Dataset Information

Cerebral Amyloid and Hypertension are Independently Associated with White Matter Lesions in Elderly.

ABSTRACT: In cognitively normal (CN) elderly individuals, white matter hyperintensities (WMH) are commonly viewed as a marker of cerebral small vessel disease (SVD). SVD is due to exposure to systemic vascular injury processes associated with highly prevalent vascular risk factors (VRFs) such as hypertension, high cholesterol, and diabetes. However, cerebral amyloid accumulation is also prevalent in this population and is associated with WMH accrual. Therefore, we examined the independent associations of amyloid burden and VRFs with WMH burden in CN elderly individuals with low to moderate vascular risk. Participants (n = 150) in the Alzheimer's Disease Neuroimaging Initiative (ADNI) received fluid attenuated inversion recovery (FLAIR) MRI at study entry. Total WMH volume was calculated from FLAIR images co-registered with structural MRI. Amyloid burden was determined by cerebrospinal fluid A?1-42 levels. Clinical histories of VRFs, as well as current measurements of vascular status, were recorded during a baseline clinical evaluation. We tested ridge regression models for independent associations and interactions of elevated blood pressure (BP) and amyloid to total WMH volume. We found that greater amyloid burden and a clinical history of hypertension were independently associated with greater WMH volume. In addition, elevated BP modified the association between amyloid and WMH, such that those with either current or past evidence of elevated BP had greater WMH volumes at a given burden of amyloid. These findings are consistent with the hypothesis that cerebral amyloid accumulation and VRFs are independently associated with clinically latent white matter damage represented by WMHs. The potential contribution of amyloid to WMHs should be further explored, even among elderly individuals without cognitive impairment and with limited VRF exposure.

SUBMITTER: Scott JA

PROVIDER: S-EPMC4664630 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Cerebral Amyloid and Hypertension are Independently Associated with White Matter Lesions in Elderly.

Scott Julia A JA Braskie Meredith N MN Tosun Duygu D Thompson Paul M PM Weiner Michael M DeCarli Charles C Carmichael Owen T OT

Frontiers in aging neuroscience 20151201

In cognitively normal (CN) elderly individuals, white matter hyperintensities (WMH) are commonly viewed as a marker of cerebral small vessel disease (SVD). SVD is due to exposure to systemic vascular injury processes associated with highly prevalent vascular risk factors (VRFs) such as hypertension, high cholesterol, and diabetes. However, cerebral amyloid accumulation is also prevalent in this population and is associated with WMH accrual. Therefore, we examined the independent associations of ...[more]

PMID: 26648866

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Project description:ImportanceThe effect of intensive blood pressure lowering on brain health remains uncertain.ObjectiveTo evaluate the association of intensive blood pressure treatment with cerebral white matter lesion and brain volumes.Design, setting, and participantsA substudy of a multicenter randomized clinical trial of hypertensive adults 50 years or older without a history of diabetes or stroke at 27 sites in the United States. Randomization began on November 8, 2010. The overall trial was stopped early because of benefit for its primary outcome (a composite of cardiovascular events) and all-cause mortality on August 20, 2015. Brain magnetic resonance imaging (MRI) was performed on a subset of participants at baseline (n = 670) and at 4 years of follow-up (n = 449); final follow-up date was July 1, 2016.InterventionsParticipants were randomized to a systolic blood pressure (SBP) goal of either less than 120 mm Hg (intensive treatment, n = 355) or less than 140 mm Hg (standard treatment, n = 315).Main outcomes and measuresThe primary outcome was change in total white matter lesion volume from baseline. Change in total brain volume was a secondary outcome.ResultsAmong 670 recruited patients who had baseline MRI (mean age, 67.3 [SD, 8.2] years; 40.4% women), 449 (67.0%) completed the follow-up MRI at a median of 3.97 years after randomization, after a median intervention period of 3.40 years. In the intensive treatment group, based on a robust linear mixed model, mean white matter lesion volume increased from 4.57 to 5.49 cm3 (difference, 0.92 cm3 [95% CI, 0.69 to 1.14]) vs an increase from 4.40 to 5.85 cm3 (difference, 1.45 cm3 [95% CI, 1.21 to 1.70]) in the standard treatment group (between-group difference in change, -0.54 cm3 [95% CI, -0.87 to -0.20]). Mean total brain volume decreased from 1134.5 to 1104.0 cm3 (difference, -30.6 cm3 [95% CI, -32.3 to -28.8]) in the intensive treatment group vs a decrease from 1134.0 to 1107.1 cm3 (difference, -26.9 cm3 [95% CI, 24.8 to 28.8]) in the standard treatment group (between-group difference in change, -3.7 cm3 [95% CI, -6.3 to -1.1]).Conclusions and relevanceAmong hypertensive adults, targeting an SBP of less than 120 mm Hg, compared with less than 140 mm Hg, was significantly associated with a smaller increase in cerebral white matter lesion volume and a greater decrease in total brain volume, although the differences were small.Trial registrationClinicalTrials.gov Identifier: NCT01206062.

Dataset Information

Cerebral Amyloid and Hypertension are Independently Associated with White Matter Lesions in Elderly.

Publications

Cerebral Amyloid and Hypertension are Independently Associated with White Matter Lesions in Elderly.

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