A prospective study of cerebral white matter abnormalities in older people with gait dysfunction

Whitman, Gregory T.; Tang, Tao; Lin, A.; Baloh, Robert W.

doi:10.1212/wnl.57.6.990

Cited by 282 publications

(214 citation statements)

References 27 publications

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“…31 We have shown that progression of PV WMH volume is associated with increased gait slowing over time. The relationship between increased rate of WMH burden and worse performance on gait testing over time has been reported, 15,32 although previous studies did not examine the potential differential relationships between subcortical and PV WMH volume change and progressive gait dysfunction. Increased progression of subcortical WMH lesions was associated with increased rate of memory decline, independent of cerebral or hippocampal atrophy.…”

Section: Figurementioning

confidence: 99%

“…The question as to whether there is likely to exist a differential effect of total WMH burden on age-related morbidity based on the location within the CNS of white matter change remains unanswered. Longitudinal studies looking at the progression of WMH have been reported [9][10][11][12][13][14][15][16][17][18][19] ; however, differences in methodologies of WMH measurement make comparisons difficult. A poor cor-relation in estimated WMH burden between differing visual rating scales 20 and increased reliability and sensitivity of WMH volumetric measurements 21 make studies using volumetric measures preferable to those that use visual rating scales.…”

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confidence: 99%

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Impact of white matter hyperintensity volume progression on rate of cognitive and motor decline

Silbert¹,

Nelson²,

Howieson³

et al. 2008

Neurology

225

216

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Section: Figurementioning

confidence: 99%

mentioning

confidence: 99%

Impact of white matter hyperintensity volume progression on rate of cognitive and motor decline

Silbert¹,

Nelson²,

Howieson³

et al. 2008

Neurology

225

216

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“…shown that, in healthy subjects, the average increase in WMH volume was 1.1cm 3 over four years in one study 41 and 0.1cm 3 over six years in another. 42 However, when subjects with only punctate lesions were excluded from the analysis, those with confluent lesions showed a WMH volume increase of up to 9.3cm 3 over the six years.…”

Section: Progressionmentioning

confidence: 80%

The Evolution of White Matter Hyperintensities

Young¹,

Kril²

2010

US Neurology

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The increasing application of neuroimaging techniques has led to the frequent discovery of cerebral white matter lesions, referred to as white matter hyperintensities (WMHs) in this article, which appear as hypodense areas on computed tomography (CT) scans or as hyperintense regions on T 2 -weighted and fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) sequences. Since their discovery, almost every aspect of WMHs has been surrounded by controversy.1 Despite the abundant literature on this subject, relatively little progress has been made in determining the etiology, pathology, or even the clinical significance of these lesions.The prevalence of WMHs in asymptomatic healthy subjects varies widely depending on the technique used for their identification, the type of lesion examined, and the characteristics of the population studied. 2,3Large-scale population-based studies have shown that prevalence rates range from 27 to 96%. 4,5 However, prevalence rates are generally higher in patients with dementia, 6 and have been found to differ among ethnic groups 7 and with gender. Many risk factors have been associated with the frequency and severity of WMHs, but the strongest and most consistently reported is increasing age. 9,10 Hypertension is the next most important risk factor, with a recent study demonstrating a reduced risk for increased WMH volume over two years in subjects with successfully treated hypertension; 11 however, there is some debate over whether systolic or diastolic blood pressure (BP) is significant. Some studies observed that both systolic and diastolic BP were higher in subjects with WMHs, 5,7 while others found that mean systolic BP was significantly higher in subjects with WMHs regardless of whether they were from a dementia or a control group. 12 Other studies showed that elevated diastolic BP, measured years earlier, was related to the presence of WMHs. 13,14 The type of BP notwithstanding, these studies suggest that the development of WMHs is a relatively slow process that is related to long-standing high BP. 13 Clinical CorrelatesAs with the risk factors associated with WMHs, the clinical correlates linked to these lesions are many and varied, due partly to the high prevalence of AbstractWhite matter hyperintensities (WMHs) are a common finding on magnetic resonance imaging (MRI) scans of elderly subjects. Despite their frequency, the clinical correlates and etiology of WMH remain controversial, with many conflicting results published. This is due, in part, to the varied populations studied. Nevertheless, the prevailing opinion is that these lesions are of vascular origin due to the strong associations with vascular risk factors and stroke. Neuropathological studies have also yielded varied results. Interestingly, while a number of associations with variables such as demyelination and gliosis have been reported, no single pathological variable has been found to account for the MRI changes. The most consistent associations are with reduced vascular integrity and inc...

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“…Glmnet requires the user to set two parameters related to the penalty: alpha was set at 0.5 to represent an exact mixture of lasso and ridge regression and lambda was determined using k-fold crossvalidation to minimize misclassification error. Fifty-seven brain regions were included as predictors and 3 additional variables (age, total intracranial volume, and log-transformed white matter hypointensity) were included as covariates, based on biological relevance (Whitman et al 2001;Debette and Markus 2010). These covariates were not subjected to the elastic net penalty.…”

Section: Discussionmentioning

confidence: 99%

“…These steps provide quantification of cerebral white matter, gray matter, and subcortical volume. It also provided white matter hypointensity volume and estimated total intracranial volume (to account for difference in head size) which we included as covariates in our analyses (Whitman et al 2001;Debette and Markus 2010). Specifically, estimated total intracranial volume is determined through Freesurfer via atlas scaling factor -a determinant of linear transformation used to align individual structural image to an atlas (Buckner et al 2004).…”

Section: 26mentioning

confidence: 99%

Structural neural correlates of impaired mobility and subsequent decline in executive functions: a 12-month prospective study

Hsu

Best

Chiu

et al. 2016

Experimental Gerontology

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Impaired mobility, such as falls, may be an early biomarker of subsequent cognitive decline and is associated with subclinical alterations in both brain structure and function. In this 12-month prospective study, we examined whether there are volumetric differences in gray matter and subcortical regions, as well as cerebral white matter, between older fallers and non-fallers. In addition, we assessed whether these baseline volumetric differences are associated with changes in cognitive function over 12 months. A total of 66 community-dwelling older adults were recruited and categorized by their falls status. Magnetic resonance imaging occurred at baseline and participants' physical and cognitive performances were assessed at baseline and 12-months. At baseline, fallers showed significantly lower volumes in gray matter, subcortical regions, and cerebral white matter compared with non-fallers. Notably, fallers had significantly lower left lateral orbitofrontal white matter volume. Moreover, lower left lateral orbitofrontal white matter volume at baseline was associated with greater decline in set-shifting performance over 12 months. Our data suggest that falls may indicate subclinical alterations in regional brain volume that are associated with subsequent decline in executive functions.

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A prospective study of cerebral white matter abnormalities in older people with gait dysfunction

Abstract: Some older people develop gait and balance dysfunction that is associated with gradual onset of cerebral white matter disease.

Cited by 282 publications

References 27 publications

Impact of white matter hyperintensity volume progression on rate of cognitive and motor decline

Impact of white matter hyperintensity volume progression on rate of cognitive and motor decline

The Evolution of White Matter Hyperintensities

Structural neural correlates of impaired mobility and subsequent decline in executive functions: a 12-month prospective study

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