"Exploring how Bio-Signals Shape Trajectories of Brain and Cognitive Aging: Implications for Alzheimer’s Disease Risk and Protection?"
An intriguing consensus has consolidated in many quarters that “the etiology of Alzheimer’s disease (AD) has proven to be more complex than expected” (NIH). The implications of this observation have led to accelerated attention to multiple new directions in AD theory, research, intervention, prevention, and translation. Among these new approaches are five that inform the perspective and research presented in this talk. First, recent attention has focused not only on the complexity of the outcome condition (AD and related brain disorders) but also on the pathways and predictors preceding such diagnoses. Second, there is, however, a paucity of foundational information about distributional and directional characteristics of preclinical brain and cognitive trajectories. Third, although a number of biomarker and risk factor predictors of AD have been identified, it is an open question whether these are also early (or the best) predictors of differential pre-impairment trajectories. Fourth, the etiological complexity of emerging and differentiating neurodegenerative diseases indicate that multiple modalities of early “bio-signals” may operate dynamically and interactively to produce differential trajectories of change. Fifth, it is conceivable that precise trajectory analyses would reveal a spectrum of trajectory phenotypes, including (a) impairment and disease-bound pathways, (b) normal brain and cognitive aging, and (c) elevated and sustained pathways of brain and cognitive resilience. By elucidating the nature and range of preclinical trajectories, as well as the bio-signal predictors determining individualized pathways, it may be possible to identify new potential prevention targets. This work is conceived and conducted in the leveraged and coordinated context of the 25-year Victoria Longitudinal Study (NIH) and the Canadian Consortium on Neurodegeneration in Aging (CIHR).