Brain Vascular Disease in Aging and Dementia
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|ClinicalTrials.gov Identifier: NCT03075007|
Recruitment Status : Enrolling by invitation
First Posted : March 9, 2017
Last Update Posted : April 8, 2019
|Condition or disease||Intervention/treatment|
|Alzheimer Disease White Matter Hyperintensities Dementia Aging||Radiation: Florbetaben F18 Procedure: Transcranial Doppler|
Alzheimer's disease (AD) is one of the most devastating international public health epidemics. There are currently no effective disease-modifying or preventative strategies. Current pathogenic models emphasize a single pathway of disease pathogenesis, but underestimate the contribution of small vessel cerebrovascular disease, which manifests primarily as white matter hyperintensities (WMH) on T2-weighted magnetic resonance imaging (MRI). Understanding of the factors that drive the relationship between vascular disease and AD remains elusive; vascular factors may be independent sources of dysfunction that contribute additively to clinical expression, they may interact mechanistically with AD pathology, and/or they may relate to each other because of a shared association with a third set of factors. These issues are particularly relevant among ethnic/racial minorities, who are at much greater risk for clinical AD, have more severe cerebrovascular disease, but appear to have similar levels of AD pathology compared with Whites.
The proposed research examines these factors in a large, longitudinal, multi-ethnic community-based cohort study of older adults in northern Manhattan, New York. The investigators demonstrated that accumulation of WMH, particularly in parietal lobes, predicts incident AD, and is associated with the presence of cerebral microbleeds, an indicator of cerebral amyloid angiopathy. The investigators extend the research to examine mechanistic interactions between cerebrovascular disease and AD. The preliminary data suggest that individuals with evidence of fibrillar amyloidosis have increased parietal lobe WMH and that hemodynamic markers of autoregulatory dysfunction are associated with both WMH and amyloid deposition, which in turn interact to promote the clinical expression of AD. These findings are buffered by new data that establish WMH as a core feature in autosomal dominant forms of AD. In this pilot study, the investigators propose to obtain cross-sectional and longitudinal MRI and amyloid PET data from participants in WHICAP.
|Study Type :||Observational|
|Estimated Enrollment :||50 participants|
|Official Title:||White Matter Hyperintensities in Aging and Dementia|
|Actual Study Start Date :||May 23, 2017|
|Estimated Primary Completion Date :||August 31, 2019|
|Estimated Study Completion Date :||August 31, 2019|
All participants will undergo an amyloid PET scan with Florbetaben F 18 contrast as well as a transcranial Doppler ultrasound.
Radiation: Florbetaben F18
10Meq of Florbetaben F 18 via intravenous injection is to be used. Visit duration is approximately 3 hours.
Procedure: Transcranial Doppler
All participants will undergo Doppler ultrasonography that measures the velocity of blood flow through the brain's blood vessels. Visit duration is approximately 45 minutes and will be scheduled for either the same day or another day as the PET scan.
- PET amyloid Standard Uptake Value ratio (SUVr) values [ Time Frame: up to 18 months ]The primary outcome is the mean standard uptake value ratio in the 4 regions of interest.
- Transcranial Doppler (TCD) dynamic autoregulatory dysfunction [ Time Frame: up to 18 months ]Cerebral blood flow velocities (CBFV) are assessed using TCD. Arterial blood pressure (ABP) is recorded simultaneously using the Finapres on the middle phalanx of the left or right middle finger. The phase shift between the two streaming signals is an indication of the extent to which oscillations in CBFV lead those in ABP and can be interpreted as active early counter-regulation. Lower phase shift reflects increased latency in cerebral vasomotion and thus poorer autoregulation.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03075007
|United States, New York|
|Columbia University Medical Center|
|New York, New York, United States, 10032|
|Principal Investigator:||Adam M Brickman, PhD||Columbia University|