A Metabolomics Analysis of a Novel Phenotype of Older Adults at Higher Risk of Dementia.

BACKGROUND: Older adults presenting with dual-decline in cognition and walking speed face a 6-fold higher risk for dementia compared with those showing no decline. We hypothesized that the metabolomics profile of dual-decliners would be unique even before they show signs of decline in cognition and gait speed. OBJECTIVE: The objective of this study was to determine if plasma metabolomics signatures can discriminate dual-decliners from no decliners, purely cognitive decliners, and purely motor decliners prior to decline. METHODS: A retrospective cross-sectional study using baseline plasma for untargeted metabolomics analyses to investigate early signals of later dual-decline status in study participants (n = 76) with convenient sampling. Dual-decline was operationalized as decline in gait speed (>10 cm/s) and cognition (>2 points decline in Montreal Cognitive Assessment score) on at least two consecutive 6-monthly assessments. The participants' decliner status was evaluated 3 years after the blood sample was collected. Pair-wise comparison of detected compounds was completed using principal components and hierarchical clustering analyses. RESULTS: Analyses did not detect any cluster separation in untargeted metabolomes across baseline groups. However, follow-up analyses of specific molecules detected 4 compounds (17-Hydroxy-12-(hydroxymethyl)-10-oxo-8 oxapentacyclomethyl hexopyranoside, Fleroxacin, Oleic acid, and 5xi-11,12-Dihydroxyabieta-8(14),9(11),12-trien-20-oic acid) were at significantly higher concentration among the dual-decliners compared to non-decliners. The pure cognitive decliner group had significantly lower concentration of six compounds (1,3-nonanediol acetate, 4-(2-carboxyethyl)-2-methoxyphenyl beta-D-glucopyranosiduronic acid, oleic acid, 2E-3-[4-(sulfo-oxy)phenyl] acrylic acid, palmitelaidic acid, and myristoleic acid) compared to the non-decliner group. CONCLUSIONS: The unique metabolomics profile of dual-decliners warrants follow-up metabolomics analysis. Results may point to modifiable pathways.

Involvement of Informal Caregivers in Preventing Falls in Older Adults with Cognitive Impairment: A Rapid Review.

BACKGROUND: The prevalence of falls and related injuries is double in older adults with cognitive impairment compared with cognitively healthy older adults. A growing body of literature shows that falls prevention interventions in the cognitively impaired are difficult to implement and that the feasibility and adherence to interventions depend on a number of factors including informal caregiver involvement. However, no systematic review exists on the topic. OBJECTIVE: Our objective is to determine whether involvement of informal caregivers can reduce falls in older adults with cognitive impairment. METHODS: Rapid review following Cochrane collaboration guidelines. RESULTS: Seven randomized controlled trials were identified involving 2,202 participants. We identified the following areas where informal caregiving may have an important role in fall prevention in older adults with cognitive impairment: 1) enhancing adherence to the exercise program; 2) identifying and recording falls incidents and circumstances; 3) identifying and modifying possible environmental falls risk factors inside patient's home; and 4) playing an active role in modifying lifestyle in terms of diet/nutrition, limiting antipsychotics, and avoiding movements risking falls. However, informal caregiver involvement was identified as an incidental finding in these studies and the level of evidence ranged from low to moderate. CONCLUSION: Informal caregiver involvement in planning and delivering interventions to reduce falls has been found to increase the adherence of individuals with cognitive impairment in falls prevention programs. Future research should address whether involvement of informal caregivers may improve efficacy of prevention programs by reducing the number of falls as a primary outcome.

Investigation of Morphological, Optical, and Dielectric Properties of RF Sputtered WOx Thin Films for Optoelectronic Applications.

Tungsten oxide (WOx) thin films were synthesized through the RF magnetron sputtering method by varying the sputtering power from 30 W to 80 W. Different investigations have been conducted to evaluate the variation in different morphological, optical, and dielectric properties with the sputtering power and prove the possibility of using WOx in optoelectronic applications. An Energy Dispersive X-ray (EDX), stylus profilometer, and atomic force microscope (AFM) have been used to investigate the dependency of morphological properties on sputtering power. Transmittance, absorbance, and reflectance of the films, investigated by Ultraviolet-Visible (UV-Vis) spectroscopy, have allowed for further determination of some necessary parameters, such as absorption coefficient, penetration depth, optical band energy gap, refractive index, extinction coefficient, dielectric parameters, a few types of loss parameters, etc. Variations in these parameters with the incident light spectrum have been closely analyzed. Some important parameters such as transmittance (above 80%), optical band energy gap (~3.7 eV), and refractive index (~2) ensure that as-grown WOx films can be used in some optoelectronic applications, mainly in photovoltaic research. Furthermore, strong dependencies of all evaluated parameters on the sputtering power were found, which are to be of great use for developing the films with the required properties.

Evaluation of Clinical Practice Guidelines on Fall Prevention and Management for Older Adults: A Systematic Review.

Importance: With the global population aging, falls and fall-related injuries are ubiquitous, and several clinical practice guidelines for falls prevention and management for individuals 60 years or older have been developed. A systematic evaluation of the recommendations and agreement level is lacking. Objectives: To perform a systematic review of clinical practice guidelines for falls prevention and management for adults 60 years or older in all settings (eg, community, acute care, and nursing homes), evaluate agreement in recommendations, and identify potential gaps. Evidence Review: A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-analyses statement methods for clinical practice guidelines on fall prevention and management for older adults was conducted (updated July 1, 2021) using MEDLINE, PubMed, PsycINFO, Embase, CINAHL, the Cochrane Library, PEDro, and Epistemonikos databases. Medical Subject Headings search terms were related to falls, clinical practice guidelines, management and prevention, and older adults, with no restrictions on date, language, or setting for inclusion. Three independent reviewers selected records for full-text examination if they followed evidence- and consensus-based processes and assessed the quality of the guidelines using Appraisal of Guidelines for Research & Evaluation II (AGREE-II) criteria. The strength of the recommendations was evaluated using Grades of Recommendation, Assessment, Development, and Evaluation scores, and agreement across topic areas was assessed using the Fleiss κ statistic. Findings: Of 11 414 records identified, 159 were fully reviewed and assessed for eligibility, and 15 were included. All 15 selected guidelines had high-quality AGREE-II total scores (mean [SD], 80.1% [5.6%]), although individual quality domain scores for clinical applicability (mean [SD], 63.4% [11.4%]) and stakeholder (clinicians, patients, or caregivers) involvement (mean [SD], 76.3% [9.0%]) were lower. A total of 198 recommendations covering 16 topic areas in 15 guidelines were identified after screening 4767 abstracts that proceeded to 159 full texts. Most (≥11) guidelines strongly recommended performing risk stratification, assessment tests for gait and balance, fracture and osteoporosis management, multifactorial interventions, medication review, exercise promotion, environment modification, vision and footwear correction, referral to physiotherapy, and cardiovascular interventions. The strengths of the recommendations were inconsistent for vitamin D supplementation, addressing cognitive factors, and falls prevention education. Recommendations on use of hip protectors and digital technology or wearables were often missing. None of the examined guidelines included a patient or caregiver panel in their deliberations. Conclusions and Relevance: This systematic review found that current clinical practice guidelines on fall prevention and management for older adults showed a high degree of agreement in several areas in which strong recommendations were made, whereas other topic areas did not achieve this level of consensus or coverage. Future guidelines should address clinical applicability of their recommendations and include perspectives of patients and other stakeholders.

Virtual Reality Experience Intervention May Reduce Responsive Behaviors in Nursing Home Residents with Dementia: A Case Series.

BACKGROUND: People with advanced dementia often exhibit responsive behaviors such as apathy, depression, agitation, aggression, and psychosis. Non-pharmacological approaches (e.g., listening to music, watching television, doing arts and crafts) are now considered as a first-line strategy to manage responsive behaviors in clinical practice due to the potential risks associated with the antipsychotic medications. To date, no evaluations of immersive non-head mounted virtual reality (VR) experience as a non-pharmacologic approach for people with advanced dementia living in nursing homes have been reported. OBJECTIVE: To evaluate the feasibility (acceptance and safety) of VR experience. METHODS: A single site case series (nonrandomized and unblinded) with a convenience sample (N = 24; age = 85.8±8.6 years; Cognitive Performance Scale score = 3.4±0.6) measuring depression and agitation before and after the intervention. The intervention was a 30-min long research coordinator- facilitated VR experience for two weeks (10 sessions). RESULTS: The intervention was feasible (attrition rate = 0% ; adverse events = 0). A reduction in depression and in agitation was observed after the intervention. However, we suggest extreme caution in interpreting this result considering the study design and small sample size. CONCLUSION: This study provides the basis for conducting a randomized controlled trial to evaluate the effect of VR experience on responsive behaviors in nursing homes. Since our intervention uses a smart remote-controlled projector without a headset, infectious exposure can be avoided following the COVID-19 pandemic-induced physical distancing policy in care homes.

Effect of Wii Fit© Exercise on Balance of Older Adults with Neurocognitive Disorders: A Meta-Analysis.

BACKGROUND: Exercise is beneficial to maintain balance. Wii Fit©, a video game-based exercise, offers an enjoyable way to exercise and is feasible for older adults with neurocognitive disorders (NCD). OBJECTIVE: To evaluate the effects of Wii Fit© exercise training on the balance of older adults with NCD. METHODS: Systematic review and meta-analysis of randomized control trials using Cochrane collaboration tools. The participants were older adults (60 years and over) with NCD. Balance was measured with Berg Balance Scale (BBS) and Timed Up and Go (TUG). Two reviewers independently searched, selected, extracted data, assessed risk of biases, and determined the quality of evidence. Outcomes were evaluated using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). A meta-analysis was performed. RESULTS: The literature search identified 522 source documents of which titles and abstracts were reviewed for 428 after removing 94 duplicates. The reviewers selected five studies out of 50 after a full text review. The overall effect of Wii Fit© exercise training on BBS was moderate, significant, and clinically meaningful (standardized mean difference [SMD] = 0.5 standard deviation [SD] [95% confidence interval CI] 0.08, 0.84]). No effect was observed with TUG scores (SMD = 0.00 SD [95% CI -0.44, 0.44]). The GRADE quality of evidence was very low. CONCLUSION: Wii Fit© exercise training has a positive effect on balance in older adults with NCD. However, further research with sufficient power is needed to evaluate its effectiveness.

A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson disease: no evidence of benefit.

IMPORTANCE: Coenzyme Q10 (CoQ10), an antioxidant that supports mitochondrial function, has been shown in preclinical Parkinson disease (PD) models to reduce the loss of dopamine neurons, and was safe and well tolerated in early-phase human studies. A previous phase II study suggested possible clinical benefit. OBJECTIVE: To examine whether CoQ10 could slow disease progression in early PD. DESIGN, SETTING, AND PARTICIPANTS: A phase III randomized, placebo-controlled, double-blind clinical trial at 67 North American sites consisting of participants 30 years of age or older who received a diagnosis of PD within 5 years and who had the following inclusion criteria: the presence of a rest tremor, bradykinesia, and rigidity; a modified Hoehn and Yahr stage of 2.5 or less; and no anticipated need for dopaminergic therapy within 3 months. Exclusion criteria included the use of any PD medication within 60 days, the use of any symptomatic PD medication for more than 90 days, atypical or drug-induced parkinsonism, a Unified Parkinson's Disease Rating Scale (UPDRS) rest tremor score of 3 or greater for any limb, a Mini-Mental State Examination score of 25 or less, a history of stroke, the use of certain supplements, and substantial recent exposure to CoQ10. Of 696 participants screened, 78 were found to be ineligible, and 18 declined participation. INTERVENTIONS: The remaining 600 participants were randomly assigned to receive placebo, 1200 mg/d of CoQ10, or 2400 mg/d of CoQ10; all participants received 1200 IU/d of vitamin E. MAIN OUTCOMES AND MEASURES: Participants were observed for 16 months or until a disability requiring dopaminergic treatment. The prospectively defined primary outcome measure was the change in total UPDRS score (Parts I-III) from baseline to final visit. The study was powered to detect a 3-point difference between an active treatment and placebo. RESULTS: The baseline characteristics of the participants were well balanced, the mean age was 62.5 years, 66% of participants were male, and the mean baseline total UPDRS score was 22.7. A total of 267 participants required treatment (94 received placebo, 87 received 1200 mg/d of CoQ10, and 86 received 2400 mg/d of CoQ10), and 65 participants (29 who received placebo, 19 who received 1200 mg/d of CoQ10, and 17 who received 2400 mg/d of CoQ10) withdrew prematurely. Treatments were well tolerated with no safety concerns. The study was terminated after a prespecified futility criterion was reached. At study termination, both active treatment groups showed slight adverse trends relative to placebo. Adjusted mean changes (worsening) in total UPDRS scores from baseline to final visit were 6.9 points (placebo), 7.5 points (1200 mg/d of CoQ10; P = .49 relative to placebo), and 8.0 points (2400 mg/d of CoQ10; P = .21 relative to placebo). CONCLUSIONS AND RELEVANCE: Coenzyme Q10 was safe and well tolerated in this population, but showed no evidence of clinical benefit. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00740714.

Association between type 2 diabetes and chronic arsenic exposure in drinking water: a cross sectional study in Bangladesh.

BACKGROUND: Chronic exposure to high level of inorganic arsenic in drinking water has been associated with Type 2 Diabetes (T2D). Most research has been ecological in nature and has focused on high levels of arsenic exposure with few studies directly measuring arsenic levels in drinking water as an index of arsenic exposure. The effect of low to moderate levels of arsenic exposure on diabetes risk is largely unknown thus our study is adding further knowledge over previous works. METHODS: This cross sectional study was conducted in 1004 consenting women and men from 1682 eligible participants yielding a participation rate of 60%. These participants are aged >30 years and were living in Bangladesh and had continuously consumed arsenic-contaminated drinking water for at least 6 months. T2D cases were diagnosed using glucometer following the new diagnostic criteria (Fasting Blood Glucose > 126 mg/dl) from the WHO guideline (WHO 2006), or a self-reported physician diagnosis of type 2 diabetes. Association between T2D and chronic arsenic exposure was estimated by multiple logistic regression with adjustment for age, sex, education, Body Mass Index (BMI) and family history of T2D. RESULTS: A total of 1004 individuals participated in the study. The prevalence of T2D was 9% (95% CI 7-11%). After adjustment for diabetes risk factors, an increased risk of type 2 diabetes was observed for arsenic exposure over 50 µg/L with those in the highest category having almost double the risk of type 2 diabetes (OR=1.9 ; 95% CI 1.1-3.5). For most levels of arsenic exposure, the risk estimates are higher with longer exposure; a dose-response pattern was also observed. CONCLUSIONS: These findings suggest an association between chronic arsenic exposure through drinking water and T2D. Risks are generally higher with longer duration of arsenic exposure. The risk of T2D is highest among those who were exposed to the highest concentration of arsenic for more than 10 years.

Causes of neonatal and maternal deaths in Dhaka slums: implications for service delivery.

BACKGROUND: Bangladesh has about 5.7 million people living in urban slums that are characterized by adverse living conditions, poor access to healthcare services and health outcomes. In an attempt to ensure safe maternal, neonatal and child health services in the slums BRAC started a programme, MANOSHI, in 2007. This paper reports the causes of maternal and neonatal deaths in slums and discusses the implications of those deaths for Maternal Neonatal and Child Health service delivery. METHODS: Slums in three areas of Dhaka city were selected purposively. Data on causes of deaths were collected during 2008-2009 using verbal autopsy form. Two trained physicians independently assigned the cause of deaths. RESULTS: A total of 260 newborn and 38 maternal deaths were identified between 2008 and 2009. The majority (75%) of neonatal deaths occurred during 0-7 days. The main causes of deaths were birth asphyxia (42%), sepsis (20%) and birth trauma (7%). Post partum hemorrhage (37%) and eclampsia (16%) were the major direct causes and hepatic failure due to viral hepatitis was the most prevalent indirect cause (11%) of maternal deaths. CONCLUSION: Delivery at a health facility with child assessment within a day of delivery and appropriate treatment could reduce neonatal deaths. Maternal mortality is unlikely to reduce without delivering at facilities with basic Emergency Obstetric Care (EOC) and arrangements for timely referral to EOC. There is a need for a comprehensive package of services that includes control of infectious diseases during pregnancy, EOC and adequate after delivery care.