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Principal Investigator: Kelsie Marie Full
Organization: VANDERBILT UNIVERSITY MEDICAL CENTER
Fiscal Year: 2024
Award: $120,177
Funding agency: National Institute on Aging
PROJECT SUMMARY. Alzheimer’s disease and related dementias (ADRD) has become a major public health
crisis. To date, therapeutic strategies for Alzheimer’s disease have been largely ineffective resulting in an
increased focus on identifying effective prevention strategies. Daily 24-hour activity behaviors (sleep, physical
activity, and sedentary time) may be modifiable risk factors for ADRD. A better understanding of these risk
factors may provide an opportunity for early prevention, particularly in the asymptomatic phase prior to the
development of ADRD-related pathology. The availability of longitudinal actigraphy data to objectively-measure
24-hour activity in a strongly ADRD-phenotyped cohort has created the ideal opportunity to investigate
potential pathways linking 24-hour activity behaviors with ADRD. The objective of this K01 is to longitudinally
investigate changes in 24-hour activity with changes in cognition, structural neuroimaging, and fluid biomarkers
of Alzheimer’s disease and concomitant pathological pathways prior to the onset of clinical dementia. I will
leverage data from the Vanderbilt Memory and Aging Project (VMAP) cohort with repeated measures of
actigraphy, brain MRI, and fluid biomarkers of Alzheimer’s disease neuropathology and concomitant injury. The
central hypothesis of this proposal is changes in 24-hour activity will be associated with cognitive decline,
structural neuroimaging changes, and Alzheimer’s disease and concomitant pathway changes, preceding
symptom onset. Based on this hypothesis, the proposal aims to 1) characterize associations between changes
in 24-hour activity and cognitive decline, 2) examine changes in 24-hour activity in relation to MRI markers of
neurodegeneration and small vessel disease, and 3) evaluate changes in 24-hour activity behaviors with fluid
biomarkers of Alzheimer’s disease neuropathology and concomitant pathways. Taken together, these aims will
combine objective measurement of 24-hour activity with cognitive, neuroimaging, and state of the art fluid
biomarker data to fill existing gaps in the research. Simultaneously, throughout the award, the candidate will
gain advanced training in 1) Alzheimer’s disease pathophysiology and epidemiology; 2) measurement and
modeling of structural imaging and fluid biomarkers of Alzheimer’s neuropathology and concomitant pathways
of injury; and 3) advanced statistical methods, positioning the candidate to become a leader in the fields of
aging and Alzheimer’s disease epidemiology. Vanderbilt University Medical Center and the Vanderbilt Memory
and Alzheimer’s Center provide the ideal environment to complete the proposed research and training
activities. The overall goal of this K01 is to inform a series of R01 awards and independent research program
focused on identifying and characterizing behavioral risk factors for ADRD. With the support of this K01 award
and expert mentorship, the candidate will achieve this goal and successfully transition to independent
investigator status by the conclusion of the training period.
Terms: <21+ years old><AD associated neurodegeneration><AD dementia><AD model><AD neurodegeneration><AD pathology><AD related dementia><ADRD><Academic Medical Centers><Adult><Adult Human><Age><Aging><Alzheimer Type Dementia><Alzheimer associated neurodegeneration><Alzheimer beta-Protein><Alzheimer disease dementia><Alzheimer related neurodegeneration><Alzheimer risk factor><Alzheimer sclerosis><Alzheimer syndrome><Alzheimer's><Alzheimer's Amyloid beta-Protein><Alzheimer's Disease><Alzheimer's amyloid><Alzheimer's and related dementias><Alzheimer's biomarker><Alzheimer's disease and related dementia><Alzheimer's disease and related disorders><Alzheimer's disease associated neurodegeneration><Alzheimer's disease biological marker><Alzheimer's disease model><Alzheimer's disease or a related dementia><Alzheimer's disease or a related disorder><Alzheimer's disease or related dementia><Alzheimer's disease pathology><Alzheimer's disease related dementia><Alzheimer's disease related neurodegeneration><Alzheimer's disease risk><Alzheimer's pathology><Alzheimers Dementia><Alzheimer’s biological marker><Alzheimer’s disease biomarker><Amentia><Ammon Horn><Amyloid Alzheimer's Dementia Amyloid Protein><Amyloid Beta-Peptide><Amyloid Protein A4><Amyloid beta-Protein><Amyloid β><Amyloid β-Peptide><Amyloid β-Protein><Award><Aβ><Behavior><Behavioral><Biological Markers><Blood - brain barrier anatomy><Blood Plasma><Blood-Brain Barrier><CD140b Antigens><Cerebrospinal Fluid><Clinical><Cognition><Cognitive><Cognitive Disturbance><Cognitive Impairment><Cognitive decline><Cognitive function abnormal><Cornu Ammonis><Cross Sectional Analysis><Cross-Sectional Analyses><Cross-Sectional Studies><Cross-Sectional Survey><Data><Dementia><Development><Disease Frequency Surveys><Disturbance in cognition><Dysfunction><Environment><Epidemiology><Functional disorder><Generalized Growth><Goals><Growth><Hemato-Encephalic Barrier><Hippocampus><Hour><Impaired cognition><Injury><Investigators><K01 Award><K01 Mechanism><K01 Program><Life Style><Lifestyle><Light><Link><Liquid substance><MR Imaging><MR Tomography><MRI><MRI biomarker><MRI marker><MRIs><MT-bound tau><Magnetic Resonance Imaging><Measurement><Measures><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Memory><Mentored Research Scientist Development Award><Mentored Training Award><Mentorship><Microvascular Dysfunction><Modeling><NMR Imaging><NMR Tomography><Nature><Nerve Degeneration><Neuron Degeneration><Nuclear Magnetic Resonance Imaging><PDGF Receptor β><PDGF beta Receptor><PDGF β Receptor><PDGFR beta><PDGFR-β><Pathologic><Pathology><Pathway interactions><Phase><Phenotype><Photoradiation><Physical activity><Physiopathology><Plasma><Plasma Serum><Platelet-Derived Growth Factor Receptor Beta Polypeptide><Platelet-Derived Growth Factor Receptor β><Platelet-Derived Growth Factor beta Receptor><Position><Positioning Attribute><Preventative strategy><Prevention><Prevention strategy><Preventive strategy><Primary Senile Degenerative Dementia><Public Health><RC3 protein><Research><Research Activity><Research Design><Research Personnel><Research Scientist Development Award><Researchers><Reticuloendothelial System, Serum, Plasma><Risk Factors><Role><Series><Sleep><Statistical Methods><Structural Models><Study Type><Sum><Symptoms><Synapses><Synaptic><Theoretic Models><Theoretical model><Therapeutic><Time><Tissue Growth><Training><Training Activity><University Medical Centers><White Matter Hyperintensity><Work><Zeugmatography><a beta peptide><abeta><actigraph><actigraphy><adulthood><ages><alzheimer model><alzheimer risk><amyloid beta><amyloid-b protein><axon damage><axon injury><axonal damage><axonal injury><beta amyloid fibril><bio-markers><biologic marker><biomarker><bloodbrain barrier><brain MR imaging><brain MRI><brain magnetic resonance imaging><cerebral MR imaging><cerebral MRI><cerebral magnetic resonance imaging><cerebral spinal fluid><cognitive dysfunction><cognitive loss><cohort><dementia risk><developmental><epidemiologic><epidemiological><fluid><hippocampal><imaging biomarker><imaging marker><imaging-based biological marker><imaging-based biomarker><imaging-based marker><improved><in vivo><injuries><late life><liquid><magnetic resonance imaging biomarker><magnetic resonance imaging marker><malleable risk><microtubule bound tau><microtubule-bound tau><microvascular complications><microvascular disease><modifiable risk><neural degeneration><neural imaging><neural inflammation><neuro-imaging><neurodegeneration><neurodegenerative><neurofilament><neurogranin><neuroimaging><neuroimaging biomarker><neuroimaging marker><neuroinflammation><neuroinflammatory><neurological degeneration><neurological imaging><neuronal degeneration><neuropathologic><neuropathological><neuropathology><ontogeny><p-tau><p-τ><p17 protein kinase C substrate><pathophysiology><pathway><phospho-tau><phospho-τ><phosphorylated tau><poor sleep><post-translational modification of tau><posttranslational modification of tau><primary degenerative dementia><programs><risk factor for dementia><risk for dementia><sedentary><senile dementia of the Alzheimer type><small vessel disease><social role><soluble amyloid precursor protein><spinal fluid><statistic methods><structural imaging><study design><synapse><tau><tau Proteins><tau factor><tau phosphorylation><tau posttranslational modification><tau-1><training module><treatment strategy><τ Proteins><τ phosphorylation>