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Principal Investigator: Hugo Javier Aparicio
Organization: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
Fiscal Year: 2024
Award: $667,131
Funding agency: National Institute on Aging
PROJECT SUMMARY
Social isolation, loneliness, and social environment continue to emerge as important factors in Alzheimer’s
disease and related dementias (ADRD), more so with the COVID-19 pandemic and observed trends in the
prevalence of social isolation, loneliness, and ADRD. Although there is increasing recognition these factors can
impact the aging brain, represent early expression of ADRD neuropathological changes, and influence health
behaviors and resource access, less is known about the biological mechanisms involved. Our overarching
hypothesis is that social isolation, loneliness, and social environment are distinct factors that alter brain biology
and influence trajectories of healthy neurocognitive aging and ADRD vulnerability. Because understanding
causal pathways and the cumulative role of these critical psychosocial factors through decades-long human
experimental trials is infeasible, here we propose a unique and innovative approach to comprehensively assess
these psychosocial determinants and temporally relate them to dynamic profiles of ADRD vulnerability,
leveraging one of the largest biologically well-characterized community-based cohorts in the US, the
Framingham Study (FS). Since 1948, FS has enrolled 3 generations of participants (ages 20-50) and 2 multi-
ethnic cohorts, examined them regularly for cognitive decline and dementia, and collected an exquisite array of
in-depth and cutting-edge “multi-omic”, imaging, and other data over their lifespan and before clinical ADRD
onset. The FS has a 70-year legacy of unique contributions to public health, and will continue make
breakthroughs in ADRD through its Brain Aging Program (3U19AG068753-02S1). We seek to leverage these
resources through the following specific aims: AIM 1 is to examine and explain associations of social
isolation, loneliness, and social network structure with ADRD vulnerability over a lifetime. Our prior work
in FS suggests a molecular pathway related to neural plasticity/repair and cognitive resilience might be involved
in these mechanisms. We will collect a new wave of data on these factors—partially harmonized with the NIH
Toolbox and integrate this data with relevant psychosocial information at multiple previous exams. AIM 2 is to
identify and validate these biological pathways using causal inference analyses and machine-learning
methods on the extensive multi-omics data available. AIM 3 is to characterize social environment’s
cumulative role in psychosocial mechanisms of ADRD risk across the adult lifespan by developing a latent
social environment index with a validated geocode-based method and conducting sophisticated analyses. We
will validate our findings with other multi-ethnic cohort datasets and share all data through dbGaP and bioLINCC.
We expect to meaningfully evaluate whether and how these psychosocial factors influence the biology of healthy
neurocognitive aging and ADRD vulnerability and identify new pathways that may serve as targets for
intervention in the preclinical stage of ADRD. This will advance our understanding of the long-term effects of
psychosocial determinants, ADRD prevention, and how to address the root causes of disparities in ADRD.
Terms: <21+ years old><AD dementia><AD related dementia><ADRD><Acceleration><Active Follow-up><Address><Adult><Adult Human><Age><Aging><Algorithms><Alzheimer Type Dementia><Alzheimer beta-Protein><Alzheimer disease dementia><Alzheimer sclerosis><Alzheimer syndrome><Alzheimer's><Alzheimer's Amyloid beta-Protein><Alzheimer's Disease><Alzheimer's amyloid><Alzheimer's and related dementias><Alzheimer's disease and related dementia><Alzheimer's disease and related disorders><Alzheimer's disease or a related dementia><Alzheimer's disease or a related disorder><Alzheimer's disease or related dementia><Alzheimer's disease related dementia><Alzheimers Dementia><Amentia><Amyloid Alzheimer's Dementia Amyloid Protein><Amyloid Beta-Peptide><Amyloid Protein A4><Amyloid beta-Protein><Amyloid β><Amyloid β-Peptide><Amyloid β-Protein><Anatomic Sites><Anatomic structures><Anatomy><Automated Indexing><Aβ><Biological><Biological Function><Biological Markers><Biological Process><Biology><Blinded><Blood><Blood Reticuloendothelial System><Brain><Brain Nervous System><Brain imaging><CNS plasticity><COVID crisis><COVID epidemic><COVID pandemic><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 pandemic><COVID-19 period><COVID-19 public health crisis><COVID-19 years><Censuses><Clinical><Clinical Trials><Cognitive><Cognitive Disturbance><Cognitive Impairment><Cognitive decline><Cognitive function abnormal><Cohort Studies><Communities><Complement><Complement Proteins><Computer Analysis><Computer Vision Systems><Computer-based Indexing><Computing Methodologies><Concurrent Studies><Data><Data Set><Dementia><Dimensions><Disparities><Disparity><Disturbance in cognition><Economic Conditions><Economical Conditions><Encephalon><Enrollment><Ethnic Origin><Ethnicity><Funding><Future><Generations><Genetic><Genetic Risk><Health><Health Resources><Health behavior><Human><Image><Impaired cognition><Incidence><Individual><Inflammation><Inflammatory><Information Networks><Intervention><Intervention Strategies><Intervention Studies><Intervention Trial><Interventional trial><Link><Loneliness><Long-Term Effects><Longterm Effects><MR Imaging><MR Tomography><MRI><MRIs><MT-bound tau><Machine Learning><Magnetic Resonance Imaging><Measures><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Methods><Modern Man><Molecular><Molecular Fingerprinting><Molecular Profiling><Multiomic Data><NIH><NMR Imaging><NMR Tomography><National Institutes of Health><Nerve Degeneration><Neurocognitive><Neuron Degeneration><Neuronal Plasticity><Neuropsychologies><Neuropsychology><Nuclear Magnetic Resonance Imaging><PET><PET Scan><PET imaging><PETSCAN><PETT><Participant><Pathway interactions><Pattern><Perfusion><Population Study><Positron Emission Tomography Medical Imaging><Positron Emission Tomography Scan><Positron-Emission Tomography><Prevalence><Prevention><Primary Senile Degenerative Dementia><Process><Proteomics><Psychosocial Assessment and Care><Psychosocial Effect><Psychosocial Factor><Public Health><Publishing><Rad.-PET><Research><Research Priority><Research Resources><Resources><Risk><Role><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SES disparity><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Sight><Social Environment><Social Network><Social isolation><Socioeconomic Factors><Stress><Structure><Translating><Treatment/Psychosocial Effects><United States National Institutes of Health><Validation><Vascular Diseases><Vascular Disorder><Vision><Work><Zeugmatography><a beta peptide><abeta><active followup><adulthood><aged brain><ages><aging brain><amyloid beta><amyloid imaging><amyloid-b protein><beta amyloid fibril><bio-markers><biologic><biologic marker><biomarker><blood vessel disorder><brain health><brain visualization><central nervous system plasticity><cognitive dysfunction><cognitive function><cognitive loss><cohort><complementation><computational analyses><computational analysis><computational methodology><computational methods><computer analyses><computer based method><computer methods><computer vision><computing method><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><cytotoxic><data integration><data sharing><database of Genotypes and Phenotypes><dbGaP><dementia risk><enroll><ethnic diversity><ethnically diverse><examination questions><follow up><follow-up><followed up><followup><health determinants><health equity><health related behavior><imaging><imaging biomarker><imaging marker><imaging-based biological marker><imaging-based biomarker><imaging-based marker><improved><indexing><innovate><innovation><innovative><interest><intervention research><interventional research><interventional strategy><interventional study><interventions research><life span><lifespan><lonely><machine based learning><machine learning based method><machine learning method><machine learning methodologies><method development><microtubule bound tau><microtubule-bound tau><molecular biomarker><molecular marker><molecular profile><molecular signature><multi-ethnic><multiethnic><multiomics><multiple omic data><multiple omics><neural degeneration><neural plasticity><neurobiological mechanism><neurodegeneration><neurodegenerative><neurological degeneration><neuronal degeneration><neuropathologic><neuropathological><neuropathology><neuroplastic><neuroplasticity><neuropsychologic><novel><open data><open science><open-source data><panomics><pathway><population health><population-based study><population-level study><positron emission tomographic (PET) imaging><positron emission tomographic imaging><positron emitting tomography><pre-clinical><preclinical><primary degenerative dementia><programs><psychosocial><psychosocial assessment><psychosocial care><psychosocial studies><psychosocial support><psychosocial variables><public health relevance><racial diversity><racially diverse><repair><repaired><resilience><resilient><response><risk factor for dementia><risk for dementia><senile dementia of the Alzheimer type><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><social><social climate><social context><social relationships><social role><socio-economic><socio-economic disparity><socio-economic factors><socio-economic inequality><socio-economic inequity><socio-economically><socioeconomic disparity><socioeconomic inequality><socioeconomic inequity><socioeconomically><socioeconomics><socioenvironment><socioenvironmental><soluble amyloid precursor protein><studies of populations><study of the population><tau><tau Proteins><tau factor><trend><validations><vascular dysfunction><vasculopathy><visual function><τ Proteins>