MMD
Monocyte to macrophage differentiation factor (Progestin and adipoQ receptor family member 11) (Progestin and adipoQ receptor family member XI) [PAQR11]
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Frailty is a geriatric syndrome represented by susceptibility to precipitating health events and reduced functional reserve. Frailty can be difficult to measure in clinical practice and research. One approach to approximate frailty is based on a deficit accumulation approach, which assesses a larger number of less specific measures such as the presence of comorbidities, physical or cognitive assessments, and lab tests, and summarizes these as a frailty index. The objective of this study was to develop such an index using the Lifestyle Interventions and Independence for Elders (LIFE) Study and evaluate the validity of the frailty measure derived based on baseline information via its association with the primary outcomes of the trial, namely major mobility disability (MMD) and persistent MMD (pMMD). Further, this study aimed to evaluate the effectiveness of the physical activity intervention among participants based on their baseline frailty score. Subjects in the LIFE Study were evaluated at baseline for demographics, clinical history, and a battery of physical and cognitive functioning assessments. In total, 75 possible deficits were scored either as present (yes/no) or based on each score's quintiles for score-based assessments. The frailty index was measured as the total sum of deficits divided by the total number of possible deficits on a continuous scale between 0 and 100 (i.e., percent of deficits present). The frailty index was further divided into quintiles for comparison. A proportional hazards model was estimated for the MMD outcome controlling for other baseline information. A data driven approach was also used to determine relevant cut-offs in the frailty index where the trial intervention appeared to be modified. Among 1635 trial participants, the mean frailty index was 30.4 ± 6.6 and normally distributed. Over 2.5 years of average follow-up, 14.6%, 16.5%, 18.6%, 22.6%, and 27.6% of participants experienced MMD in quintiles 1-5, respectively. Each 1-unit increase in the frailty index increased the hazard of MMD by 4% (2-5%), and there was a nearly 2-fold increase in MMD between the highest and lowest frailty quintiles. Using log-rank criteria, a cut-point at the median was identified. Further, iterations tested for a frailty cut-off and indicated a subgroup beyond the 85th percentile wherein the physical activity intervention appeared to be no longer be effective. This internally derived deficit accumulation frailty index was uniquely able to identify individuals at higher risk of MMD and pMMD and showed that along the spectrum of frailty, the physical activity intervention remained effective for the majority of participants.
Keywords
- LIFE Study
- deficit accumulation
- disability
- frailty
- healthy aging
- mobility
- older adults
Anticholinergic cognitive burden (ACB) may be associated with detrimental effects on mobility and physical independence in older adults. We evaluated the incidence of major mobility disability (MMD), persistent major mobility disability (PMMD), and injurious falls among participants within the Lifestyle Interventions for Elders (LIFE) trial according to varied anticholinergic burden levels. Participants aged 70-89 years were randomized to a physical activity (PA) or successful aging (SA) intervention and evaluated by ACB medication use as a summed score of a previously developed ACB scale. Confounders included demographic characteristics, physical function, cognitive function, and fall history. Average participant follow-up was 2.6 years and included outcome assessment for MMD, PMMD, and injurious falls every six months. Adjusted proportional hazards models evaluated the independent effects of ACB scores as well as interaction effects with the intervention. Of the 1635 participants, 986 (60%) used ≥1 anticholinergic medication. Compared to those with no burden, participants with an ACB score of 1 demonstrated increased MMD (HR = 1.42 [1.13-1.78]), PMMD (HR = 1.53 [1.12-2.09]), and injurious falls (HR = 1.60 [1.10-2.32]). Results similar in magnitude were observed for all other ACB levels versus the no burden group. Stepwise dose-response comparisons between ACB groupings did not demonstrate significant differences in outcomes. Stratification by PA or SA interventions demonstrated few differences from the combined overall trial results. Compared to those not taking anticholinergic medications, participants taking anticholinergic medications generally demonstrated increased risk of MMD, PMMD, and injurious falls. Total anticholinergic burden was not associated with a stepwise dose-response relationship in mobility disability and may lack sensitivity to capture varied responses.
Keywords
- anticholinergic burden
- falls
- mobility
- physical activity
- successful aging
Walking independently is basic to human functioning. The Lifestyle Interventions and Independence for Elders (LIFE) studies were developed to assess whether initiating physical activity could prevent major mobility disability (MMD) in sedentary older adults. We review the development and selected findings of the LIFE studies from 2000 through 2019, including the planning phase, the LIFE-Pilot Study, and the LIFE Study. The planning phase and the LIFE-Pilot provided key information for the successful implementation of the LIFE Study. The LIFE Study, involving 1635 participants randomized at eight sites throughout the United States, showed that compared with health education, the physical activity program reduced the risk of the primary outcome of MMD (inability to walk 400 m: hazard ratio = 0.82; 95% confidence interval = 0.69-0.98; P = .03), and that the intervention was cost-effective. There were no significant effects on cognitive outcomes, cardiovascular events, or serious fall injuries. In addition, the LIFE studies provided relevant findings on a broad range of other outcomes, including health, frailty, behavioral outcomes, biomarkers, and imaging. To date, the LIFE studies have generated a legacy of 109 peer-reviewed publications, 19 ancillary studies, and 38 independently funded grants and clinical trials, and advanced the development of 59 early career scientists. Data and biological samples of the LIFE Study are now publicly available from a repository sponsored by the National Institute on Aging (https://agingresearchbiobank.nia.nih.gov). The LIFE studies generated a wealth of important scientific findings and accelerated research in geriatrics and gerontology, benefiting the research community, trainees, clinicians, policy makers, and the general public. J Am Geriatr Soc 68:872-881, 2020.
Keywords
- aging
- mobility disability
- multicenter trialphysical activity
Increasing reports of pregnancy events leading to maternal microbiome dysbiosis (MMD) show strong correlates with atypical neurodevelopmental outcomes. However, the mechanism(s) driving microbiome-mediated behavioral dysfunction in offspring remain understudied. Here, we demonstrate the presence of a novel gut commensal bacterium strain, Lactobacillus murinus HU-1, was sufficient to rescue behavioral deficits and brain region-specific microglial activationobserved in MMD-reared murine offspring. We furtheridentified a postnatal window of susceptibility that could prevent social impairments with timed maternal administration of the symbiotic bacterium. Moreover, MMD increased expression of microglial senescence genes, Trp53 and Il1β, and Cx3cr1 protein in the prefrontal cortex, which correlated with dysfunctional modeling of synapses and accompanied dysbiosis-induced microglial activation. MMD male offspring harboring Lactobacillus murinus HU-1 or lacking Cx3cr1 showed amelioration of these effects. The current study describes a new avenue of influence by which maternally transferred Lactobacillus drives proper development of social behavior in the offspring through microglia-specific regulation of Cx3cr1 signaling.
MeSH Terms
- Animals
- Autism Spectrum Disorder
- CX3C Chemokine Receptor 1
- Dysbiosis
- Female
- Gastrointestinal Microbiome
- Interleukin-1beta
- Lactobacillus
- Male
- Mice
- Mice, Inbred C57BL
- Microbiota
- Microglia
- Neurodevelopmental Disorders
- Prefrontal Cortex
- Pregnancy
- Social Behavior
- Tumor Suppressor Protein p53
Keywords
- Autism spectrum disorders
- Cx3cr1
- Gut bacteria
- Microbiota
- Neurodevelopment
- Senescence
- Social behavior
- Trp53
The movement profile of older adults with compromised function is unknown, as is the relationship between these profiles and the development of major mobility disability (MMD)-a critical clinical outcome. We first describe the dimensions of movement in older adults with compromised function and then examine whether these dimensions predict the onset of MMD. Older adults at risk for MMD (N = 1,022, mean age = 78.7 years) were randomized to receive a structured physical activity intervention or health education control. We assessed MMD in 6-month intervals (average follow-up of 2.2 years until incident MMD), with activity assessed at baseline, 6-, 12- and 24-month follow-up via accelerometry. A principal components analysis of 11 accelerometer-derived metrics yielded three components representing lifestyle movement (LM), extended bouts of moderate-to-vigorous physical activity (MVPA), and stationary body posture. LM accounted for the greatest proportion of variance in movement (53%). Within health education, both baseline LM (HR = 0.74; 95% CI 0.62 to 0.88) and moderate-to-vigorous physical activity (HR = 0.69; 95% CI 0.54 to 0.87) were associated with MMD, whereas only LM was associated with MMD within physical activity (HR = 0.74; 95% CI 0.61 to 0.89). There were similar nonlinear relationships present for LM in both physical activity and health education (p < .04), whereby risk for MMD was lower among individuals with higher levels of LM. Both LM and moderate-to-vigorous physical activity should be central in treatment regimens for older adults at risk for MMD. clinicaltrials.gov Identifier NCT01072500.
MeSH Terms
- Acceleration
- Age Factors
- Aged
- Aged, 80 and over
- Aging
- Confidence Intervals
- Disability Evaluation
- Female
- Geriatric Assessment
- Humans
- Linear Models
- Male
- Mobility Limitation
- Physical Fitness
- Prognosis
- Sex Factors
- Single-Blind Method
- Walking Speed
Keywords
- Accelerometry
- Disability
- Exercise
- Physical activity
- Sedentary
To enable the diagnosis of moyamoya disease (MMD), detection of distal internal carotid artery stenosis and hazy network of basal collaterals (BCs) are required. This study aimed at evaluating the factors that could determine the degree of BCs in patients with angiographically confirmed MMD. We analyzed 146 consecutive patients with MMD (age 26.2 ± 19.6, range 1-75). The degree of BCs (%) was measured based on conventional angiography. Factors associated with the degree of BCs, including clinico-radiological and genetic factors (p.Arg4810Lys variant), were analyzed. The degree of BCs varied among MMD patients and significantly decreased with an increase in the age of diagnosis of MMD (coefficient -1.55; p < 0.001). Although the degree of BC development depends on the MMD stage (Suzuki stage), it is less prominent in adult-onset (>18 years) MMD compared to childhood MMD. The presence of p.Arg4810Lys variant, types of MMD (bilateral vs. unilateral) and stroke (ischemic, hemorrhagic, or asymptomatic), shrinkage (outer diameter) of intracranial vessels, external carotid collateral status, and cortical neovascularization were not associated with the degree of BCs. Although prominent BCs are required for diagnosis of MMD, BCs are decreased with aging, suggesting that angiogenic capacity is altered in adult onset MMD compared to childhood MMD.
MeSH Terms
- Adolescent
- Adult
- Aged
- Aging
- Brain
- Child
- Child, Preschool
- Collateral Circulation
- Female
- Humans
- Infant
- Male
- Middle Aged
- Moyamoya Disease
- Neovascularization, Pathologic
- Young Adult
This subgroup analysis of the Lifestyle Intervention and Independence for Elders trial evaluates the impact of a long-term physical activity (PA) intervention on rates of major mobility disability (MMD) among older adults according to their antihypertensive medication use. Lifestyle Intervention and Independence for Elders study participants were randomized to center-based PA or health education for a median of 2.7 years. Participants were sedentary men and women aged 70-89 years with objectively measured physical limitations. This analysis evaluated rates of MMD and persistent MMD among 1,633 participants, according to antihypertensive medication use. Participants were designated as either (i) an angiotensin-converting enzyme (ACE) inhibitor user (ACEi ), (ii) a user of other antihypertensives not including ACEi (ACEi-), or (iii) nonusers of antihypertensive medications (AHT-). Interactions were explored between antihypertensive use and randomized arm. Interaction terms for MMD (p = .214) and persistent MMD (p = .180) did not reach statistical significance. For MMD, PA displayed marginal effects among ACEi (hazard ratio [HR] = 0.76; 95% confidence interval [CI] = 0.57, 1.02) and ACEi- (HR = 0.76; 95% CI = 0.60, 0.97) but not AHT- (HR = 1.19; 95% CI = 0.75, 1.87). For persistent MMD, the effect of PA was greatest among ACEi (HR = 0.57; 95% CI = 0.39, 0.84) when compared to ACEi- (HR = 0.76; 95% CI = 0.55, 1.06) or AHT- (HR = 1.18; 95% CI = 0.59, 2.36). The effects of long-term PA on the incidence of MMD and persistent MMD were similar among three subgroups of older adults stratified by their antihypertensive medication use. However, though statistical interactions did not reach significance, several findings may warrant future study in other cohorts given the post hoc nature of this study.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Antihypertensive Agents
- Disability Evaluation
- Exercise
- Exercise Therapy
- Female
- Health Education
- Humans
- Hypertension
- Life Style
- Male
- Mobility Limitation
- Outcome Assessment, Health Care
- Preventive Health Services
- Time
- United States
Keywords
- Clinical trials
- Exercise
- Physical activity
- Physical function
Moyamoya disease (MMD) is characterized by unique angiographic features of collateralization. However, a detailed quantification as well as comparative analysis with cerebrovascular atherosclerotic disease (CAD) and healthy controls have not been performed to date. We reviewed 67 patients with MMD undergoing Xenon-enhanced computed tomography, as well as 108 patients with CAD and 5 controls. In addition to cortical, central, and infratentorial regions of interest, particular emphasis was put on regions that are typically involved in MMD (pericallosal territory, basal ganglia). Cerebral blood flow (CBF), cerebrovascular reserve capacity (CVRC), and hemodynamic stress distribution were calculated. MMD is characterized by a significant, ubiquitous decrease in CVRC and a cortical but not pericallosal decrease in CBF when compared with controls. Baseline perfusion is maintained within the basal ganglia, and hemodynamic stress distribution confirmed a relative preservation of central regions of interest in MMD, indicative for its characteristic proximal collateralization pattern. In MMD and CAD, cortical and central CBF decreased significantly with age, whereas CVRC and hemodynamic stress distribution are relatively unaffected by age. No difference in CVRC of comparable regions of interest was seen between MMD and CAD, but stress distribution was significantly higher in MMD, illustrating the functionality of the characteristic rete mirabilis. Our data provide quantitative support for a territory-specific perfusion pattern that is unique for MMD, including central preservation of CBF compared with controls and patients with CAD. This correlates well with its characteristic feature of proximal collateralization. CVRC and hemodynamic stress distribution seem to be more robust parameters than CBF alone for assessment of disease severity.
MeSH Terms
- Aging
- Cerebral Angiography
- Cerebrovascular Circulation
- Humans
- Image Processing, Computer-Assisted
- Magnetic Resonance Angiography
- Magnetic Resonance Imaging
- Moyamoya Disease
- Retrospective Studies
- Tomography, X-Ray Computed
- Xenon
Keywords
- Moyamoya disease
- Xenon
- computed tomography
- perfusion
multi-compartment medication devices (MMDs) are widely used, primarily by older people, to aid correct-medication taking. Several MMD types are available yet little is known about the ease with which patients with varying functional ability use these devices and whether some types are easier than others. Such knowledge would assist healthcare practitioners in advising patients on a suitable choice of device. this study investigates the ease with which patients with differing functional ability use three types of MMD. participants were recruited from an older person's medical ward. Demographic and medication information, cognitive function, visual acuity and manual dexterity were recorded. The Venalink®, Nomad Clear® and Dosett® MMDs were tested. Participants rated each MMD according to text readability, ease of opening, ease of medication removal, transportability and overall rating. These ratings were compared between MMDs for all patients and for subgroups with differing functional abilities. the MMDs were trialled by 50 patients; the majority rated text readability well but rated MMDs poorly according to the other criteria. Cognitively impaired participants may encounter difficulties in opening and removing medication from Venalink® and Nomad®. The Dosett® consistently rated better across all criteria. Transportability was the most influential criterion for overall MMD usability. the poor patient rating of MMDs which are widely used in practice is of concern. Some MMDs may be difficult to open and access, especially for patients with cognitive impairment. This offers some guidance to health professionals in advising patients on MMD choice however, overall MMD rating appears dominated by transportability.
MeSH Terms
- Age Factors
- Aged
- Aged, 80 and over
- Aging
- Cognition
- Cognition Disorders
- Drug Administration Schedule
- Drug Packaging
- Equipment Design
- Female
- Functional Laterality
- Health Knowledge, Attitudes, Practice
- Humans
- Male
- Medication Adherence
- Patient Satisfaction
- Polypharmacy
- Reminder Systems
- Time Factors
- Visual Acuity
Keywords
- adherence
- compliance aid
- functional ability
- medication organiser
- medication packaging
- older people