Volume 71, Supplement 1, IN PRESS

Supplement: Gait Disorders in Alzheimer’s Disease and Other Dementias (Guest Editors: Manuel Montero-Odasso and George Perry)

Manuel Montero-Odasso, George Perry
Gait Disorders in Alzheimer’s Disease and Other Dementias: There Is Something in the Way You Walk

Oshadi Jayakody, Monique Breslin, Velandai Srikanth, Michele Callisaya
Gait Characteristics and Cognitive Decline: A Longitudinal Population-Based Study
Abstract: Background: Gait impairments are emerging predictors of dementia. However, few studies have examined whether gait predicts decline in specific cognitive domains. Objective: This study aimed to determine whether gait speed or other gait characteristics were associated with decline in specific cognitive domains and the role of the ApoE4 genotype in modifying these associations. Methods: Participants (n=410; mean age 72.0±7.0 years) were randomly selected from the electoral roll. At baseline, gait speed was assessed using the GAITRite walkway. Gait variability in step time, step length, step width, and double support time (DST) was calculated as the standard deviation of each measure across all steps. In a subsample (n=177), speed was measured under fast pace. The difference between usual and fast pace was calculated. At baseline, 2.6 and 4.6 years processing speed, memory, executive and visuospatial function were measured using neuropsychological tests. Multivariable mixed models were used to examine 1) associations between gait and the different cognitive domains over time and 2) whether the presence of ApoE4 genotype modified these associations. Results: Higher DST variability was associated with greater decline in memory (p for interaction 0.03). Slow gait speed predicted decline in processing speed (p=0.02) and visuospatial function (p=0.03). In ApoE4 carriers, gait speed also predicted decline in memory (p=0.02). Other gait characteristics did not predict decline in any of the cognitive domains (p>0.05). Conclusions: These findings add to the evidence that gait is an early indicator of cognitive decline, but that specific gait measures may provide diagnostic insights into specific cognitive domains.

Annika T.M. Toots, Morag E. Taylor, Stephen R. Lord, Jacqueline C.T. Close
Associations Between Gait Speed and Cognitive Domains in Older People with Cognitive Impairment
Abstract: Background: While gait has been linked with cognition, few studies have contrasted the strength of the relationships between gait speed and cognitive domains in people with cognitive impairment (CI). Objectives: Investigate the association between gait speed and global cognitive function and cognitive domains in older people with CI. Method: Three-hundred-and-nine community-dwelling people with CI (mean age 82 years, 47% female, and mean gait speed 0.62±0.23 m/s) were included using baseline data from the Intervention-Falls in Older Cognitively Impaired Study (iFOCIS). Usual gait speed (m/s) was measured over 2.4 m. Global cognitive function and individual cognitive domains (attention; memory; verbal fluency; language; visuospatial ability) were assessed using the Addenbrooke’s Cognitive Examination-III (ACE-III). Additionally, executive function was assessed using the Frontal Assessment Battery (FAB). Results: Participants mean±standard deviation ACE-III and FAB scores were 62.8±19.3 and 11.4±4.6, respectively. In separate multiple linear regression analyses adjusting for confounders, global cognitive function, and each cognitive domain, was significantly associated with gait speed. Executive function demonstrated the strongest association (FAB: standardized β=0.278, p<0.001, adjusted R2=0.431), and remained significantly associated with gait speed when adjusted for attention, memory, language, and visuospatial ability. Conclusion: In this large study of older people with CI, global cognition and each cognitive domain were associated with gait speed. Executive function had the strongest association, possibly reflecting the higher-level cognitive processes and complex motor task responses required for gait control. Future longitudinal studies are needed to explore the temporal relationships between declines in executive function and gait, and whether the facilitation of executive function lessens gait decline.

Antoine Langeard, Ramzi Houdeib, Kathia Saillant, Navin Kaushal, Maxime Lussier, Louis Bherer
Switching Ability Mediates the Age-Related Difference in Timed Up and Go Performance
Abstract: Age-related mobility and cognitive declines are closely linked, but their relationship is complex and needs to be further investigated. The present study aimed to test if cognition (processing speed, inhibition and switching performances) mediates the age-related difference in mobility. Mediation analyses were used to test whether processing speed, inhibition and switching performances on the Stroop test independently mediate the relationship between age and performances at the Timed Up and Go (TUG). Results revealed that only switching performances mediated the age-related difference in TUG (65.1% of the total effect) supporting the notion that executive control plays a critical role in older adults’ mobility.

Gilles Allali, Maxime Montembeault, Arnaud Saj, Chek Hooi Wong, Liam Anders Cooper-Brown, Louis Bherer, Olivier Beauchet
Structural Brain Volume Covariance Associated with Gait Speed in Patients with Amnestic and Non-Amnestic Mild Cognitive Impairment: A Double Dissociation
Abstract: Background: Gait impairment is observed in early stages of dementia, such as mild cognitive impairment (MCI), and is associated with morphological brain volume changes like atrophy. Objective: This study aims to characterize the brain’s grey matter (GM) volume covariance associated with gait speed in patients with amnestic mild cognitive impairment (aMCI) and non-amnestic MCI (naMCI). Methods: Gait speed was measured in 170 patients with MCI (age 72.0 ± 5.1; 36.8% female; 41 with aMCI and 130 naMCI) at normal and rapid gait speeds. Brain GM covariance networks were computed using voxel-based morphometry, using the main neural correlates of gait speed in each group and for each walking condition as seed regions. Results: Normal gait speed correlated with GM volume in the left frontal cortex in patients with aMCI, and in bilateral caudate and left putamen in those with naMCI. Rapid gait speed correlated with GM volume in the bilateral caudate and right cerebellum in naMCI, but without any GM region in aMCI. For normal gait speed, the left caudate nucleus volume in naMCI covaried with subcortico-frontal regions, while the left frontal cortex covaried with cortical regions involving the frontal cortex in aMCI. For rapid gait speed, subcortico-frontal regions were similar as for normal speed in naMCI. Conclusion: Brain GM volume covariance associated with gait speed varies according to the type of MCI; it involved subcortico-frontal regions for patients with naMCI and the frontal cortex in those with aMCI.

Elizabeth Dao, Ging-Yuek Robin Hsiung, Vesna Sossi, Roger Tam, Elham Shahinfard, Eloise Nicklin, Walid Al Keridy, Teresa Liu-Ambrose
Cerebral Amyloid-β Deposition Is Associated with Impaired Gait Speed and Lower Extremity Function
Abstract: Background: Impaired physical function (i.e., slowing of gait, muscle weakness, and poor mobility) is common in older adults with cognitive impairment and dementia. Evidence suggests that cerebral small vessel disease, specifically white matter lesions (WMLs), is associated with impaired physical function, but little research has been conducted to understand the specific role of AD pathology in physical outcomes. Objective: The objective of this study was to examine the association between cerebral amyloid-β (Aβ) deposition and physical function in people with cognitive impairment. Methods: Thirty participants completed an 11C Pittsburgh compound B (PIB) position emission tomography (PET) scan to quantify global Aβ deposition using standardized uptake value ratio (SUVR). We assessed usual gait speed, muscle strength of the lower extremities, balance, and functional mobility using the Short Physical Performance Battery (SPPB) and the Timed Up and Go Test (TUGT). Multiple linear regression analyses examined the association between Aβ and each measure of physical function, adjusting for age, body mass index, and WML load. Results: Global PIB SUVR was significantly associated with usual gait speed (β = -0.52, p = 0.01) and SPPB performance (β = -0.47, p = 0.02), such that increased Aβ deposition was associated with reduced performance on both measures. Global PIB SUVR was not significantly associated with TUGT performance (β = 0.32, p = 0.08). Conclusions: Cerebral Aβ deposition is associated with reduced gait speed, muscle strength, and balance in older adults with cognitive impairment independent of WML load. However, Aβ deposition was not associated with functional mobility.

Short Communication
Joe R. Nocera, Idil Arsik, Pinar Keskinocak, Amy Lepley-Flood, James J. Lah, Allan I. Levey, Greg J. Esper
The Feasibility of Measuring Gait in an Outpatient Cognitive Neurology Clinical Setting
Abstract: There is increasing interest in gait evaluations in clinical settings given the associations between gait and health outcomes. However, efforts examining implementation of gait evaluation in neurological clinics are lacking. Herein, gait implementation within a cognitive neurology clinic is presented. Over a 21-month period, a gait evaluation was collected on 81% of eligible patients (n=2,622; mean age 73.2 ± 9.5; age range 49-94 years; 47% female). Patients and staff reported being satisfied with the gait assessment. These finding have implications for gait evaluations in clinical settings and for clinical research aimed at understanding the impact of cognitive symptomatology on gait.

Stephanie Cullen, Michael Borrie, Susan Carroll, Yanina Sarquis-Adamson, Frederico Pieruccini-Faria, Scott McKay, Manuel Montero-Odasso
Are Cognitive Subtypes Associated with Dual-Task Gait Performance in a Clinical Setting?
Abstract: Background: Poor dual-task gait (walking while performing a cognitively demanding task) has been linked to progression to dementia in older adults with mild cognitive impairment (MCI). However, many of these findings come from research environments; gait performance across the cognitive spectrum has not previously been studied in a clinical setting. Objective: To examine whether patients from a memory clinic show differences in usual and dual-task gait speed and dual-task cost (DTC) based on cognitive diagnosis. Methods: Patients in the Aging Brain and Memory Clinic (London, ON) performed a usual gait walk and three dual-task gait walks: counting backwards by ones, naming animals, and counting backwards by seven (serial sevens) out loud. Patients were timed with a stopwatch over a six-meter path marked on the floor. One-way ANOVA was performed to evaluate associations between gait speed and DTC (%) across groups. Results: One hundred ninety-four patients with subjective cognitive impairment (SCI; n=46), MCI (n=77), or dementia (n=71) were assessed. Performance in usual (p<0.001) and dual-task gait speed (counting gait p<0.001; naming animals p<0.001; serial sevens p=0.004) decreased across the spectrum of cognitive impairment. Patients with dementia had significantly higher DTC in both counting gait (p=0.02) and naming animals (p=0.04) conditions compared with patients with SCI and MCI, who had statistically similar DTC in all conditions. Conclusion: Dual-task gait performance significantly declines across the cognitive spectrum in a clinical setting. Dual-task gait testing may be used in conjunction with traditional assessments for diagnosing cognitive impairments.

Andrea L. Rosso, Andrea L. Metti, Kimberly Faulkner, Mark Redfern, Kristine Yaffe, Lenore Launer, C. Elizabeth Shaaban, Neelesh K. Nadkarni, Caterina Rosano
Complex Walking Tasks and Risk for Cognitive Decline in High Functioning Older Adults
Abstract: Background: Performance on complex walking tasks may provide a screen for future cognitive decline. Objective: To identify walking tasks that are most strongly associated with subsequent cognitive decline. Methods: Community-dwelling older adults with Modified Mini-Mental State (3MS)>85 at baseline (n=223; mean age=78.7, 52.5% women, 25.6% black) completed usual-pace walking and three complex walking tasks (fast-pace, narrow-path, visuospatial dual-task). Slope of 3MS scores for up to 9 subsequent years (average=5.2) were used to calculate a cognitive maintainer (slope≥0) or decliner (< 0) outcome variable. Logistic regression models assessed associations between gait speeds and being a cognitive decliner. A sensitivity analysis in a subsample of individuals (n=66) confirmed results with adjudicated mild cognitive impairment (MCI) or dementia at 8-9 years post-walking assessment. Results: Cognitive decliners were 52.5% of the sample and on average were slower for all walking tasks compared to maintainers. In models adjusted for demographic and health variables, faster fast-pace (OR=0.87 per 0.1 m/s, 95% CI: 0.78, 0.97) and dual-task (OR=0.84 per 0.1 m/s, 95% CI: 0.73, 0.96) gait speeds were associated with lower likelihood of being a cognitive decliner. Usual-pace gait speed was not associated (OR=0.96 per 0.1 m/s, 95% CI: 0.85, 1.08). Results were nearly identical in analyses with adjudicated MCI or dementia as the outcome. Conclusion: Fast-pace and dual-task walking may provide simple and effective tools for assessing risk for cognitive decline in older individuals with high cognitive function. Such screening tools are important for strategies to prevent or delay onset of clinically meaningful change.

Hanna Bozkurt Åhman, Vilmantas Giedraitis, Ylva Cedervall, Björn Lennhed, Lars Berglund, Kevin McKee, Lena Kilander, Erik Rosendahl, Martin Ingelsson, Anna Cristina Åberg
Dual-Task Performance and Neurodegeneration: Correlations Between Timed Up-and-Go Dual-Task Test Outcomes and Alzheimer’s Disease Cerebrospinal Fluid Biomarkers
Abstract: Background: Tools to identify individuals at preclinical stages of dementia disorders are needed to enable early interventions. Alterations in dual-task performance have been detected early in progressive neurodegenerative disorders. Hence, dual-task testing may have the potential to screen for cognitive impairment caused by neurodegeneration. Exploring correlations between dual-task performance and biomarkers of neurodegeneration is therefore of interest. Objective: To investigate correlations between Timed Up-and-Go dual-task (TUGdt) outcomes and Alzheimer’s disease (AD) cerebrospinal fluid (CSF) biomarkers amyloid-β 42 (Aβ42,), total tau (t-tau), and phosphorylated tau (p-tau). Methods: This cross-sectional cohort study included 90 participants (age range 49-84 years) undergoing memory assessment, who were subsequently diagnosed with AD, other dementia disorders, mild cognitive impairment, or subjective cognitive impairment. TUG combined with “Naming Animals” (TUGdt NA) and “Months Backwards” (TUGdt MB), respectively, were used to assess dual-task performance. The number of correct words and time taken to complete the tests were measured. The CSF biomarkers were analysed by ELISA. Spearman’s rank correlation was used for analyses between TUGdt outcomes (TUGdt NA and TUGdt MB), and CSF biomarkers, adjusted for age, gender, and educational level. Results: The number of correct words, as well as the number of correct words/10 s during TUGdt NA correlated negatively to CSF t-tau and p-tau. No correlations were found between any time scores and CSF biomarkers. Conclusion: The correlations between TUGdt NA and t-tau and p-tau may indicate that neurodegeneration affects dual-task performance. Longitudinal studies are needed to further explore dual-task testing in screening for cognitive impairment due to neurodegeneration.

Sanish Sathyan, Emmeline Ayers, Tina Gao, Sofiya Milman, Nir Barzilai, Kenneth Rockwood, Joe Verghese
Frailty and Risk of Incident Motoric Cognitive Risk Syndrome
Abstract: Background: Frailty is highly prevalent among older adults, and associated with cognitive decline. Relationship between frailty and motoric cognitive risk syndrome (MCR), a pre-dementia syndrome characterized by the presence of subjective cognitive complaints and slow gait, is yet to be elucidated. Objective: To examine whether frailty increases the risk of developing incident MCR. Methods: We analyzed 641 adults, aged 65 and above, participating in the LonGenity study. Frailty was defined using a 41-point cumulative deficit frailty index (FI). MCR was diagnosed at baseline and annual follow-up visits using established criteria. Cox proportional hazard models were used to study the association of baseline frailty with incident MCR, and reported as hazard ratio (HR) with 95% confidence intervals (CI) adjusted for age, sex, and education. Results: At baseline, 70 participants (10·9%) had prevalent MCR. Of the remaining 571 non-MCR participants (mean age 75.0, 57.3% women), 70 developed incident MCR (median follow-up 2.6 years). Higher frailty scores at baseline were associated with an increased risk of incident MCR (HR for each 0.01 increase in the FI: 1.07; 95% CI 1.03–1.11; p = 0.0002). The result was unchanged even after excluding mobility related or chronic illnesses items from the FI as well as accounting for reverse causation, competing risk of death, baseline cognitive status, social vulnerability, and excluding participants with mild cognitive impairment syndrome. Conclusions: Higher levels of frailty increase risk for developing MCR and suggest shared mechanisms. This association merits further study to identify strategies to prevent cognitive decline.

Emmeline Ayers, Joe Verghese
Gait Dysfunction in Motoric Cognitive Risk Syndrome
Abstract: Background: Motoric cognitive risk (MCR) syndrome is a cognitive-motor syndrome associated with increased risk of transition to dementia. The clinical phenotype of MCR is not yet established. Objective: To systematically assess clinical gait abnormalities in older adults with MCR. Methods: Of the 522 community-dwelling non-demented adults aged 65 and older enrolled in the Central Control of Mobility in Aging study, 43 were diagnosed with MCR (47% women) based on presence of cognitive complaints and slow gait velocity (MCRv). Four additional subtypes of MCR were defined by substituting slow gait with short stride length (MCRsl, n=41), slow swing time (MCRsw, n=21), high stride length variability (MCRslv, n=24), and high swing time variability (MCRswv, n=25). The prevalence of clinical gait abnormalities (neurological or non-neurological) in MCR overall (n=81) and subtypes was studied. We also examined if gait abnormalities predicted further cognitive and functional decline in MCR cases. Results: Most clinical gait abnormalities were mild (walked without assistance) in the five MCR subtypes (44 to 61%). Neurological (range 24 to 46%) and non-neurological gait abnormalities (33 to 61%) were common in all MCR subtypes. Neurological gaits were most frequent in MCRsl (46%) and non-neurological gaits in MCRv (61%). Over a median 3.02 years of follow-up, presence of gait abnormality in MCR cases at baseline predicted worsening disability scores (estimate 0.17, p-value = 0.033) but not decline on cognitive scores (p-value = 0.056). Conclusion: Clinical gait abnormalities are common in MCR syndrome and its subtypes, and are associated with accelerated functional decline.

Susan W. Hunter, Alison Divine, Humberto Omana, Walter Wittich, Keith D. Hill, Andrew M. Johnson, Jeffrey D. Holmes
Effect of Learning to Use a Mobility Aid on Gait and Cognitive Demands in People with Mild to Moderate Alzheimer’s Disease: Part I – Cane
Abstract: Background: People with Alzheimer’s disease (AD) exhibit balance and walking impairments that increase falls risk. Prescription of a mobility aid is done to improve stability, yet also requires increased cognitive resources. Single-point canes require unique motor sequencing for safe use. The effect of learning to use a single-point cane has not been evaluated in people with AD. Objectives: In people with AD and healthy adult controls: 1) examine changes in gait while using a cane under various walking conditions; and 2) determine the cognitive and gait costs associated with concurrent cane walking while multi-tasking. Methods: Seventeen participants with AD (age 82.1±5.6 years) and 25 healthy controls (age 70.8±14.1 years) walked using a single-point cane in a straight (6 meter) and a complex (Figure of 8) path under three conditions: single-task (no aid), dual-task (walking with aid), and multi-task (walking with aid while counting backwards by ones). Velocity and stride time variability were recorded with accelerometers. Results: Gait velocity significantly slowed for both groups in all conditions and stride time variability was greater in the AD group. Overall, multi-tasking produced a decrease in gait and cognitive demands for both groups, with more people with AD self-prioritizing the cognitive task over the gait task. Conclusion: Learning to use a cane demands cognitive resources that lead to detrimental changes in velocity and stride time variability. This was most pronounced in people with mild to moderate AD. Future research needs to investigate the effects of mobility aid training on gait performance.

Susan W. Hunter, Alison Divine, Humberto Omana, Walter Wittich, Keith D. Hill, Andrew M. Johnson, Jeffrey D. Holmes
Effect of Learning to Use a Mobility Aid on Gait and Cognitive Demands in People with Mild to Moderate Alzheimer’s Disease: Part II – 4-Wheeled Walker
Abstract: Background: Cognitive deficits and gait problems are common and progressive in Alzheimer’s disease (AD). Prescription of a 4-wheeled walker is a common intervention to improve stability and independence, yet can be associated with an increased falls risk. Objectives: 1) To examine changes in spatial-temporal gait parameters while using a 4-wheeled walker under different walking conditions, and 2) to determine the cognitive and gait task costs of walking with the aid in adults with AD and healthy older adults. Methods: Twenty participants with AD (age 79.1±7.1 years) and 22 controls (age 68.5±10.7 years) walked using a 4-wheeled walker in a straight (6 m) and Figure of 8 path under three task conditions: single-task (no aid), dual-task (walking with aid), and multi-task (walking with aid while counting backwards by ones). Results: Gait velocity was statistically slower in adults with AD than the controls across all conditions (all p values <0.025). Stride time variability was significantly different between groups for straight path single task (p=0.045), straight path multi-task (p=0.031), and Figure of 8 multi-task (0.036). Gait and cognitive task costs increased while multi-tasking, with performance decrement greater for people with AD. None of the people with AD self-prioritized gait over the cognitive task while walking in a straight path, yet 75% were able to shift prioritization to gait in the complex walking path. Conclusion: Learning to use a 4-wheeled walker is cognitively demanding and any additional tasks increases the demands, further adversely affecting gait. The increased cognitive demands result in a decrease in gait velocity that is greatest in adults with AD. Future research needs to investigate the effects of mobility aid training on gait performance.

Morag E. Taylor, Matthew A. Brodie, Kimberley S. van Schooten, Kim Delbaere, Jacqueline C.T. Close, Narelle Payne, Lyndell Webster, Jessica Chow, Garth McInerney, Susan E. Kurrle, Stephen R. Lord
Older People with Dementia Have Reduced Daily-Life Activity and Impaired Daily-Life Gait When Compared to Age-Sex Matched Controls
Abstract: Understanding the characteristics of physical activity and daily-life gait in older people with dementia may help identify those at risk of negative health outcomes and inform targeted interventions. Questionnaires are often used to assess physical activity but may be more affected by recall bias in people with dementia and provide little information about daily-life gait characteristics. The aim of the study was to assess differences in daily-life activity levels and gait characteristics between community-dwelling older people with mild to moderate dementia (n=45; mean age 81±6 years, 42% female) and age-sex matched (1:2) cognitively-healthy controls (n=90). Participants wore a tri-axial accelerometer (DynaPort MoveMonitor, McRoberts) on their lower back for 7 days and were assessed on neuropsychological and physical performance. Compared to age-sex matched controls, participants with dementia demonstrated reduced daily-life activity (fewer steps per day, fewer and shorter walking bouts, and lower daily walk time) and walking intensity (reduced speed, stride length and cadence). Participants with dementia also had significantly increased within-walk variability (stride time) and less regular gait (higher sample entropy). Within the group of participants with dementia, higher daily-life activity levels were associated with greater self-reported physical activity and better executive function. Fallers (1+ falls past year) with dementia had significantly reduced daily-life activity and walking speed when compared to non-fallers with dementia. In conclusion, people with dementia are less active in daily-life and present with significant impairments across multiple gait domains when compared to age-sex matched controls. These findings highlight opportunities for targeted interventions and support further research to examine interventions aimed at addressing these deficits.