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Published on: March 17, 2016
Cerebral white matter disease and functional decline in older adults from the Northern Manhattan Study: A
Mandip S Dhamoon1, Ying-Kuen Cheung2, Yeseon Moon3
1Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Background:
Cerebral white matter hyperintensities (WMHs) on MRI are common and associated with vascular and functional outcomes. However, the relationship between WMHs and longitudinal trajectories of functional status is not well characterized. We hypothesized that whole brain WMHs are associated with functional decline independently of intervening clinical vascular events and other vascular risk factors.
Methods And Findings:
In the Northern Manhattan Study (NOMAS), a population-based racially/ethnically diverse prospective cohort study, 1,290 stroke-free individuals underwent brain MRI and were followed afterwards for a mean 7.3 years with annual functional assessments using the Barthel index (BI) (range 0-100) and vascular event surveillance. Whole brain white matter hyperintensity volume (WMHV) (as percentage of total cranial volume [TCV]) was standardized and treated continuously. Generalized estimating equation (GEE) models tested associations between whole brain WMHV and baseline BI and change in BI, adjusting for sociodemographic, vascular, and cognitive risk factors, as well as stroke and myocardial infarction (MI) occurring during follow-up. Mean age was 70.6 (standard deviation [SD] 9.0) years, 40% of participants were male, 66% Hispanic; mean whole brain WMHV was 0.68% (SD 0.84). In fully adjusted models, annual functional change was -1.04 BI points (-1.20, -0.88), with -0.74 additional points annually per SD whole brain WMHV increase from the mean (-0.99, -0.49). Whole brain WMHV was not associated with baseline BI, and results were similar for mobility and non-mobility BI domains and among those with baseline BI 95-100. A limitation of the study is the possibility of a healthy survivor bias, which would likely have underestimated the associations we found.
Conclusions:
In this large population-based study, greater whole brain WMHV was associated with steeper annual decline in functional status over the long term, independently of risk factors, vascular events, and baseline functional status. Subclinical brain ischemic changes may be an independent marker of long-term functional decline.
Insights
Greater white matter hyperintensities (WMH) volume on MRI is linked to faster functional decline in older adults. This association persists even when accounting for vascular risk factors and events, suggesting WMH as an independent marker of long-term decline.
Area of Science:
- Neurology
- Radiology
- Gerontology
Background:
- Cerebral white matter hyperintensities (WMHs) are common findings on MRI scans.
- WMHs are associated with vascular disease and impact functional outcomes.
- The longitudinal relationship between WMHs and functional status decline is not fully understood.
Purpose of the Study:
- To investigate the association between whole brain white matter hyperintensity volume (WMHV) and longitudinal functional status trajectories.
- To determine if WMHs predict functional decline independently of clinical vascular events and other risk factors.
Main Methods:
- The study analyzed data from 1,290 stroke-free participants in the prospective, population-based Northern Manhattan Study (NOMAS).
- Participants underwent brain MRI for WMHV assessment and were followed for a mean of 7.3 years with annual functional assessments using the Barthel index (BI).
- Generalized estimating equation (GEE) models were used to assess the association between WMHV and baseline BI and change in BI, adjusting for multiple covariates.
Main Results:
- A greater whole brain WMHV was significantly associated with a steeper annual decline in functional status.
- Each standard deviation increase in WMHV was linked to an additional annual decline of 0.74 Barthel index points.
- This association remained significant after adjusting for sociodemographic factors, vascular risk factors, cognitive status, and occurrence of stroke or myocardial infarction during follow-up.
Conclusions:
- Increased whole brain white matter hyperintensity volume is an independent predictor of long-term functional decline.
- Subclinical ischemic changes in the brain, as indicated by WMHs, may serve as a crucial marker for predicting future functional impairment.
- These findings highlight the importance of assessing WMHs for understanding and potentially mitigating age-related functional decline.
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