Age differences in brain activity in dorsolateral prefrontal cortex and supplementary motor areas during three different walking speed tasks.

BACKGROUND: Functional Near-Infrared Spectrometry (fNIRS) is a novel neuroimaging method that can detect brain activity during functional activities. The prefrontal cortex and supplemental motor area (SMA) are active during normal and fast speed walking. However, it is unclear how age difference affects brain activity in the dorsolateral prefrontal cortex (DLPFC) and SMA when walking at different speeds. The purpose of this study was to investigate the age differences in DLPFC and SMA activation during different walking speeds. METHOD: 10 younger (5F; 25 ± 8 y.o.) and 10 older adults (5F; 73 ± 6 y.o.) completed three visits in this study. Functional Near-Infrared Spectroscopy was used to detect hemodynamic changes on right and left hemispheres over the DLPFC and SMA during self-selected slow, preferred, and fast walking speeds. RESULTS: The results showed significantly increased DLPFC and SMA activity in older adults compared to younger adults when walking at preferred normal, fast, and slow speeds. Older adults also had a higher left DLPFC activation during preferred fast walking speed than younger adults. CONCLUSION: The results suggest that there are age differences in the DLPFC and SMA activation, with older adults demonstrating increased DLPFC and SMA activity across all walk conditions compared to younger adults. This may indicate older adults require higher cognitive demand and need to recruit indirect motor pathways when changing gait speed by increasing SMA activation.

Validation of perceived physical fatigability using the simplified-Chinese version of the Pittsburgh Fatigability Scale.

BACKGROUND: The Pittsburgh Fatigability Scale (PFS) was developed to capture fatigue and demand in a single tool, filling a gap that no validated questionnaire existed to measure perceived fatigability. Since fatigability is a more sensitive measure of a person's susceptibility to fatigue, we validated the simplified-Chinese version of the PFS among Chinese community-dwelling older adults. METHODS: This cross-sectional study was conducted in an urban community in Beijing between November 2018 and July 2019. The PFS was translated into simplified-Chinese by the translation, retro-translation method. Internal consistency of the Physical subscale of the PFS was evaluated by Cronbach's alpha. Convergent validity and discriminant validity were evaluated against physical performance measures (i.e., Short Physical Performance Battery & Timed Up and Go Test) and daily living performance (i.e., Barthel Index & Instrumental activity of daily living). RESULTS: Our study included 457 participants, including 182 men (39.8%) and 275 women (60.2%). The age range of the included participants was 61-96 years (mean = 84.8 years, SD = 5.8 years). The simplified-Chinese version of PFS Physical scores showed strong internal consistency (Cronbach's alpha = 0.81). Higher PFS Physical scores were associated with worse physical performance, and daily living performance (|correlation coefficient| range: 0.36-0.56, p < .001). Age- and sex-adjusted PFS Physical scores had moderate to good overall discrimination for correctly classifying people by their physical performance and daily living performance (AUCs range 0.70-0.87, p < .001). CONCLUSIONS: The PFS simplified-Chinese version is a valid instrument to assess perceived physical fatigability in Chinese-speaking older adults with good convergent validity. Thus, the PFS, with low cost and greater feasibility, is a desired tool to measure fatigability in large population studies.

A cross-sectional study of functional and metabolic changes during aging through the lifespan in male mice.

Aging is associated with distinct phenotypical, physiological, and functional changes, leading to disease and death. The progression of aging-related traits varies widely among individuals, influenced by their environment, lifestyle, and genetics. In this study, we conducted physiologic and functional tests cross-sectionally throughout the entire lifespan of male C57BL/6N mice. In parallel, metabolomics analyses in serum, brain, liver, heart, and skeletal muscle were also performed to identify signatures associated with frailty and age-dependent functional decline. Our findings indicate that declines in gait speed as a function of age and frailty are associated with a dramatic increase in the energetic cost of physical activity and decreases in working capacity. Aging and functional decline prompt organs to rewire their metabolism and substrate selection and toward redox-related pathways, mainly in liver and heart. Collectively, the data provide a framework to further understand and characterize processes of aging at the individual organism and organ levels.

Prediagnostic markers of idiopathic Parkinson's disease: Gait, visuospatial ability and executive function.

BACKGROUND: Idiopathic Parkinson's disease (IPD) has a long preclinical phase. RESEARCH QUESTION: This study assesses data on prediagnostic markers of IPD from a longitudinal, natural history study of aging. METHODS: Participants were selected from the database of the Baltimore Longitudinal Study of Aging, and included 10 prediagnosed IPD cases (eight men and two women) and 30 age and sex matched healthy controls. Patients with prediagnosed IPD had already had an assessment for IPD 2.6 ± 1.3 years (range 1.0-5.3 years) before the actual diagnosis, including: gait speed (six-meter corridor walk), spatio-temporal gait parameters using Vicon motion capture, balance, upper-limb motor skills, neuropsychological profile, and non-motor symptoms. RESULTS: Prediagnosed IPD cases compared to controls had slower gait speed (Δ=-0.13 m.s-1, p = 0.03) due to shorter step length (Δ=-5 cm, p = 0.004), worse visuospatial ability (card rotation test, Δ=-42, p = 0.0001) and worse executive function (category fluency test, Δ=-2.6, p = 0.04). SIGNIFICANCE: Our findings identify dimensions that merit further study as prediagnostic markers of Idiopathic Parkinson's disease to identify patients who might benefit from future neuroprotective therapy in order to delay, or prevent, clinical manifestations.

Of Aging Mice and Men: Gait Speed Decline Is a Translatable Trait, With Species-Specific Underlying Properties.

In the last two decades, great strides were made in our ability to extend the life span of model organisms through dietary and other manipulations. Survival curves provide evidence of altered aging processes but are uninformative on what lead to that increase in life span. Longitudinal assessments of health and function during intervention studies could help in the identification of predictive biomarkers for health and survival. Comparable biomarkers of healthspan are necessary to effectively translate interventions into human clinical trials. Gait speed is a well-established predictive biomarker of healthspan in humans for risk of disability, health outcomes and mortality, and is relatively simple to assess noninvasively in rodents. In this study, we assessed and compared gait speed in males from two species (mice and humans), from young adulthood to advanced old age. Although gait speed decreases nonlinearly with age in both species, the underlying drivers of this change in gait speed were different, with humans exhibiting a shortened step length, and mice displaying a decrease in cadence. Future longitudinal and interventional studies in mice should examine the predictive value of longitudinal declines in gait speed for health and survival.

ß-amyloid deposition is associated with gait variability in usual aging.

BACKGROUND: Higher amyloid burden predicts gait slowing in aging. Whether and which gait characteristics are associated with amyloid burden is less clear. Gait variability may be more sensitive to amyloid burden than mean gait characteristics. METHODS: In the Baltimore Longitudinal Study of Aging, 99 older participants without neurological disease had concurrent amyloid imaging and assessment of gait characteristics. ß-amyloid burden was measured using 11C-Pittsburgh compound B (PiB) positron emission tomography. PiB+/- status was based on a mean cortical distribution volume ratio (DVR) cut point. Gait characteristics were quantified by 3D motion analysis. Cross-sectional associations of PiB+/- status and DVR in motor-related regions (primary motor cortex, putamen, caudate) with gait characteristics were examined using linear regression, adjusted for age, sex, height, body mass index, gait speed and covariates (memory, executive function, visuoperceptual speed, depressive symptoms, cardiovascular risk, ApoE ε4, cerebrovascular burden, neurodegeneration, peripheral arterial disease, knee pain). RESULTS: Being PiB+ and higher DVR in motor-related regions were associated with greater gait speed variability, cadence variability, and gait cycle time variability but not with mean gait characteristics. Associations remained similar after adjustment for gait speed and covariates, except for memory, which attenuated associations of PiB+/- with cadence variability and gait cycle time variability. Associations were prominent in men but were not found in women. CONCLUSIONS: In usual aging, integrated temporal gait variability measures, but not mean performance, appear related to amyloid burden from cortical and motor-related cortical and subcortical regions, especially in men. Increased gait variability may be a subclinical indicator of increased amyloid burden in men.

Relationship Between Head-Turn Gait Speed and Lateral Balance Function in Community-Dwelling Older Adults.

OBJECTIVE: To determine and compare gait speed during head-forward and side-to-side head-turn walking in individuals with lower versus greater lateral balance. DESIGN: Cross-sectional study. SETTING: University research laboratory. PARTICIPANTS: Older adults (N=93; 42 men, 51 women; mean age ± SD, 73 ± 6.08y) who could walk independently. MAIN OUTCOME MEASURES: (1) Balance tolerance limit (BTL), defined as the lowest perturbation intensity where a multistep balance recovery pattern was first evoked in response to randomized lateral waist-pull perturbations of standing balance to the left and right sides, at 6 different intensities (range from level 2: 4.5-cm displacement at 180cm/s2 acceleration, to level 7: 22.5-cm displacement at 900cm/s2 acceleration); (2) gait speed, determined using an instrumented gait mat; (3) balance, evaluated with the Activities-specific Balance Confidence Scale; and (4) mobility, determined with the Timed Up and Go (TUG). RESULTS: Individuals with low versus high BTL had a slower self-selected head-forward gait speed and head-turn gait speed (P=.002 and P<.001, respectively); the magnitude of difference was greater in head-turn gait speed than head-forward gait speed (Cohen's d=1.0 vs 0.6). Head-turn gait speed best predicted BTL. BTL was moderately and positively related (P=.003) to the ABC Scale and negatively related (P=.017) to TUG. CONCLUSIONS: Head-turn gait speed is affected to a greater extent than head-forward gait speed in older individuals with poorer lateral balance and at greater risk of falls. Moreover, head-turn gait speed can be used to assess the interactions of limitations in lateral balance function and gait speed in relation to fall risk in older adults.

Single and multiple step balance recovery responses can be different at first step lift-off following lateral waist-pull perturbations in older adults.

An inability to recover lateral balance with a single step is predictive of future falls in older adults. This study investigated if balance stability at first step lift-off (FSLO) would be different between multiple and single stepping responses to lateral perturbations. 54 healthy older adults received left and right waist-pulls at 5 different intensities (levels 1-5). Crossover stepping responses at and above intensity level 3 that induced both single and multiple steps were analyzed. Whole-body center of mass (COM) and center of pressure (COP) positions in the medio-lateral direction with respect to the base of support were calculated. An inverted pendulum model was used to define the lateral stability boundary, which was also adjusted using the COP position at FSLO (functional boundary). No significant differences were detected in the COP positions between the responses at FSLO (p≥0.075), indicating no difference in the functional boundaries between the responses. Significantly smaller stability margins were observed at first step landing for multiple steps at all levels (p≤0.024), while stability margins were also significantly smaller at FSLO for level 3 and 4 (p≤0.048). These findings indicate that although reduced stability at first foot contact would be associated with taking additional steps, stepping responses could also be attributable to the COM motion state as early as first step lift-off, preceding foot contact. Perturbation-based training interventions aimed at improving the reactive control of stability would reduce initial balance instability at first step lift-off and possibly the consequent need for multiple steps in response to balance perturbations.

The brain map of gait variability in aging, cognitive impairment and dementia-A systematic review.

While gait variability may reflect subtle changes due to aging or cognitive impairment (CI), associated brain characteristics remain unclear. We summarize structural and functional neuroimaging findings associated with gait variability in older adults with and without CI and dementia. We identified 17 eligible studies; all were cross-sectional; few examined multiple brain areas. In older adults, temporal gait variability was associated with structural differences in medial areas important for lower limb coordination and balance. Both temporal and spatial gait variability were associated with structural and functional differences in hippocampus and primary sensorimotor cortex and structural differences in anterior cingulate cortex, basal ganglia, association tracts, and posterior thalamic radiation. In CI or dementia, some associations were found in primary motor cortex, hippocampus, prefrontal cortex and basal ganglia. In older adults, gait variability may be associated with areas important for sensorimotor integration and coordination. To comprehend the neural basis of gait variability with aging and CI, longitudinal studies of multiple brain areas are needed.

Role of Hip Abductor Muscle Composition and Torque in Protective Stepping for Lateral Balance Recovery in Older Adults.

OBJECTIVES: To examine differences in hip abductor strength and composition between older adults who primarily use medial step versus cross-step recovery strategies to lateral balance perturbations. DESIGN: Cross-sectional. SETTING: University research laboratory. PARTICIPANTS: Community-dwelling older adults (N=40) divided into medial steppers (n=14) and cross-steppers (n=26) based on the first step of balance recovery after a lateral balance perturbation. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Computed tomography scans to quantify lean tissue and intramuscular adipose tissue (IMAT) areas in the hip abductor, hip abductor isokinetic torque, and first step length. RESULTS: Medial steppers took medial steps in 71.1% of trials versus 4.6% of trials with cross-steps. The cross-steppers when compared with medial steppers, had lower hip abductor IMAT (24.7±0.7% vs 29.9±2.8%; P<.05), greater abductor torque (63.3±3.6Nm vs 48.4±4.1Nm; P<.01), and greater normalized first step length (.75±.03 vs .43±.08; P<.001). There was no difference in hip abductor lean tissue between the groups (P>.05). CONCLUSIONS: Our findings suggest that older adults who initially use a medial step to recover lateral balance have lower hip abductor torque and may be less able to execute a biomechanically more stable cross-step. This may be related to increased IMAT levels. Assessments and interventions for enhancing balance and decreasing fall risk should take the role of the hip abductor into account.