Potentially Modifiable Risk Factors for Dementia and Mild Cognitive Impairment: An Umbrella Review and Meta-Analysis.

INTRODUCTION: The prevalence of mild and major neurocognitive disorders (NCDs), also referred to as mild cognitive impairment and dementia, is rising globally. The prevention of NCDs is a major global public health interest. We sought to synthesize the literature on potentially modifiable risk factors for NCDs. METHODS: We conducted an umbrella review using a systematic search across multiple databases to identify relevant systematic reviews and meta-analyses. Eligible reviews examined potentially modifiable risk factors for mild or major NCDs. We used a random-effects multi-level meta-analytic approach to synthesize risk ratios for each risk factor while accounting for overlap in the reviews. We further examined risk factors for major NCD due to two common etiologies: Alzheimer's disease and vascular dementia. RESULTS: A total of 45 reviews with 212 meta-analyses were synthesized. We identified fourteen broadly defined modifiable risk factors that were significantly associated with these disorders: alcohol consumption, body weight, depression, diabetes mellitus, diet, hypertension, less education, physical inactivity, sensory loss, sleep disturbance, smoking, social isolation, traumatic brain injury, and vitamin D deficiency. All 14 factors were associated with the risk of major NCD, and five were associated with mild NCD. We found considerably less research for vascular dementia and mild NCD. CONCLUSION: Our review quantifies the risk associated with 14 potentially modifiable risk factors for mild and major NCDs, including several factors infrequently included in dementia action plans. Prevention strategies should consider approaches that reduce the incidence and severity of these risk factors through health promotion, identification, and early management.

The Effects of Cognitive Ability, Mental Health, and Self-Quarantining on Functional Ability of Older Adults During the COVID-19 Pandemic: Results From the Canadian Longitudinal Study on Aging.

OBJECTIVES: Determine whether levels of anxiety and depression, cognitive ability, and self-quarantining during and prior to the pandemic predict decreases in perceived functional ability. DESIGN AND SETTING: Longitudinal data collected from the Canadian Longitudinal Study on Aging (CLSA) COVID-19 Questionnaire Study (2020) and core CLSA study (Follow-Up 1; 2014-2018). PARTICIPANTS: 17 541 CLSA participants. MEASUREMENTS: Self-quarantining behaviours from questionnaires administered at Baseline (April 2020), Monthly, and Exit (December 2020) time points of the CLSA COVID-19 Questionnaire Study, levels of anxiety and depression at Baseline, perceived change in functional ability at Exit, and performance on neuropsychological tests (Rey Auditory Verbal Learning Task, Mental Alternation Task, Animal Fluency Test) and functional ability (Older Americans Resources and Services [OARS] Multidimensional Assessment Questionnaire) from the core CLSA study. RESULTS: Greater cognitive ability pre-pandemic (B = -.003, P < .01), higher levels of anxiety (B = -.024, P < .01) and depressive symptoms (B = -.110, P < .01) at Baseline, and higher frequency of engaging in self-quarantining throughout the COVID-19 survey period (B = -.098, P < .01) were associated with perceived loss in functional ability at Exit. Self-quarantining behaviour was associated with perceived loss in functional ability only at average and high levels of depressive symptoms (B = -.013, P < .01). CONCLUSIONS: Older adults with higher cognitive and lower functional ability prior to the pandemic were at greater risk of decreased perceived functional ability during the first year of the pandemic, as were those who experienced greater levels of anxiety and depressive symptoms during the pandemic. Strategies/interventions to preserve functional ability in older adults with cognitive independence prior to future pandemics are warranted.

Molecular characterization of chronic cutaneous wounds reveals subregion- and wound type-specific differential gene expression.

A limited understanding of the pathology underlying chronic wounds has hindered the development of effective diagnostic markers and pharmaceutical interventions. This study aimed to elucidate the molecular composition of various common chronic ulcer types to facilitate drug discovery strategies. We conducted a comprehensive analysis of leg ulcers (LUs), encompassing venous and arterial ulcers, foot ulcers (FUs), pressure ulcers (PUs), and compared them with surgical wound healing complications (WHCs). To explore the pathophysiological mechanisms and identify similarities or differences within wounds, we dissected wounds into distinct subregions, including the wound bed, border, and peri-wound areas, and compared them against intact skin. By correlating histopathology, RNA sequencing (RNA-Seq), and immunohistochemistry (IHC), we identified unique genes, pathways, and cell type abundance patterns in each wound type and subregion. These correlations aim to aid clinicians in selecting targeted treatment options and informing the design of future preclinical and clinical studies in wound healing. Notably, specific genes, such as PITX1 and UPP1, exhibited exclusive upregulation in LUs and FUs, potentially offering significant benefits to specialists in limb preservation and clinical treatment decisions. In contrast, comparisons between different wound subregions, regardless of wound type, revealed distinct expression profiles. The pleiotropic chemokine-like ligand GPR15L (C10orf99) and transmembrane serine proteases TMPRSS11A/D were significantly upregulated in wound border subregions. Interestingly, WHCs exhibited a nearly identical transcriptome to PUs, indicating clinical relevance. Histological examination revealed blood vessel occlusions with impaired angiogenesis in chronic wounds, alongside elevated expression of genes and immunoreactive markers related to blood vessel and lymphatic epithelial cells in wound bed subregions. Additionally, inflammatory and epithelial markers indicated heightened inflammatory responses in wound bed and border subregions and reduced wound bed epithelialization. In summary, chronic wounds from diverse anatomical sites share common aspects of wound pathophysiology but also exhibit distinct molecular differences. These unique molecular characteristics present promising opportunities for drug discovery and treatment, particularly for patients suffering from chronic wounds. The identified diagnostic markers hold the potential to enhance preclinical and clinical trials in the field of wound healing.

Obesity and adverse childhood experiences in relation to stress during the COVID-19 pandemic: an analysis of the Canadian Longitudinal Study on Aging.

BACKGROUND: People with obesity are at increased risk of chronic stress, and this may have been exacerbated during the COVID-19 pandemic. Adverse childhood experiences (ACE) are also associated with both obesity and stress, and may modify risk of stress among people with obesity. The objectives of this study were to evaluate the associations between obesity, ACEs, and stress during the pandemic, and to determine if the association between obesity and stress was modified by ACEs. METHODS: A longitudinal study was conducted among adults aged 50-96 years (n = 23,972) from the Canadian Longitudinal Study on Aging (CLSA) COVID-19 Study. Obesity and ACEs were collected pre-pandemic (2015-2018), and stress was measured at COVID-19 Exit Survey (Sept-Dec 2020). We used logistic, Poisson, and negative binomial regression to estimate relative risks (RRs) and 95% confidence intervals (CIs) for the associations between obesity, ACEs, and stress outcomes during the pandemic. Interaction by ACEs was evaluated on the additive and multiplicative scales. RESULTS: People with obesity were more likely to experience an increase in overall stressors (class III obesity vs. healthy weight RR = 1.19; 95% CI: 1.12-1.27) as well as increased health related stressors (class III obesity vs. healthy weight RR: 1.25; 95% CI: 1.12-1.39) but did not perceive the consequences of the pandemic as negative. ACEs were also associated an increase in overall stressors (4-8 ACEs vs. none RR = 1.38; 95% CI: 1.33-1.44) and being more likely to perceive the pandemic as negative (4-8 ACEs vs. none RR = 1.32; 95% CI: 1.19-1.47). The association between obesity and stress was not modified by ACEs. CONCLUSIONS: Increased stress during the first year of the COVID-19 pandemic was observed among people with obesity or ACEs. The long-term outcomes of stress during the pandemic need to be determined.

An investigation of psychoactive polypharmacy and related gender-differences in older adults with dementia: a retrospective cohort study.

BACKGROUND: Older adults living with dementia may express challenging responsive behaviours. One management strategy is pharmacologic treatment though these options often have limited benefit, which may lead to multiple treatments being prescribed. METHODS: The aim of the present study was to describe psychoactive medication polypharmacy and explore factors associated with psychoactive polypharmacy in a cohort of older adults living with dementia in Nova Scotia, Canada, including a gender-stratified analysis. This was a retrospective cohort study of those aged 65 years or older with a recorded diagnosis of dementia between 2005 and 2015. Medication dispensation data was collected from April 1, 2010, or dementia diagnosis (cohort entry) to either death or March 31, 2015 (cohort exit). Psychoactive medication claims were captured. Psychoactive medication polypharmacy was defined as presence of three or more psychoactive prescription medications dispensed to one subject and overlapping for more than 30 days. Psychoactive polypharmacy episodes were described in duration, quantity, and implicated medications. Regression analysis examined factors associated with experience and frequency of psychoactive polypharmacy. All analysis were stratified by gender. RESULTS: The cohort included 15,819 adults living with dementia (mean age 80.7 years; 70.0% female), with 99.4% (n = 15,728) receiving at least one psychoactive medication over the period of follow-up. Psychoactive polypharmacy was present in 19.3% of the cohort. The gender specific logistic regressions demonstrated that for both men and women a younger age was associated with an increased risk of psychoactive polypharmacy (women: OR 0.97, 95%CI[0.96, 0.98], men: OR 0.96, 95%CI[0.95, 0.97]). Men were less likely to experience psychoactive polypharmacy if their location of residence was urban (OR 0.86, 95%CI[0.74, 0.99]). There was no significant association between location of residence (urban or rural) and psychoactive polypharmacy for women living with dementia. Antidepressants were the most dispensed medication class, while quetiapine was the most dispensed medication. CONCLUSIONS: This study suggests that of adults living with dementia those of younger ages were more likely to experience psychoactive polypharmacy and that men living with dementia in rural locations may benefit from increased access to non-pharmacological options for dementia management.

Increased prevalence of loneliness and associated risk factors during the COVID-19 pandemic: findings from the Canadian Longitudinal Study on Aging (CLSA).

BACKGROUND: Older adults have been disproportionately impacted by COVID-19 and related preventative measures undertaken during the pandemic. Given clear evidence of the relationship between loneliness and health outcomes, it is imperative to better understand if, and how, loneliness has changed for older adults during the COVID-19 pandemic, and whom it has impacted most. METHOD: We used "pre-pandemic" data collected between 2015-2018 (n = 44,817) and "during pandemic" data collected between Sept 29-Dec 29, 2020 (n = 24,114) from community-living older adults participating in the Canadian Longitudinal Study on Aging. Loneliness was measured using the 3-item UCLA Loneliness Scale. Weighted generalized estimating equations estimated the prevalence of loneliness pre-pandemic and during the pandemic. Lagged logistic regression models examined individual-level factors associated with loneliness during the pandemic. RESULTS: We found the adjusted prevalence of loneliness increased to 50.5% (95% CI: 48.0%-53.1%) during the pandemic compared to 30.75% (95% CI: 28.72%-32.85%) pre-pandemic. Loneliness increased more for women (22.3% vs. 17.0%), those in urban areas (20.8% vs. 14.6%), and less for those 75 years and older (16.1% vs. 19.8% or more in all other age groups). Loneliness during the pandemic was strongly associated with pre-pandemic loneliness (aOR 4.87; 95% CI 4.49-5.28) and individual level sociodemographic factors [age < 55 vs. 75 + (aOR 1.41; CI 1.23-1.63), women (aOR 1.34; CI 1.25-1.43), and no post-secondary education vs. post-secondary education (aOR 0.73; CI 0.61-0.86)], living conditions [living alone (aOR 1.39; CI 1.27-1.52) and urban living (aOR 1.18; CI 1.07-1.30)], health status [depression (aOR 2.08; CI 1.88-2.30) and having two, or ≥ three chronic conditions (aOR 1.16; CI 1.03-1.31 and aOR 1.34; CI 1.20-1.50)], health behaviours [regular drinker vs. non-drinker (aOR 1.15; CI 1.04-1.28)], and pandemic-related factors [essential worker (aOR 0.77; CI 0.69-0.87), and spending less time alone than usual on weekdays (aOR 1.32; CI 1.19-1.46) and weekends (aOR 1.27; CI 1.14-1.41) compared to spending the same amount of time alone]. CONCLUSIONS: As has been noted for various other outcomes, the pandemic did not impact all subgroups of the population in the same way with respect to loneliness. Our results suggest that public health measures aimed at reducing loneliness during a pandemic should incorporate multifactor interventions fostering positive health behaviours and consider targeting those at high risk for loneliness.

Pandemic-related factors predicting physician burnout beyond established organizational factors: cross-sectional results from the COPING survey.

The COVID-19 pandemic has increased physician burnout beyond high baseline levels. We aimed to determine whether pandemic-related factors contribute to physician burnout beyond known organizational factors. This was a cross-sectional survey of Canadian physicians using a convenience sample. Eligible participants included any physician currently holding a license to practice in Canada. Responses were gathered from May 13 to 12 June 2020. Risk factors measured included the newly developed Pandemic Experiences and Perceptions Scale (PEPS) subscales, contact with virus, pandemic preparation, and provincial caseload. The primary outcome was the Maslach Burnout Inventory (MBI). The primary outcome was completed by 309 respondents. Latent profile analysis found 107 (34.6%) respondents were burned out. In multivariate analysis, exhaustion was independently associated with PEPS adequacy, risk perception, and worklife subscales (adjusted R2 = 0.236, P < 0.001). Cynicism was associated with exhaustion, and PEPS worklife (adjusted R2 = 0.543, P < 0.001). Efficacy was associated with cynicism, PEPS worklife, and active cases (adjusted R2 = 0.152, P < 0.001). Structural equation modelling showed statistically significant direct paths between PEPS areas of worklife and all MBI subscales. Contact with virus, preparation, and PEPS risk perception added to the prediction of MBI exhaustion. Among a sample of Canadian physicians during the COVID-19 pandemic, adequacy of resources, risk perception, and quality of worklife were associated with burnout indices. To mitigate physician burnout organizations should work to improve working conditions, ensure adequate resources, and foster perceived control of risk of transmission.Trial Registration: NCT04379063.

Factors Associated With Willingness to Receive a COVID-19 Vaccine Among 23,819 Adults Aged 50 Years or Older: An Analysis of the Canadian Longitudinal Study on Aging.

Identifying persons who are least willing to receive a coronavirus disease 2019 (COVID-19) vaccine is critical for increasing uptake via targeted outreach. We conducted a survey of 23,819 Canadian Longitudinal Study on Aging participants from September 29 to December 29, 2020, to assess factors associated with COVID-19 vaccination willingness and reasons for willingness or lack thereof. Among adults aged 50-96 years, 84.1% (95% confidence interval (CI): 83.7, 84.6) were very or somewhat willing to receive a COVID-19 vaccine; 15.9% (95% CI: 15.4, 16.3) were uncertain or very or somewhat unwilling. Based on logistic regression, those who were younger, female, had lower education and income, were non-White, and lived in a rural area were less willing to receive a COVID-19 vaccine. After controlling for these factors, recent receipt of influenza vaccine (adjusted odds ratio = 14.3, 95% CI: 12.5, 16.2) or planning to receive influenza vaccine (adjusted odds ratio = 10.5, 95% CI: 9.5, 11.6), as compared with no receipt or planning, was most strongly associated with COVID-19 vaccination willingness. Willingness was also associated with believing one had never been infected with severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) and experiencing negative pandemic consequences. Safety concerns were most common among those unwilling. Our comprehensive assessment of COVID-19 vaccination willingness among older adults in Canada, a prioritized group for vaccination due to their risk of severe COVID-19 outcomes, provides a road map for conducting outreach to increase uptake, which is urgently needed.

Frailty indices based on self-report, blood-based biomarkers and examination-based data in the Canadian Longitudinal Study on Aging.

BACKGROUND: Frailty can be operationalised using the deficit accumulation approach, which considers health deficits across multiple domains. We aimed to develop, validate and compare three different frailty indices (FI) constructed from self-reported health measures (FI-Self Report), blood-based biomarkers (FI-Blood) and examination-based assessments (FI-Examination). METHODS: Up to 30,027 participants aged 45-85 years from the baseline (2011-2015) comprehensive cohort of the Canadian Longitudinal Study on Aging were included in the analyses. Following standard criteria, three FIs were created: a 48-item FI-Self Report, a 23-item FI-Blood and a 47-item FI-Examination. In addition a 118-item FI-Combined was constructed. Mortality status was ascertained in July 2019. RESULTS: FI-Blood and FI-Examination demonstrated broader distributions than FI-Self Report. FI-Self Report and FI-Blood scores were higher in females, whereas FI-Examination scores were higher in males. All FI scores increased nonlinearly with age and were highest at lower education levels. In sex and age-adjusted models, a 0.01 increase in FI score was associated with a 1.08 [95% confidence interval (CI): 1.07,1.10], 1.05 (1.04,1.06), 1.07 (1.05,1.08) and a 1.13 (1.11,1.16) increased odds of mortality for FI-Self Report, FI-Blood, FI-Examination and FI-Combined, respectively. Inclusion of the three distinct FI types in a single model yielded the best prognostic accuracy and model fit, even compared to the FI-Combined, with all FIs remaining independently associated with mortality. CONCLUSION: Characteristics of all FIs were largely consistent with previously established FIs. To adequately capture frailty levels and to improve our understanding of the heterogeneity of ageing, FIs should consider multiple types of deficits including self-reported, blood and examination-based measures.

Frailty and the impacts of the COVID-19 pandemic on community-living middle-aged and older adults: an analysis of data from the Canadian Longitudinal Study on Aging (CLSA).

BACKGROUND: frailty imparts a higher risk for hospitalisation, mortality and morbidity due to COVID-19 infection, but the broader impacts of the pandemic and associated public health measures on community-living people with frailty are less known. METHODS: we used cross-sectional data from 23,974 Canadian Longitudinal Study on Aging participants who completed a COVID-19 interview (Sept-Dec 2020). Participants were included regardless of whether they had COVID-19 or not. They were asked about health, resource, relationship and health care access impacts experienced during the pandemic. Unadjusted and adjusted prevalence of impacts was estimated by frailty index quartile. We further examined if the relationship with frailty was modified by sex, age or household income. RESULTS: community-living adults (50-90 years) with greater pre-pandemic frailty reported more negative impacts during the first year of the pandemic. The frailty gradient was not explained by socio-demographic or health behaviour factors. The largest absolute difference in adjusted prevalence between the most and least frail quartiles was 15.1% (challenges accessing healthcare), 13.3% (being ill) and 7.4% (increased verbal/physical conflict). The association between frailty and healthcare access differed by age where the youngest age group tended to experience the most challenges, especially for those categorised as most frail. CONCLUSION: although frailty has been endorsed as a tool to inform estimates of COVID-19 risk, our data suggest it may have a broader role in primary care and public health by identifying people who may benefit from interventions to reduce health and social impacts of COVID-19 and future pandemics.

Symptoms of depression and anxiety, and unmet healthcare needs in adults during the COVID-19 pandemic: a cross-sectional study from the Canadian Longitudinal Study on Aging.

BACKGROUND: The COVID-19 pandemic disrupted access to healthcare services in Canada. Research prior to the pandemic has found that depression and anxiety symptoms were associated with increased unmet healthcare needs. The primary objective of this study was to examine if mental health was associated with perceived access to healthcare during the pandemic METHODS: A cross-sectional study was conducted using data from 23,972 participants (aged 50-96) in the Canadian Longitudinal Study on Aging COVID-19 Exit Survey (Sept-Dec 2020). We used logistic regression to estimate how the presence of depression and anxiety symptoms, defined using scores of ≥10 on the Center for Epidemiologic Studies Depression Scale and ≥10 on the Generalized Anxiety Disorder Scale, were associated with the odds of reporting: 1) challenges accessing healthcare, 2) not going to a hospital or seeing a doctor when needed, 3) experiencing barriers to COVID-19 testing. Models were adjusted for sex, age, region, urban/rural residence, racial background, immigrant status, income, marital status, work status, chronic conditions, and pre-pandemic unmet needs. RESULTS: The presence of depressive (aOR=1.96; 95% CI=1.82, 2.11) and anxiety symptoms (aOR=2.33; 95% CI=2.04, 2.66) compared to the absence of these symptoms were independently associated with higher odds of challenges accessing healthcare. A statistically significant interaction with sex suggested stronger associations in females with anxiety. Symptoms of depression (aOR=2.88; 95% CI=2.58, 3.21) and anxiety (aOR=3.05; 95% CI=2.58, 3.60) were also associated with increased odds of not going to a hospital or seeing a doctor when needed. Lastly, depressive (aOR=1.99; 95% CI=1.71, 2.31) and anxiety symptoms (aOR=2.01; 95% CI=1.58, 2.56) were associated with higher odds of reporting barriers to COVID-19 testing. There was no significantly significant interaction with sex for the latter two outcomes. CONCLUSION: The presence of depression and anxiety symptoms were strongly associated with perceived unmet healthcare needs during the COVID-19 pandemic. Interventions to improve healthcare access for adults with depression and anxiety during the pandemic may be necessary.

Frailty among middle-aged and older Canadians: population norms for the frailty index using the Canadian Longitudinal Study on Aging.

BACKGROUND: frailty is a public health priority now that the global population is ageing at a rapid rate. A scientifically sound tool to measure frailty and generate population-based reference values is a starting point. OBJECTIVE: in this report, our objectives were to operationalize frailty as deficit accumulation using a standard frailty index (FI), describe levels of frailty in Canadians ≥45 years old and provide national normative data. DESIGN: this is a secondary analysis of the Canadian Longitudinal Study on Aging (CLSA) baseline data. SETTING/PARTICIPANTS: about 51,338 individuals (weighted to represent 13,232,651 Canadians), aged 45-85 years, from the tracking and comprehensive cohorts of CLSA. METHODS: after screening all available variables in the pooled dataset, 52 items were selected to construct an FI. Descriptive statistics for the FI and normative data derived from quantile regressions were developed. RESULTS: the average age of the participants was 60.3 years (95% confidence interval [CI]: 60.2-60.5), and 51.5% were female (95% CI: 50.8-52.2). The mean FI score was 0.07 (95% CI: 0.07-0.08) with a standard deviation of 0.06. Frailty was higher among females and with increasing age, and scores >0.2 were present in 4.2% of the sample. National normative data were identified for each year of age for males and females. CONCLUSIONS: the standardized frailty tool and the population-based normative frailty values can help inform discussions about frailty, setting a new bar in the field. Such information can be used by clinicians, researchers, stakeholders and the general public to understand frailty, especially its relationship with age and sex.

An examination of three prescribing cascades in a cohort of older adults with dementia.

BACKGROUND: Prescribing cascades are a source of inappropriate prescribing for older adults with dementia. We aimed to study three prescribing cascades in older Nova Scotians with dementia using administrative databases. METHODS: Cohort entry for Nova Scotia Seniors' Pharmacare Program beneficiaries was the date of dementia diagnosis. Prescription drug dispensing data was extracted for inciting medication and second treatment (cholinesterase inhibitor and bladder anticholinergic, metoclopramide and Parkinson's disease medication, or calcium channel blocker (CCB) and diuretic) over the six-year period April 1, 2009 to March 31, 2015. In three separate analyses, dispensing an inciting medication signaled a look back of 365 days from the date of first dispensing to confirm that the second treatment was started after the inciting medication. The prescribing cascade was considered when the second treatment was started within 180 days of the inciting treatment. Sex differences in the prescribing cascade were tested using t-tests or chi square tests as appropriate. Both univariate (unadjusted) and multivariate (adjusted) logistic regression (adjusted for age, rurality, and sex) and Cox proportional hazards regression was used to identify risk factors for the prescribing cascade. RESULTS: From March 1, 2005 to March 31, 2015, 28,953 Nova Scotia Seniors' Pharmacare beneficiaries with dementia (NSSPBD) were identified. There were 60 cases of bladder anticholinergics following cholinesterase inhibitors, 11 cases of Parkinson's disease medication following metoclopramide, and 289 cases of a diuretic following CCB in the cohort. Regression analysis demonstrated that risk of bladder anticholinergics following cholinesterase inhibitors and diuretics following CCBs were associated with female sex. Cox regression suggested that bladder anticholinergics were less often used by those on cholinesterase inhibitors and did not identify CCB use as leading more frequently to diuretic use. CONCLUSIONS: The combination of diuretics following CCB was the most common prescribing cascade and bladder anticholinergics following cholinesterase inhibitors the second most common. However, exposure to the inciting medications did not increase risk of exposure to the second treatments. Combinations of bladder anticholinergics following cholinesterase inhibitors and diuretics following CCBs were more common for women raising concern that women may be at increased risk of these prescribing cascades.

Comparisons of disease cluster patterns, prevalence and health factors in the USA, Canada, England and Ireland.

BACKGROUND: Identification of those who are most at risk of developing specific patterns of disease across different populations is required for directing public health policy. Here, we contrast prevalence and patterns of cross-national disease incidence, co-occurrence and related risk factors across population samples from the U.S., Canada, England and Ireland. METHODS: Participants (n = 62,111) were drawn from the US Health and Retirement Study (n = 10,858); the Canadian Longitudinal Study on Ageing (n = 36,647); the English Longitudinal Study of Ageing (n = 7938) and The Irish Longitudinal Study on Ageing (n = 6668). Self-reported lifetime prevalence of 10 medical conditions, predominant clusters of multimorbidity and their specific risk factors were compared across countries using latent class analysis. RESULTS: The U.S. had significantly higher prevalence of multimorbid disease patterns and nearly all diseases when compared to the three other countries, even after adjusting for age, sex, BMI, income, employment status, education, alcohol consumption and smoking history. For the U.S. the most at-risk group were younger on average compared to Canada, England and Ireland. Socioeconomic gradients for specific disease combinations were more pronounced for the U.S., Canada and England than they were for Ireland. The rates of obesity trends over the last 50 years align with the prevalence of eight of the 10 diseases examined. While patterns of disease clusters and the risk factors related to each of the disease clusters were similar, the probabilities of the diseases within each cluster differed across countries. CONCLUSIONS: This information can be used to better understand the complex nature of multimorbidity and identify appropriate prevention and management strategies for treating multimorbidity across countries.

Potentially Inappropriate Drug Duplication in a Cohort of Older Adults with Dementia.

BACKGROUND: Concurrent use of 2 nonsteroidal anti-inflammatory drugs, selective serotonin reuptake inhibitors, loop diuretics, angiotensin-converting enzyme inhibitors, or anticoagulants is considered potentially inappropriate by Screening Tool of Older Persons' Prescriptions and Screening Tool to Alert to Right Treatment criteria. OBJECTIVE: The objective was to examine drug duplication in a cohort of older adults with dementia. METHODS: Cohort entry for Nova Scotia Seniors' Pharmacare Program beneficiaries was the date an International Classification of Diseases ninth edition or 10th edition code for dementia was recorded in accessed databases between March 1, 2005, and March 31, 2015. Medication dispensation and sociodemographic data were captured from the Nova Scotia Seniors' Pharmacare Program database between April 1, 2010, and March 31, 2015. Duplication was considered when 2 drugs from the same class were dispensed such that the supply in the patient's possession could overlap for more than 30 days. We reported number of cases of duplication and duration of overlap. Sex differences in drug duplication were assessed with bivariate logistic regression. RESULTS: In the cohort of 28,953 Nova Scotia Seniors' Pharmacare Program beneficiaries with dementia, we documented concurrent use in 101 (1.7%) nonsteroidal anti-inflammatory drugs users (mean duration = 75.6 days), 95 (1.0%) selective serotonin reuptake inhibitors users (mean duration = 146.6 days), 5 (0.07%) loop diuretic users (mean duration = 530.6 days), 183 (2.0%) angiotensin-converting enzyme inhibitor users (mean duration = 123.9 days), and 160 (3.5%) anticoagulant users (mean duration = 63.6 days). Nonsteroidal anti-inflammatory drug pairs were most commonly celecoxib with naproxen or diclofenac. Selective serotonin reuptake inhibitors duplication was most commonly sertraline with citalopram. No sex differences in risk for drug duplication were identified. CONCLUSIONS: Drug duplication was identified in a cohort of older adults with dementia and is a feasible target for intervention. (Curr Ther Res Clin Exp. 2021; 82:XXX-XXX).

Osteoporotic fractures and obesity affect frailty progression: a longitudinal analysis of the Canadian multicentre osteoporosis study.

BACKGROUND: Despite knowing better how to screen older adults, understanding how frailty progression might be modified is unclear. We explored effects of modifiable and non-modifiable factors on changes in frailty in community-dwelling adults aged 50+ years who participated in the Canadian Multicentre Osteoporosis Study (CaMos). METHODS: Rates of change in frailty over 10 years were examined using the 30-item CaMos Frailty Index (CFI). Incident and prevalent low-trauma fractures were categorized by fracture site into hip, clinical vertebral and non-hip-non-vertebral fractures. Multivariable generalized estimating equation models accounted for the time of frailty assessment (baseline, 5 and 10 years), sex, age, body mass index (BMI, kg/m2), physical activity, bone mineral density, antiresorptive therapy, health-related quality of life (HRQL), cognitive status, and other factors for frailty or fractures. Multiple imputation and scenario analyses addressed bias due to attrition or missing data. RESULTS: The cohort included 5566 women (mean ± standard deviation: 66.8 ± 9.3 years) and 2187 men (66.3 ± 9.5 years) with the mean baseline CFI scores of 0.15 ± 0.11 and 0.12 ± 0.10, respectively. Incident fractures and obesity most strongly predicted frailty progression in multivariable analyses. The impact of fractures differed between the sexes. With each incident hip fracture, the adjusted mean CFI accelerated per 5 years by 0.07 in women (95% confidence interval [CI]: 0.03 to 0.11) and by 0.12 in men (95% CI: 0.08 to 0.16). An incident vertebral fracture increased frailty in women (0.05, 95% CI: 0.02 to 0.08) but not in men (0.01, 95% CI: -0.07 to 0.09). Irrespective of sex and prevalent fractures, baseline obesity was associated with faster frailty progression: a 5-year increase in the adjusted mean CFI ranged from 0.01 in overweight (BMI: 25.0 to 29.9 kg/m2) to 0.10 in obese individuals (BMI: ≥ 40 kg/m2). Greater physical activity and better HRQL decreased frailty over time. The results remained robust in scenario analyses. CONCLUSIONS: Older women and men with new vertebral fractures, hip fractures or obesity represent high-risk groups that should be considered for frailty interventions.

Gene-centric meta-analyses for central adiposity traits in up to 57 412 individuals of European descent confirm known loci and reveal several novel associations.

Waist circumference (WC) and waist-to-hip ratio (WHR) are surrogate measures of central adiposity that are associated with adverse cardiovascular events, type 2 diabetes and cancer independent of body mass index (BMI). WC and WHR are highly heritable with multiple susceptibility loci identified to date. We assessed the association between SNPs and BMI-adjusted WC and WHR and unadjusted WC in up to 57 412 individuals of European descent from 22 cohorts collaborating with the NHLBI's Candidate Gene Association Resource (CARe) project. The study population consisted of women and men aged 20-80 years. Study participants were genotyped using the ITMAT/Broad/CARE array, which includes ∼50 000 cosmopolitan tagged SNPs across ∼2100 cardiovascular-related genes. Each trait was modeled as a function of age, study site and principal components to control for population stratification, and we conducted a fixed-effects meta-analysis. No new loci for WC were observed. For WHR analyses, three novel loci were significantly associated (P < 2.4 × 10(-6)). Previously unreported rs2811337-G near TMCC1 was associated with increased WHR (ß ± SE, 0.048 ± 0.008, P = 7.7 × 10(-9)) as was rs7302703-G in HOXC10 (ß = 0.044 ± 0.008, P = 2.9 × 10(-7)) and rs936108-C in PEMT (ß = 0.035 ± 0.007, P = 1.9 × 10(-6)). Sex-stratified analyses revealed two additional novel signals among females only, rs12076073-A in SHC1 (ß = 0.10 ± 0.02, P = 1.9 × 10(-6)) and rs1037575-A in ATBDB4 (ß = 0.046 ± 0.01, P = 2.2 × 10(-6)), supporting an already established sexual dimorphism of central adiposity-related genetic variants. Functional analysis using ENCODE and eQTL databases revealed that several of these loci are in regulatory regions or regions with differential expression in adipose tissue.

The Long-Term Pelvic Floor Health Outcomes of Women After Childbirth: The Influence of Labour in the First Pregnancy.

OBJECTIVE: To estimate the influence of labour and pregnancy factors on long-term pelvic floor health outcomes. METHODS: This population-based cohort study was conducted using linkage between the Nova Scotia Atlee Perinatal Database, the Medical Services Insurance Database, and the Canadian Institute for Health Information's Discharge Abstract Database from 1988 to 2006; this allowed for the evaluation of patient utilization of care providers for pelvic floor disorders and captured conservative and surgical interventions. We compared rates of urinary and anal incontinence, pelvic organ prolapse, and fistula disorders in women undergoing Caesarean section (CS) without labour and women undergoing labour with any method of delivery. Multivariate logistic regression and survival (time-to-event) analyses were performed. RESULTS: Absolute risks for the selected pelvic floor health outcomes were low, regardless of whether labour was experienced in the first pregnancy. Women with one or more deliveries who had a CS without labour in their first pregnancy had reduced risks for all pelvic floor health outcomes, except fistula formation, and they were also less likely to develop these outcomes during the study period. CONCLUSION: Women undergoing obstetrically indicated CS without labour in their first delivery may have reduced risks of pelvic floor health disorders, even after multiple deliveries. These findings contribute important information for health care providers when counselling women and their families who are weighing the risk of long-term pelvic floor disorders against the benefits of spontaneous vaginal delivery.

Frailty in people aging with human immunodeficiency virus (HIV) infection.

The increasing life spans of people infected with human immunodeficiency virus (HIV) reflect enormous treatment successes and present new challenges related to aging. Even with suppression of viral loads and immune reconstitution, HIV-positive individuals exhibit excess vulnerability to multiple health problems that are not AIDS-defining. With the accumulation of multiple health problems, it is likely that many people aging with treated HIV infection may be identified as frail. Studies of frailty in people with HIV are currently limited but suggest that frailty might be feasible and useful as an integrative marker of multisystem vulnerability, for organizing care and for comprehensively measuring the impact of illness and treatment on overall health status. This review explains how frailty has been conceptualized and measured in the general population, critically reviews emerging data on frailty in people with HIV infection, and explores how the concept of frailty might inform HIV research and care.

Prospectively measured 10-year changes in health-related quality of life and comparison with cross-sectional estimates in a population-based cohort of adult women and men.

PURPOSE: To prospectively assess changes in health-related quality of life (HRQOL) over 10 years, by age and sex, and to compare measured within-person change to estimates of change based on cross-sectional data. METHODS: Participants in the Canadian Multicentre Osteoporosis Study completed the 36-item short form (SF-36) in 1995/1997 and 2005/2007. Mean within-person changes for domain and summary components were calculated for men and women separately, stratified by 10-year age groups. Projected changes based on published age- and sex-stratified cross-sectional data were also calculated. Mean differences between the two methods were then estimated, along with the 95 % credible intervals of the differences. RESULTS: Data were available for 5,569/9,423 (59.1 %) of the original cohort. Prospectively collected 10-year changes suggested that the four physically oriented domains declined in all but the youngest group of men and women, with declines in the elderly men exceeding 25 points. The four mentally oriented domains tended to improve over time, only showing substantial declines in vitality and role emotional in older women, and all four domains in older men. Cross-sectional estimates identified a similar pattern of change but with a smaller magnitude, particularly in men. Correspondence between the two methods was generally high. CONCLUSIONS: Changes in HRQOL may be minimal over much of the life span, but physically oriented HRQOL can decline substantially after middle age. Although clinically relevant declines were more evident in prospectively collected data, differences in 10-year age increments of cross-sectional data may be a reasonable proxy for longitudinal changes, at least in those under 65 years of age. Results provide additional insight into the natural progression of HRQOL in the general population.