The interrelationships between gait, cerebral small vessel disease (CSVD), and cognitive impairments in aging are not well-understood—despite their common co-occurrence.
Objective:
To systematically review studies of gait impairment in CSVD, pre-dementia, and dementia, and to identify key gaps for future research and novel pathways toward intervention.
Methods:
A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided search strategy was implemented in PubMed to identify relevant studies. Potential articles (n = 263) published prior to 1 December 2021 were screened by two reviewers. Studies with sample sizes >20 and including some adults over > 65 years (n = 202) were included.
Results:
The key findings were that (1) adverse gait and cognitive outcomes were associated with several (rather than select) CSVD pathologies distributed across the brain, and (2) poor gait and CSVD pathologies were more strongly associated with dementia with a vascular, rather than an Alzheimer’s disease-related, cause.
Discussion:
A better understanding of the interrelationships between gait performance in CSVD, pre-dementia, and dementia requires studies examining (1) comprehensive patterns in the clinical manifestations of CSVD, (2) racially/ethnically diverse samples, (3) samples followed for extended periods of time or across the adult life span, (4) non-traditional CSVD neuroimaging markers (e.g. resting-state functional magnetic resonance imaging (fMRI)), and (5) continuous (e.g. wearable sensors) and complex (e.g. dual-task) walking performance.
PageMJMcKenzieJEBossuytPM, et alThe PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Syst Rev2021; 10: n71.
2.
BalohRWYueQSocotchTMJacobsonKM.White matter lesions and disequilibrium in older people: I. Case-control comparison. Arch Neurol1995; 52: 970–974.
3.
BrileyDPWasayMSergentSThomasS.Cerebral white matter changes (leukoaraiosis), stroke, and gait disturbance. J Am Geriatr Soc1997; 45: 1434–1438.
4.
PohjasvaaraTMäntyläRYlikoskiRKasteMErkinjunttiT.Clinical features of MRI-defined subcortical vascular disease. Alzheimer Dis Assoc Disord2003; 17: 236–242.
5.
MorettiMCarlucciGDi CarloA, et alCorpus callosum atrophy is associated with gait disorders in patients with leukoaraiosis. Neurol Sci2005; 26: 61–66.
6.
KimYJKwonHKLeeJM, et alGray and white matter changes linking cerebral small vessel disease to gait disturbances. Neurology2016; 86: 1199–1207.
7.
OkroglicSWidmannCNUrbachHScheltensPHenekaMT.Clinical symptoms and risk factors in cerebral microangiopathy patients. PLoS ONE2013; 8: e53455.
8.
FlingBWDaleMLCurtzeCSmuldersKNuttJGHorakFB.Associations between mobility, cognition and callosal integrity in people with parkinsonism. NeuroImage Clin2016; 11: 415–422.
9.
DobryninaLAZabitovaMRShabalinaAA, et alMRI types of cerebral small vessel disease and circulating markers of vascular wall damage. Diagnostics2020; 10: 354.
10.
PodsiadloDRichardsonS.The timed “up & go”: a test of basic functional mobility for frail elderly persons. J Am Geriatr Soc1991; 39: 142–148.
11.
GuttmannCRBensonRWarfieldS, et alWhite matter abnormalities in mobility-impaired older persons. Neurology2000; 54: 1277–1283.
12.
BensonRRGuttmannCWeiX, et alOlder people with impaired mobility have specific loci of periventricular abnormality on MRI. Neurology2002; 58: 48–55.
13.
BrodoefelHRamachandranRPantolG, et alAssociation between linear measurements of corpus callosum and gait in the elderly. Eur Radiol2013; 23: 2252–2257.
14.
BhadeliaRAPriceLLTedescoKL, et alDiffusion tensor imaging, white matter lesions, the corpus callosum, and gait in the elderly. Stroke2009; 40: 3816–3820.
15.
DumurgierJCrivelloFMazoyerB, et alMRI atrophy of the caudate nucleus and slower walking speed in the elderly. NeuroImage2012; 60: 871–878.
16.
BolandzadehNLiu-AmbroseTAizensteinH, et alPathways linking regional hyperintensities in the brain and slower gait. NeuroImage2014; 99: 7–13.
IsekiKHanakawaTHashikawaK, et alGait disturbance associated with white matter changes: a gait analysis and blood flow study. NeuroImage2010; 49: 1659–1666.
19.
ZhouXZhangCLiL, et alAltered brain function in cerebral small vessel disease patients with gait disorders: a resting-state functional MRI study. Front Aging Neurosci2020; 12: 234.
20.
StarrJMLeaperSMurrayAD, et alBrain white matter lesions detected by magnetic resonance imaging are associated with balance and gait speed. J Neurol Neurosurg Psychiatry2003; 74: 94–98.
21.
RosanoCBrachJLongstrethWTJrNewmanAB.Quantitative measures of gait characteristics indicate prevalence of underlying subclinical structural brain abnormalities in high-functioning older adults. Neuroepidemiology2006; 26: 52–60.
22.
RosanoCBrachJStudenskiSLongstrethWTJrNewmanAB.Gait variability is associated with subclinical brain vascular abnormalities in high-functioning older adults. Neuroepidemiology2007; 29: 193–200.
23.
SrikanthVPhanTGChenJBeareRStapletonJMReutensDC.The location of white matter lesions and gait—a voxel-based study. Ann Neurol2010; 67: 265–269.
24.
De LaatKFVan NordenAGGonsRA, et alGait in elderly with cerebral small vessel disease. Stroke2010; 41: 1652–1658.
25.
De LaatKFTuladharAMVan NordenAGNorrisDGZwiersMPde LeeuwF-E.Loss of white matter integrity is associated with gait disorders in cerebral small vessel disease. Brain2010; 134: 73–83.
26.
MurrayMESenjemMLPetersenRC, et alFunctional impact of white matter hyperintensities in cognitively normal elderly subjects. Arch Neurol2010; 67: 1379–1385.
27.
SuNZhaiFFZhouLX, et alCerebral small vessel disease burden is associated with motor performance of lower and upper extremities in community-dwelling populations. Front Aging Neurosci2017; 9: 313.
28.
StijntjesMde CraenAJvan der GrondJMeskersCGSlagboomPEMaierAB.Cerebral microbleeds and lacunar infarcts are associated with walking speed independent of cognitive performance in middle-aged to older adults. Gerontology2016; 62: 500–507.
29.
CallisayaMLSrikanthVKLordSR, et alSub-cortical infarcts and the risk of falls in older people: combined results of TASCOG and Sydney MAS studies. Int J Stroke2014; 9: 55–60.
30.
EzzatiAKatzMJLiptonMLLiptonRBVergheseJ.The association of brain structure with gait velocity in older adults: a quantitative volumetric analysis of brain MRI. Neuroradiology2015; 57: 851–861.
31.
BlumenHMBrownLLHabeckC, et alGray matter volume covariance patterns associated with gait speed in older adults: a multi-cohort MRI study. Brain Imaging Behav2019; 13: 446–460.
32.
TripathiSVergheseJBlumenHM.Gray matter volume covariance networks associated with dual-task cost during walking-while-talking. Hum Brain Mapp2019; 40: 2229–2240.
33.
VergheseJHoltzerRLiptonRBWangC.Mobility stress test approach to predicting frailty, disability, and mortality in high-functioning older adults. J Am Geriatr Soc2012; 60: 1901–1905.
34.
YuanJBlumenHMVergheseJHoltzerR.Functional connectivity associated with gait velocity during walking and walking-while-talking in aging: a resting-state fMRI study. Hum Brain Mapp2015; 36: 1484–1493.
35.
HouYLiYYangSQinWYangLHuW.Gait impairment and upper extremity disturbance are associated with total magnetic resonance imaging cerebral small vessel disease burden. Front Aging Neurosci2021; 13: 640844.
36.
CallisayaMLBeareRPhanTGChenJSrikanthVK.Global and regional associations of smaller cerebral gray and white matter volumes with gait in older people. PLoS ONE2014; 9: e84909.
37.
RosanoCAizensteinHBrachJLongenbergerAStudenskiSNewmanAB.Gait measures indicate underlying focal gray matter atrophy in the brain of older adults. J Gerontol A Biol Sci Med Sci2008; 63: 1380–1388.
38.
RosanoCAizensteinHJStudenskiSNewmanAB.A regions-of-interest volumetric analysis of mobility limitations in community-dwelling older adults. J Gerontol A Biol Sci Med Sci2007; 62: 1048–1055.
39.
JayakodyOBreslinMBeareRSrikanthVKBlumenHMCallisayaML.The associations between grey matter volume covariance patterns and gait variability—the Tasmanian Study of Cognition and Gait. Brain Topogr2021; 34: 478–488.
40.
JayakodyOBreslinMBeareRBlumenHMSrikanthVKCallisayaML.Regional associations of cortical thickness with gait variability —the Tasmanian Study of Cognition and Gait. J Gerontol B Biol Sci2020; 75: 1537–1544.
41.
SilbertLNelsonCHowiesonDMooreMMKayeJA.Impact of white matter hyperintensity volume progression on rate of cognitive and motor decline. Neurology2008; 71: 108–113.
42.
SoumaréAElbazAZhuY, et alWhite matter lesions volume and motor performances in the elderly. Ann Neurol2009; 65: 706–715.
43.
CallisayaMLBeareRPhanTG, et alBrain structural change and gait decline: a longitudinal population-based study. J Am Geriatr Soc2013; 61: 1074–1079.
44.
WilleyJZScarmeasNProvenzanoFALuchsingerJAMayeuxRBrickmanAM.White matter hyperintensity volume and impaired mobility among older adults. J Neurol2013; 260: 884–890.
45.
van der HolstHMTuladharAMZerbiV, et alWhite matter changes and gait decline in cerebral small vessel disease. NeuroImage Clin2018; 17: 731–738.
46.
Van Der HolstHMVan UdenIWDe LaatKF, et alBaseline cerebral small vessel disease is not associated with gait decline after five years. Mov Disord Clin Pract2017; 4: 374–382.
47.
AnnweilerCBeauchetOBarthaR, et alMotor cortex and gait in mild cognitive impairment: a magnetic resonance spectroscopy and volumetric imaging study. Brain2013; 136: 859–871.
48.
AnnweilerCBeauchetOBarthaRMontero-OdassoM and WALK Team-Working Group Angers-London for Knowledge. Slow gait in MCI is associated with ventricular enlargement: results from the Gait and Brain Study. J Neural Transm2013; 120: 1083–1092.
49.
DoiTBlumenHMVergheseJ, et alGray matter volume and dual-task gait performance in mild cognitive impairment. Brain Imaging Behav2017; 11: 887–898.
50.
BlumenHMSchwartzEAllaliG, et alCortical thickness, volume, and surface area in the motoric cognitive risk syndrome. J Alzheimers Dis2021; 81: 651–665.
51.
BlumenHMAllaliGBeauchetOLiptonRBVergheseJ.A gray matter volume covariance network associated with the motoric cognitive risk syndrome: a multicohort MRI study. J Gerontol A Biol Sci2019; 74: 884–889.
52.
WangNAllaliGKesavadasC, et alCerebral small vessel disease and motoric cognitive risk syndrome: results from the Kerala-Einstein study. J Alzheimers Dis2016; 50: 699–707.
53.
StaekenborgSSvan der FlierWMvan StraatenECLaneRBarkhofFScheltensP.Neurological signs in relation to type of cerebrovascular disease in vascular dementia. Stroke2008; 39: 317–322.
54.
AllaliGMontembeaultMSajA, et alStructural brain volume covariance associated with gait speed in patients with amnestic and non-amnestic mild cognitive impairment: a double dissociation. J Alzheimers Dis2019; 71: S29–S39.
55.
BoylePWilsonRAggarwalN, et alParkinsonian signs in subjects with mild cognitive impairment. Neurology2005; 65: 1901–1906.
56.
VergheseJRobbinsMHoltzerR, et alGait dysfunction in mild cognitive impairment syndromes. J Am Geriatr Soc2008; 56: 1244–1251.
AllanLMBallardCGBurnDJKennyRA.Prevalence and severity of gait disorders in Alzheimer’s and non-Alzheimer’s dementias. J Am Geriatr Soc2005; 53: 1681–1687.
59.
AllaliGAnnweilerCBlumenHM, et alGait phenotype from mild cognitive impairment to moderate dementia: results from the GOOD initiative. Eur J Neurol2016; 23: 527–541.
60.
DodgeHMattekNAustinDHayesTLKayeJA.In-home walking speeds and variability trajectories associated with mild cognitive impairment. Neurology2012; 78: 1946–1952.
61.
TanakaAOkuzumiHKobayashiIMuraiNMeguroKNakamuraT.Gait disturbance of patients with vascular and Alzheimer-type dementias. Percept Mot Skills1995; 80: 735–738.
62.
FritzNEKegelmeyerDAKloosAD, et alMotor performance differentiates individuals with Lewy body dementia, Parkinson’s and Alzheimer’s disease. Gait Posture2016; 50: 1–7.
63.
GillainSWarzeeELekeuF, et alThe value of instrumental gait analysis in elderly healthy, MCI or Alzheimer’s disease subjects and a comparison with other clinical tests used in single and dual-task conditions. Ann Phys Rehabil Med2009; 52: 453–474.
64.
MacAulayRKWagnerMTSzelesDMilanoNJ.Improving sensitivity to detect mild cognitive impairment: cognitive load dual-task gait speed assessment. J Int Neuropsychol Soc2017; 23: 493–501.
65.
XieHWangYTaoSHuangSZhangCLvZ.Wearable sensor-based daily life walking assessment of gait for distinguishing individuals with amnestic mild cognitive impairment. Front Aging Neurosci2019; 11: 285.
66.
GhoraaniBBoettcherLNHssayeniMDRosenfeldAToleaMIGalvinJE.Detection of mild cognitive impairment and Alzheimer’s disease using dual-task gait assessments and machine learning. Biomed Signal Process Control2021; 64: 102249.
67.
BeauchetOAllaliGThierySGautierJFantinoBAnnweilerC.Association between high variability of gait speed and mild cognitive impairment: a cross-sectional pilot study. J Am Geriatr Soc2011; 59: 1973–1974.
68.
NadkarniNKMawjiEMcIlroyWEBlackSE.Spatial and temporal gait parameters in Alzheimer’s disease and aging. Gait Posture2009; 30: 452–454.
69.
MielkeMMRobertsROSavicaR, et alAssessing the temporal relationship between cognition and gait: slow gait predicts cognitive decline in the Mayo Clinic Study of Aging. J Gerontol A Biol Sci Med Sci2012; 68: 929–937.
70.
SavicaRWennbergAMHagenC, et alComparison of gait parameters for predicting cognitive decline: the Mayo Clinic Study of Aging. J Alzheimers Dis2017; 55: 559–567.
71.
GaleCRAllerhandMSayerAACooperCDearyIJ.The dynamic relationship between cognitive function and walking speed: the English Longitudinal Study of Ageing. Age2014; 36: 9682–9611.
72.
JayakodyOBreslinMSrikanthVKCallisayaML.Gait characteristics and cognitive decline: a longitudinal population-based study. J Alzheimers Dis2019; 71: S5–S14.
73.
RossoALMettiALFaulknerK, et alComplex walking tasks and risk for cognitive decline in high functioning older adults. J Alzheimers Dis2019; 71: S65–S73.
74.
BeauchetOLaunayCPSekhonH, et alAssociation of increased gait variability while dual tasking and cognitive decline: results from a prospective longitudinal cohort pilot study. Geroscience2017; 39: 439–445.
75.
MarquisSMooreMMHowiesonDB, et alIndependent predictors of cognitive decline in healthy elderly persons. Arch Neurol2002; 59: 601–606.
VergheseJLiptonRBHallCBKuslanskyGKatzMJBuschkeH.Abnormality of gait as a predictor of non-Alzheimer’s dementia. N Engl J Med2002; 347: 1761–1768.
78.
DumurgierJArtaudFTouraineC, et alGait speed and decline in gait speed as predictors of incident dementia. J Gerontol A Biol Sci2017; 72: 655–661.
79.
Abellan van KanGRollandYGillette-GuyonnetS, et alGait speed, body composition, and dementia. The EPIDOS-Toulouse cohort. J Gerontol A Biol Sci Med Sci2012; 67: 425–432.
80.
VergheseJWangCLiptonRBHoltzerRXueX.Quantitative gait dysfunction and risk of cognitive decline and dementia. J Neurol Neurosurg Psychiatry2007; 78: 929–935.
81.
CeïdeMEAyersEILiptonRVergheseJ.Walking while talking and risk of incident dementia. Am J Geriatr Psychiatry2018; 26: 580–588.
82.
Montero-OdassoMSarquis-AdamsonYSpeechleyM, et alAssociation of dual-task gait with incident dementia in mild cognitive impairment: results from the gait and brain study. JAMA Neurol2017; 74: 857–865.
83.
YakushijiYWilsonDAmblerG, et alDistribution of cerebral microbleeds in the East and West: individual participant meta-analysis. Neurology2019; 92: e1086–e1097.
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