Uncovering Midlife Dementia Risks from Altered Structural and Functional Coupling Mechanisms

2023 Award: $47,761

Dementia is a syndrome of cognitive and functional decline, commonly occurring in later life as a result of neurodegenerative and cerebrovascular processes beginning earlier in the life course. Mounting evidence shows that genetic, demographic, and lifespan environmental exposures closely interact to determine vulnerability to dementia. In this context, we aim to discover the smoking gun of dementia risks and understand the neurobiological mechanism of how these dementia risk factors affect brain structures and functions over time.

Need/Problem: Mounting evidence shows that genetic, demographic, and lifespan environmental exposures closely interact to determine vulnerability to dementia. Since pre-symptomatic or early symptomatic interventions may ultimately constitute the best long-term therapeutic strategy, a life-course approach is critical to disentangle the nature and timing of dementia risks that contribute to disparities in the incidence and prevalence of dementia.

Grant Summary: Many neuroscience studies have found that the disruption of structural connectivity (SC) and functional connectivity (FC) in the brain is an early sign of dementia years before any clinical signs of the disease progression. Since the changes in SC-FC coupling may provide a potential putative biomarker that detects subtle brain network dysfunction more sensitively than does a single modality, we aim to apply our novel SC-FC coupling tools to elucidate the synergistic effect of midlife course risks on dementia and investigate the clinical value of predicting dementia risk from large-scale public dataset.

Goals and Projected Outcomes: The overarching goal of this proposal is to answer the following scientific questions: (i) What neural circuits are linked with midlife dementia risks that affect the cognitive function of aging brains? (ii) What is the root cause of midlife dementia risks on cognitive decline in old age? (iii) Does midlife engagement in healthy lifestyles reduce the risk of developing dementia? At the completion of the proposed research, our expected outcomes are to contribute a collection of analytic tools for analyzing existing human connectomes that allow us to address the current challenges related to dementia prevention.

Guorong Wu, PhD

Grant Details: First, we will conduct a collection of studies to understand the biological role of SC-FC coupling mechanism in the context of aging brains. Second, we will further elucidate the causal effects that midlife dementia risks affect cognitive function via dementia-related SC-FC alterations. Third, we will develop cutting-edge statistical learning methods to identify the protective factors which have causal effects to slow the progression of dementia. Specifically, we will investigate the survival advantages through the lens of SC-FC coupling changes, where a combination of healthy environmental exposures could substantially delay the event of developing dementia.