A Neuropsychological Perspective on Defining Cognitive Impairment in the Clinical Study of Alzheimer’s Disease: Towards a More Continuous Approach

Article type: Review Article

Authors: Jutten, Roos J.^{a; 1} | Thompson, Louisa^{b; c; 1; *} | Sikkes, Sietske A.M.^d | Maruff, Paul^e | Molinuevo, José Luis^{f; g} | Zetterberg, Henrik^{h; i; j; k} | Alber, Jessica^{l; m} | Faust, Davidⁿ | Gauthier, Serge^o | Gold, Michael^p | Harrison, John^{d; q; r} | Lee, Athene K.W.^{b; c} | Snyder, Peter J.^l

Affiliations: [a] Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA | [b] Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA | [c] Memory and Aging Program, Butler Hospital, Providence, RI, USA | [d] Alzheimer Center Amsterdam, Department of Neurology, Amsterdam UMC, Vrije Universiteit, Amsterdam, the Netherlands | [e] The Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia | [f] Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain | [g] Alzheimer’s Disease and Other Cognitive Disorders Unit, Hospital Clinic, Barcelona, Spain | [h] Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden | [i] Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden | [j] Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK | [k] UK Dementia Research Institute at UCL, London, UK | [l] Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, The University of Rhode Island, Kingston, RI, USA | [m] George and Anne Ryan Institute for Neuroscience, University of Rhode Island, Kingston, RI, USA | [n] Department of Psychology, University of Rhode Island, Kingston, RI, USA | [o] McGill Centre for Studies in Aging, Montréal, Canada | [p] AbbVie Inc., North Chicago, IL, USA | [q] Metis Cognition Ltd, Kilmington Common, UK | [r] Institute of Psychiatry, Psychology & Neuroscience, King’s College London, UK

Correspondence: [*] Correspondence to: Louisa Thompson, PhD, Memory & Aging Program, Butler Hospital, 345 Blackstone Blvd., Providence, RI 02906, USA. E-mail: [email protected].

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

Abstract: The global fight against Alzheimer’s disease (AD) poses unique challenges for the field of neuropsychology. Along with the increased focus on early detection of AD pathophysiology, characterizing the earliest clinical stage of the disease has become a priority. We believe this is an important time for neuropsychology to consider how our approach to the characterization of cognitive impairment can be improved to detect subtle cognitive changes during early-stage AD. The present article aims to provide a critical examination of how we define and measure cognitive status in the context of aging and AD. First, we discuss pitfalls of current methods for defining cognitive impairment within the context of research shifting to earlier (pre)symptomatic disease stages. Next, we introduce a shift towards a more continuous approach for identifying early markers of cognitive decline and characterizing progression and discuss how this may be facilitated by novel assessment approaches. Finally, we summarize potential implications and challenges of characterizing cognitive status using a continuous approach.

Keywords: Cognitive assessment, early diagnosis, neuropsychology, preclinical Alzheimer’s disease, progression

DOI: 10.3233/JAD-215098

Journal: Journal of Alzheimer's Disease, vol. 86, no. 2, pp. 511-524, 2022