e; 1} | Perneczky, Robert^{a; d; f; g; 1; *} | for the Alzheimer’s Disease Neuroimaging Initiative²

Affiliations: [a] Neuroepidemiology and Ageing Research Unit, School of Public Health, Faculty of Medicine, The Imperial College of Science, Technology and Medicine, London, UK | [b] MRC Centre for Synaptic Plasticity, School of Clinical Sciences, University of Bristol, Bristol, UK | [c] Institute for Medical Biometry, Epidemiology and Medical Informatics, Universität des Saarlandes, Campus Homburg, Germany | [d] Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-Universität München, Munich, Germany | [e] Department of Psychiatry, University of Patras, Rion Patras, Greece | [f] West London Mental Health NHS Trust, London, UK | [g] German Center for Neurodegenerative Diseases (DZNE) Munich, Munich, Germany

Correspondence: [*] Correspondence to: Prof. Robert Perneczky, Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-Universität München, Nußbaumstr. 7, 81679 München, Germany. Tel.: +49 89 4400 55772; Fax: +49 89 4400 53413; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Note: [2] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

Abstract: Background: Little is known of possible associations between Alzheimer’s disease (AD) biomarkers and instrumental activities of daily living (IADL) change over time. Objective: The present study seeks to identify relationships between baseline imaging and fluid biomarker profiles, and decline in IADL utilizing data collated from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Methods: Generalized estimating equations analysis, adjusted for cognitive deterioration, was applied to a cohort of 509 individuals from all stages of ADNI, including 156 healthy controls, 189 early mild cognitive impairment (MCI) patients and 164 MCI patients. Results: A significant correlation was found between baseline biomarkers, specifically CSF Aβ and FDG PET, and IADL change over a 3-year period in individuals with MCI. Importantly, comparable correlations between presence of pathological biomarker levels and temporal decline in both functional and cognitive performance were also noted. Discussion: We show that distinct baseline biomarkers may predict latent changes in IADL. Our results necessitate a revision of the commonly held view upholding cognitive changes as the predominant endpoint measure associated with presence of abnormal baseline biomarkers.

Keywords: Activities of daily living, Alzheimer’s disease, biomarker, cerebrospinal fluid, early diagnosis, magnetic resonance imaging, positron emission tomography, prediction

DOI: 10.3233/JAD-161162

Journal: Journal of Alzheimer's Disease, vol. 58, no. 1, pp. 69-78, 2017