Accelerated progression of white matter hyperintensities and subsequent risk of mortality: a 12-year follow-up study

Sabayan, Behnam; Westendorp, Rudi G.J.; Buchem, Mark A. van; Craen, Anton J. M. de

doi:10.1016/j.neurobiolaging.2015.03.003

Cited by 27 publications

(23 citation statements)

References 25 publications

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“…White matter hyperintensites have been previously associated with mobility (47) and cognitive impairment (48), depression (14, 18, 21-25), and mortality (49) in older adults. This includes past literature that has linked visually-rated white matter grades to physical functioning (50), dementia (51), depression (17), and mortality (52).…”

Section: Discussionmentioning

confidence: 99%

Brain Structural Markers and Caregiving Characteristics as Interacting Correlates of Caregiving Strain

Smagula

Beach

Rosso

et al. 2017

The American Journal of Geriatric Psychiatry

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Objective To evaluate the association between brain structural markers and caregiving strain among older informal caregivers. Design A secondary data analysis combining data from the Caregiver Health Effects Study (1993-1994) and the Cardiovascular Health Study MRI examination (1992-1994). Setting Four United States communities. Participants Co-residing spousal caregivers (n=237, mean age=76.2, standard deviation=2.2). Measurements Visually-rated ventricular and white matter (WM) grades from MRI, caregiving strain defined as “emotional or physical strain associated with providing care” for any of 12 activities of daily living (ADLs) and instrumental activities of daily living (IADLs), plus measures of caregiving characteristics and caregiver's health. Results Overall, 56% of caregivers reported strain. We detected an interaction where strain was very common (>82%) among caregivers who helped with ≥4 IADLs, regardless of WM grades, and among caregivers with the worst WM grades (WM grades ≥4), regardless of the number of IADLs they helped with. Among caregivers helping with <4 IADLs, having WM grades ≥4 was associated with a 55% higher prevalence ratio for reporting strain. This association remained statistically significant but was most markedly attenuated by adjustments for: care recipient's memory and behavioral problems, caregiver's depression symptoms, and caregiver's ADL impairment. Conclusions Caregiving strain is very common among older informal caregivers who provide help with many IADLs, and among caregivers who help with fewer IADLs, but have manifest signs of white matter pathology. Modern quantitative-neuroimaging studies are needed to evaluate whether more subtle variability in brain structure confers caregiving strain and the related health consequences.

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Section: Discussionmentioning

confidence: 99%

Brain Structural Markers and Caregiving Characteristics as Interacting Correlates of Caregiving Strain

Smagula

Beach

Rosso

et al. 2017

The American Journal of Geriatric Psychiatry

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“…31 The reported prevalence and speed of LA progression differ greatly in various cohorts due to the different duration of observation and definition of progression. In the Austrian Stroke Prevention Study (ASPS) with healthy volunteers aged 50-75 years, participants with early confluent and confluent WMHs at baseline underwent median increases of 2·7 (IQR 0.5-5.9) cm 3 and 9·3(7.1-21.0) cm 3 , respectively, in lesion volume over 6 years.…”

Section: Current Evaluation Of La Progression and Its Limitationsmentioning

confidence: 99%

“…Progression of LA has been linked to cognitive worsening,30 increased risk of depression3 and mortality 31. The reported prevalence and speed of LA progression differ greatly in various cohorts due to the different duration of observation and definition of progression.…”

Section: Introductionmentioning

confidence: 99%

Multimodal imaging findings in normal-appearing white matter of leucoaraiosis: a review

Zhong

Lou

2016

Stroke Vasc Neurol

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Leucoaraiosis (LA), also referred to as white matter hyperintensities (WMHs), are usually seen as patchy or confluent hyperintense areas on T2-weighted or fluid-attenuated inversion recovery MRI in the elderly. It is often asymptomatic in its early stages, yet its persistent evolution to more advanced stages may lead to substantial neurological dysfunction including dementia, stroke and death. Despite its clinical significance, the pathogenic mechanisms underlying LA development are uncertain. In patients with LA, the pathophysiological changes in white matter (WM) are suggested to be continuous from WMHs to its neighbourhood ‘normal-appearing white matter (NAWM)’ on conventional MRI sequences. Multimodal imaging studies revealed that the so-called ‘NAWM’ was actually abnormal with regard to underlying haemodynamic and microstructural changes. On the basis of positron emission tomography CT, xenon-CT, perfusion MRI, etc, the cerebral blood flow of NAWM was found to be significantly reduced in patients with LA, compared with healthy controls. Meanwhile, the integrity of microstructures and blood–brain barrier in NAWM was also demonstrated to be impaired with diffusion tensor imaging and dynamic contrast-enhanced MRI studies, respectively. In addition,the integrity of NAWM correlated much stronger with cognitive performance than did WMHs load. It is reasonable to assume that the subtle injury of NAWM would be more reversible than WMHs themselves. Therefore, multimodal imaging modalities could be appropriately applied to future interventional studies targeting at early pathophysiological changes of NAWM. In this paper, we summarise current knowledge about NAWM of LA mainly acquired from multimodal imaging studies in vivo, and attempt to give options for future work.

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“…Many larger WMHs are ischemic in origin (Thomas et al ., ; Thomas et al ., ) and indicate damage to the microstructural integrity of white matter tracts (Taylor et al ., ). WMHs are clinically relevant as they are associated with important negative outcomes including cognitive deficits, dementia, stroke, disability, and mortality (Maillard et al ., ; Sabayan et al ., ; Steffens et al ., ; Taylor et al ., ).…”

Section: Introductionmentioning

confidence: 99%

Effects of stressful life events on cerebral white matter hyperintensity progression

Johnson

McQuoid

Steffens

et al. 2016

Int J Geriat Psychiatry

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Objective Exposure to stressful events is associated both with occurrence of depression and also vascular disease. The objective of this study was to determine whether higher levels of stress exposure was related to measures of pathological brain aging, specifically white matter hyperintensity volumes, in older adults with and without depression. Methods The sample included 130 depressed and 110 never-depressed older adults aged 60 years or older enrolled in a longitudinal study at an academic medical center. Participants completed clinical assessments, assessment of stressful event exposure and perceived stress, and magnetic resonance imaging at baseline and after two years. Analyses examined both cross-sectional and longitudinal relationships between stress measures and white matter hyperintensity volumes. Results There were no statistically significant relationships observed between cross-sectional baseline stress measures and either baseline hyperintensity volume or two-year change in hyperintensity volume. However, after controlling for demographic variables and baseline measures, change in stressor exposure was associated with change in hyperintensity volumes. In this analysis, increased stressor exposure was associated with greater increases in white matter hyperintensity volume, while reductions in stressor exposure was associated with less increase in hyperintensity volume. This relationship did not significantly differ based on the presence of either depression or medical comorbidities. Conclusions This work adds to a growing literature associating exposure to stressful events in later life with more rapid pathological brain aging. Work is needed to understand the physiological mechanisms by which stress exposure has this effect and examine whether stress reduction techniques may modify these observed outcomes.

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Accelerated progression of white matter hyperintensities and subsequent risk of mortality: a 12-year follow-up study

Cited by 27 publications

References 25 publications

Brain Structural Markers and Caregiving Characteristics as Interacting Correlates of Caregiving Strain

Brain Structural Markers and Caregiving Characteristics as Interacting Correlates of Caregiving Strain

Multimodal imaging findings in normal-appearing white matter of leucoaraiosis: a review

Effects of stressful life events on cerebral white matter hyperintensity progression

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