Understanding Gait in Aging - Part 1

Finding the Way Forward
 

Contributed by Richard Camicioli and Caterina Rosano

April 2012

Introduction

Gait disorders are common both with aging and in the setting of specific neurological disorders and are a risk factor for dependence, cognitive decline, falls and death. After age 70 years, 35% of people have abnormal gait (1); after the age 85 years gait changes are found in the majority of people. Therefore, gait change is as common as cognitive syndromes including mild cognitive impairment and dementia. While gait changes, specifically slowing and decreased stride length are common occurrence in older people, the presence of gait abnormalities suggests overt or covert pathologies (2). Both nervous system and non-nervous system changes (e.g., cardiorespiratory and musculoskeletal changes) contribute to age-related changes in gait. New molecular and imaging research tools and the recognition of neural systems involved in cognitive and motor function are opening the door to better understand the mechanisms of gait change in vivo.

The New 'Classic' Approach to Gait Disorders

The classic neurological approach to localization allows for the identification of levels of involvement leading to gait impairment. Nutt and colleagues rekindled this Sherringtonian approach in a seminal paper published in Neurology (3). Importantly these authors highlighted evidence for gait disorders that are not explained by basic sensori-motor deficits, termed high-level gait disorders in contrast to lower level and middle level disorders. With aging, changes at each level occur conspiring to reduce mobility. Common spatio-temporal changes that can be attributed to changes from various neurological disorders include slowing, decreased stride-length, a slightly widened base and decreased ground clearance. (4). Some of these features can be accounted for by shortened stride length, but in pathological disorders changes include reduced cadence (5). A recent review summarized and operationalized the clinical approach to analysis of gait impairment (6).

"Lower level" changes, include loss of muscle function, which can be caused by muscle or neuromuscular junction dysfunction (7). The term saropenia refers to muscle mass loss with aging. Sarcopenia, associated with muscle wasting and weakness, is one of the components of one definition of frailty that additionally includes weakness, exhaustion, decreased activity, and slowed walking (8). Loss of muscle mass is also seen with motor neuron loss may occur with progressive pathological loss found in amyotrophic lateral sclerosis, wherein gait change include contributions from both weakness and pyramidal system involvement (9). In older people changes may be significant enough to justify a specific diagnosis but may occur at a sub-clinical level as well.

Basic visual, vestibular and peripheral nerve function all contribute to maintaining balance and are critical to effective mobility. At the level of the peripheral nerve, neuropathy is common in older people, most commonly associated with diabetes or glucose intolerance, which can itself be challenging to detect. Visual and vestibular changes also occur with aging and can be a component of age-related mobility decline (10).

At the "middle level" Parkinson's and Huntington's diseases are the paradigmatic basal ganglia disorders. Early in the course Parkinson disease, gait is characterized by bradykinesia, with short stride length and slowing, distinct from other middle level gait disorders (11). As PD evolves freezing of gait occurs, which might be considered a "higher level" disorder. Alternate diagnoses, such as progressive supranuclear palsy, multiple system atrophy, normal pressure hydrocephalus and vascular parkinsonism are considerations if there is early freezing. Primary progressive freezing of gait can be an isolated phenomenon, albeit with varied pathology (12).

Gait in Huntington's disease at the earlier diagnostic stage features chorea and dystonia superimposed on relatively normal gait, but quantitative studies show changes in spatiotemporal characteristics (such as slowing, decreased stride length, increased base-width and increased step to step variability) over time, that is evident even in pre-manifest gene carriers (13). Clinical and subclinical cerebrovascular disease can lead to hemiparesis and paraparesis which are associated with signs of upper motor neuron dysfunction. Spinal cord lesions typically lead to a more straight-forward spastic gait with added contributions from sensory impairment. These changes lead to decreased mobility. Cerebellar gait is characterized by variable stepping; however increased variability in timing or step length can occur at multiple levels (14). Interestingly the gait in people with essential tremor shows features that overlap with cerebellar disorders (15). Increased gait variability is a feature that can be also seen with sub-cortical white matter disease, whether due to a vascular or non-vascular etiology (i.e., multiple sclerosis). The basis and "localization" of variability in gait parameters remains to be fully understood.

"High level" gait disorders, alternatively termed frontal-subcortical gait disorder, or gait apraxia (a term which is not favored) are not completely understood. Features that indicate a higher order gait disorder include disequilibrium unexplained by basic sensori-motor deficits, problems initiation or maintaining stepping (freezing), and difficulty with appropriate foot placement when standing up or walking. These deficits can be brought out when adaptation is demanded (stopping and starting, turning, changing directions) and ultimately impede locomotion. These deficits can be amplified by performing a simultaneous cognitive task (dual-tasking).

Increased variability may represent a higher level problem since gait variability is related to cognitive decline (16). Further evidence for variability being at least partially mediated by cognition is the impact of dual-tasking (performing a simultaneous cognitive task while walking) on gait variability, which is particularly evident in people with mild cognitive impairment and dementia (17).

Fear of falling can sometimes lead to odd gaits. For example individuals might walk as if they are on ice. (18). Less extreme cautious gait patterns can also be observed. Some of the changes seen in typical aging may represent appropriate adaptations to sensori-motor changes of aging. At the extreme, psychogenic gait disorders may represent a higher level gait problem related to volitional or subconscious implementation of an abnormal walk. These don't generally fit with recognizable gait patterns (19).

Summary

The phenomenological approach to gait disorders is important from a clinical perspective. Disease models may provide some insight into age-related changes. A full understanding of the mechanisms of gait dysfunction will require an integrative approach that takes descriptive and quantitative aspects of gait and links to neural and non-neural processes. Current imaging tools (see companion piece) are providing novel insights. Without a doubt these will evolve. Although animal models cannot fully recapitulate human bipedal walking they too will be helpful in providing mechanistic insights.

Table: Pathological and age-related neurological changes that might contribute to gait impairment in older people.

Level Specific Anatomic Localization Pathology Age-related correlate Gait Characteristics/
Associated Findings
Lower Muscle Myopathy Sarcopenia Waddling, slow/ Weakness, difficutlty rising from a chair
  Neuromuscular Junction Myasthenia gravis Neuromuscular junction dysfunction with aging Slow, weak, fatiguable/
Oculomotor impairment, ptosis, fatiguable proximal weakness
  Peripheral Nerve Neuropathy Sensorimotor changes with aging Slow, wide-based, steppage/
Hyporeflexia, weakness, senory deficit
  Motor neuron Amyotrophic lateral sclerosis Motor neuron loss Slow, spastic/
Upper and lower motor neuron signs
Middle White Matter Stroke, White matter disease Neurovascular coupling Increased variability, shortened stride length, wide based/
Hyperreflexia, pyramidal sighs
  Basal Ganglia Parkinson disease (Lewy body disease) Parkinsonism Decreased stride length, narrow base/
Bradykinesia, rigidity, tremor
  Basal Ganglia Huntington Disease "Senile" chorea Variable base, flinging movements with chorea superimposed/
Cognitive impairment, chorea
  Cerebellar Alcoholism, Multiple System Atrophy, Spinocerebellar ataxias, Essential tremor Age-related cerebellar atrophy Wide-based variable gait/Neuropathy (Alcohol), Parkinsonism and autonomic features (MSA)
High Frontal-subcortical gait Vascular, Progressive Supranuclear Palsy (PSP), Late Parkinson Disease, Normal Pressure Hydrocephalus Most likely related to pathology Impaired foot placement and stepping, Wide or variable base, dysquilibrium/
Cognitive impairment, frontal release signs, Vertical gaze palsy (PSP), pyramidal findings
  Gait Ignition Failure Vascular, PSP, Late Parkinson's Disease, Normal Pressure Hydrocephalus Patient with extreme cautious gait Inability to initiate walking, getting stuck on turns or after stopping. Festination/
Signs consistent with diagnosis, but can be seen in isolation
  Cautious Gait Fear of Falling Slowing with aging, to a lesser degree than seen with fear of falling Very slow walking, needing to hold onto items to walk/
Anxiety, Normal physical exam

 

Summary

While intervention studies to improve gait in older adults appear premature because of the sparse evidence on the pathogenesis of mobility impairment, the rapid methodological advancements and the recent intervention trials are very promising.  Specifically, there remains the need for longitudinal studies of mobility control that integrate both peripheral and central components to fully understand the mechanisms underlying motor control.

As a step in this direction the NIA in cooperation with the Gerontological Society of America is sponsoring a series of workshops coupled to a thematic scientific program. The goal of this new initiative is to bring clinical and basic science and to develop a paradigm for the understanding of gait disorders of aging.

There is strong evidence that generalized brain atrophy, small vessel disease and lacunar infarcts are associated with slower gait and balance difficulties in older adults who live in the community and are free from overt neurological disorders or gait complaints. These associations have been shown in cross-sectional [1-6]  [7] [8] [9, 10] [11] [12] and in longitudinal [13, 14] [15] [16] [17] studies.

In the past decade, there has been a strong impetus to apply advanced neuroimaging technology to further understand these relationships and examine the spatial distribution of the neuro-anatomical correlates of slowing gait. Cross-sectional investigations of connectivity and gait speed underscore the importance of tracts localized in the anterior lobes, around the ventricles, [18] [19] [20] [21-23] and in the corpus callosum [24] [25-27].   In addition to  smaller sensorimotor regions and cerebellum,[28] [29] slowing gait is associated with smaller frontal lobes[30] and with atrophy of regions known to be related to information processing [28, 29, 31]. One study also identified significant correlations with the memory-related hippocampal region[32] . Consistent with these initial structural neuroimaging investigations, functional neuroimaging studies have also found significant associations between basal ganglia and prefrontal motor regions in relationship with gait [33-35].

Next steps

The emerging concept of brain adaptation in older adults [39] and the rapid progress of neuroimaging technology have the potential to change the approach to study physical functional impairment in older adults. The use of stronger magnetic fields, including 3Tesla and 7 Tesla, remarkably increases the precision and spatial localization of abnormalities quantification.  The application of imaging methods in carefully characterized populations of older adults living in the community can promote future studies to shift current research and clinical practice paradigms in several ways. First, these neuroimaging markers can be related to cognitive and motor behaviors to advance our understanding of the underlying mechanisms of mobility control (e.g. via overall processing speed and/or through distinct pathways). Secondly, they can advance our intervention approaches to ameliorate gait, including pharmacological and behavioral strategies such as exercise and diet. Lastly, neuroimaging measures can be used as biomarkers to identify the individuals that might benefit the most from intervention and to quantify response to therapy - type and dose, and as newer targets of therapies.

What therapies deserve attention?

If the role of white matter abnormalities in determining physical functional loss is as prominent as studies suggest,   then intervention trials should focus on white matter biomarkers. Specific attention should be given to the fronto-parietal and subcortical areas, which are intrinsically vulnerable to damage, most likely due to poor collateral vascularization.[39, 40]   Recent findings that antihypertensive treatments stop or delay progression of small vessel disease,[41-44] and subsequent cognitive impairment,[45, 46] suggest the potential to prevent mobility impairment through hypertension control especially at younger and middle ages.  Additionally, there is the potential to use growth factors to stimulate production of new white matter cells even very late in age [47, 48].  White matter regeneration is already one of the main therapeutic targets in models of acute neuronal damage.[49, 50] Recent animal studies have shown that promoters of axonogenesis and of myelination have beneficial effects on behavioral measures and motor tasks.[47] Recent evidence [51] also points to the potential for cross-over benefits of therapies targeting different domains. Therefore, studies should explore whether psychological intervention (e.g. to improve processing speed) alone or combined with motor intervention could delay the trajectories of slowing gait.

References

    de Laat, K.F., et al., Cortical thickness is associated with gait disturbances in cerebral small vessel disease. Neuroimage, 2012. 59(2): p. 1478-84.
    de Laat, K.F., et al., Gait in elderly with cerebral small vessel disease. Stroke, 2010. 41(8): p. 1652-8.
    Hennerici, M.G., et al., Are gait disturbances and white matter degeneration early indicators of vascular dementia? Dementia, 1994. 5(3-4): p. 197-202.
    Murray, M.E., et al., Functional impact of white matter hyperintensities in cognitively normal elderly subjects. Arch Neurol, 2010. 67(11): p. 1379-85.
    Palm, W.M., et al., Ventricular dilation: association with gait and cognition. Ann Neurol, 2009. 66(4): p. 485-93.
    Baezner, H., et al., Association of gait and balance disorders with age-related white matter changes: the LADIS study. Neurology, 2008. 70(12): p. 935-42.
    Briley, D.P., et al., Cerebral white matter changes (leukoaraiosis), stroke, and gait disturbance. J Am Geriatr Soc, 1997. 45(12): p. 1434-8.
    Longstreth, W.T., Jr., et al., Incidence, manifestations, and predictors of worsening white matter on serial cranial magnetic resonance imaging in the elderly: the Cardiovascular Health Study. Stroke, 2005. 36(1): p. 56-61.
    Rosano, C., et al., Quantitative measures of gait characteristics indicate prevalence of underlying subclinical structural brain abnormalities in high-functioning older adults. Neuroepidemiology, 2006. 26(1): p. 52-60.
    Guo, X., et al., A population-based study on motor performance and white matter lesions in older women. J Am Geriatr Soc, 2000. 48(8): p. 967-70.
    Carmelli, D., et al., The joint effect of apolipoprotein E epsilon4 and MRI findings on lower-extremity function and decline in cognitive function. J Gerontol A Biol Sci Med Sci, 2000. 55(2): p. M103-9.
    Masdeu, J.C., et al., Brain white-matter changes in the elderly prone to falling. Arch Neurol, 1989. 46(12): p. 1292-6.
    Wolfson, L., et al., Accrual of MRI white matter abnormalities in elderly with normal and impaired mobility. J Neurol Sci, 2005. 232(1-2): p. 23-7.
    Rosano, C., et al., Subclinical brain magnetic resonance imaging abnormalities predict physical functional decline in high-functioning older adults. J Am Geriatr Soc, 2005. 53(4): p. 649-54.
    Baloh, R.W., S.H. Ying, and K.M. Jacobson, A longitudinal study of gait and balance dysfunction in normal older people. Arch Neurol, 2003. 60(6): p. 835-9.
    Whitman, G.T., et al., A prospective study of cerebral white matter abnormalities in older people with gait dysfunction. Neurology, 2001. 57(6): p. 990-4.
    Bazner, H., et al., Assessment of gait in subcortical vascular encephalopathy by computerized analysis: a cross-sectional and longitudinal study. J Neurol, 2000. 247(11): p. 841-9.
    Benson, R.R., et al., Older people with impaired mobility have specific loci of periventricular abnormality on MRI. Neurology, 2002. 58(1): p. 48-55.
    Starr, J.M., et al., Brain white matter lesions detected by magnetic resonance [correction of resosnance] imaging are associated with balance and gait speed. J Neurol Neurosurg Psychiatry, 2003. 74(1): p. 94-8.
    Camicioli, R., et al., Age-related brain changes associated with motor function in healthy older people. J Am Geriatr Soc, 1999. 47(3): p. 330-4.
    Silbert, L.C., et al., Impact of white matter hyperintensity volume progression on rate of cognitive and motor decline. Neurology, 2008. 71(2): p. 108-13.
    Soumare, A., et al., White matter lesions volume and motor performances in the elderly. Ann Neurol, 2009. 65(6): p. 706-15.
    Srikanth, V., et al., Cerebral white matter lesions, gait, and the risk of incident falls: a prospective population-based study. Stroke, 2009. 40(1): p. 175-80.
    Ryberg, C., et al., Clinical significance of corpus callosum atrophy in a mixed elderly population. Neurobiol Aging, 2006.
    de Laat, K.F., et al., Loss of white matter integrity is associated with gait disorders in cerebral small vessel disease. Brain, 2011. 134(Pt 1): p. 73-83.
    Moretti, M., et al., Corpus callosum atrophy is associated with gait disorders in patients with leukoaraiosis. Neurol Sci, 2005. 26(2): p. 61-6.
    Moscufo, N., et al., Brain regional lesion burden and impaired mobility in the elderly. Neurobiol Aging, 2011. 32(4): p. 646-54.
    Rosano, C., Aizenstein H, Brach J, Longenberger A, Studenski S, Newman AB., Special article: gait measures indicate underlying focal gray matter atrophy in the brain of older adults. J Gerontol A Biol Sci Med Sci, 2008 63(12): p. 1380-8.
    Rosano, C., et al., A regions-of-interest volumetric analysis of mobility limitations in community-dwelling older adults. J Gerontol A Biol Sci Med Sci, 2007. 62(9): p. 1048-55.
    Novak, V., et al., White matter hyperintensities and dynamics of postural control. Magn Reson Imaging, 2009. 27(6): p. 752-9.
    Sparto, P.J., et al., Delays in auditory-cued step initiation are related to increased volume of white matter hyperintensities in older adults. Exp Brain Res, 2008. 188(4): p. 633-40.
    Zimmerman, M.E., et al., MRI- and MRS-derived hippocampal correlates of quantitative locomotor function in older adults. Brain Res, 2009. 1291: p. 73-81.
    Ben Salem, D., et al., Brain flexibility and balance and gait performances mark morphological and metabolic abnormalities in the elderly. J Clin Neurosci, 2008. 15(12): p. 1360-5.
    Iseki, K., et al., Gait disturbance associated with white matter changes: a gait analysis and blood flow study. Neuroimage, 2010. 49(2): p. 1659-66.
    la Fougere, C., et al., Real versus imagined locomotion: a [18F]-FDG PET-fMRI comparison. Neuroimage, 2010. 50(4): p. 1589-98.
    Rosano, C., et al., Gait variability is associated with subclinical brain vascular abnormalities in high-functioning older adults. Neuroepidemiology, 2007. 29(3-4): p. 193-200.
    Rosano, C., et al., Magnetization transfer imaging, white matter hyperintensities, brain atrophy and slower gait in older men and women, Epub 2008 Sep 7. Neurobiol Aging, 2010. 31(7): p. 1197-204.
    Zheng, J.J., et al., Brain White Matter Hyperintensities, Executive Dysfunction, Instability, and Falls in Older People: A Prospective Cohort Study. J Gerontol A Biol Sci Med Sci, 2012.
    Park, D.C. and P. Reuter-Lorenz, The adaptive brain: aging and neurocognitive scaffolding. Annu Rev Psychol, 2009. 60: p. 173-96.
    Peters, A., The effects of normal aging on myelin and nerve fibers: a review. J Neurocytol, 2002. 31(8-9): p. 581-93.
    Applegate, W.B., et al., Impact of the treatment of isolated systolic hypertension on behavioral variables. Results from the systolic hypertension in the elderly program. Arch Intern Med, 1994. 154(19): p. 2154-60.
    Dufouil, C., et al., Longitudinal study of blood pressure and white matter hyperintensities: the EVA MRI Cohort. Neurology, 2001. 56(7): p. 921-6.
    Forette, F., et al., Prevention of dementia in randomised double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial. Lancet, 1998. 352(9137): p. 1347-51.
    de Leeuw, F.E., et al., Aortic atherosclerosis at middle age predicts cerebral white matter lesions in the elderly. Stroke, 2000. 31(2): p. 425-9.
    Haag, M.D., et al., Duration of antihypertensive drug use and risk of dementia: A prospective cohort study. Neurology, 2009. 72(20): p. 1727-34.
    Waldstein, S.R., et al., Nonlinear relations of blood pressure to cognitive function: the Baltimore Longitudinal Study of Aging. Hypertension, 2005. 45(3): p. 374-9.
    Papadopoulos, C.M., et al., Dendritic plasticity in the adult rat following middle cerebral artery occlusion and Nogo-a neutralization. Cereb Cortex, 2006. 16(4): p. 529-36.
    Rosano, C., E. Felipe-Cuervo, and P.M. Wood, Regenerative potential of adult O1+ oligodendrocytes. Glia, 1999. 27(3): p. 189-202.
    Benowitz, L.I., D.E. Goldberg, and N. Irwin, Inosine stimulates axon growth in vitro and in the adult CNS. Prog Brain Res, 2002. 137: p. 389-99.
    Park, E., A.A. Velumian, and M.G. Fehlings, The role of excitotoxicity in secondary mechanisms of spinal cord injury: a review with an emphasis on the implications for white matter degeneration. J Neurotrauma, 2004. 21(6): p. 754-74.
    Segev-Jacubovski, O., Herman T, Yogev-Seligmann G, Mirelman A, Giladi N, Hausdorff JM., The interplay between gait, falls and cognition: can cognitive therapy reduce fall risk? Expert Rev Neurother, 2011. 11(7): p. 1057-75.
 

About Dr. Rosano, MD, MPH

Dr. RosanoDr. Rosano has obtained her MD from the School of Medicine, Palermo, Italy, in 1995 and her Master in Epidemiology from the Graduate School of Public Health at the University of Pittsburgh in 2003. Dr. Rosano is the PI of the e-BRAIN research group (www.epidemiology.pitt.edu/rosano.asp).

The E-BRAIN group investigates the interactions and synergisms between brain structure and function in relationship with mobility impairment in aging. In the E-BRAIN projects, Dr. Rosano applies cutting-edge neuroimaging technology to precisely identify early subclinical markers of brain abnormalities in large population studies with comprehensive information on health-related factors and determinants of mobility impairment. Accordingly, Dr. Rosano's work integrates three complementary approaches: a) quantify markers of brain abnormalities related to slowing in cognitive and physical domains; b) characterize the mechanisms underlying these relationships; c) identify the modifiable risk factors and causes of such brain changes.

"The results of these projects have the potential to augment our understanding of brain aging and l contribute to the discovery of new approaches to the promotion of survival free from disabilities." - Dr. Rosano


About Dr. Richard Camicioli, MD

Dr. CamicioliRichard Camicioli is a Geriatric Neurologist with an interest in both cognitive and movement disorders. He obtained his MDCM from McGill University in 1987 and completed his neurology residency at McGill in 1991. He then began a VA Fellowship in Geriatric Neurology at the Oregon Health and Sciences University and the Portland VA Medical Center. He then developed an interest in the relationship between motor function and cognition.

This led to work with the Oregon Brain Aging study. Since coming to the University of Alberta, he has focused on cognitive decline in people with Parkinson's disease and has continued work with older "controls." Recently he has rekindled studying people with mild cognitive impairment in order to define clinically distinct phenotypes.

Top

We use cookies to give you the best possible experience with our website. These cookies are also used to ensure we show you content that is relevant to you. If you continue without changing your settings, you are agreeing to our use of cookies to improve your user experience. You can click the cookie settings link on our website to change your cookie settings at any time. Note: The MDS site uses related multiple domains, including mds.movementdisorders.org and mds.execinc.com. This cookie policy only covers the primary movementdisorders.org and mdscongress.org domain. Please refer to the MDS Privacy Policy for information on how to configure cookies for all other domains on the MDS site.
Cookie PolicyPrivacy Notice