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.

Burden of chronic cough on social participation, healthcare resource utilisation and activities of daily living in the Canadian Longitudinal Study on Aging (CLSA).

BACKGROUND: Chronic cough is a common troublesome condition, but it is unclear whether dry or productive chronic cough and sex, impacts the burden of cough differently. METHODS: The Canadian Longitudinal Study on Aging is a nationally generalizable, stratified random sample of adults aged 45-85 years. Chronic cough was identified based on a self-reported daily cough in the last 12 months assessed at baseline (2011-2015) and follow-up (2015-2018). Odds ratios (95 % CI) for cough status and change in social participation activities (SPA), healthcare resource utilisation (HCRU), basic activities of daily living (ADLs) and instrumental activities of daily living (IADLs) were estimated using a weighted generalised estimating equation (WGEE). Results were stratified by sex, and adjusted for age, sex, smoking, body mass index, education, respiratory diseases and retirement status. RESULTS: Overall, chronic cough was associated with less SPA, greater HCRU and impaired ADL/IADLs. Productive chronic cough in males was associated with SPA limited by health, ED visits and hospitalisation. Females with productive chronic cough was associated with reduced frequency of SPA and ED visit. Dry chronic cough in females was associated with SPA limited by health and ED visits. Both types of cough was associated with at least 1 impaired basic ADL, but only in females with productive chronic cough was there an association with any impairment in IADLs. CONCLUSION: Chronic cough is associated with a greater burden on social participation, healthcare use and personal care.

Impact of productive and dry chronic cough on mortality in the Canadian Longitudinal Study on Aging (CLSA).

Background: Chronic cough is a common troublesome condition and accounts for a high burden on quality of life. Previous data investigating the mortality associated with chronic cough has been derived in patients with chronic bronchitis. No data exists on chronic dry cough. Therefore, we investigated if chronic dry and productive cough is independently associated with increased mortality. Methods: The Canadian Longitudinal Study on Ageing (CLSA) is a prospective, nationally generalizable, stratified random sample of adults aged 45-85 years at baseline recruited between 2011-2015 and followed up three years later. Chronic cough was identified based on a self-reported daily cough in the last 12 months. Deaths were confirmed by the Ministry of Health and/or completion of descendent questionnaire by a family member. Models were investigated for dry and productive chronic cough and was adjusted for age, sex, smoking, body mass index (BMI), and respiratory diseases. Results: Of the 30,016 participants, 4,783 (15.9%) reported chronic cough at baseline; 2,724 (57%) had a dry cough, and 2,059 (43%) had productive chronic cough. There was a total of 561 deaths between baseline and follow-up-1 (3 years later). There was a 49% higher risk of death in participants with chronic productive cough {adjusted odds ratio (aOR) 1.49 [95% confidence intervals (CI): 1.08-2.07]}, but not dry chronic cough [aOR 0.85 (0.60-1.20)]. The effects of chronic productive cough on mortality were persistent in those with no airflow obstruction [chronic productive cough aOR 1.90 (1.09-3.31)]. Conclusions: Chronic productive cough is associated with a higher risk of death, while chronic dry cough has no impact on mortality risk of death in middle-aged and older adults. This highlights the importance of careful evaluation of patients with chronic cough.

Prevalence, incidence and characteristics of chronic cough among adults from the Canadian Longitudinal Study on Aging.

The global prevalence of chronic cough is highly variable, ranging from 2% to 18%. There is a lack of data on the prevalence and incidence of chronic cough in the general population. The objective of this study was to investigate the prevalence and incidence of chronic cough in a sample of Canadian adults, and how these are influenced by age, sex, smoking, respiratory symptoms, medical comorbidities and lung function. Participants with chronic cough were identified from the Canadian Longitudinal Study on Aging (CLSA) based on self-reported daily cough in the past 12 months. This is a prospective, nationally generalisable, stratified random sample of adults aged 45-85 years at baseline recruited between 2011 and 2015, and followed-up 3 years later. The prevalence and incidence per 100 person-years are described, with adjustments for age, sex and smoking. Of the 30 097 participants, 29 972 completed the chronic cough question at baseline and 26 701 did so at follow-up. The prevalence of chronic cough was 15.8% at baseline and 17.6% at follow-up with 10.4-17.1% variation across seven provinces included in the CLSA comprehensive sample. Prevalence increased with age and current smoking, and was higher in males (15.2%), Caucasians (14%) and those born in North America, Europe or Oceania (14%). The incidence of chronic cough adjusted for age, sex and smoking was higher in males and in underweight and obese subjects. Subjects with respiratory symptoms, airway diseases, lower forced expiratory volume in 1 s (% predicted), cardiovascular diseases, psychological disorders, diabetes and chronic pain had a higher incidence of chronic cough. The prevalence and incidence of chronic cough is high in the CLSA sample with geographic, ethnic and gender differences, influenced by a number of medical comorbidities.

The combined effect of behavioural risk factors on disability in aging adults from the Canadian Longitudinal Study on Aging (CLSA).

The objective of this study was to explore how behavioural risk factors (smoking, physical activity, and nutrition) cluster together and assess how clusters of behavioural risk factors are associated with functional disability by age and sex at the individual and population level. We used currently available baseline cross-sectional data from the Canadian Longitudinal Study on Aging (CLSA). The CLSA is a national, population-based longitudinal study established to understand and examine health of an aging population. This study included 51,338 Canadian men and women aged 45 to 85 years residing in the community in 10 Canadian provinces. Behavioural risk factors included smoking, physical activity, and nutrition. The main outcome used in the study was functional disability, which was assessed using a questionnaire adapted from the Older Americans Resources and Services Multidimensional Assessment Questionnaire. In this analyses of unique combinations of the risk factors of smoking, physical activity, and nutritional risk, the magnitude of the association of the behavioural risk factors with functional disability was dependent on which risk factors were included and differed by age and sex strata. Of the risk factors, physical activity accounted for between 70% to 90% of the total population level risk in individuals with all three risk factors, suggesting it is a key driver of the population burden of disability. Together, these results show that considering unique clusters of risk factors, as well as age and sex, is essential for tailoring public health strategies to reduce the burden of disability among aging populations.

The association between primary ovarian insufficiency and osteoporosis in the Canadian Longitudinal Study on Aging.

OBJECTIVE: The objective of this study is to describe the association of premature ovarian insufficiency (POI) and early menopause on bone mineral density (BMD) and osteoporosis in a large cohort of women living in Canada. METHODS: Cross-sectional baseline data from a deeply characterized cohort (female participants) of the Canadian Longitudinal Study on Aging was used. Additional bio-psycho-social characteristics that may influence bone health and the development of osteoporosis were explored. RESULTS: The mean age of women at the time of baseline assessment was 65 years (N = 12,339). When comparing women with POI to those with early and normal age of menopause, there was no difference in hip BMD between groups, but women in the POI group were more likely to have a higher rate of self-reported osteoporosis (21.9% vs 16.7%) and have used osteoporosis drugs (11.39% vs 7.63%). After adjustment, POI was found to increase the odds of osteoporosis, as diagnosed using BMD. Current cigarette smoking was found to influence this association. Protective factors included obesity and current hormone therapy use, but not the duration of hormone therapy use. Women in the POI group were more likely to be obese, have decreased physical activity, and were more likely to be current smokers. CONCLUSION: These results confirm findings from smaller cohorts illustrating that POI is associated with osteoporosis. Increasing understanding of the sequelae associated with an earlier loss of ovarian function will aid in targeting earlier screening and intervention strategies for women in Canada and abroad.

Body mass index, waist circumference, waist-to-hip ratio, and body fat in relation to health care use in the Canadian Longitudinal Study on Aging.

BACKGROUND/OBJECTIVES: Obesity is associated with increased health care use (HCU), but it is unclear whether this is consistent across all measures of adiposity. The objectives were to compare obesity defined by body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and percent body fat (%BF), and to estimate their associations with HCU. SUBJECTS/METHODS: Baseline data from 30,092 participants aged 45-85 years from the Canadian Longitudinal Study on Aging were included. Measures of adiposity were recorded by trained staff and obesity was defined as BMI ≥ 30.0 kg/m2 for all participants and WC ≥ 88 cm and ≥102 cm, WHR ≥ 0.85 and ≥0.90, and %BF > 35% and >25% (measured using dual energy x-ray absorptiometry) for females and males, respectively. Self-reported HCU in the past 12 months was collected for any contact with a general practitioner, specialist, emergency department, and hospitalization. Pearson correlation coefficients (r) compared each measure to %BF-defined obesity, the reference standard. Relative risks (RR) and risk differences (RD) adjusted for age, sex, education, income, urban/rural, marital status, smoking status, and alcohol use were calculated, and results were age- and sex-stratified. RESULTS: Obesity prevalence varied by measure: BMI (29%), WC (42%), WHR (62%), and %BF (73%). BMI and WC were highly correlated with %BF (r ≥ 0.70), while WHR demonstrated a weaker relationship with %BF, with differences by sex (r = 0.29 and r = 0.46 in females and males, respectively). There were significantly increased RR and RD for all measures and health care services, for example, WC-defined obesity was associated with an increased risk of hospitalization (RR: 1.40, 95% CI: 1.28-1.54 and RD per 100: 2.6, 95% CI:1.9-3.3). Age-stratified results revealed that older adult groups with obesity demonstrated weak or no associations with HCU. CONCLUSIONS: All measures of adiposity were positively associated with increased HCU although obesity may not be a strong predictor of HCU in older adults.

The impact of different diagnostic criteria on the association of sarcopenia with injurious falls in the CLSA.

BACKGROUND: Sarcopenia definitions recommend different combinations of variables (lean mass, strength, and physical function) and different methods of adjusting lean mass. The purpose of this paper was to address the gaps in the literature regarding how differences in the operationalization of sarcopenia impact the association between sarcopenia and injurious falls. METHODS: Participants included 9936 individuals from the Canadian Longitudinal Study on Aging aged ≥65 years at baseline (2012-2015), with complete data for sarcopenia-related variables, injurious falls, and covariates. Sarcopenia was defined using all combinations of muscle variables (lean mass, grip strength, chair rise test, and gait speed) and methods of adjusting lean mass (height2 , weight, body mass index (BMI), and regressing on height and fat mass) recommended by the expert group sarcopenia definitions. Multiple cut off values for the measures were explored. The association between sarcopenia and injurious falls (0, 1, or 2+ falls) measured 18 months after baseline data collection were assessed using proportional odds regression models. RESULTS: In men (n = 5162, 72.9 ± 5.6 years), the odds of having a higher level of injurious falls was between 1.43 and 2.14 greater when sarcopenia was defined as (i) lean mass adjusted for weight only; (ii) grip strength (<30 or <26 kg) only; (iii) lean mass adjusted for weight and grip strength (<30 or <26 kg); (iv) lean mass adjusted for BMI and grip strength (<26 kg); and (v) lean mass adjusted using the regression technique and grip strength (<30 or <26 kg). In women (n = 4774, 72.8 ± 5.6 years), only the combination of lean mass adjusted using regression with gait speed (<0.8 m/s) was associated with a significantly higher odds (1.46, 95% confidence interval: 1.01-2.10, P = 0.04) of having a higher level of injurious falls. CONCLUSIONS: Sarcopenia definitions based on different combinations of muscle variables and methods of adjusting lean mass are not equally associated with injurious falls. In men, definitions including grip strength but not gait speed or the chair rise test, and adjusting lean mass for weight, BMI, or using the residual technique but not height2 , tended to be associated with injurious falls. In women, sarcopenia was generally not associated with injurious falls regardless of the definition used.

Oral Health, Diet, and Frailty at Baseline of the Canadian Longitudinal Study on Aging.

OBJECTIVES: Poor diet due to poor oral health was proposed as a potential mediator of the association between poor oral health and frailty. This study explores the cross-sectional associations between poor oral health, poor diet, and frailty in Canadian adults, aged 45 to 85 years, and then tests whether the expected oral health-frailty association is changed by taking into account the pathway through poor diet. DESIGN: Cross-sectional study. SETTING: The baseline wave of the Canadian Longitudinal Study on Aging, a nationally representative population study. PARTICIPANTS: Data from 28 738 community-dwelling participants, aged 45 to 85 years. MEASUREMENTS: We characterized poor oral health (cumulative count of 24 items of oral health problems), poor diet (scale of poor food consumption from 7 healthy foods groups), and frailty (cumulative frailty index of 76 items). Regression-based path analyses were used to investigate associations between poor oral health, poor diet, and frailty, adjusted for age group, sex, income, smoking, living alone, education, physical activity, social support, and dental visit. RESULTS: Poorer oral health was associated with low income, smoking, low physical activity, low social support, and no dental visit. There were associations between poorer oral health and poorer diet (effect size ß adjusted = .40; 95% confidence interval [CI] = .20-.61) and between poorer oral health and increased frailty (ß adjusted = .85; 95% CI = .68-1.02). The indirect effect through the path of poor diet was approximately 0.01 (95% CI = 0.01-0.02) (ie, explaining ∼1% of the effect of poor oral health on frailty). CONCLUSIONS: Poor oral health was associated with poor diet and frailty. Each additional oral health problem was associated with an increase of approximately 1 frailty index point, even after full adjustment for poor diet. The indirect effect of poor oral health through poor diet was modest. Though poor oral health was associated with poorer diet quality, a more direct effect of poor oral health on increasing frailty may be indicated. J Am Geriatr Soc 68:959-966, 2020.

Association Between Hormone Therapy and Muscle Mass in Postmenopausal Women: A Systematic Review and Meta-analysis.

Importance: Hormone therapy (HT) has been suggested for protection against age-related muscle weakness in women. However, the potential for HT-associated health risks necessitates a better understanding of the direction and magnitude of the association between HT and health outcomes, such as lean body mass (LBM). Objective: To determine whether HT was associated with reduced LBM loss compared with not receiving HT among postmenopausal women aged 50 years and older. Data Sources: MEDLINE, Embase, AgeLine, CINAHL, and SportDiscus (searched from inception until April 25, 2018). Study Selection: For this systematic review and meta-analysis, randomized clinical trials including postmenopausal women undergoing HT and control groups of women not receiving HT were selected by 2 reviewers. Studies were included if LBM or fat-free mass were measured as an outcome. Studies with participants from hospitals, long-term care facilities, or with specific diseases were excluded. Data Extraction and Synthesis: Information regarding study characteristics and outcome measures were extracted by 1 reviewer and verified by another. Risk of bias was evaluated. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were used to abstract data and assess data quality/validity. Data were pooled using a fixed-effects model. Main Outcomes and Measures: The primary study outcome was the overall absolute change in LBM (measured in kilograms), captured by dual-energy x-ray absorptiometry, dual-photon absorptiometry, or bioelectrical impedance analysis imaging. Results: Of 8961 studies that met selection criteria, 12 were included, with a total of 4474 recruited participants. Of the participants, mean (SD) age was 59.0 (6.1) years. Data on ethnicity were collected by 2 of the studies. Of the 22 HT intervention arms, 15 used estrogen-progesterone combination HT and 7 used estrogen-only HT. Control participants were women who received no HT at all or who received placebo. The median follow-up duration was 2 years (range, 6 months to 6 years). Seven treatment arms showed a loss of LBM, and 14 were protective. Overall, HT users lost 0.06 kg (95% CI, -0.05 to 0.18) less LBM compared with control participants, but the difference was not statistically significant (P = .26). The results were unchanged when stratified based on treatment type and dosage, duration of follow-up, time since menopause, study quality, and type of LBM measurement, with HT users losing between 0.06 kg more to 0.20 kg less LBM compared with control participants for all strata. The quality of evidence based on GRADE was low. Conclusions and Relevance: This systematic review and meta-analysis did not show a significant beneficial or detrimental association of HT with muscle mass. Although muscle retention in aging women is of crucial importance, these findings suggest that interventions other than HT should be explored.

Rationale and design of GENEiUS: a prospective observational study on the genetic and environmental determinants of body mass index evolution in Canadian undergraduate students.

INTRODUCTION: Obesity is a global epidemic and is a risk factor for developing other comorbidities. Young adulthood is a critical period for body weight change and establishing healthy lifestyle behaviours. The 'Freshman 15' suggests that undergraduate students gain 15 lbs (6.8 kg) during their first year of university, although evidence estimates a more modest weight gain of approximately 3-5 lbs (1.4-2.3 kg). Previous studies have only investigated weight change in the first year and do not study potential risk factors. Genetic and EnviroNmental Effects on weight in University Students (GENEiUS) is a prospective observational study which will investigate the environmental and biological determinants of weight change in undergraduate students over 4 years. METHODS AND ANALYSIS: The GENEiUS study will recruit 2500 multiethnic undergraduates aged 17-25 years at McMaster University at the start of their first year and will follow them every 6 months for 4 years. Primary outcomes are obesity traits: body mass index, waist circumference, waist-to-hip ratio, body fat mass and body fat percentage. The contribution of well-established and novel genetic variants for obesity traits and heritability values will be derived from whole-genome single-nucleotide polymorphism genotyping arrays. Civil status, age, sex, ethnicity, length of residence in Canada, religiosity, energy intake, physical activity, exercise motivation, electronic screen time, sleep patterns, history of assault, smoking status, alcohol consumption, medication and drug use, stress, impulsivity, body image perception, self-esteem, anxiety, eating disorders and depression will be investigated for their effect on obesity traits. The findings of the GENEiUS study will be used to help design obesity prevention programme in North American universities with multiethnic populations. ETHICS AND DISSEMINATION: Ethical approval of the study protocol has been obtained from the Hamilton Integrated Research Ethics Board. Study results will be disseminated through scientific publications, scholarly meetings, and collaborative meetings with university administration and student groups.