Journal
NEUROBIOLOGY OF AGING
Volume 34, Issue 8, Pages 1996-2002Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2013.02.003
Keywords
Alzheimer's disease; Vascular disease; Mild cognitive impairment (MCI); Volumetric MRI; Normal aging
Categories
Funding
- Medical Research Council [GO 601846, MR/J014257/1]
- Alzheimer Research UK
- National Institute for Health Research (NIHR) Biomedical Research Unit in Dementia based at University College London Hospitals (UCLH), University College London (UCL)
- Wellcome Trust [091593/Z/10/Z]
- Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- Canadian Institutes of Health Research
- NIH [P30 AG010129, K01 AG030514]
- Dana Foundation
- MRC [G0601846, MR/J014257/1] Funding Source: UKRI
- Alzheimers Research UK [ART-EG2010B-1, ARUK-Network2011-6-ICE] Funding Source: researchfish
- Medical Research Council [G0601846, MR/J014257/1] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0512-10033, NF-SI-0508-10123] Funding Source: researchfish
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This study assessed relationships among white matter hyperintensities (WMH), cerebrospinal fluid (CSF), Alzheimer's disease (AD) pathology markers, and brain volume loss. Subjects included 197 controls, 331 individuals with mild cognitive impairment (MCI), and 146 individuals with AD with serial volumetric 1.5-T MRI. CSF A beta 1-42 (n = 351) and tau (n = 346) were measured. Brain volume change was quantified using the boundary shift integral (BSI). We assessed the association between baseline WMH volume and annualized BSI, adjusting for intracranial volume. We also performed multiple regression analyses in the CSF subset, assessing the relationships of WMH and A beta 1-42 and/or tau with BSI. WMH burden was positively associated with BSI in controls (p = 0.02) but not MCI or AD. In multivariable models, WMH (p = 0.003) and A beta 1-42 (p = 0.001) were independently associated with BSI in controls; in MCI A beta 1-42 (p < 0.001) and tau (p = 0.04) were associated with BSI. There was no evidence of independent effects of WMH or CSF measures on BSI in AD. These data support findings that vascular damage is associated with increased brain atrophy in the context of AD pathology in pre-dementia stages. (c) 2013 Elsevier Inc. All rights reserved.
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