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Principal Investigator: MARILYN S. ALBERT
Organization: JOHNS HOPKINS UNIVERSITY
Fiscal Year: 2024
Award: $1,309,997
Funding agency: National Institute of Neurological Disorders and Stroke
Project Summary/Abstract:
Small-vessel-related vascular contributions to cognitive impairment and dementia (VCID) represent the
second leading cause of cognitive dysfunction in older individuals. However, quantitative biomarkers indexing
key vascular processes related to VCID that are suitable for use as endpoints in clinical trials are still lacking.
The goals of the present application are to 1) participate in the multi-site clinical validation of up to six
biomarkers selected by the NINDS through a longitudinal study of diverse all-comers with cognitive complaints
and/or early symptomatic signs of cognitive impairment and dementia potentially associated with small vessel
disease; 2) lead the multi-site clinical validation of cerebrovascular reactivity (CVR) biomarker in all-comers, if
the CVR biomarker is selected to move onto the next-phase study.
The present application is a Renewal of UH2/3 NS100588 under RFA-NS-16-020. As one of the funded
participating sites of the above-mentioned RFA, hereafter referred to as MarkVCID I study, our team at JHU
has made significant contributions to the Consortium: 1) In the UH2 phase, we developed CVR MRI candidate
biomarker and collected data to support its selection by the NINDS to become one of the eleven biomarkers
that transited into the UH3 phase; 2) In the UH2 phase, we worked with other sites to standardize MRI, biofluid,
clinical, and neuropsychological measures and implemented candidate biomarkers proposed by other sites
locally at our site; 3) In the UH3 phase, we participated in the multi-site instrumental and biological validation of
biomarkers approved by the NINDS; 4) In the UH3 phase, we led the multi-site instrumental and biological
validation of the CVR candidate biomarker. Importantly, our site has the scientific expertise and equipment that
are necessary to perform any of the 11 biomarkers currently under consideration; 5) We participated in all
Consortium-wide activities such as annual conferences, committee meetings, and calls.
In the present application, we propose four Specific Aims. Aim 1 will enroll 220 participants of diverse all-
comers that are typical in clinical settings in the United States during the first two years of the project and
collect the NINDS-approved biomarker measures. Aim 2 will conduct longitudinal follow-up in a minimum of
200 participants in the latter three years of the project. Aim 3 will provide inputs and participate in the
Consortium-wide activities such as serving on committees, discussing protocols, attending and presenting in
the annual conferences, participating in multi-site data processing and validation, and sharing of data and
biospecimens with researchers within and outside the Consortium. In Aim 4 we will lead multi-site clinical
validation of a cerebrovascular reactivity (CVR) biomarker, if CVR is selected to move on to the next phase.
Impact: Upon the completion of this project, we will have developed a set of VCID biomarkers that are
ready for future clinical trials, including large phase III trials, of VCID.
Terms: <AD dementia><Active Follow-up><African American><Afro American><Afroamerican><Alzheimer Type Dementia><Alzheimer disease dementia><Alzheimer sclerosis><Alzheimer syndrome><Alzheimer's><Alzheimer's Disease><Alzheimers Dementia><Amentia><Asian group><Asian individual><Asian people><Asian population><Asians><Biological><Biological Markers><Blood><Blood Reticuloendothelial System><Blood Vessels><Brain Vascular reactivity><Caucasian><Caucasian Race><Caucasians><Caucasoid><Caucasoid Race><Clinical><Clinical Trials><Cognitive><Cognitive Disturbance><Cognitive Impairment><Cognitive decline><Cognitive function abnormal><Consensus><Data><Data Analyses><Data Analysis><Dementia><Diabetes Mellitus><Disturbance in cognition><Enrollment><Equipment><Event><Functional Imaging><Funding><Future><Goals><Hispanic><Hypercholesteremia><Hypertension><Image><Impaired cognition><Investigators><Lead><Liquid substance><Long-term cohort study><Longitudinal Studies><Longitudinal cohort study><Longterm cohort study><MR Imaging><MR Tomography><MRI><MRIs><Magnetic Resonance Imaging><Manuscripts><Measures><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Memory><Microvascular Dysfunction><Mission><NINDS><NMR Imaging><NMR Tomography><National Institute of Neurological Diseases and Stroke><National Institute of Neurological Disorders and Stroke><Neuropsychologies><Neuropsychology><Nuclear Magnetic Resonance Imaging><Obesity><Occidental><Older Population><Paper><Participant><Pb element><Persons><Phase><Physiologic Imaging><Primary Senile Degenerative Dementia><Procedures><Process><Protocol><Protocols documentation><Quality Control><Research><Research Personnel><Researchers><Site><Smoking><Source><Standardization><Testing><Training><United States><Validation><Vascular Hypertensive Disease><Vascular Hypertensive Disorder><Work><Zeugmatography><active followup><adiposity><bio-markers><biologic><biologic marker><biomarker><biomarker selection><biomarker validation><candidate biomarker><candidate marker><cardiac disease induced cognitive impairment><cerebral vascular reactivity><cerebrovascular reactivity><clinical research site><clinical site><cognitive dysfunction><cognitive loss><cohort><computerized data processing><conference><convention><corpulence><data interpretation><data processing><data sharing><diabetes><enroll><experience><flexibility><flexible><fluid><follow up><follow up assessment><follow-up><followed up><followup><followup assessment><heavy metal Pb><heavy metal lead><high blood cholesterol><high blood pressure><human subject><hypercholesterolemia><hyperpiesia><hyperpiesis><hypertensive disease><hypertensive disorder><imaging><imaging biomarker><imaging marker><imaging-based biological marker><imaging-based biomarker><imaging-based marker><indexing><liquid><long-term study><longitudinal outcome studies><longterm study><marker validation><meeting><meetings><microvascular complications><microvascular disease><mild cognitive disorder><mild cognitive impairment><neural imaging><neuro-imaging><neuroimaging><neurological imaging><neuropsychologic><older groups><older individuals><older person><participant enrollment><participant retention><patient enrollment><phase 3 trial><phase III trial><physiological imaging><primary degenerative dementia><recruit><senile dementia of the Alzheimer type><small vessel disease><summit><symposia><symposium><treatment center><validations><vascular><vascular cognitive impairment and dementia><vascular contributions to cognition/dementia><vascular contributions to cognitive impairment and dementia><vascular risk factor><white race>