Amyloid-related Imaging Abnormalities (Microbleeds) in Atypical AD
| Status: | Completed |
|---|---|
| Conditions: | Alzheimer Disease, Neurology, Women's Studies |
| Therapuetic Areas: | Neurology, Reproductive |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/21/2016 |
| Start Date: | November 2012 |
| End Date: | March 2015 |
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.
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.
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.
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.
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)
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