Vascular burden and Alzheimer disease pathologic progression
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Abstract
Objective: To investigate the vascular contribution to longitudinal changes in Alzheimer disease (AD) biomarkers.
Methods: The Alzheimer's Disease Neuroimaging Initiative is a clinic based, longitudinal study with CSF, PET, and MRI biomarkers repeatedly measured in participants with normal cognition (NC), mild cognitive impairment (MCI), and mild AD. Participants with severe cerebrovascular risks were excluded. Cardiovascular risk scores and MRI white matter hyperintensities (WMHs) were treated as surrogate markers for vascular burden. Generalized estimating equations were applied, and both vascular burden and its interaction with time (vascular burden × time) or time-varying WMHs were entered into regression models to assess whether biomarker rates of change were modified by vascular burden.
Results: Cardiovascular risk profiles were not predictive of progression in CSF β42-amyloid, [18F]fluorodeoxyglucose (FDG) PET uptake, and MRI hippocampal atrophy. Greater baseline cardiovascular risks or WMHs were generally associated with cognitive impairment, particularly poor executive function. WMHs increased over time with a faster rate in MCI and AD than in NC. Increased time-varying WMH was associated with faster decline in executive function and lower FDG uptake in NC. Otherwise, WMH was not associated with CSF and MRI biomarkers in the 3 groups. These findings remained unchanged after accounting for APOE4.
Conclusion: Increased WMHs are associated with aging, decreased glucose metabolism, and decline in executive function but do not affect AD-specific pathologic progression, suggesting that the vascular contribution to dementia is probably additive although not necessarily independent of the amyloid pathway.
GLOSSARY
- Aβ=
- β-amyloid;
- AD=
- Alzheimer disease;
- ADNI=
- Alzheimer's Disease Neuroimaging Initiative;
- ASAD-cog=
- Alzheimer's Disease Assessment Scale–Cognitive Subscale;
- FDG=
- [18F]fluorodeoxyglucose;
- GEE=
- generalized estimating equation;
- MCI=
- mild cognitive impairment;
- MMSE=
- Mini-Mental State Examination;
- NC=
- normal cognition;
- WMH=
- white matter hyperintensity
Footnotes
Study funding: Funding information is provided at the end of the article.
Supplemental data at www.neurology.org
Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (http%3A//adni.loni.ucla.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found on the Neurology® Web site at www.neurology.org.
- Received March 22, 2012.
- Accepted May 15, 2012.
- Copyright © 2012 by AAN Enterprises, Inc.
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