Slow gait speed – an indicator of lower cerebral vasoreactivity in type 2 diabetes mellitus

Objective: Gait speed is an important predictor of health that is negatively affected by aging and type 2 diabetes. Diabetes has been linked to reduced vasoreactivity, i.e., the capacity to regulate cerebral blood flow in response to CO2 challenges. This study aimed to determine the relationship between cerebral vasoreactivity and gait speed in older adults with and without diabetes. Research design and methods: We studied 61 adults with diabetes (65 ± 8 years) and 67 without diabetes (67 ± 9 years) but with similar distribution of cardiovascular risk factors. Preferred gait speed was calculated from a 75 m walk. Global and regional perfusion, vasoreactivity and vasodilation reserve were measured using 3-D continuous arterial spin labeling MRI at 3 Tesla during normo-, hyper- and hypocapnia and normalized for end-tidal CO2. Results: Diabetic participants had slower gait speed as compared to non-diabetic participants (1.05 ± 0.15 m/s vs. 1.14 ± 0.14 m/s, p < 0.001). Lower global vasoreactivity (r2adj = 0.13, p = 0.007), or lower global vasodilation reserve (r2adj = 0.33, p < 0.001), was associated with slower walking in the diabetic group independently of age, BMI and hematocrit concentration. For every 1 mL/100 g/min/mmHg less vasodilation reserve, for example, gait speed was 0.05 m/s slower. Similar relationships between vasodilation reserve and gait speed were also observed regionally within the cerebellum, frontal, temporal, parietal, and occipital lobes (r2adj = 0.27–0.33, p < 0.0001). In contrast, vasoreactivity outcomes were not associated with walking speed in non-diabetic participants, despite similar vasoreactivity ranges across groups. Conclusion: In the diabetic group only, lower global vasoreactivity was associated with slower walking speed. Slower walking in older diabetic adults may thus hallmark reduced vasomotor reserve and thus the inability to increase perfusion in response to greater metabolic demands during walking

Multi-Scale Glycemic Variability: A Link to Gray Matter Atrophy and Cognitive Decline in Type 2 Diabetes

Objective: Type 2 diabetes mellitus (DM) accelerates brain aging and cognitive decline. Complex interactions between hyperglycemia, glycemic variability and brain aging remain unresolved. This study investigated the relationship between glycemic variability at multiple time scales, brain volumes and cognition in type 2 DM. Research Design and Methods Forty-three older adults with and 26 without type 2 DM completed 72-hour continuous glucose monitoring, cognitive tests and anatomical MRI. We described a new analysis of continuous glucose monitoring, termed Multi-Scale glycemic variability (Multi-Scale GV), to examine glycemic variability at multiple time scales. Specifically, Ensemble Empirical Mode Decomposition was used to identify five unique ultradian glycemic variability cycles (GVC1–5) that modulate serum glucose with periods ranging from 0.5–12 hrs. Results: Type 2 DM subjects demonstrated greater variability in GVC3–5 (period 2.0–12 hrs) than controls (P<0.0001), during the day as well as during the night. Multi-Scale GV was related to conventional markers of glycemic variability (e.g. standard deviation and mean glycemic excursions), but demonstrated greater sensitivity and specificity to conventional markers, and was associated with worse long-term glycemic control (e.g. fasting glucose and HbA1c). Across all subjects, those with greater glycemic variability within higher frequency cycles (GVC1–3; 0.5–2.0 hrs) had less gray matter within the limbic system and temporo-parietal lobes (e.g. cingulum, insular, hippocampus), and exhibited worse cognitive performance. Specifically within those with type 2 DM, greater glycemic variability in GVC2–3 was associated with worse learning and memory scores. Greater variability in GVC5 was associated with longer DM duration and more depression. These relationships were independent of HbA1c and hypoglycemic episodes. Conclusions: Type 2 DM is associated with dysregulation of glycemic variability over multiple scales of time. These time-scale-dependent glycemic fluctuations might contribute to brain atrophy and cognitive outcomes within this vulnerable population

The effects of cognitive impairment on the multi-scale dynamics of standing postural control during visual-search in older men

BackgroundCognitive impairment disrupts postural control, particularly when standing while performing an unrelated cognitive task (i.e., dual-tasking). The temporal dynamics of standing postural sway are “complex,” and such complexity may reflect the capacity of the postural control system to adapt to task demands. We aimed to characterize the impact of cognitive impairment on such sway complexity in older adults.MethodsForty-nine older adult males (Alzheimer’s disease (AD): n = 21; mild cognitive impairment (MCI): n = 13; cognitively-intact: n = 15) completed two 60-s standing trials in each of single-task and visual-search dual-task conditions. In the dual-task condition, participants were instructed to count the frequency of a designated letter in a block of letters projected on screen. The sway complexity of center-of-pressure fluctuations in anterior–posterior (AP) and medial-lateral (ML) direction was quantified using multiscale entropy. The dual-task cost to complexity was obtained by calculating the percent change of complexity from single- to dual-task condition.ResultsRepeated-measures ANOVAs revealed significant main effects of group (F &gt; 4.8, p &lt; 0.01) and condition (F = 7.7, p &lt; 0.007) on both AP and ML sway complexity; and significant interaction between group and condition for ML sway complexity (F = 3.7, p = 0.03). The AD group had the lowest dual-task ML complexity, as well as greater dual-task cost to ML (p = 0.03) compared to the other two groups. Visual-search task accuracy was correlated with ML sway complexity in the dual-task condition (r = 0.42, p = 0.007), and the dual-task cost to ML sway complexity (r = 0.39, p = 0.01) across all participants.ConclusionAD-related cognitive impairment was associated with a greater relative reduction in postural sway complexity from single- to dual-tasking. Sway complexity appears to be sensitive to the impact of cognitive impairment on standing postural control

Complexity-Based Measures Inform Tai Chi\u27s Impact on Standing Postural Control in Older Adults with Peripheral Neuropathy

Background: Tai Chi training enhances physical function and may reduce falls in older adults with and without balance disorders, yet its effect on postural control as quantified by the magnitude or speed of center-of-pressure (COP) excursions beneath the feet is less clear. We hypothesized that COP metrics derived from complex systems theory may better capture the multi-component stimulus that Tai Chi has on the postural control system, as compared with traditional COP measures. Methods: We performed a secondary analysis of a pilot, non-controlled intervention study that examined the effects of Tai Chi on standing COP dynamics, plantar sensation, and physical function in 25 older adults with peripheral neuropathy. Tai Chi training was based on the Yang style and consisted of three, one-hour group sessions per week for 24 weeks. Standing postural control was assessed with a force platform at baseline, 6, 12, 18, and 24 weeks. The degree of COP complexity, as defined by the presence of fluctuations existing over multiple timescales, was calculated using multiscale entropy analysis. Traditional measures of COP speed and area were also calculated. Foot sole sensation, six-minute walk (6MW) and timed up-and-go (TUG) were also measured at each assessment. Results: Traditional measures of postural control did not change from baseline. The COP complexity index (mean±SD) increased from baseline (4.1±0.5) to week 6 (4.5±0.4), and from week 6 to week 24 (4.7±0.4) (p=0.02). Increases in COP complexity—from baseline to week 24—correlated with improvements in foot sole sensation (p=0.01), the 6MW (p=0.001) and TUG (p=0.01). Conclusions: Subjects of the Tai Chi program exhibited increased complexity of standing COP dynamics. These increases were associated with improved plantar sensation and physical function. Although more research is needed, results of this non-controlled pilot study suggest that complexity-based COP measures may inform the study of complex mind-body interventions, like Tai Chi, on postural control in those with peripheral neuropathy or other age-related balance disorders

Repetitive Transcranial Magnetic Stimulation in Spinocerebellar Ataxia: A Pilot Randomized Controlled Trial

Spinocerebellar ataxia (SCA) is a neurodegenerative disorder caused by dysfunction of the cerebellum and its connected neural networks. There is currently no cure for SCA and symptomatic treatment remains limited. We aimed here to examine the effects of a repetitive transcranial magnetic stimulation (rTMS) targeting the cerebellum on clinical impression, postural control and gait in patients with SCA. In this randomized, double-blinded and sham-controlled study, 20 individuals aged 18–75 years with SCA confirmed by genetic testing completed rTMS or sham intervention comprising 20 sessions of MRI-guided stimulation over the cerebellum. Baseline assessments included the Standard Ataxia Rating Assessment (SARA), the 9-hole peg test of manual dexterity, the Timed Up-and-Go (TUG) test, standing postural control with eyes-open and eyes-closed, and gait. Immediate (within 1-week) and 1-month follow-ups were completed. Intervention compliance was high (19 ± 2 of 20 sessions) and no rTMS-related adverse events were reported. rTMS, compared to sham, was associated with greater percent improvement in SARA total score from baseline to the 1-month follow-up (p = 0.008). Secondary analyses of individual SARA items revealed that rTMS improved performance within the “stance” sub-score only (p = 0.002). This functional change was accompanied by improvement to several objective metrics of postural sway during eyes-open and eyes-closed standing (p &lt; 0.008). rTMS did not influence the 9-hole peg test, TUG, or gait kinematics. A 20-session rTMS intervention is safe and feasible for those with SCA. Additional research is warranted to confirm the observed longer-term benefits of this intervention on standing postural control.Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT0197590

Patterns, Predictors, and Outcomes of Falls Trajectories in Older Adults: The MOBILIZE Boston Study with 5 Years of Follow-Up

Background: Falls may occur as unpredictable events or in patterns indicative of potentially modifiable risks and predictive of adverse outcomes. Knowing the patterns, risks, and outcomes of falls trajectories may help clinicians plan appropriate preventive measures. We hypothesized that clinically distinct trajectories of falls progression, baseline predictors and their coincident clinical outcomes could be identified. Methods: We studied 765 community-dwelling participants in the MOBILIZE Boston Study, who were aged 70 and older and followed prospectively for falls over 5 years. Baseline demographic and clinical data were collected by questionnaire and a comprehensive clinic examination. Falls, injuries, and hospitalizations were recorded prospectively on daily calendars. Group-Based Trajectory Modeling (GBTM) was used to identify trajectories. Results: We identified 4 distinct trajectories: No Falls (30.1%), Cluster Falls (46.1%), Increasing Falls (5.8%) and Chronic Recurring Falls (18.0%). Predictors of Cluster Falls were faster gait speed (OR 1.69 (95CI, 1.50–2.56)) and fall in the past year (OR 3.52 (95CI, 2.16–6.34)). Predictors of Increasing Falls were Diabetes Mellitus (OR 4.3 (95CI, 1.4–13.3)) and Cognitive Impairment (OR 2.82 (95CI, 1.34–5.82)). Predictors of Chronic Recurring Falls were multi-morbidity (OR 2.24 (95CI, 1.60–3.16)) and fall in the past year (OR 3.82 (95CI, 2.34–6.23)). Symptoms of depression were predictive of all falls trajectories. In the Chronic Recurring Falls trajectory group the incidence rate of Hospital visits was 121 (95% CI 63–169) per 1,000 person-years; Injurious falls 172 (95% CI 111–237) per 1,000 person-years and Fractures 41 (95% CI 9–78) per 1,000 person-years. Conclusions: Falls may occur in clusters over discrete intervals in time, or as chronically increasing or recurring events that have a relatively greater risk of adverse outcomes. Patients with multiple falls, multimorbidity, and depressive symptoms should be targeted for preventive measures

The comparison between effects of Taichi and conventional exercise on functional mobility and balance in healthy older adults: a systematic literature review and meta-analysis

BackgroundTaichi is beneficial for functional mobility and balance in older adults. However, such benefits of Taichi when comparing to conventional exercise (CE) are not well understood due to large variance in study protocols and observations.MethodsWe reviewed publications in five databases. Eligible studies that examined the effects of Taichi on the outcomes of functional mobility and balance in healthy older adults as compared to CE were included. Subgroup analyses compared the effects of different types of CE (e.g., single and multiple-type exercise) and different intervention designs (e.g., Taichi types) on those outcomes (Registration number: CRD42022331956).ResultsTwelve studies consisting of 2,901 participants were included. Generally, compared to CE, Taichi induced greater improvements in the performance of Timed-Up-and-Go (SMD = −0.18, [−0.33 to −0.03], p = 0.040, I2 = 59.57%), 50-foot walking (MD = −1.84 s, [−2.62 to −1.07], p &lt; 0.001, I2 = 0%), one-leg stance with eyes open (MD = 6.00s, [2.97 to 9.02], p &lt; 0.001, I2 = 83.19%), one-leg stance with eyes closed (MD = 1.65 s, [1.35 to 1.96], p &lt; 0.001, I2 = 36.2%), and functional reach (SMD = 0.7, [0.32 to 1.08], p &lt; 0.001, I2 = 86.79%) tests. Subgroup analyses revealed that Taichi with relatively short duration (&lt;20 weeks), low total time (≤24 h), and/or using Yang-style, can induce significantly greater benefits for functional mobility and balance as compared to CE. Uniquely, Taichi only induced significantly greater improvements in Timed-Up-and-Go compared to single- (SMD = −0.40, [−0.55 to −0.24], p &lt; 0.001, I2 = 6.14%), but not multiple-type exercise. A significant difference between the effects of Taichi was observed on the performance of one-leg stance with eyes open when compared to CE without balance (MD = 3.63 s, [1.02 to 6.24], p = 0.006, I2 = 74.93%) and CE with balance (MD = 13.90s, [10.32 to 17.48], p &lt; 0.001, I2 = 6.1%). No other significant difference was shown between the influences of different CE types on the observations.ConclusionTaichi can induce greater improvement in functional mobility and balance in older adults compared to CE in a more efficient fashion, especially compared to single-type CE. Future studies with more rigorous design are needed to confirm the observations here

Tele-supervised home-based transcranial alternating current stimulation (tACS) for Alzheimer's disease : a pilot study

Over 55 million people worldwide are currently diagnosed with Alzheimer's disease (AD) and live with debilitating episodic memory deficits. Current pharmacological treatments have limited efficacy. Recently, transcranial alternating current stimulation (tACS) has shown memory improvement in AD by normalizing high-frequency neuronal activity. Here we investigate the feasibility, safety, and preliminary effects on episodic memory of an innovative protocol where tACS is administered within the homes of older adults with AD with the help of a study companion (HB-tACS). Eight participants diagnosed with AD underwent multiple consecutive sessions of high-definition HB-tACS (40 Hz, 20-min) targeting the left angular gyrus (AG), a key node of the memory network. The Acute Phase comprised 14-weeks of HB-tACS with at least five sessions per week. Three participants underwent resting state electroencephalography (EEG) before and after the 14-week Acute Phase. Subsequently, participants completed a 2-3-month Hiatus Phase not receiving HB-tACS. Finally, in the Taper phase, participants received 2-3 sessions per week over 3-months. Primary outcomes were safety, as determined by the reporting of side effects and adverse events, and feasibility, as determined by adherence and compliance with the study protocol. Primary clinical outcomes were memory and global cognition, measured with the Memory Index Score (MIS) and Montreal Cognitive Assessment (MoCA), respectively. Secondary outcome was EEG theta/gamma ratio. Results reported as mean ± SD. All participants completed the study, with an average of 97 HB-tACS sessions completed by each participant; reporting mild side effects during 25% of sessions, moderate during 5%, and severe during 1%. Acute Phase adherence was 98 ± 6.8% and Taper phase was 125 ± 22.3% (rates over 100% indicates participants completed more than the minimum of 2/week). After the Acute Phase, all participants showed memory improvement, MIS of 7.25 ± 3.77, sustained during Hiatus 7.00 ± 4.90 and Taper 4.63 ± 2.39 Phases compared to baseline. For the three participants that underwent EEG, a decreased theta/gamma ratio in AG was observed. Conversely, participants did not show improvement in the MoCA, 1.13 ± 3.80 after the Acute Phase, and there was a modest decrease during the Hiatus −0.64 ± 3.28 and Taper −2.56 ± 5.03 Phases. This pilot study shows that the home-based, remotely-supervised, study companion administered, multi-channel tACS protocol for older adults with AD was feasible and safe. Further, targeting the left AG, memory in this sample was improved. These are preliminary results that warrant larger more definite trials to further elucidate tolerability and efficacy of the HB-tACS intervention. NCT04783350. , identifier NCT04783350

Self-Reported Head Trauma Predicts Poor Dual Task Gait in Retired National Football League Players

Symptomatic head trauma associated with American-style football (ASF) has been linked to brain pathology, along with physical and mental distress in later life. However, the longer-term effects of such trauma on objective metrics of cognitive-motor function remain poorly understood. We hypothesized that ASF-related symptomatic head trauma would predict worse gait performance, particularly during dual task conditions (ie, walking while performing an additional cognitive task), in later life. Sixty-six retired professional ASF players aged 29 to 75 years completed a health and wellness questionnaire. They also completed a validated smartphone-based assessment in their own homes, during which gait was monitored while they walked normally and while they performed a verbalized serial-subtraction cognitive task. Participants who reported more symptomatic head trauma, defined as the total number of impacts to the head or neck followed by concussion-related symptoms, exhibited greater dual task cost (ie, percentage increase) to stride time variability (ie, the coefficient of variation of mean stride time). Those who reported ≥1 hit followed by loss of consciousness, compared to those who did not, also exhibited greater dual task costs to this metric. Relationships between reported trauma and dual task costs were independent of age, body mass index, National Football League career duration, and history of musculoskeletal surgery. Symptomatic head trauma was not correlated with average stride times in either walking condition. Remote, smartphone-based assessments of dual task walking may be utilized to capture meaningful data sensitive to the long-term impact of symptomatic head trauma in former professional ASF players and other contact sport athletes. ANN NEUROL 2020;87:75-8