Amyloid-related Imaging Abnormalities (Microbleeds) in Atypical AD
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|ClinicalTrials.gov Identifier: NCT01723553|
Recruitment Status : Completed
First Posted : November 8, 2012
Last Update Posted : December 21, 2015
|Condition or disease||Intervention/treatment||Phase|
|Atypical Alzheimers Disease Logopenic Variant of Primary Progressive Aphasia (LPA) Posterior Cortical Atrophy (PCA)||Drug: C-11 PiB||Phase 1|
Alzheimer's disease (AD) is associated with amyloid-related imaging abnormalities (ARIA). Microbleeds (MBs) represent part of the spectrum of ARIA and can be identified as small hypointense lesions on gradient-recalled echo (GRE) T2*-weighted MRI. They are thought to represent hemosiderin deposits (and hence have been classified as ARIA-H1) and occur as a consequence of leakage of blood products out of vessels that have been damaged by deposition of the protein β-amyloid in cerebral vessels; cerebral amyloid angiopathy (CAA). However, it is also possible that cerebrovascular disease could contribute to the presence of MBs in AD. Subjects with MBs are at a greater risk of bleeds which could impact the use of anti-coagulation treatment approaches.
The presence of CAA has been particularly associated with AD and studies have demonstrated that MBs occur in 12-33% of subjects with typical Alzheimer's dementia, with a large proportion of subjects showing multiple MBs. The presence of MBs has been associated with older age and a greater degree of white matter hyperintensities (WMH) in Alzheimer's dementia. The association between MBs and WMH, a marker of cerebrovascular disease, suggests cerebrovascular disease may also play a role in the etiology of MBs in AD. However, approximately 16% of AD subjects do not present with episodic memory loss, but instead display language problems such as poor naming and impaired sentence repetition, or visuospatial and visual perceptual deficits, and are referred to as atypical AD. Since AD is associated with CAA, one would assume that CAA and hence MBs, would also occur in atypical AD, although no studies have assessed MBs in atypical AD.
Amyloid-binding ligands, such as Pittsburgh Compound B (PiB), that can be detected using PET scanning have now been developed and provide an invaluable biomarker to infer the presence of β-amyloid. The presence of CAA has been shown to be associated with elevated PiB uptake, and hence the assessment of PiB-PET in subjects with MBs will provide important information on the association of MBs and β-amyloid deposition in AD.
The goal of the study is to assess the associations between MBs and demographic/clinical features, assess the associations between MBs and imaging features as well as a possible correlate to the number of MBs a subject has in atypical AD.
Patients found to be eligible and willing to enroll in this study will be asked to undergo a Neurologic Examination, Neuropsychometric testing, an MRI scan, and a PiB PET scan of the brain. This will be done over a period of two days at the Mayo Clinic in Rochester, Minnesota.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||27 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Amyloid-related Imaging Abnormalities (Microbleeds) in Atypical AD|
|Study Start Date :||November 2012|
|Actual Primary Completion Date :||March 2015|
|Actual Study Completion Date :||March 2015|
Experimental: PiB positron emission tomography (PET)
All subjects will receive PET imaging with C-11 PiB on approximately day 1 or day 2 of study to determine if they have beta-amyloid deposits in their brains.
Drug: C-11 PiB
One time intravenous administration of ~740 megabecquerel (MBq) of [N-methyl-C-11]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole (PiB) (range 370 - 740 MBq).
- Proportion of subjects with and without microbleeds [ Time Frame: up to day 2 of study ]
- Percentage of white matter hyperintensity burden on MRI and ratio of amyloid burden on PiB PET scan [ Time Frame: Study entry, approximately day 1 or day 2 of study ]
- Number of microbleeds per subject [ Time Frame: Study entry, approximately day 1 or day 2 of study ]
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): NCT01723553
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||Jennifer Whitwell, PhD||Mayo Clinic|