Data-based modeling of cerebral hemodynamics quantifies impairment of cerebral blood flow regulation in type-2 diabetes.

We studied the regulation dynamics of cerebral blood velocity (CBv) at middle cerebral arteries (MCA) in response to spontaneous changes of arterial blood pressure (ABP), termed dynamic cerebral autoregulation (dCA), and end-tidal CO2 as proxy for blood CO2 tension, termed dynamic vasomotor reactivity (DVR), by analyzing time-series data collected at supine rest from 36 patients with Type-2 Diabetes Mellitus (T2DM) and 22 age/sex-matched non-diabetic controls without arterial hypertension. Our analysis employed a robust dynamic modeling methodology that utilizes Principal Dynamic Modes (PDM) to estimate subject-specific dynamic transformations of spontaneous changes in ABP and end-tidal CO2 (viewed as two "inputs") into changes of CBv at MCA measured via Transcranial Doppler ultrasound (viewed as the "output"). The quantitative results of PDM analysis indicate significant alterations in T2DM of both DVR and dCA in terms of two specific PDM contributions that rise to significance (p < 0.05). Our results further suggest that the observed DVR and dCA alterations may be due to reduction of cholinergic activity (based on previously published results from cholinergic blockade data) that may disturb the sympatho-vagal balance in T2DM. Combination of these two model-based "physio-markers" differentiated T2DM patients from controls (p = 0.0007), indicating diabetes-related alteration of cerebrovascular regulation, with possible diagnostic implications.

Daily intranasal insulin at 40IU does not affect food intake and body composition: A placebo-controlled trial in older adults over a 24-week period with 24-weeks of follow-up.

Centrally administered insulin stimulates the reward system to reduce appetite in response to food intake in animal studies. In humans, studies have shown conflicting results, with some studies suggesting that intranasal insulin (INI) in relatively high doses may decrease appetite, body fat, and weight in various populations. These hypotheses have not been tested in a large longitudinal placebo-controlled study. Participants in the Memory Advancement with Intranasal Insulin in Type 2 Diabetes (MemAID) trial were enrolled in this study. This study on energy homeostasis enrolled 89 participants who completed baseline and at least 1 intervention visit (42 women; age 65 ± 9 years; 46 INI, 38 with type 2 diabetes) and 76 completed treatment (16 women, age 64 ± 9; 38 INI, 34 with type 2 diabetes). The primary outcome was the INI effect on food intake. Secondary outcomes included the effect of INI on appetite and anthropometric measures, including body weight and body composition. In exploratory analyses, we tested the interaction of treatment with gender, body mass index (BMI), and diagnosis of type 2 diabetes. There was no INI effect on food intake or any of the secondary outcomes. INI also showed no differential effect on primary and secondary outcomes when considering gender, BMI, and type 2 diabetes. INI did not alter appetite or hunger nor cause weight loss when used at 40 I.U. intranasally daily for 24 weeks in older adults with and without type 2 diabetes.

Dropout risk and effectiveness of retention strategies in the Memory Advancement by Intranasal Insulin in Type 2 Diabetes (MemAID) Clinical Trial.

BACKGROUND: Effective recruitment and retention strategies are essential in clinical trials. METHODS: The MemAID trial consisted of 12 visits during 24 weeks of intranasal insulin or placebo treatment and 24 weeks of post-treatment follow-up in older people with and without diabetes. Enhanced retention strategies were implemented mid study to address high drop-out rate. Baseline variables used in Cox regression models to identify dropout risk factors were: demographics and social characteristics, functional measures, metabolic and cardiovascular parameters, and medications. RESULTS: 244 participants were randomized; 13 (5.3%) were discontinued due to adverse events. From the remaining 231 randomized participants, 65 (28.1%) dropped out, and 166 (71.9%) did not. The Non-retention group included 95 participants not exposed to retention strategies, of which 43 (45.2%) dropped out. The Retention group included 136 participants exposed to enhanced retention strategies, of which 22 (16.2%) dropped out. Dropout risk factors included being unmarried, a longer diabetes duration, using oral antidiabetics as compared to not using, worse executive function and chronic pain. After adjusting for exposure to retention strategies, worse baseline executive function composite score (p = 0.001) and chronic pain diagnosis (p = 0.032) were independently associated with a greater risk of dropping out. The probability of dropping out decreased with longer exposure to retention strategies and the dropout rate per month decreased from 4.1% to 1.8% (p = 0.04) on retention strategies. CONCLUSIONS: Baseline characteristics allow prediction of dropping out from a clinical trial in older participants. Retention strategies has been effective at minimizing the impact of dropout-related risk factors. TRIAL REGISTRATION: Clinical trials.gov NCT2415556 3/23/2015 (www. CLINICALTRIALS: gov).

Depressive symptoms exacerbate disability in older adults: A prospective cohort analysis of participants in the MemAID trial.

BACKGROUND: Maintaining independence in older age is an important aspect of quality of life. We investigated depressive symptoms as an important modifiable risk factor that may mediate the effects of physical and cognitive decline on disability. METHODS: We prospectively analyzed data from 223 adults (age 50-85; 117 controls and 106 with type-2 diabetes) over 48 weeks who were participating in a clinical trial "Memory Advancement by Intranasal Insulin in Type 2 Diabetes." Data from self-reported disability (World Health Organization Disability Assessment Schedule) and depressive symptoms (Geriatric Depression Scale) were obtained from baseline, week 25, and week 48 visits. Cognition (Mini-mental status examination) and medical comorbidities (Charlson Comorbidity Index) were assessed at baseline. Longitudinal analysis assessed the extent to which change in depressive symptoms predicted worsening disability. Mediation analyses were performed to determine the extent to which depressive symptoms accounted for disability associated with worse cognition, walking speed, and comorbidities. RESULTS: At baseline, depressive symptoms, cognition, and walking speed were within normal limits, but participants had a high 10-year risk of cardiovascular mortality. Depressive symptoms were related to disability at baseline (p<0.001), and longitudinally (p<0.001). Cognition, walking speed, and comorbidities were associated with disability at baseline (p-values = 0.027-0.001). Depressive symptoms had a large mediating effect on disability longitudinally: the indirect effect on disability via depression accounts for 51% of the effect of cognition, 34% of the effect of mobility, and 24% of the effect of comorbidities. CONCLUSIONS: Depressive symptoms substantially exacerbated the effects of worsening cognition, gait speed, and comorbidities on disability. In our sample, most individuals scored within the "normal" range of the Geriatric Depression Scale, suggesting that even subclinical symptoms can lead to disability. Treating subclinical depression, which may be under-recognized in older adults, should be a public health priority to help preserve independence with aging.

MemAID: Memory advancement with intranasal insulin vs. placebo in type 2 diabetes and control participants: a randomized clinical trial.

BACKGROUND: This study aimed at assessing the long-term effects of intranasal insulin (INI) on cognition and gait in older people with and without type 2 diabetes mellitus (T2DM). METHODS: Phase 2 randomized, double-blinded trial consisted of 24 week treatment with 40 IU of INI (Novolin® R, off-label use) or placebo (sterile saline) once daily and 24 week follow-up. Primary outcomes were cognition, normal (NW), and dual-task (DTW) walking speeds. Of 244 randomized, 223 completed baseline (51 DM-INI, 55 DM-Placebo, 58 Control-INI, 59 Control-Placebo; 109 female, 65.8 ± 9.1; 50-85 years old); 174 completed treatment (84 DM, 90 Controls); 156 completed follow-up (69 DM). RESULTS: DM-INI had faster NW (~ 7 cm/s; p = 0.025) and DTW on-treatment (p = 0.007; p = 0.812 adjusted for baseline difference) than DM-Placebo. Control-INI had better executive functioning on-treatment (p = 0.008) and post-treatment (p = 0.007) and verbal memory post-treatment (p = 0.004) than Control-Placebo. DM-INI increased cerebral blood flow in medio-prefrontal cortex (p < 0.001) on MRI. Better vasoreactivity was associated with faster DTW (p < 0.008). In DM-INI, plasma insulin (p = 0.006) and HOMA-IR (p < 0.013) decreased post-treatment. Overall INI effect demonstrated faster walking (p = 0.002) and better executive function (p = 0.002) and verbal memory (p = 0.02) (combined DM-INI and Control-INI cohort, hemoglobin A1c-adjusted). INI was not associated with serious adverse events, hypoglycemic episodes, or weight gain. CONCLUSION: There is evidence for positive INI effects on cognition and gait. INI-treated T2DM participants walked faster, showed increased cerebral blood flow and decreased plasma insulin, while controls improved executive functioning and verbal memory. The MemAID trial provides proof-of-concept for preliminary safety and efficacy and supports future evaluation of INI role to treat T2DM and age-related functional decline.

Glycemic variability of acute stroke patients and clinical outcomes: a continuous glucose monitoring study.

INTRODUCTION: Glycemic variability (GV) has been associated with worse prognosis in critically ill patients. We sought to evaluate the potential association between GV indices and clinical outcomes in acute stroke patients. METHODS: Consecutive diabetic and nondiabetic, acute ischemic or hemorrhagic stroke patients underwent regular, standard-of-care finger-prick measurements and continuous glucose monitoring (CGM) for up to 96 h. Thirteen GV indices were obtained from CGM data. Clinical outcomes during hospitalization and follow-up period (90 days) were recorded. Hypoglycemic episodes disclosed by CGM but missed by finger-prick measurements were also documented. RESULTS: A total of 62 acute stroke patients [48 ischemic and 14 hemorrhagic, median NIHSS score: 9 (IQR: 3-16) points, mean age: 65 ± 10 years, women: 47%, nondiabetic: 79%] were enrolled. GV expressed by higher mean absolute glucose (MAG) values was associated with a lower likelihood of neurological improvement during hospitalization before and after adjusting for potential confounders (OR: 0.135, 95% CI: 0.024-0.751, p = 0.022). There was no association of GV indices with 3-month clinical outcomes. During CGM recording, 32 hypoglycemic episodes were detected in 17 nondiabetic patients. None of these episodes were identified by the periodic blood glucose measurements and therefore they were not treated. CONCLUSIONS: Greater GV of acute stroke patients may be related to lower odds of neurological improvement during hospitalization. No association was disclosed between GV indices and 3-month clinical outcomes.

Deep transfer learning and data augmentation improve glucose levels prediction in type 2 diabetes patients.

Accurate prediction of blood glucose variations in type 2 diabetes (T2D) will facilitate better glycemic control and decrease the occurrence of hypoglycemic episodes as well as the morbidity and mortality associated with T2D, hence increasing the quality of life of patients. Owing to the complexity of the blood glucose dynamics, it is difficult to design accurate predictive models in every circumstance, i.e., hypo/normo/hyperglycemic events. We developed deep-learning methods to predict patient-specific blood glucose during various time horizons in the immediate future using patient-specific every 30-min long glucose measurements by the continuous glucose monitoring (CGM) to predict future glucose levels in 5 min to 1 h. In general, the major challenges to address are (1) the dataset of each patient is often too small to train a patient-specific deep-learning model, and (2) the dataset is usually highly imbalanced given that hypo- and hyperglycemic episodes are usually much less common than normoglycemia. We tackle these two challenges using transfer learning and data augmentation, respectively. We systematically examined three neural network architectures, different loss functions, four transfer-learning strategies, and four data augmentation techniques, including mixup and generative models. Taken together, utilizing these methodologies we achieved over 95% prediction accuracy and 90% sensitivity for a time period within the clinically useful 1 h prediction horizon that would allow a patient to react and correct either hypoglycemia and/or hyperglycemia. We have also demonstrated that the same network architecture and transfer-learning methods perform well for the type 1 diabetes OhioT1DM public dataset.

Placebo controlled phase II clinical trial: Safety and efficacy of combining intranasal insulin & acute exercise.

A growing number of investigations are exploring the utility of intranasal insulin as a means of mitigating cognitive decline. However, as a basic tenant of dementia prevention programs is increasing physical activity, it is essential to obtain a preliminary assessment of the safety profile of combining intranasal insulin with physical activity; to ensure that undue risks are not incurred. Utilizing a randomized double-blind placebo-controlled design, a sample of 116 non-diabetic, fasted college-aged adults were randomly assigned to receive a dose of 0-to-120 IU of NovoLog (Insulin Aspart) before being randomized to 20 min of exercise or sitting control condition. The safety of intranasal insulin was assessed by examining the incidence of potential symptoms of hypoglycemia and changes in peripheral blood glucose. The efficacy of a combination therapeutic approach was assessed using behavioral measures of inhibition and sustained attention alongside neuroelectric indices of attentional engagement. The frequency of symptoms reported following administration of intranasal insulin were not observed to interact with exercise so as to make their occurrence any more or less prominent, nor was the frequency observed to relate to the dose of intranasal insulin. However, doses of intranasal insulin of 100 IU or more were observed to result in a 7-fold increase in the likelihood of a level 1 hypoglycemic event for those individuals in the exercise condition. This study provides preliminary evidence to suggest that exercise is not associated with an increase in risk when combined with lower doses of intranasal insulin.Clinical trial registration The trial is registered at ClinicalTrials.gov, number NCT04292535.

Tai Chi training's effect on lower extremity muscle co-contraction during single- and dual-task gait: Cross-sectional and randomized trial studies.

BACKGROUND: Tai Chi (TC) mind-body exercise has been shown to reduce falls and improve balance and gait, however, few studies have evaluated the role of lower extremity muscle activation patterns in the observed benefits of TC on mobility. PURPOSE: To perform an exploratory analysis of the association between TC training and levels of lower extremity muscle co-contraction in healthy adults during walking under single-task (ST) and cognitive dual-task (DT) conditions. METHODS: Surface electromyography of the anterior tibialis and lateral gastrocnemius muscles was recorded during 90 sec trials of overground ST (walking normally) and DT (walking with verbalized serial subtractions) walking. A mean co-contraction index (CCI), across all strides, was calculated based on the percentage of total muscle activity when antagonist muscles were simultaneously activated. A hybrid study design investigated long-term effects of TC via a cross-sectional comparison of 27 TC experts and 60 age-matched TC-naïve older adults. A longitudinal comparison assessed the shorter-term effects of TC; TC-naïve participants were randomly allocated to either 6 months of TC training or to usual care. RESULTS: Across all participants at baseline, greater CCI was correlated with slower gait speed under DT (ß(95% CI) = -26.1(-48.6, -3.7)) but not ST (ß(95% CI) = -15.4(-38.2, 7.4)) walking. Linear models adjusting for age, gender, BMI and other factors that differed at baseline indicated that TC experts exhibited lower CCI compared to TC naives under DT, but not ST conditions (ST: mean difference (95% CI) = -7.1(-15.2, 0.97); DT: mean difference (95% CI) = -10.1(-18.1, -2.4)). No differences were observed in CCI for TC-naive adults randomly assigned to 6 months of TC vs. usual care. CONCLUSION: Lower extremity muscle co-contraction may play a role in the observed benefit of longer-term TC training on gait and postural control. Longer-duration and adequately powered randomized trials are needed to evaluate the effect of TC on neuromuscular coordination and its impact on postural control. TRIAL REGISTRATION: The randomized trial component of this study was registered at ClinicalTrials.gov (NCT01340365).

Dysregulation of behavioral and autonomic responses to emotional and social stimuli following bidirectional pharmacological manipulation of the basolateral amygdala in macaques.

The amygdala is a key component of the neural circuits mediating the processing and response to emotionally salient stimuli. Amygdala lesions dysregulate social interactions, responses to fearful stimuli, and autonomic functions. In rodents, the basolateral and central nuclei of the amygdala have divergent roles in behavioral control. However, few studies have selectively examined these nuclei in the primate brain. Moreover, the majority of non-human primate studies have employed lesions, which only allow for unidirectional manipulation of amygdala activity. Thus, the effects of amygdala disinhibition on behavior in the primate are unknown. To address this gap, we pharmacologically inhibited by muscimol or disinhibited by bicuculline methiodide the basolateral complex of the amygdala (BLA; lateral, basal, and accessory basal) in nine awake, behaving male rhesus macaques (Macaca mulatta). We examined the effects of amygdala manipulation on: (1) behavioral responses to taxidermy snakes and social stimuli, (2) food competition and social interaction in dyads, (3) autonomic arousal as measured by cardiovascular response, and (4) prepulse inhibition of the acoustic startle (PPI) response. All modalities were impacted by pharmacological inhibition and/or disinhibition. Amygdala inhibition decreased fear responses to snake stimuli, increased examination of social stimuli, reduced competitive reward-seeking in dominant animals, decreased heart rate, and increased PPI response. Amygdala disinhibition restored fearful response after habituation to snakes, reduced competitive reward-seeking behavior in dominant animals, and lowered heart rate. Thus, both hypoactivity and hyperactivity of the basolateral amygdala can lead to dysregulated behavior, suggesting that a narrow range of activity is necessary for normal functions.

Complexity-Based Measures of Heart Rate Dynamics in Older Adults Following Long- and Short-Term Tai Chi Training: Cross-sectional and Randomized Trial Studies.

Measures characterizing the complexity of heart rate (HR) dynamics have been informative in predicting age- and disease-related decline in cardiovascular health, but few studies have evaluated whether mind-body exercise can impact HR complexity. This study evaluated the effects of long-term Tai Chi (TC) practice on the complexity of HR dynamics using an observational comparison of TC experts and age- and gender-matched TC-naïve individuals. Shorter-term effects of TC were assessed by randomly assigning TC-naïve participants to either TC group to receive six months of TC training or to a waitlist control group. 23 TC experts (age = 63.3 ± 8.0 y; 24.6 ± 12.0 y TC experience) and 52 TC-naïve (age = 64.3 ± 7.7 y) were enrolled. In cross-sectional analyses, TC experts had a higher overall complexity index (CI, p = 0.004) and higher entropy at multiple individual time scales (p < 0.05); these findings persisted in models accounting for age, gender, body mass index (BMI), and physical activity levels. Longitudinal changes in complexity index did not differ significantly following random assignment to six months of TC vs. a waitlist control; however, within the TC group, complexity at select time scales showed statistically non-significant trends toward increases. Our study supports that longer-term TC mind-body training may be associated with increased complexity of HR dynamics.

Safety and preliminary efficacy of intranasal insulin for cognitive impairment in Parkinson disease and multiple system atrophy: A double-blinded placebo-controlled pilot study.

Parkinson disease (PD) is associated with cognitive impairment. We aimed to determine the effects of intranasal insulin (INI) on cognition and motor performance in PD. This was a proof of concept, randomized, double-blinded, placebo-controlled trial evaluating the effects of 40 international units (IU) of insulin or saline once daily for four weeks on cognitive and functional performance. Of 16 subjects enrolled, eight in the INI group and six in the placebo group completed verbal fluency (FAS), Unified Parkinson Disease Scale (UPDRS), and modified Hoehn and Yahr scale (HY, PD severity) at baseline and post-treatment and were included in the analyses. After treatment, the INI group had a better total FAS score (p = 0.02) (41 ± 8.2 vs. 30.8 ± 7.1, mean ±SD, p = 0.02) compared to the placebo group. The INI group also had improved HY (p = 0.04) and UPDRS-Motor (Part III) (p = 0.02) scores when compared to baseline. One INI treated patient with multiple system atrophy (MSA) remained stable and did not show disease progression. The placebo group had no change. INI administration was well tolerated and there were no hypoglycemic episodes or serious study related adverse events or medications interactions. INI is safe in PD and MSA patients and may provide clinically relevant functional improvement. Larger studies are warranted to determine the INI effect in treatment of cognitive and motor impairment in Parkinson disease. Trial Registration: ClinicalTrial.gov NCT02064166.

Development of Postural Stability Index to Distinguish Different Stability States.

A key factor for fall prevention involves understanding the pathophysiology of stability. This study proposes the postural stability index (PSI), which is a novel measure to quantify different stability states on healthy subjects. The results of the x-, y-, and z-axes of the acceleration signals were analyzed from 10 healthy young adults and 10 healthy older adults under three conditions as follows: Normal walking, walking with obstacles, and fall-like motions. The ensemble empirical mode decomposition (EEMD) was used to reconstruct the acceleration signal data. Wearable accelerometers were located on the ankles and knees of the subjects. The PSI indicated a decreasing trend of its values from normal walking to the fall-like motions. Free-walking data were used to determine the stability based on the PSI. The segmented free-walking data indicated changes in the stability states that suggested that the PSI is potentially helpful in quantifying gait stability.

Improved perfusion pattern score association with type 2 diabetes severity using machine learning pipeline: Pilot study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with alterations in the blood-brain barrier, neuronal damage, and arterial stiffness, thus affecting cerebral metabolism and perfusion. There is a need to implement machine-learning methodologies to identify a T2DM-related perfusion pattern and possible relationship between the pattern and cognitive performance/disease severity. PURPOSE: To develop a machine-learning pipeline to investigate the method's discriminative value between T2DM patients and normal controls, the T2DM-related network pattern, and association of the pattern with cognitive performance/disease severity. STUDY TYPE: A cross-sectional study and prospective longitudinal study with a 2-year time interval. POPULATION: Seventy-three subjects (41 T2DM patients and 32 controls) aged 50-85 years old at baseline, and 42 subjects (19 T2DM and 23 controls) aged 53-88 years old at 2-year follow-up. FIELD STRENGTH/SEQUENCE: 3T pseudocontinuous arterial spin-labeling MRI. ASSESSMENT: Machine-learning-based pipeline (principal component analysis, feature selection, and logistic regression classifier) to generate the T2DM-related network pattern and the individual scores associated with the pattern. STATISTICAL TESTS: Linear regression analysis with gray matter volume and education years as covariates. RESULTS: The machine-learning-based method is superior to the widely used univariate group comparison method with increased test accuracy, test area under the curve, test positive predictive value, adjusted McFadden's R square of 4%, 12%, 7%, and 24%, respectively. The pattern-related individual scores are associated with diabetes severity variables, mobility, and cognitive performance at baseline (P < 0.05, |r| > 0.3). More important, the longitudinal change of individual pattern scores is associated with the longitudinal change of HbA1c (P = 0.0053, r = 0.64), and baseline cholesterol (P = 0.037, r = 0.51). DATA CONCLUSION: The individual perfusion diabetes pattern score is a highly promising perfusion imaging biomarker for tracing the disease progression of individual T2DM patients. Further validation is needed from a larger study. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:834-844.

Dynamic Cerebral Autoregulation Is an Independent Functional Outcome Predictor of Mild Acute Ischemic Stroke.

Background and Purpose- Cerebral autoregulation is impaired in patients with acute ischemic stroke. The purpose of this study was to investigate whether dynamic cerebral autoregulation (dCA) indices constitute an independent functional outcome predictor of acute ischemic stroke. Methods- In this study, 86 patients at days 3 to 7 after acute ischemic stroke and 40 age- and sex-matched controls were enrolled for assessing their dCA indices under spontaneous hemodynamic fluctuations. The dCA indices of patients with favorable outcomes (modified Rankin Scale score ≤1 at 3 months, n=65), patients with unfavorable outcomes (modified Rankin Scale score ≥2 at 3 months, n=21), and controls were compared. Results- The dCA indices, namely the phase shift at very low frequency band (phase_VLF), in the patients with unfavorable outcomes were significantly worse than those in the patients with favorable outcomes. However, the phase_VLF in the patients with favorable outcomes did not differ from those in the controls. Impaired dCA was associated with elevated mean arterial pressure and large infarction volume but was also present in patients with normal mean arterial pressure or small infarction volume. Phase_VLF was a predictor of outcomes in the receiver operating characteristic analysis (area under the curve: 0.722; P<0.001). Multivariate analysis revealed that a phase_VLF value of <61° was independently associated with unfavorable outcomes (odds ratio=4.90; P=0.024). Conclusions- Phase_VLF is an independent functional outcome predictor of acute ischemic stroke.

Lower cerebral vasoreactivity as a predictor of gait speed decline in type 2 diabetes mellitus.

Gait speed is an indicator of overall functional health and is correlated with survival in older adults. We prospectively evaluated the long-term association between cerebral vasoreactivity and gait speed during normal walking (NW) and dual-task walking (DTW) in older adults with and without type 2 diabetes mellitus (T2DM). 40 participants (aged 67.3 ± 8.8 years, 20 with T2DM) completed a 2-year prospective study consisting of MRI, blood sampling, and gait assessments. The whole brain vasoreactivity was quantified using continuous arterial spin labeling MRI. Gait speed during DTW was assessed by subtracting serial sevens. Dual-task cost was calculated as the percent change in gait speed from NW to DTW. In the entire cohort, higher glycemic profiles were associated with a slower gait speed. In the diabetic group, lower vasoreactivity was associated with a slower gait speed during NW ([Formula: see text] = 0.30, p = 0.019) and DTW ([Formula: see text] = 0.35, p = 0.01) and a higher dual-task cost ([Formula: see text] = 0.69, p = 0.009) at 2-year follow-up. The participants with T2DM and lower cerebral vasoreactivity had a greater decrease in gait speed during NW and DTW after the 2-year follow-up ([Formula: see text] = 0.17, p = 0.04 and [Formula: see text] = 0.28, p = 0.03, respectively). Longer diabetes duration was associated with a higher dual-task cost ([Formula: see text] = 0.19, p = 0.04) and a greater decrease in gait speed during NW ([Formula: see text] = 0.17, p = 0.02). These findings indicate that in older adults with type 2 diabetes, gait performance is highly dependent on the integrity of cerebrovascular regulation.

White matter microstructure and cognitive decline in metabolic syndrome: a review of diffusion tensor imaging.

Metabolic syndrome is a cluster of cardiovascular risk factors defined by the presence of abdominal obesity, glucose intolerance, hypertension and/or dyslipidemia. It is a major public health epidemic worldwide, and a known risk factor for the development of cognitive dysfunction and dementia. Several studies have demonstrated a positive association between the presence of metabolic syndrome and worse cognitive outcomes, however, evidence of brain structure pathology is limited. Diffusion tensor imaging has offered new opportunities to detect microstructural white matter changes in metabolic syndrome, and a possibility to detect associations between functional and structural abnormalities. This review analyzes the impact of metabolic syndrome on white matter microstructural integrity, brain structure abnormalities and their relationship to cognitive function. Each of the metabolic syndrome components exerts a specific signature of white matter microstructural abnormalities. Metabolic syndrome and its components exert both additive/synergistic, as well as, independent effects on brain microstructure thus accelerating brain aging and cognitive decline.

Transcranial Doppler in autonomic testing: standards and clinical applications.

When cerebral blood flow falls below a critical limit, syncope occurs and, if prolonged, ischemia leads to neuronal death. The cerebral circulation has its own complex finely tuned autoregulatory mechanisms to ensure blood supply to the brain can meet the high metabolic demands of the underlying neuronal tissue. This involves the interplay between myogenic and metabolic mechanisms, input from noradrenergic and cholinergic neurons, and the release of vasoactive substrates, including adenosine from astrocytes and nitric oxide from the endothelium. Transcranial Doppler (TCD) is a non-invasive technique that provides real-time measurements of cerebral blood flow velocity. TCD can be very useful in the work-up of a patient with recurrent syncope. Cerebral autoregulatory mechanisms help defend the brain against hypoperfusion when perfusion pressure falls on standing. Syncope occurs when hypotension is severe, and susceptibility increases with hyperventilation, hypocapnia, and cerebral vasoconstriction. Here we review clinical standards for the acquisition and analysis of TCD signals in the autonomic laboratory and the multiple methods available to assess cerebral autoregulation. We also describe the control of cerebral blood flow in autonomic disorders and functional syndromes.

Long-term Tai Chi Training Is Associated With Better Dual-task Postural Control and Cognition in Aging Adults.

OBJECTIVE: Many activities within our daily lives require us to stand upright while concurrently performing a cognitive task (ie, dual tasking). The "costs" of dual tasking can present as a detriment to either task, or even both. Evidence supports that tai chi (TC), a mind-body exercise, improves both postural control and cognition. The purpose of this study was to (1) determine whether long-term TC training reduces dual-task costs to standing postural control, and (2) determine whether it characterizes the relationship between these costs and cognition in aging adults with and without long-term TC training. METHODS: Twenty-six TC experts (age 63 ± 8 y, TC experience 24 ± 11 y) and 60 controls (TC naïve: age 64 ± 8 y) were studied. Center-of-pressure sway speed and elliptical area were recorded during quiet and dual-task standing. In addition, postural sway speed and range were analyzed in the anterior-posterior and medial-lateral direction. Dual-task cost was calculated as the percent change in center-of-pressure outcomes from quiet to dual-task conditions. Cognition was assessed with the digit span (verbal memory), trail making test (working memory and task switching ability), category naming (semantic verbal fluency), and F-A-S test (phonemic verbal fluency). RESULTS: TC experts had significantly lower dual-task costs to postural control in elliptical area (16.1 vs 110.4%, 95% confidence interval [CI], -94.27 to -0.07) compared with TC-naïves. TC experts also performed better on the digit span (23.5 vs 19.2; 95% CI, 0.68 to 3.59), trail making test A (28.5 vs 32.6 s; 95% CI, -3.83 to -0.21), and category naming (46.2 vs 41.3, 95%, CI 0.80 to 4.09), compared with TC naïves. There was not a clear significant association between better cognitive functioning and lower dual-task costs for either groups. These group differences and associations were independent of age, body mass index, education, and physical activity level. CONCLUSIONS: These observations suggest cognitive-motor benefits from TC and the need for future controlled trials.

Can Tai Chi training impact fractal stride time dynamics, an index of gait health, in older adults? Cross-sectional and randomized trial studies.

PURPOSE: To determine if Tai Chi (TC) has an impact on long-range correlations and fractal-like scaling in gait stride time dynamics, previously shown to be associated with aging, neurodegenerative disease, and fall risk. METHODS: Using Detrended Fluctuation Analysis (DFA), this study evaluated the impact of TC mind-body exercise training on stride time dynamics assessed during 10 minute bouts of overground walking. A hybrid study design investigated long-term effects of TC via a cross-sectional comparison of 27 TC experts (24.5 ± 11.8 yrs experience) and 60 age- and gender matched TC-naïve older adults (50-70 yrs). Shorter-term effects of TC were assessed by randomly allocating TC-naïve participants to either 6 months of TC training or to a waitlist control. The alpha (α) long-range scaling coefficient derived from DFA and gait speed were evaluated as outcomes. RESULTS: Cross-sectional comparisons using confounder adjusted linear models suggest that TC experts exhibited significantly greater long-range scaling of gait stride time dynamics compared with TC-naïve adults. Longitudinal random-slopes with shared baseline models accounting for multiple confounders suggest that the effects of shorter-term TC training on gait dynamics were not statistically significant, but trended in the same direction as longer-term effects although effect sizes were very small. In contrast, gait speed was unaffected in both cross-sectional and longitudinal comparisons. CONCLUSION: These preliminary findings suggest that fractal-like measures of gait health may be sufficiently precise to capture the positive effects of exercise in the form of Tai Chi, thus warranting further investigation. These results motivate larger and longer-duration trials, in both healthy and health-challenged populations, to further evaluate the potential of Tai Chi to restore age-related declines in gait dynamics. TRIAL REGISTRATION: The randomized trial component of this study was registered at ClinicalTrials.gov (NCT01340365).