Age of Symptom Onset and Longitudinal Course of Sporadic Alzheimer’s Disease, Frontotemporal Dementia, and Vascular Dementia: A Systematic Review and Meta-Analysis

Article type: Research Article

Authors: Day, Sally^a | Roberts, Stefanie^{b; c} | Launder, Nathalie H.^b | Goh, Anita M.Y.^{b; c} | Draper, Brian^d | Bahar-Fuchs, Alex^b | Loi, Samantha M.^{b; e} | Laver, Kate^f | Withall, Adrienne^{g; h} | Cations, Monica^{a; *}

Affiliations: [a] College of Education, Psychology and Social Work, Flinders University, Adelaide, SA, Australia | [b] Department of Psychiatry, The University of Melbourne, Melbourne, VIC, Australia | [c] National Ageing Research Institute, Melbourne, VIC, Australia | [d] School of Psychiatry, UNSW Sydney, Sydney, NSW, Australia | [e] Neuropsychiatry, Royal Melbourne Hospital, Parkville VIC, Australia | [f] College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia | [g] School of Population Health, UNSW Sydney, NSW, Australia | [h] Ageing Futures Institute, UNSW Sydney, NSW, Australia

Correspondence: [*] Correspondence to: Monica Cations, College of Education, Psychology and Social Work, Flinders University, GPO Box 2100, Adelaide SA 5001, Australia. Tel.: +61882013058; E-mail: [email protected].

Abstract: Background: Understanding how the age of dementia symptom onset affects the longitudinal course of dementia can assist with prognosis and care planning. Objective: To synthesize evidence regarding the relationship of age of symptom onset with the longitudinal course of sporadic Alzheimer’s disease (AD), vascular dementia (VaD), and frontotemporal dementia (FTD). Methods: We searched Medline, CINAHL, Embase, PsycINFO, PubMed, and Scopus for longitudinal studies that examined the impact of sporadic AD, VaD, or FTD symptom onset age on measures of cognition, function, or behavioral symptoms. Studies that examined age at diagnosis only were excluded. Quantitative meta-analysis was conducted where studies reported sufficient data for pooling. Results: Thirty studies met all inclusion criteria (people with AD (n = 26), FTD (n = 4)) though no studies examined VaD. Earlier onset of AD was associated with more rapid annual cognitive decline (estimate = –0.07; 95% CI –0.14 to 0.00; p = 0.045). Most studies that stratified their sample reported that younger AD onset (usually < 65 years) was associated with more rapid cognitive decline. Other evidence was inconclusive. Conclusion: Younger people with AD appear to have a poorer prognosis in terms of faster cognitive decline than older people with AD. More research is required to determine the impact of symptom onset age in VaD and FTD, and on functional decline in all dementias.

Keywords: Alzheimer’s disease, disease progression, frontotemporal dementia, prognosis, vascular dementia

DOI: 10.3233/JAD-215360

Journal: Journal of Alzheimer's Disease, vol. 85, no. 4, pp. 1819-1833, 2022