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Amyloid-related Imaging Abnormalities (Microbleeds) in Atypical AD

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01723553
Recruitment Status : Completed
First Posted : November 8, 2012
Last Update Posted : December 21, 2015
Information provided by (Responsible Party):
Jennifer Whitwell, Mayo Clinic

Brief Summary:
The study is designed to assess the demographic, clinical and imaging associations with the presence of microbleeds in atypical Alzheimer's disease. The primary hypothesis is that cognitive and functional performance will be poorer in atypical Alzheimer's subjects with microbleeds compared to those without microbleeds.

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

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
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

Arm Intervention/treatment
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).
Other Names:
  • Pittsburgh Compound B
  • PiB

Primary Outcome Measures :
  1. Proportion of subjects with and without microbleeds [ Time Frame: up to day 2 of study ]

Secondary Outcome Measures :
  1. 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 ]
  2. Number of microbleeds per subject [ Time Frame: Study entry, approximately day 1 or day 2 of study ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • over the age of 21
  • will have an informant/study partner who will be able to provide independent evaluation of functioning
  • must fulfill clinical diagnostic criteria for atypical AD, and hence should either have a chief complaint of difficulty with language and fulfill criteria for logopenic variant of primary progressive aphasia, or present with visuospatial/perceptual deficits and fulfill criteria for posterior cortical atrophy
  • speaks English as their primary language (including bilingual patients whose primary language is English)
  • agrees to and is eligible to undergo MRI and PET scanning
  • if woman of child bearing age, must agree to pregnancy test no more than 48 hours before the PET scans

Exclusion Criteria:

  • subjects with concurrent illnesses that could account for the presenting syndrome, such as traumatic brain injury, strokes or developmental syndromes
  • subjects meeting criteria for another neurodegenerative disease, particularly typical Alzheimer's dementia
  • women that are pregnant or post-partum and breast-feeding
  • subjects will also be excluded if MRI is contraindicated (metal in head, cardiac pace maker, e.t.c.), if there is severe claustrophobia, and if there are conditions that may confound brain imaging studies (e.g. structural abnormalities, including subdural hematoma or intracranial neoplasm)
  • subjects will also be excluded if they do not have an informant, do not consent to research or do not complete all components of the study (neurological exam, neuropsychometric tests, MRI, PiB PET)

Information from the National Library of Medicine

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 identifier (NCT number): NCT01723553

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United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
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Principal Investigator: Jennifer Whitwell, PhD Mayo Clinic
Additional Information:
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Responsible Party: Jennifer Whitwell, PI, Mayo Clinic Identifier: NCT01723553    
Other Study ID Numbers: 12-007139
First Posted: November 8, 2012    Key Record Dates
Last Update Posted: December 21, 2015
Last Verified: December 2015
Keywords provided by Jennifer Whitwell, Mayo Clinic:
Additional relevant MeSH terms:
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Alzheimer Disease
Aphasia, Primary Progressive
Pick Disease of the Brain
Frontotemporal Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Speech Disorders
Language Disorders
Communication Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Frontotemporal Lobar Degeneration
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Anti-Inflammatory Agents