Brain Vascular Disease in Aging and Dementia

September 11, 2019 updated by: Adam Brickman, Columbia University

White Matter Hyperintensities in Aging and Dementia

This study examines the factors that may drive the relationship between vascular disease and Alzheimer's Disease (AD) in a large, longitudinal, multi-ethnic community-based cohort study of older adults in northern Manhattan, New York. In past research, the investigators demonstrated that accumulation of brain vascular disease is associated with risk for development of AD. The study now extends the research to examine how brain vascular disease and AD interact. In this pilot study, the investigators will obtain positron emission tomography (PET) scans to measure amyloid (one of the protein pathological markers of AD) from participants in an ongoing community-based study of aging and dementia (WHICAP). The study will include subjects who are already enrolled in the parent project. Further, this study will enroll both subjects who have never been evaluated with PET scans and those who received a previous baseline PET scan. The study plans to obtain approximately 30 repeat amyloid PET scans and 20 baseline PET scans. The investigators will also conduct transcranial Doppler studies to measure blood flow in the participants with amyloid PET scans. The potential benefits to society should be considerable if this study reveals new information about risk factors for or contributions to AD.

Study Overview

Detailed Description

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

Enrollment (Actual)

48

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Potential participants are recruited from a list of active members in the Washington Heights/Hamilton Heights/ Inwood Columbia Aging Project, known as WHICAP (CU IRB# AAAO9804), who previously completed a repeat MRI as part of a neuroimaging sub-study (IRB# AAAO9758). Some participants (n=30) will already have had baseline amyloid PET imaging under PI IRB protocol # 7130R (BAY 949172PET/CT in Older Adults).

Description

Inclusion Criteria:

  • current participant in WHICAP (Washington Heights/Inwood Columbia Aging Project)
  • subject previously participated in baseline MRI sub-study
  • post-menopausal

Exclusion Criteria:

  • allergic to Florbetaben
  • claustrophobic
  • liver problems
  • history of epilepsy/seizures
  • pre-menopausal
  • serious medical conditions

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Group A
All participants will undergo an amyloid PET scan with Florbetaben F 18 contrast as well as a transcranial Doppler ultrasound.
10Meq of Florbetaben F 18 via intravenous injection is to be used. Visit duration is approximately 3 hours.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
up to 18 months
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.
up to 18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Adam M Brickman, PhD, Columbia University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 23, 2017

Primary Completion (Actual)

August 31, 2019

Study Completion (Actual)

August 31, 2019

Study Registration Dates

First Submitted

March 6, 2017

First Submitted That Met QC Criteria

March 6, 2017

First Posted (Actual)

March 9, 2017

Study Record Updates

Last Update Posted (Actual)

September 12, 2019

Last Update Submitted That Met QC Criteria

September 11, 2019

Last Verified

September 1, 2019

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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