Neuropsychological Profiles, Etiologies, and Medical Comorbidities in Early-Onset Dementia and Cognitive Impairment: A Memory Outpatient Clinic Cohort Study

Article type: Research Article

Authors: Heikkinen, Anna-Leena^{a; b; c; d} | Paajanen, Teemu I.^d | Hänninen, Tuomo^e | Tikkanen, Veera^{a; b; c} | Hublin, Christer^d | Koivisto, Anne M.^{e; f; g; h} | Remes, Anne M.^{a; h} | Krüger, Johanna^{a; b; c; *}

Affiliations: [a] Research Unit of Clinical Medicine, Neurology, University of Oulu, Oulu, Finland | [b] Medical Research Center, Oulu University Hospital, Oulu, Finland | [c] Neurocenter, Neurology, Oulu University Hospital, Oulu, Finland | [d] Work Ability and Working Careers, Finnish Institute of Occupational Health, Helsinki, Finland | [e] Neurocenter, Neurology, Kuopio University Hospital, Kuopio, Finland | [f] Unit of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland | [g] Department of Geriatrics, Helsinki University Hospital, Helsinki, Finland | [h] Clinical Neurosciences, University of Helsinki, Helsinki, Finland

Correspondence: [*] Correspondence to: Johanna Krüger, MD, PhD, Adjunct Professor, Neurologist, Neurocenter, Neurology, Oulu University Hospital, Oulu, Finland, Research Unit of Clinical Medicine, Neurology, University of Oulu, P.O. Box 5000, 90014 Oulu, Finland. Tel.: +35840 637 8906; E-mail: [email protected].

Abstract: Background:Although early-onset dementia (EOD) is associated with diagnostic challenges that differ from those of related to late-onset dementia, only limited studies have addressed the neuropsychological and health characteristics or specified the diagnoses underlying early-onset cognitive impairment in a real-world clinical setting. Objective:To investigate the neuropsychological profiles, etiologies, and comorbidities of an unselected cohort of memory clinic patients (≤65 years at symptom onset). Methods:The patients’ (n = 210) diagnoses were determined based on comprehensive diagnostic workup. Medical comorbidities and neuropsychological profiles were compared between clinically relevant patient groups, namely early-onset dementia (n = 55), mild cognitive impairment due to vascular or suspected neurodegenerative (MCI-n, n = 35) or non-neurodegenerative (MCI-o, n = 106) etiologies, and subjective cognitive decline (n = 14). Results:The most prevalent diagnoses were Alzheimer’s disease (AD, 14%) and depression (11%). Multiple prior medical conditions were common (67%); however, EOD patients had fewer other diagnoses (p = 0.008) than MCI-o patients. Compared to other groups, EOD patients had more severe deficits (p < 0.001) on immediate and delayed memory, processing speed, symptom awareness, and global cognition. AD patients had weaker memory retention ability but less behavioral symptoms than frontotemporal dementia (FTD) patients (p≤0.05). Depression was associated with better immediate memory, symptom awareness, and global cognition than AD and FTD (p < 0.05). Conclusions:EOD is associated with more severe and widespread neuropsychological deficits but fewer prior medical diagnoses than nondegenerative etiologies of cognitive impairment. AD and depression are common etiologies and the neuropsychological profiles are partly overlapping; however, memory, symptom awareness and global cognitive impairment measures may help in the differential diagnosis.

Keywords: Alzheimer’s disease, cognition, dementia, depression, frontotemporal dementia, multimorbidity

DOI: 10.3233/JAD-230877

Journal: Journal of Alzheimer's Disease, vol. 97, no. 4, pp. 1765-1776, 2024