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

Silbert, Lisa C.; Nelson, Charles R.; Howieson, Diane B.; Moore, M. M.; Kaye, Jeffrey

doi:10.1212/01.wnl.0000316799.86917.37

Cited by 227 publications

(250 citation statements)

References 33 publications

(36 reference statements)

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“…A systematic review revealed that WML affected physical function and elevated fall risk (Zheng et al 2011). Our study also supports other studies showing that WML were associated with gait variables (Bolandzadeh et al 2014;Murray et al 2010;Rosano et al 2010;Silbert et al 2008). Furthermore, WML induced deficits in dual-task performance and elevated the risk of falling (Zheng et al 2012a;Zheng et al 2012b).…”

Section: Discussionsupporting

confidence: 88%

“…Structural changes in the aging brain are related to gait performance (for reviews, see Holtzer et al 2014a;Seidler et al 2010). In particular, white matter hyperintensities or lesions (WMLs) have been linked to deficits in physical function among cognitively normal older adults (Bolandzadeh et al 2014;Murray et al 2010;Rosano et al 2010;Silbert et al 2008). WMLs were also shown to affect dual-task performance requiring executive function but not gait task among cognitively normal older adults (Zheng et al 2012a).…”

mentioning

confidence: 99%

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Effects of white matter lesions on trunk stability during dual-task walking among older adults with mild cognitive impairment

Doi¹,

Shimada

Makizako

et al. 2015

AGE

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The linkage between gait and cognition has been shown in cases of white matter lesion (WML) that affect gait in older adults. Dual-task walking is believed to be cognitively demanding and to alter trunk movement, and gait impairment in people with mild cognitive impairment (MCI) is highlighted under this condition. However, the association between dual-task walking and structural changes in the brain, particularly with WML, in people with MCI is still unclear. The aim of this study was to examine the association between trunk stability during dual-task walking and WML in 560 older adults with MCI. We measured magnetic resonance imaging (MRI) and gait variables. Gait variables included harmonic ratio in vertical, mediolateral, and anteroposterior directions, analyzed using a tri-axial accelerometer attached to the lower trunk. Walking conditions were normal walking and dual-task walking (counting backwards while walking) conditions. Demographical data and brain atrophy were measured as covariates. Subjects were classified into non-severe WML (n=451, mean age=73.2 years) and severe WML (n=109, mean age=75.9 years) groups. Linear mixedeffects model analysis controlled for covariates showed dual-task-related changes in all harmonic ratios associated with WML (p<0.05). Even after adjustment for executive function, harmonic ratio in the mediolateral direction was significantly associated with WML (p<0.05). Our findings revealed that WMLs were associated with trunk stability in dual-task walking. Further studies are required to investigate the neural basis for deficits in gait ability among MCI subjects.

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Section: Discussionsupporting

confidence: 88%

mentioning

confidence: 99%

Effects of white matter lesions on trunk stability during dual-task walking among older adults with mild cognitive impairment

Doi¹,

Shimada

Makizako

et al. 2015

AGE

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“…Longitudinal studies consistently reported a relationship between WML progression and decline in global as well as specific cognitive performance. 10,18,23,24,26,29,[39][40][41][42][43][44][45] In the Cardiovascular Health Study, increase in WML grades was related to global cognitive decline. 24 In the Rotterdam Study, progression of periventricular WMLs was associated with decline in general cognitive performance and information processing speed.…”

Section: White Matter Lesionsmentioning

confidence: 99%

Longitudinal change of small-vessel disease-related brain abnormalities

Schmidt

Seiler

Loitfelder

2015

J Cereb Blood Flow Metab

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Knowledge about the longitudinal change of cerebral small-vessel disease-related magnetic resonance imaging abnormalities increases our pathophysiologic understanding of cerebral microangiopathy. The change of specific lesion types may also serve as secondary surrogate endpoint in clinical trials. A surrogate endpoint needs to progress fast enough to allow monitoring of treatment effects within a reasonable time period, and change of the brain abnormality needs to be correlated with clinical change. Confluent white matter lesions show fast progression and correlations with cognitive decline. Thus, the change of confluent white matter lesions may be used as a surrogate marker in proof-of-concept trials with small patient numbers needed to show treatment effects on lesion progression. Nonetheless if the expected change in cognitive performance resulting from treatment effects on lesion progression is used as outcome, the sample size needed to show small to moderate treatment effects becomes very large. Lacunes may also fulfill the prerequisites of a surrogate marker, but in the general population the incidence of lacunes over short observational periods is small. For other small-vessel disease-related brain abnormalities including microbleeds and microstructural changes in normalappearing white matter longitudinal change and correlations with clinical decline is not yet fully determined.

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“…Studies that did not compare subjects based on cognitive status Subcortical vs. periventricular WML Five studies [24][25][26][27][28] -four cross-sectional studies and one prospective study -compared the association of subcortical versus periventricular WMLs with cognitive function. In the first cross-sectional study of 1077 older adults [24], WMLs were defined as T2 and PD hyperintensities that were not T1 hypointensities.…”

Section: Overview Of Studiesmentioning

confidence: 99%

P3‐200: The association between cognitive function and white matter lesion location in older adults: A systematic review

Bolandzadeh

Davis

Tam

et al. 2012

Alzheimer's & Dementia

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Background: Maintaining cognitive function is essential for healthy aging and to function autonomously within society. White matter lesions (WMLs) are associated with reduced cognitive function in older adults. However, whether their anatomical location moderates these associations is not well-established. This review systematically evaluates peer-reviewed evidence on the role of anatomical location in the association between WMLs and cognitive function. Methods: In accordance with the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement, databases of EMBASE, PUBMED, MEDLINE, and CINAHL, and reference lists of selected papers were searched. We limited our search results to adults aged 60 years and older, and studies published in the English language from 2000 to 2011. Studies that investigated the association between cognitive function and WML location were included. Two independent reviewers extracted: 1) study characteristics including sample size, sample characteristic, and study design; 2) WML outcomes including WML location, WML quantification method (scoring or volume measurement), strength of the MRI magnet in Tesla, and MRI sequence used for WML detection; and 3) cognitive function outcomes including cognitive tests for two cognitive domains of memory and executive function/processing speed. Results: Of the 14 studies included, seven compared the association of subcortical versus periventricular WMLs with cognitive function. Seven other studies investigated the association between WMLs in specific brain regions (e.g., frontal, parietal lobes) and cognitive function. Overall, the results show that a greater number of studies have found an association between periventricular WMLs and executive function/processing speed, than subcortical WMLs. However, whether WMLs in different brain regions have a differential effect on cognitive function remains unclear. Conclusions: Evidence suggests that periventricular WMLs may have a significant negative impact on cognitive abilities of older adults. This finding may be influenced by study heterogeneity in: 1) MRI sequences, WML quantification methods, and neuropsychological batteries; 2) modifying effect of cardiovascular risk factors; and 3) quality of studies and lack of sample size calculation.

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

Abstract: Background: White matter hyperintensity (WMH) change on brain MRI is observed with increased

Cited by 227 publications

References 33 publications

Effects of white matter lesions on trunk stability during dual-task walking among older adults with mild cognitive impairment

Effects of white matter lesions on trunk stability during dual-task walking among older adults with mild cognitive impairment

Longitudinal change of small-vessel disease-related brain abnormalities

P3‐200: The association between cognitive function and white matter lesion location in older adults: A systematic review

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