Pathways linking regional hyperintensities in the brain and slower gait.
OBJECTIVE
Cerebral white matter hyperintensities (WMHs) are involved in the evolution of impaired mobility and executive functions. Executive functions and mobility are also associated. Thus, WMHs may impair mobility directly, by disrupting mobility-related circuits, or indirectly, by disrupting circuits responsible for executive functions. Understanding the mechanisms underlying impaired mobility in late life will increase our capacity to develop effective interventions.


OBJECTIVE
To identify regional WMHs most related to slower gait and to examine whether these regional WMHs directly impact mobility, or indirectly by executive functions.


METHODS
Cross-sectional study. Twenty-one WMH variables (i.e., total WMH volume and WMHs in 20 tracts), gait speed, global cognition (Modified Mini-Mental State Examination; 3MS), and executive functions and processing speed (Digit-Symbol Substitution Test; DSST) were assessed. An L1-L2 regularized regression (i.e., Elastic Net model) identified the WMH variables most related to slower gait. Multivariable linear regression models quantified the association between these WMH variables and gait speed. Formal tests of mediation were also conducted.


METHODS
Community-based sample.


METHODS
Two hundred fifty-three adults (mean age: 83years, 58% women, 41% black).


METHODS
Gait speed.


RESULTS
In older adults with an average gait speed of 0.91m/sec, total WMH volume, WMHs located in the right anterior thalamic radiation (ATRR) and frontal corpuscallosum (CCF) were most associated with slower gait. There was a >10% slower gait for each standard deviation of WMH in CCF, ATRR or total brain (standardized beta in m/sec [p value]: -0.11 [p=0.046], -0.15 [p=0.007] and -0.14 [p=0.010], respectively). These associations were substantially and significantly attenuated after adjustment for DSST. This effect was stronger for WMH in CCF than for ATRR or total WMH (standardized beta in m/sec [p value]: -0.07 [p=0.190], -0.12 [p=0.024] and -0.10 [p=0.049], respectively). Adjustment for 3MS did not change these associations. The mediation analyses also found that DSST significantly mediated the associations between WMHs and gait speed. Our models were adjusted for age, sex, BMI, quadriceps strength, years of education, standing height, and prevalent hypertension.


CONCLUSIONS
The impact, direct or indirect, of WMHs on gait speed depended on their location and was mediated by executive function. Thus, multi-faceted interventions targeting executive control functions as well as motor functions, such as balance and strength training, are candidates to the maintenance of mobility across the lifespan.
Aging, Mobility, and Cognitive Neuroscience Laboratory, Department of Physical Therapy, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada; Brain Research Centre, University of British Columbia, Vancouver, BC, Canada; Experimental Medicine Graduate Program, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
Niousha
N
Bolandzadeh
Aging, Mobility, and Cognitive Neuroscience Laboratory, Department of Physical Therapy, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada; Brain Research Centre, University of British Columbia, Vancouver, BC, Canada.
Teresa
T
Liu-Ambrose
Geriatric Psychiatry Neuroimaging Laboratory, Faculty of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Howard
H
Aizenstein
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MD, USA.
Tamara
T
Harris
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MD, USA.
Lenore
L
Launer
Department of Psychiatry, University of California, San Francisco, CA, USA.
Kristine
K
Yaffe
Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Stephen B
SB
Kritchevsky
Center for Aging and Population Health, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
Anne
A
Newman
Center for Aging and Population Health, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: RosanoC@edc.pitt.edu.
Caterina
C
Rosano
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology; D015992:Body Mass Index; D001921:Brain / Q000473:pathology*; D059350:Chronic Pain / Q000473:pathology; D003071:Cognition; D003430:Cross-Sectional Studies; D004522:Educational Status; D005260:Female; D005684:Gait; D020233:Gait Disorders, Neurologic / Q000473:pathology*; D006801:Humans; D006973:Hypertension / Q000473:pathology; D008297:Male; D009434:Neural Pathways / Q000473:pathology*; D009483:Neuropsychological Tests; D066127:White Matter / Q000473:pathology
Cognitive function; Executive function; Gait speed; Mediation; Mobility; White matter hyperintensities