November/December 2014

Gait Speed Reflects Cognitive Function
By Emmeline Ayers, MPH; and Joe Verghese, MBBS
Today's Geriatric Medicine
Vol. 7 No. 6 P. 26

As populations around the world age over the coming decades, the number of cases of dementia is projected to triple by 2050, creating a major public health concern across the globe.1 Identifying older adults early in the course of dementia offers the best opportunity to introduce preventive interventions to reduce the global dementia burden. Moreover, efficient case detection can also help identify modifiable risk factors for dementia. Gait and cognition are controlled by brain circuits that are vulnerable to multiple age-related pathologies such as vascular and neurodegenerative diseases. Hence, clinical strategies that help clinicians identify gait and cognitive deficits early can lead to improved risk prediction and improve management of high-risk older patients.

Motoric Dysfunction
Gait speed, recognized as a vital sign in older adults, is a screening measure reflective of both physical and cognitive function.2 Motor impairments, including gait slowing and disorders, are increasingly common with advancing age and have been identified as risk factors for the development of cognitive decline and dementia.3,4 Although the simultaneous existence of both motor and cognitive impairments in older adults may simply reflect common unconnected age-related syndromes, studies have increasingly shown the coexistence of these two impairments is a strong indicator of underlying pathologies.5 For example, gait abnormalities have been found to be more common and significant predictors of dementia in those with mild cognitive impairment (MCI) compared with individuals without cognitive impairments.3 Therefore, incorporating measures of motor abnormalities, such as gait speed, into dementia risk assessments may help improve their predictive power for cognitive decline and dementia.

Recently increasing evidence indicates that gait slowing occurs early in the course of dementia and may precede declines in cognitive tests, indicating that gait speed may be a sensitive marker of cognitive changes in aging.6 However, despite evidence of the link between cognitive and motor performance, there is a paucity of research capitalizing on these findings to improve dementia risk assessments.

Cognitive Dysfunction and Predementia Syndromes
Cognitive disorders are categorized on a spectrum of cognitive decline, beginning with cognitive normalcy, moving to transitional states defined as predementia, and frequently ending in a dementia diagnosis. The transitional state of predementia is important for gaining insight into dementia processes and identifying individuals who are at high risk of converting to dementia. MCI is a widely used predementia syndrome; it is defined as cognitive impairment that is beyond age- and education-based norms on neuropsychological tests that assess abilities in one or more domains of cognitive function, and without interference in daily activities in nondemented individuals.7

Although many predementia syndromes have been previously described, most rely on procedures such as neuropsychological testing, biomarker assays, or neuroimaging. These procedures are costly and time consuming and may not be practical in many clinical settings around the world with limited resources.

Furthermore, incidence and prevalence rates of various clinical predementia syndromes are inconsistent across the world. This is likely due to the broad guidelines of diagnosis that have not been adapted to account for social and cultural differences across countries.1 This is particularly apparent in low- and middle-income countries where a low prevalence of amnestic-MCI has been reported, and suggests that many high-risk seniors are not being identified by the current predementia syndromes.1 There exists a critical need to improve the accessibility, efficiency, and specificity of clinical dementia risk assessments for high-risk patients who can benefit from preventive measures.

Motoric Cognitive Risk Syndrome
Motoric cognitive risk (MCR) syndrome, a newly described predementia assessment tool characterized by the presence of cognitive complaints and slow gait, provides a simple and accessible clinical method to assess individuals at risk of converting to dementia.8,9 MCR is operationalized using the following four criteria: subjective cognitive complaints, assessed using responses relating to cognitive status on standardized questionnaires; slow gait, defined as one standard deviation or more below age- and sex-appropriate mean gait speed value; ability to ambulate; and absence of a dementia diagnosis.8,9 The MCR criteria are built on those used to define MCI, substituting the cognitive test performance with gait speed and retaining the remaining operational criteria.

Global Prevalence of MCR
In a recent global study of more than 26,000 people aged 60 and older from 17 countries, MCR was common, affecting nearly one in 10 older adults.9 Increasing age was significantly associated with MCR; however, there were no differences between the sexes in MCR prevalence.9 Participants with MCR had a higher disease burden and performed worse on tests of global cognitive status than non-MCR participants.9 Participants with MCR at baseline had a 70% risk of major cognitive decline, which was defined as a change during follow-up in Mini-Mental State Examination (MMSE) scores of greater than three.9

The association of MCR with major cognitive decline remained strong even when the analysis was restricted to a subset of very cognitively healthy participants with baseline MMSE scores greater than 27,9 supporting the concept that MCR was capturing very early stages of the dementia process.

The figure below (derived from the recent global study9) illustrates that subjects with MCR at baseline were twice as likely to develop dementia over the next 10 years compared with those without an MCR diagnosis at baseline. In addition, subjects with MCR had more than twice the risk of developing Alzheimer's disease compared with those without MCR.

Adjustments to the individual criterion of MCR may help to refine, standardize, and enhance the current operational definition. For instance, instrumented gait assessments yield markers other than speed that could be used to improve the motoric criterion.10 However, utilization of instrumented methods comes at the cost of reduced accessibility in clinical settings but could be considered in research settings. In addition, we considered using a single uniform cutscore globally to define slow gait. Although this is a more simple strategy, single cutscores will not take into account variability in gait performance due to age, sex, or population differences.9 Self-report of mobility or walking difficulties suffers from lower sensitivity and specificity if being considered for use in defining slow gait.11

Cognitive complaints were assessed using a number of different standardized questionnaires in the global MCR prevalence study;9 however, use of a standardized method to assess subjective cognitive complaint questions, as well as use of informant reports may improve the specificity of this core MCR criterion.

Clinical Use
From a diagnostic perspective, MCR offers several benefits in detecting cognitive risk over other predementia assessment tools. Gait speed has high reliability between different protocols, excellent validity in predicting health outcomes, and is recommended as a geriatric vital sign.2 Nonprofessionals can easily be trained to measure gait speed, which requires a minimal amount of time and no specialized equipment. Therefore, the MCR approach is particularly useful in resource-poor settings and can help streamline high-risk individuals for further etiological investigations. The concept provides an accessible, efficient, and inexpensive clinical approach to identify high-risk individuals that can be easily applied in a variety of settings worldwide.

The MCR definition does not require cognitive tests for assigning the diagnosis. We have shown that there is partial overlap between participants diagnosed with MCR and MCI syndromes.8 These findings suggest that there are significant proportions of at-risk individuals who are not captured by any one predementia syndrome alone. Future studies could consider combining cognitive and motor criteria in settings where both these assessments are feasible to capture a larger pool of at-risk individuals.

Treatment and Interventions
Diagnosing MCR affords clinicians the opportunity to prescribe treatments early for underlying pathologies to reduce the risk of future development of dementia. The MCR diagnosis serves as a prompt for further evaluation of underlying conditions. For example, are vascular diseases present that may have caused the patient to present with simultaneous slow gait and cognitive complaints? Or are these cognitive-motor symptoms being caused by unconnected underlying causes? In the elderly, vascular lesions, which are strongly associated with cerebrovascular and cardiovascular diseases, can accumulate over time and account for decline in cognitive12 as well as gait domains.13 Determining the underlying cause of MCR provides clinicians and patients opportunities to modify lifestyle factors or start treatments that may reduce the risk of cognitive decline and dementia.

What if there are no treatable diseases or causes for MCR? The diagnosis of MCR also allows clinicians time to recommend preventive strategies that might be effective in reducing the future risk of dementia. It also provides both patients and caregivers an opportunity to prepare with the knowledge that identified patients are at higher risk of developing dementia. For example, cognitive remediation approaches using computerized programs or cognitive training have demonstrated an improvement in higher level brain function in cognitively normal older adults. A small study of 24 frail older adults who participated in a computerized cognitive remediation program showed an improvement in gait velocity compared with their baseline performance, suggesting that cognitive remediation could be a new nonpharmacological way of improving mobility performance.14 Moreover, research has shown that low physical activity is associated with increased dementia risk,15 indicating the importance of keeping physically and mentally active to delay the onset of, or even prevent, cognitive decline and dementia.

In general, the MCR concept provides a way of thinking about identifying risk and preventing dementia the same way we think about preventing other kinds of illnesses through maintaining a healthful lifestyle throughout the life course.

— Emmeline Ayers, MPH, is the research coordinator for the Division of Cognitive and Motor Aging (Neurology) and Geriatrics (Medicine) at Albert Einstein College of Medicine in New York.

— Joe Verghese, MBBS, is a professor of neurology and chief of the Integrated Divisions of Cognitive and Motor Aging (Neurology) and Geriatrics (Medicine) at Albert Einstein College of Medicine.

References
1. World Health Organization and Alzheimer's Disease International. Dementia: A Public Health Priority. http://www.who.int/mental_health/publications/dementia_report_2012/en/. Published 2012.

2. Guralnik JM, Ferrucci L, Pieper CF, et al. Lower extremity function and subsequent disability: consistency across studies, predictive models, and value of gait speed alone compared with the short physical performance battery. J Gerontol A Biol Sci Med Sci. 2000;55(4):M221-231.

3. Verghese J, Wang C, Lipton RB, Holtzer R, Xue X. Quantitative gait dysfunction and risk of cognitive decline and dementia. J Neurol Neurosurg Psychiatry. 2007;78(9):929-935.

4. Camicioli R, Howieson D, Oken B, Sexton G, Kaye J. Motor slowing precedes cognitive impairment in the oldest old. Neurology. 1998;50(5):1496-1498.

5. Holtzer R, Verghese J, Xue X, Lipton RB. Cognitive processes related to gait velocity: results from the Einstein Aging Study. Neuropsychology. 2006;20(2):215-223.

6. Buracchio T, Dodge HH, Howieson D, Wasserman D, Kaye J. The trajectory of gait speed preceding mild cognitive impairment. Arch Neurol. 2010;67(8):980-986.

7. Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med. 2004;256(3):183-194.

8. Verghese J, Wang C, Lipton RB, Holtzer R. Motoric cognitive risk syndrome and the risk of dementia. J Gerontol A Biol Sci Med Sci. 2013;68(4):412-418.

9. Verghese J, Annweiler C, Ayers E, et al. Motoric cognitive risk syndrome: multicountry prevalence and dementia risk. Neurology. 2014;83(8):718-726.

10. Hausdorff JM, Buchman AS. What links gait speed and MCI with dementia? A fresh look at the association between motor and cognitive function. J Gerontol A Biol Sci Med Sci. 2013;68(4):409-411.

11. Verghese J, Katz MJ, Derby CA, Kuslansky G, Hall CB, Lipton RB. Reliability and validity of a telephone-based mobility assessment questionnaire. Age Ageing. 2004;33(6):628-632.

12. Garde E, Mortensen EL, Krabbe K, Rostrup E, Larsson HBW. Relation between age-related decline in intelligence and cerebral white-matter hyperintensities in healthy octogenarians: a longitudinal study. Lancet. 2000;356(9230):628-634.

13. Rosano C, Brach J, Longstreth Jr WT, Newman AB. Quantitative measures of gait characteristics indicate prevalence of underlying subclinical structural brain abnormalities in high-functioning older adults. Neuroepidemiology. 2006;26(1):52-60.

14. Verghese J, Mahoney J, Ambrose AF, Wang C, Holtzer R. Effect of cognitive remediation on gait in sedentary seniors. J Gerontol A Biol Sci Med Sci. 2010;65(12):1338-1343.

15. Larson EB, Wang L, Bowen JD, et al. Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older. Ann Intern Med. 2006;144(2):73-81.