University of California, San Francisco (UCSF)

Behavioral Novelty to Promote Synaptic Function in Older Adults

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The overarching goal of the proposed study is to characterize the relationship between lifestyle cognitive and physical behaviors and molecular markers of neural health in typically aging adults. Alzheimer’s disease is an untreatable public health crisis with dementia care costs projected to cross $1 trillion this year. Lifestyle clearly impacts brain aging trajectories; in fact, poor lifestyle is estimated to account for >1/3 of dementia cases. Yet, our biological understanding of how lifestyle behaviors impact the brain in humans has lagged, limiting the potency of non-pharmacological prevention strategies. Identification of the molecular mechanisms driving the relationship between lifestyle behaviors and brain health would help identify: 1) which interventions are likely to have greatest impact, 2) which individuals are at-risk and should be targeted, and 3) therapeutically active pathways for direct monitoring. In our study, we will randomize 90 at-risk typically aging adults into one of three 6-week behavior training conditions: 1) physical training; 2) cognitive training; 3) active control. We will capture blood and cerebrospinal fluid (CSF) before and after training to quantify changes in protein concentrations reflective of neural functioning (i.e., neurogranin, SNAP25, synaptotagmin, BDNF, NfL). Our translational project aims to identify daily activities that can be used to improve neural health in aging and, ultimately, be leveraged to develop biologically-targeted behavioral interventions to prevent dementia.