Dementia

Understanding Neurodevelopmental Origin of Alzheimer's Disease Using Lifespan Approach 2025 Award: $198,959 Early-life development is characterized by dramatic changes, impacting lifespan function more than changes in any other period. Although the developmental origins of neurodegenerative diseases in later life are recognized, there is a lack of detailed longitudinal neuroimaging studies that link early development and brain maturation with the neurobiological mechanisms of dementia. We will answer the outstanding questions by capitalizing on large-scale neuroimaging data alongside environmental exposures and demographic information. Need/Problem: Human brain development spans the first thirty years of life, with brain maturation during the first two decades playing a critical role in shaping its vulnerability to neurodegenerative diseases as we age. However, due to the absence of large-scale lifespan data ranging from childhood to late adulthood, our understanding of early-life dementia risk remains limited. Grant Summary: [...]

Investigating Psychiatric Symptoms of Dementia 2024 Award: $110,000 Psychiatric symptoms like agitation, aggression, disinhibition, and impulsivity, amongst others, are common psychiatric symptoms that may precede cognitive decline that is associated with dementia. This project uses a mouse model of dementia (the P301S tauopathy model) to mechanistically examine these psychiatric symptoms antecedent to cognitive decline. We hypothesize that we will observe differences in neurotransmission (both dopaminergic and glutamatergic) in these animals as compared to age matched controls. Furthermore, we expect to observe differences in responses to commonly prescribed psychiatric medications in these mice. By uncovering neural mechanisms impinged upon by tauopathy, we hope to aid in the discovery of biomarkers and development of therapies to alleviate the symptoms associated with dementia. Need/Problem: Behavioral and psychiatric symptoms of dementia (including but not limited to hyperactivity, agitation, mood disturbance, aggression) often precede [...]

Epigenetic mechanisms linking psychological stress with dementia risk in minoritized individuals 2024 Award: $147,167 Dementia has an enormous impact worldwide and disproportionately affects minoritized populations. Such health disparities have been attributed to discrimination and other social determinants of health, but the underlying mechanisms are unknown. This project examines the epigenetic mechanisms through which stress contributes to dementia risk in Black individuals. Need/Problem: Alzheimer’s disease and related dementias (ADRD) have an enormous impact on individuals and societies, with Alzheimer’s disease alone currently afflicting ~6.7 million persons age 65 and older in the US. Importantly, ADRD disproportionately affect minoritized populations, with older Black adults having an estimated two to three times higher risk for cognitive impairment and dementia as compared to older non-Hispanic White adults. However, the mechanisms underlying this health disparity are unknown and no reliable biomarkers exist to guide [...]

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 [...]