Visual-Somatosensory Integration and Quantitative Gait Performance in Aging

Background: The ability to integrate information across sensory modalities is an integral aspect of mobility. Yet, the association between visual-somatosensory (VS) integration and gait performance has not been well-established in aging.Methods: A total of 333 healthy older adults (mean age 76.53 ± 6.22; 53% female) participated in a visual-somatosensory simple reaction time task and underwent quantitative gait assessment using an instrumented walkway. Magnitude of VS integration was assessed using probability models, and then categorized into four integration classifications (superior, good, poor, or deficient). Associations of VS integration with three independent gait factors (Pace, Rhythm, and Variability derived by factor analysis method) were tested at cross-section using linear regression analyses. Given overlaps in neural circuitry necessary for both multisensory integration and goal-directed locomotion, we hypothesized that VS integration would be significantly associated with pace but not rhythm which is a more automatic process controlled mainly through brainstem and spinal networks.Results: In keeping with our hypothesis, magnitude of VS integration was a strong predictor of pace (β = 0.12, p < 0.05) but not rhythm (β = −0.01, p = 0.83) in fully-adjusted models. While there was a trend for the association of magnitude of VS integration with variability (β = −0.11, p = 0.051), post-hoc testing of individual gait variables that loaded highest on the variability factor revealed that stride length variability (β = −0.13, p = 0.03) and not swing time variability (β = −0.08, p = 0.15) was significantly associated with magnitude of VS integration. Of the cohort, 29% had superior, 26% had good, 29% had poor, and 16% had deficient VS integration effects.Conclusions: Worse VS integration in aging is associated with worse spatial but not temporal aspects of gait performance

The evolution of mild parkinsonian signs in aging

The progression of mild parkinsonian signs in the absence of idiopathic Parkinson's disease in aging is unclear. This study aims to identify predictors of the evolution of mild parkinsonian signs in non-dementedolder adults. Two hundred ten participants (76.25±7.10years, 57% women) were assessed at baseline and 1-year follow-up. Mild parkinsonian signs were defined as the presence of bradykinesia, rigidity and/or rest tremor. Depending upon the presence of these features at baseline and follow-up, participants were divided into one of four groups (no, transient, persistent or new-onset mild parkinsonian signs). Physical function was assessed using gait velocity. Ninety-five participants presented with mild parkinsonian signs at baseline. At 1-year follow-up, 59 demonstrated persistent mild parkinsonian signs, while 36 recovered (i.e., transient). Participants with persistent mild parkinsonian signs were older (79.66±7.15 vs. 75.81±7.37years, p=0.01) and evidenced slower gait velocity (90.41±21.46 vs. 109.92±24.32cm/s, p<0.01) compared to those with transient mild parkinsonian signs. Gait velocity predicted persistence of mild parkinsonian signs, even after adjustments (OR: 0.96, 95% CI: 0.94-0.98). Fifty-five participants demonstrated new-onset of mild parkinsonian signs. In comparison to participants without mild parkinsonian signs, presence of cardiovascular but not cerebrovascular disease at baseline was associated with new-onset mild parkinsonian signs. Our study reveals that gait velocity was the main predictor of persistent mild parkinsonian signs, whereas cardiovascular disease was associated with new-onset mild parkinsonian signs. These findings suggest a vascular mechanism for the onset of mild parkinsonian signs and a different mechanism, possibly neurodegenerative, for the persistence of mild parkinsonian signs

COGNITIVE CORRELATES OF GAIT SPEED AMONG OLDER ADULTS FROM SIX COUNTRIES: FINDINGS FROM THE COSMIC COLLABORATION

Using data from population-based cohorts of older adults 65+ from six countries across three continents (N=6472), we aimed to (1) describe and (2) identify predictors of usual and rapid gait speed from studies participating in the Cohort Studies of Memory in an International Consortium (COSMIC) collaboration. We investigated whether clinical (BMI, hypertension, stroke, APOE status), psychological (cognition, mood, general health) and behavioral factors (smoking, drinking, physical activity) predicted gait speed similarly across cohorts; we used regression models controlling for demographics. Unadjusted usual gait speed ranged from 0.52-1.09 m/s and rapid gait speed ranged from 1.20-1.68 m/s. Lower BMI and better cognitive function consistently predicted faster usual and rapid gait speed in all cohorts. These patterns were not attenuated by demographics. Other psychological and behavioral factors were less consistently associated with gait. Taken together, gait speed is variable across ethnogeographic regions, but the influence of cognitive on gait is remarkably consistent

Visual-somatosensory integration (VSI) as a novel marker of Alzheimer’s disease: A comprehensive overview of the VSI study

Identification of novel, non-invasive, non-cognitive based markers of Alzheimer’s disease (AD) and related dementias are a global priority. Growing evidence suggests that Alzheimer’s pathology manifests in sensory association areas well before appearing in neural regions involved in higher-order cognitive functions, such as memory. Previous investigations have not comprehensively examined the interplay of sensory, cognitive, and motor dysfunction with relation to AD progression. The ability to successfully integrate multisensory information across multiple sensory modalities is a vital aspect of everyday functioning and mobility. Our research suggests that multisensory integration, specifically visual-somatosensory integration (VSI), could be used as a novel marker for preclinical AD given previously reported associations with important motor (balance, gait, and falls) and cognitive (attention) outcomes in aging. While the adverse effect of dementia and cognitive impairment on the relationship between multisensory functioning and motor outcomes has been highlighted, the underlying functional and neuroanatomical networks are still unknown. In what follows we detail the protocol for our study, named The VSI Study, which is strategically designed to determine whether preclinical AD is associated with neural disruptions in subcortical and cortical areas that concurrently modulate multisensory, cognitive, and motor functions resulting in mobility decline. In this longitudinal observational study, a total of 208 community-dwelling older adults with and without preclinical AD will be recruited and monitored yearly. Our experimental design affords assessment of multisensory integration as a new behavioral marker for preclinical AD; identification of functional neural networks involved in the intersection of sensory, motor, and cognitive functioning; and determination of the impact of early AD on future mobility declines, including incident falls. Results of The VSI Study will guide future development of innovative multisensory-based interventions aimed at preventing disability and optimizing independence in pathological aging

Phenytoin dosing and serum concentrations in paediatric patients requiring 20 mg/kg intravenous loading

Introduction Phenytoin has complex pharmacokinetics. The intravenous loading dose of phenytoin for children in status epilepticus has recently been increased from 18 to 20mg/kg. There are no data on the clinical effectiveness and safety of this new dose. Methods The use of intravenous loading doses of phenytoin was audited over 27 months to evaluate the pharmacokinetic, clinical and toxic effects of the new dose in clinical practice. Serum phenytoin concentrations were compared with both dose (weight-adjusted) and time. Results Serum phenytoin concentrations were measured on 48 occasions from 41 children (39 retrospective and 9 prospective), of which 24 were within 60-180 (median 105) minutes following completion of infusion of the loading dose. Use of estimated weights meant patients received between 15.5 and 27.5mg/kg (78-138% expected dose). Supra-therapeutic serum concentrations (>20µg/ml were present in 5/24 (20.1%) (after doses based on actual weight in three, and estimated weight in two patients). Three adverse effects consistent with phenytoin toxicity were noted in children with supra-therapeutic concentrations. Two errors in dose prescriptions were found. Conclusion The majority of serum phenytoin concentrations were in the therapeutic range. Estimating weight in children for the 20mg/kg intravenous loading dose of phenytoin is often clinically necessary but inaccurate, resulting in up to 138% of the expected and recommended dose in this cohort

Community-Based Activity and Sedentary Patterns Are Associated With Cognitive Performance in Mobility-Limited Older Adults

Over the last few decades, considerable evidence shows that greater levels of aerobic exercise and cardiovascular fitness benefit cognitive performance. However, the degree to which free-living activity in community settings is related to cognitive performance remains unclear, particularly in older adults vulnerable to disability. Also, it is unknown whether the manner in which daily physical activity (PA) and sedentary time are accumulated throughout the day is associated with cognition. Cross-sectional associations between accelerometer-characterized PA and sedentary patterns and cognitive performance were examined in 1,274 mobility-limited older adults. Percent time spent in various bout lengths of PA (≥1, ≥2, and ≥5 min) and sedentary (≥1, ≥30, and ≥60 min) was defined as the number of minutes registered divided by total wear time × 100. Percent time was then tertiled for each bout length. Multiple linear regression models were used to estimate the associations between accelerometer bout variables and separate cognitive domains that included processing speed (Digit Symbol Coding; DSC), immediate and delayed recall (Hopkins Verbal Learning Test; HVLT), information processing and selective attention (Flanker), working memory (n-back), reaction time (switch and non-switch reaction time), and a composite score that averaged results from all cognitive tests. After adjusting for demographics, behavioral factors, and morbid conditions, more time spent in PA was associated with higher DSC for all bout lengths (p &lt; 0.03 for all). Higher PA was associated with higher HVLT and global cognition scores but only for longer bout lengths (p &lt; 0.05 for all). The association was largely driven by participants who spent the lowest amount of time performing activity while awake (p &lt; 0.04). An inverse linear relationship was observed between total sedentary time and DSC (p = 0.02), but not for other measures of cognition. These results suggest that, while higher PA was associated with higher cognitive performance, PA’s association with memory was sensitive to bout duration. The time, but not the manner, spent in sedentary behaviors showed a minor association with executive function. Further research is warranted to characterize longitudinal changes in daily activity and sedentary patterns as potential biophysical markers of cognitive status in older adults

Brain health: the importance of recognizing cognitive impairment: an IAGG consensus conference

Cognitive impairment creates significant challenges for patients, their families and friends, and clinicians who provide their health care. Early recognition allows for diagnosis and appropriate treatment, education, psychosocial support, and engagement in shared decision-making regarding life planning, health care, involvement in research, and financial matters. An IAGG-GARN consensus panel examined the importance of early recognition of impaired cognitive health. Their major conclusion was that case-finding by physicians and health professionals is an important step toward enhancing brain health for aging populations throughout the world. This conclusion is in keeping with the position of the United States' Centers for Medicare and Medicaid Services that reimburses for detection of cognitive impairment as part the of Medicare Annual Wellness Visit and with the international call for early detection of cognitive impairment as a patient's right. The panel agreed on the following specific findings: (1) validated screening tests are available that take 3 to 7 minutes to administer; (2) a combination of patient- and informant-based screens is the most appropriate approach for identifying early cognitive impairment; (3) early cognitive impairment may have treatable components; and (4) emerging data support a combination of medical and lifestyle interventions as a potential way to delay or reduce cognitive decline

Motoric Cognitive Risk Syndrome: Multicountry Prevalence and Dementia Risk

OBJECTIVES: Our objective is to report prevalence of motoric cognitive risk syndrome (MCR), a newly described predementia syndrome characterized by slow gait and cognitive complaints, in multiple countries, and its association with dementia risk. METHODS: Pooled MCR prevalence analysis of individual data from 26,802 adults without dementia and disability aged 60 years and older from 22 cohorts from 17 countries. We also examined risk of incident cognitive impairment (Mini-Mental State Examination decline ≥4 points) and dementia associated with MCR in 4,812 individuals without dementia with baseline Mini-Mental State Examination scores ≥25 from 4 prospective cohort studies using Cox models adjusted for potential confounders. RESULTS: At baseline, 2,808 of the 26,802 participants met MCR criteria. Pooled MCR prevalence was 9.7% (95% confidence interval [CI] 8.2%-11.2%). MCR prevalence was higher with older age but there were no sex differences. MCR predicted risk of developing incident cognitive impairment in the pooled sample (adjusted hazard ratio [aHR] 2.0, 95% CI 1.7-2.4); aHRs were 1.5 to 2.7 in the individual cohorts. MCR also predicted dementia in the pooled sample (aHR 1.9, 95% CI 1.5-2.3). The results persisted even after excluding participants with possible cognitive impairment, accounting for early dementia, and diagnostic overlap with other predementia syndromes. CONCLUSION: MCR is common in older adults, and is a strong and early risk factor for cognitive decline. This clinical approach can be easily applied to identify high-risk seniors in a wide variety of settings

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24&nbsp;months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500&nbsp;steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30&nbsp;minutes spent performing activities ≥500&nbsp;counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24&nbsp;months), both the number of steps per day (per 500&nbsp;steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500&nbsp;counts per minute (per 30&nbsp;minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score &gt;10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500