A5023974130- Dementia and Cognitive Impairment Research
- Alzheimer's disease research and treatments
- Physical Activity and Health
- GDF15 and Related Biomarkers
- Health, Environment, Cognitive Aging
- Diet and metabolism studies
- Nutritional Studies and Diet
- Blood Pressure and Hypertension Studies
- Biochemical effects in animals
- Amyotrophic Lateral Sclerosis Research
- Nutrition and Health in Aging
- Folate and B Vitamins Research
- S100 Proteins and Annexins
- Neuroinflammation and Neurodegeneration Mechanisms
- Traumatic Brain Injury and Neurovascular Disturbances
- Intracerebral and Subarachnoid Hemorrhage Research
- Advanced Neuroimaging Techniques and Applications
- Bioinformatics and Genomic Networks
- Health Systems, Economic Evaluations, Quality of Life
- Technology Use by Older Adults
- Identity, Memory, and Therapy
- Parkinson's Disease Mechanisms and Treatments
- Infectious Encephalopathies and Encephalitis
- Amino Acid Enzymes and Metabolism
- Cerebrovascular and genetic disorders
University Memory and Aging Center
2021-2025
University of California, San Francisco
2021-2025
Palo Alto University
2021-2025
Physical activity (PA) is widely recommended for age-related brain health, yet its neurobiology not well understood. Animal models indicate PA synaptogenic. We examined the relationship between and synaptic integrity markers in older adults.Four hundred four decedents from Rush Memory Aging Project completed annual actigraphy monitoring (Mean visits = 3.5±2.4) post mortem evaluation. Brain tissue was analyzed presynaptic proteins (synaptophysin, synaptotagmin-1, vesicle-associated membrane...
Wearables have great potential to improve monitoring and delivery of physical activity interventions older adults with downstream benefits multisystem health longevity; however, obtained from wearables depend on their uptake usage. Few studies examined person-specific factors that relate wearable adherence. We characterized adherence using a tracker for 30 days associations between demographics, cognitive functioning, brain volumes, technology familiarity among community-dwelling...
Physical activity (PA) is associated with preserved age-related body and brain health. However, PA quantification can vary. Commercial-grade wearable monitors are objective, low burden tools to capture but less well validated in older adults. Self-report questionnaires widely accepted more frequently used carry inherent limitations. We aimed compare these commonly measures against one another examine their convergent validity a host of relevant outcomes. also examined the factors that drive...
Physical activity relates to reduced dementia risk, but the cellular and molecular mechanisms are unknown. We translated animal
Physical activity (PA) is linked to lower dementia risk, but molecular pathways underpinning PA-related risk are poorly understood. We conducted plasma proteomics (SomaScan v4.1) and 30-day Fitbit-based PA monitoring (average daily step count) in 65 cognitively unimpaired older adults from the UCSF BrANCH cohort. Differential regression network analyses identified proteomic signatures tied extracellular matrix (ECM), immune response, lipid metabolism. Protein module M12 ECM/neurodevelopment...
Background : Dementia risk is significantly shaped by cardiovascular health, with elevated blood pressure emerging as a key factor for adverse brain aging. Blood biomarkers such pTau181, Aβ42/40, NfL, and GFAP have improved our understanding of dementia pathophysiology, however, few studies explored how specific metrics relate to biomarker levels, which could inform personalized prevention strategies these move into clinic. We examined different associated molecular markers astrocytic...
Abstract Background Dementia risk is significantly shaped by cardiovascular health, with elevated blood pressure emerging as a key factor for adverse brain aging. Blood biomarkers such pTau181, Aβ42/40, NfL, and GFAP have improved our understanding of dementia pathophysiology, however, few studies explored how specific metrics relate to biomarker levels, which could inform personalized prevention strategies these move into clinic. We examined different associated molecular markers astrocytic...
Abstract INTRODUCTION Sex differences are apparent in neurodegenerative diseases but have not been comprehensively characterized frontotemporal dementia (FTD). METHODS Participants included 337 adults with autosomal dominant FTD enrolled the ALLFTD Consortium. Clinical assessments and plasma were collected annually for up to 6 years. Linear mixed‐effects models investigated how sex disease stage associated longitudinal trajectories of cognition, function, neurofilament light chain (NfL)....
Many factors outside of cardiovascular health can impact the structure white matter. Identification reliable and clinically meaningful biomarkers neural effects systemic are needed to refine etiologic predictions. We examined whether corpus callosum demonstrates regional vulnerability risk factors. Three hundred ninety-four older adults without dementia completed brain MRI, neurobehavioral evaluations, blood draws. A subset (n = 126, n 128) individuals had plasma analyzed for inflammatory...
Abstract The largest risk factor for dementia is age. Heterochronic blood exchange studies have uncovered age-related factors that demonstrate ‘pro-aging’ or ‘pro-youthful’ effects on the mouse brain. clinical relevance and combined of these humans unclear. We examined five previously identified brain rejuvenation in cerebrospinal fluid adults with autosomal dominant forms frontotemporal sporadic Alzheimer’s disease. Our cohort included 100 observationally followed carrying mutations (Mage =...
Objective: To determine the synergistic effects of nutrition, specifically adherence to Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, and physical activity on cognition brain outcomes in a cross-sectional healthy aging cohort. Methods: A total 132 adults (age range 52–91; Clinical Dementia Rating = 0) from UCSF Brain Aging Project completed 15-item MIND diet food frequency questionnaire an 11-item self-report measure weekly (Physical Activity Scale [PASE])....
Abstract Background Modifiable lifestyle behaviors account for a large proportion of dementia risk. However, the combined contributions multidomain patterns to cognitive aging are poorly understood, as most studies have examined individual in isolation and without neuropathological characterization. This study data-driven across multiple domains among older adults tested their associations with disease-specific burden decline. Methods Participants included 2059 enrolled longitudinal Memory...
Physical activity (PA) is linked to better cognitive and brain health, though its mechanisms are unknown. While iron essential for normal function, levels increase with age and, when excessive, can cause detrimental neural effects. We examined how objectively measured PA relates cerebral deposition memory functioning in older adults. Sixty-eight cognitively unimpaired adults from the UCSF Memory Aging Center completed neuropsychological testing magnetic resonance imaging, followed by 30-day...
Abstract Background Physical activity is associated with >30% reduced risk of dementia. However, the biological mechanisms underlying exercise as a protective factor against cognitive decline remain unclear. Astrocytic activation and axonal breakdown, measured by plasma glial fibrillary acidic protein (GFAP) neurofilament light chain (NfL), respectively, are pathways disrupted early in aging neurodegenerative disease. We aimed to examine whether an objective measure physical (Fitbit TM )...
Abstract INTRODUCTION Cardiovascular health is important for brain aging, yet its role in the clinical manifestation of autosomal dominant or atypical forms dementia has not been fully elucidated. We examined relationships between Life's Simple 7 (LS7) and trajectories individuals with frontotemporal lobar degeneration (FTLD). METHODS Two hundred forty‐seven adults carrying FTLD pathogenic genetic variants (53% asymptomatic) 189 non‐carrier controls completed baseline LS7, longitudinal...
INTRODUCTION: Sex differences are apparent in neurodegenerative diseases, but have not been comprehensively characterized frontotemporal dementia (FTD). METHODS: Participants included 337 adults with autosomal dominant FTD enrolled the ALLFTD Consortium. Clinical assessments and plasma were collected annually for up to six years. Linear mixed-effects models investigated how sex disease stage associated longitudinal trajectories of cognition, function, neurofilament light chain (NfL)....
Abstract Background Sex differences in neurodegenerative diseases can impact accurate diagnosis and management. Emerging data suggest there may be sex frontotemporal dementia (FTD) prevalence clinical manifestation. However, prior studies lacked longitudinal assessment were limited capturing earliest stages of disease (e.g., preclinical). We evaluated how impacts outcomes individuals carrying autosomal dominant variants for FTD. Method 337 participants pathogenic MAPT , GRN or C9orf72...
Abstract Background Frontotemporal dementia (FTD) is a common young‐onset dementia. Challenges to in‐person FTD evaluations (e.g., behavioral symptoms, disease rarity), highlight the need develop remote, low‐burden assessment techniques. A growing literature supports passive digital phenotyping for monitoring neurobehavioral change. Thus, we examined utility of passively collected data from smartphones detect prodromal or symptomatic compared that Montreal Cognitive Assessment (MoCA),...
Abstract Background Physical activity (PA) is associated with lower dementia risk; however, underlying molecular pathways are poorly understood. We leveraged large‐scale plasma proteomics to identify biological signatures of objectively‐monitored PA in cognitively unimpaired (CU) older adults and cross‐validated independent exercise intervention Alzheimer’s disease (AD) cohorts. Method Discovery cohort included 65 CU (mean age = 76.6; 60% female; 34% PET Ab+) from the UCSF Memory Aging...
Abstract Background Osteoarthritis (OA) is a degenerative disorder of bone aging and risk factor for cognitive decline. Bone morphogenetic proteins (BMPs) are growth that regulate skeletal neural development, circulating BMPs may mediate molecular cross‐talk between brain. The present study examined plasma BMP levels in relation to OA neurobehavioral outcomes cognitively unimpaired (CU) older adults. Methods Participants included 65 CU adults (mean age= 76.45, 60% female) enrolled the UCSF...
Abstract Background Growth Differentiation Factor 15 (GDF15) is a TGF‐beta superfamily protein upregulated during immune‐mediated stress responses. Peripheral GDF15 linked to adverse aging across organ systems including the brain. Immune dysregulation implicated in frontotemporal dementia (FTD) pathogenesis. We examined how plasma levels associated with longitudinal cognitive and neurofilament light chain (NfL) trajectories adults FTD controls. Furthermore, we tested utility of as prognostic...
Abstract Background Cardiovascular disease (CVD) is among the strongest modifiable risk factors for dementia. However, vascular health multifaceted, and its neurobiological underpinnings are unclear. A recent study (Williams et al. 2022) leveraged blood proteomics machine learning to identify a novel group of 27 proteins that robustly predicted 4‐year likelihood myocardial infarction, stroke, heart failure, or death. We examined whether these CVD‐related also relate brain outcomes in older...
Abstract Background Physical activity (PA) is associated with increased release of brain derived neurotrophic factor (BDNF), a mechanism that may underlie protective effects PA on cognitive and aging. The Met allele the BDNF Val66Met single‐nucleotide polymorphism reduces activity‐dependent phosphorylated tau (p‐tau181) in dementia populations. We sought to determine whether influences plasma p‐tau181 cognition older adults without dementia. Method 123 from UCSF Memory Aging Center completed...
Abstract Background Modifiable risk factors are important for prevention of age‐related cognitive decline. Prior research has linked both physical activity (PA) and sleep with better memory outcomes. To understand their potential synergistic effects, we examined independent interactive effects actigraphy‐based PA total time on functioning in cognitively unimpaired older adults. Method Participants included 40 adults (age = 71.1 ± 10.8yrs; 52% female; 75% White; mean education 18.2yrs)...