Older people with impaired mobility have specific loci of periventricular abnormality on MRI

Benson, Randall R.; Guttmann, Charles R.G.; Wei, Xing‐Chang; Warfield, Simon K.; Hall, Charles B.; Schmidt, Julia A.; Kikinis, R.; Wolfson, Leslie

doi:10.1212/wnl.58.1.48

Cited by 116 publications

(104 citation statements)

References 20 publications

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“…Imaging studies have shown that slowing gait and parkinsonism are related to periventricular white matter changes. 33,34 Increased total and periventricular white matter hyperintensity (WMH) burden and progression of periventricular WMH burden are associated with decreased gait performance over time, whereas progression of subcortical WMH volume is associated with memory decline in cognitively intact elderly individuals. 35 In postmortem studies, motor dysfunction has been associated with the presence of neuronal loss 36 or neurofibrillary tangles in the substantia nigra 37 and amyloid plaques in the frontal lobes and basal ganglia.…”

Section: Discussionmentioning

confidence: 99%

In-home walking speeds and variability trajectories associated with mild cognitive impairment

Dodge¹,

Mattek²,

Austin³

et al. 2012

Neurology

197

163

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Objective: To determine whether unobtrusive long-term in-home assessment of walking speed and its variability can distinguish those with mild cognitive impairment (MCI) from those with intact cognition. Methods:Walking speed was assessed using passive infrared sensors fixed in series on the ceiling of the homes of elderly individuals participating in the Intelligent Systems for Assessing Aging Change (ISAAC) cohort study. Latent trajectory models were used to analyze weekly mean speed and walking speed variability (coefficient of variation [COV]).Results: ISAAC participants living alone included 54 participants with intact cognition, 31 participants with nonamnestic MCI (naMCI), and 8 participants with amnestic MCI at baseline, with a mean follow-up of 2.6 Ϯ 1.0 years. Trajectory models identified 3 distinct trajectories (fast, moderate, and slow) of mean weekly walking speed. Participants with naMCI were more likely to be in the slow speed group than in the fast (p ϭ 0.01) or moderate (p ϭ 0.04) speed groups. For COV, 4 distinct trajectories were identified: group 1, the highest baseline and increasing COV followed by a sharply declining COV; groups 2 and 3, relatively stable COV; and group 4, the lowest baseline and decreasing COV. Participants with naMCI were more likely to be members of either highest or lowest baseline COV groups (groups 1 or 4), possibly representing the trajectory of walking speed variability for early-and late-stage MCI, respectively. It is of substantial importance to detect dementia at its earliest phases to sustain independence, to optimize treatment, to understand preclinical biology, and to ultimately develop prevention strategies. Past studies have found that slower walking speed and poorer motor function are associated with mild cognitive impairment (MCI) and are predictors of progression to frank dementia. [1][2][3][4] However, it is difficult to identify changes in these functions because changes evolve slowly over time and change measures have high test-to-test variability. Further, current methods for assessing this change rely largely on sparsely spaced or annual assessments that provide too few data points to discern subtle changes. An alternative to this approach is to deploy unobtrusive passive monitoring systems in people's homes, providing continuous assessment of daily activity and behaviors of interest. This kind of pervasive computing model has been established by the Intelligent Systems for Assessing Aging Change (ISAAC) study, 5,6 Conclusion:

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Section: Discussionmentioning

confidence: 99%

In-home walking speeds and variability trajectories associated with mild cognitive impairment

Dodge¹,

Mattek²,

Austin³

et al. 2012

Neurology

197

163

View full text Add to dashboard Cite

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“…WMH in these tracts can disrupt neural transmission, leading to gait slowing in older adults. 10,11,37 Tracts that traverse large areas of watershed WM are more prone to WM injury and WMH. 38 Recent evidence also suggests that inflammation influences corpus callosal changes.…”

Section: Baseline Characteristics Valuesmentioning

confidence: 99%

“…9 WMH are related to slow gait in older adults. 10,11 In regions that are free of WMH, which we refer to here as normal-appearing white matter (NAWM), subtle changes are detected on diffusion tensor imaging (DTI) as a reduction in fractional anisotropy of NAWM (NAWM-FA), denoting loss of myelin and astrogliosis at the microstructural level.…”

mentioning

confidence: 99%

Slow gait, white matter characteristics, and prior 10-year interleukin-6 levels in older adults

et al. 2016

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Objective: To examine the relationship between gait speed and prior 10 years interleukin-6 (IL-6) burden in older adults. We then assessed whether white matter characteristics influence this relationship.Methods: In 179 community-dwelling older adults, gait speed was assessed on an automated walkway and serum IL-6 was assayed on ELISA. Concurrently, white matter characteristics were assessed on MRI by quantifying volume of white matter hyperintensities (WMH), a marker of small vessel disease, and normal-appearing white matter on fractional anisotropy (NAWM-FA), a marker of axonal integrity. IL-6 was assayed at regular intervals at gait assessment and over the prior 10 years and estimates of sustained 10-year IL-6 exposure and the rate of change in IL-6 over 10 years were obtained. Multivariate linear regressions were used to examine the relationships among sustained IL-6 exposure, rate of change in IL-6, gait speed, and white matter characteristics.Results: In this sample (age 83 years, 58% female, 41% black, gait speed 0.9 m/s), higher sustained IL-6 levels, but not the rate of change in IL-6 or IL-6 at gait assessment, was significantly related to slower gait (b 5 20.27, p , 0.001) and to higher WMH (b 5 0.23, p 5 0.002), but not NAWM-FA, withstanding covariate adjustments. WMH accounted for 30% attenuation in the relationship between higher sustained IL-6 levels and slower gait speed (p 5 0.043) in the mediation analyses.Conclusions: Sustained exposure to high IL-6 over 10 years rather than the rate of change in or an isolated high IL-6 level may adversely affect gait speed by influencing cerebral WMH. Increased levels of inflammatory cytokines such as interleukin-6 (IL-6) are cross-sectionally and longitudinally associated with poor physical function in older adults.1-5 IL-6 assayed at regular intervals over a long-term period may better capture sustained IL-6 exposure and rate of change rather than random assays spread apart over time. It is not known whether the sustained longterm exposure to IL-6 or rate of change in IL-6 contributes to the relationship between IL-6 and gait speed beyond a single concurrent indicator of inflammation.Higher IL-6 is linked to greater volume of white matter hyperintensities (WMH) on MRI in most studies [6][7][8] but not in all. 9 WMH are related to slow gait in older adults. 10,11 In regions that are free of WMH, which we refer to here as normal-appearing white matter (NAWM), subtle changes are detected on diffusion tensor imaging (DTI) as a reduction in fractional anisotropy of NAWM (NAWM-FA), denoting loss of myelin and astrogliosis at the microstructural level.

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“…Previous research suggests that the location or distribution of WMHs is associated with specific symptoms (Benson, et al 2002). Most previous research focused only on WMH visual inspection or volume measurement and did not distinguish anatomically distinct WMHs, while a few groups have explored semi-automated or automated methods to localize WMHs into large compartments or catergories such as periventricular white matter hyperintensities (PVWMHs) and deep white matter hyperintensities (DWMHs).…”

Section: Introductionmentioning

confidence: 99%

A fully automated method for quantifying and localizing white matter hyperintensities on MR images

Rosano

Butters

et al. 2006

Psychiatry Research: Neuroimaging

180

165

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White matter hyperintensities (WMH), commonly found on T2-weighted FLAIR brain MR images in the elderly, are associated with a number of neuropsychiatric disorders, including vascular dementia, Alzheimer's disease, and late-life depression. Previous MRI studies of WMHs have primarily relied on the subjective and global (i.e., full-brain) ratings of WMH grade. In the current study we implement and validate an automated method for quantifying and localizing WMHs. We adapt a fuzzy connected algorithm to automate the segmentation of WMHs and use a demons-based image registration to automate the anatomic localization of the WMHs using the Johns Hopkins University White Matter Atlas. The method is validated using the brain MR images acquired from eleven elderly subjects with late-onset late-life depression (LLD) and eight elderly controls. This dataset was chosen because LLD subjects are known to have significant WMH burden. The volumes of WMH identified in our automated method are compared with the accepted gold standard (manual ratings). A significant correlation of the automated method and the manual ratings is found (P<0.0001), thus demonstrating similar WMH quantifications of both methods. As has been shown in other studies e.g. (Taylor, et al. 2003)), we found there was a significantly greater WMH burden in the LLD subjects versus the controls for both the manual and automated method. The effect size was greater for the automated method, suggesting that it is a more specific measure. Additionally, we describe the anatomic localization of the WMHs in LLD subjects as well as in the control subjects, and detect the regions of interest (ROIs) specific for the WMH burden of LLD patients. Given the emergence of large neuroimage databases, techniques, such as that described here, will allow for a better understanding of the relationship between WMHs and neuropsychiatric disorders.

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Older people with impaired mobility have specific loci of periventricular abnormality on MRI

Abstract: These results suggest that damage to discrete frontal and occipitoparietal periventricular white matter locations may be associated with a mobility disorder of aging.

Cited by 116 publications

References 20 publications

In-home walking speeds and variability trajectories associated with mild cognitive impairment

In-home walking speeds and variability trajectories associated with mild cognitive impairment

Slow gait, white matter characteristics, and prior 10-year interleukin-6 levels in older adults

A fully automated method for quantifying and localizing white matter hyperintensities on MR images

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