title: BioAge: toward a multi-determined, mechanistic account of cognitive aging.
abstract: The search for reliable early indicators of age-related cognitive decline represents a critical avenue for progress in aging research. Chronological age is a commonly used developmental index; however, it offers little insight into the mechanisms underlying cognitive decline. In contrast, biological age (BioAge), reflecting the vitality of essential biological systems, represents a promising operationalization of developmental time. Current BioAge models have successfully predicted age-related cognitive deficits. Research on aging-related cognitive function indicates that the interaction of multiple risk and protective factors across the human lifespan confers individual risk for late-life cognitive decline, implicating a multi-causal explanation. In this review, we explore current BioAge models, describe three broad yet pathologically relevant biological processes linked to cognitive decline, and propose a novel operationalization of BioAge accounting for both moderating and causal mechanisms of cognitive decline and dementia. We argue that a multivariate and mechanistic BioAge approach will lead to a greater understanding of disease pathology as well as more accurate prediction and early identification of late-life cognitive decline.
authors.affiliation: Department of Psychology, University of Victoria, Victoria, BC, Canada; Centre on Aging, University of Victoria, Victoria, BC, Canada. Electronic address: decarloc@uvic.ca.
authors.forename: Correne A
authors.initials: CA
authors.lastname: DeCarlo
authors.affiliation: Department of Psychology, University of Victoria, Victoria, BC, Canada; Centre on Aging, University of Victoria, Victoria, BC, Canada.
authors.forename: Holly A
authors.initials: HA
authors.lastname: Tuokko
authors.affiliation: Department of Geriatrics, West Coast General Hospital, Port Alberni, BC, Canada.
authors.forename: Dorothy
authors.initials: D
authors.lastname: Williams
authors.affiliation: Department of Psychology, University of Alberta, Edmonton, AB Canada.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Dixon
authors.affiliation: Department of Psychology, University of Victoria, Victoria, BC, Canada; Centre on Aging, University of Victoria, Victoria, BC, Canada.
authors.forename: Stuart W S
authors.initials: SW
authors.lastname: MacDonald
mesh_terms: D000367:Age Factors; D000375:Aging / Q000473:pathology / Q000523:psychology*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D003071:Cognition; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D006304:Health Status; D006801:Humans; D007249:Inflammation / Q000150:complications; D018384:Oxidative Stress; D012307:Risk Factors; D014652:Vascular Diseases / Q000150:complications
keywords: Biological age; Cognitive aging; Early identification; Inflammation; Oxidative stress; Vascular health