Omega-3 Blood Levels and Stroke Risk: A Pooled and Harmonized Analysis of 183 291 Participants From 29 Prospective Studies.

BACKGROUND: The effect of marine omega-3 PUFAs on risk of stroke remains unclear. METHODS: We investigated the associations between circulating and tissue omega-3 PUFA levels and incident stroke (total, ischemic, and hemorrhagic) in 29 international prospective cohorts. Each site conducted a de novo individual-level analysis using a prespecified analytical protocol with defined exposures, covariates, analytical methods, and outcomes; the harmonized data from the studies were then centrally pooled. Multivariable-adjusted HRs and 95% CIs across omega-3 PUFA quintiles were computed for each stroke outcome. RESULTS: Among 183 291 study participants, there were 10 561 total strokes, 8220 ischemic strokes, and 1142 hemorrhagic strokes recorded over a median of 14.3 years follow-up. For eicosapentaenoic acid, comparing quintile 5 (Q5, highest) with quintile 1 (Q1, lowest), total stroke incidence was 17% lower (HR, 0.83 [CI, 0.76-0.91]; P<0.0001), and ischemic stroke was 18% lower (HR, 0.82 [CI, 0.74-0.91]; P<0.0001). For docosahexaenoic acid, comparing Q5 with Q1, there was a 12% lower incidence of total stroke (HR, 0.88 [CI, 0.81-0.96]; P=0.0001) and a 14% lower incidence of ischemic stroke (HR, 0.86 [CI, 0.78-0.95]; P=0.0001). Neither eicosapentaenoic acid nor docosahexaenoic acid was associated with a risk for hemorrhagic stroke. These associations were not modified by either baseline history of AF or prevalent CVD. CONCLUSIONS: Higher omega-3 PUFA levels are associated with lower risks of total and ischemic stroke but have no association with hemorrhagic stroke.

Examining a Healthy Lifestyle as a Moderator of the Relationship between Psychological Distress and Cognitive Decline among Older Adults in the NuAge Study.

INTRODUCTION: The objective of this study was to examine whether a healthy lifestyle composite score of social engagement, physical activity, and Mediterranean diet adherence moderates the association between psychological distress and global cognitive decline among cognitively healthy older adults (67+ years of age at baseline). METHODS: A total of 1,272 cognitively intact older adults (Mage = 74.1 ± 4.1 years, 51.9% female) in the Quebec Longitudinal Study on Nutrition and Successful Aging (NuAge) completed a series of self-reported questionnaires to measure psychological distress and lifestyle behaviors, and the Modified Mini-Mental Examination (3MS) to assess cognitive performance at baseline and annually over 3 years. RESULTS: Controlling for sociodemographic and health-related characteristics, greater psychological distress was associated with steeper cognitive decline over time among males (B = -0.07, 95% CI: [-0.12, -0.02]), but not females (B = 0.008, 95% CI: [0.03, 0.04]). Although a healthy lifestyle composite score did not statistically significantly moderate the distress-cognition relationship (B = -0.005, 95% CI: [-0.02, 0.01]), there was an association between higher psychological distress and greater cognitive decline at low levels of social engagement (B = -0.05, 95% CI: [-0.09, -0.006]), but not at high levels of social engagement (B = 0.02, 95% CI: [-0.03, 0.07]). CONCLUSION: This study suggests that the potentially harmful impact of stress on cognitive function may be malleable through specific healthy lifestyle behaviors and emphasizes the importance of taking a sex-based approach to cognitive aging research.

Older Adults' Perceptions of the 2019 Canada's Food Guide: A Qualitative Study.

Purpose: Major changes were made to Canada's Food Guide (CFG) in 2019. This study aimed to understand the perceptions of older adults toward this newest version.Methods: Older adults were invited to participate via newsletters sent to older adults and retirees' organizations in the Province of Quebec. Participants completed an online survey about their baseline familiarity with the 2019 CFG using a 5-point Likert scale and took part in an individual semi-structured online interview, which explored their perceptions toward the 2019 CFG. A thematic qualitative analysis of the interview transcripts was performed.Results: Fifty-eight older adults (>65 years, 30 women, 28 men, including 19 consumers and 39 non-consumers of plant-based protein (PBP) foods) participated in the study. Older adults were mostly familiar with the 2019 CFG and had a positive perception of its features. They appreciated the design, proposed recipes, and healthy eating recommendations. Perceptions about the three food groups were mixed, mainly regarding the decreased emphasis on dairy products. Some appreciated that animal proteins were less prominent, while others raised issues on how to integrate PBP into their diet. Perceptions appeared to be influenced by sex and PBP consumption.Conclusion: Older adults in the Province of Quebec view most of the 2019 CFG recommendations positively. Our observations may be useful to dietitians and public health practitioners when developing strategies to improve adherence.

Beliefs underlying older adults' intention to consume plant-based protein foods: A qualitative study.

The revised Canada's food guide released in 2019 promotes the consumption of plant-based protein foods (PBP). Yet, older adults consume little of them. This qualitative study aimed to identify older adults' beliefs about consuming PBP and to assess differences in beliefs by gender and baseline PBP consumption. Recruitment was done to obtain an equal number of men and women, 20 PBP-consumers and 40 non-consumers. Each participant completed an online questionnaire collecting sociodemographic data and took part in an individual semi-structured interview based on the Theory of Planned Behavior. A thematic analysis was performed using the Nvivo software. Health benefits, good taste and protecting the environment were perceived as advantages of consuming PBP, whereas difficulty digesting and not liking the taste were reported as disadvantages. Family members were frequently named as people who would approve and/or disapprove the consumption of PBP. Having more knowledge about PBP would facilitate consumption, while lack of motivation to change eating habits and lack of knowledge on how to prepare PBP meals were perceived barriers. Several differences in beliefs by gender and baseline PBP consumption were observed. Future interventions should focus on the beliefs that were identified as important to older adults (i.e., health benefits and food preparation skills), and should be tailored to their gender and PBP consumption.

Serum ω-3 Fatty Acids and Cognitive Domains in Community-Dwelling Older Adults from the NuAge Study: Exploring the Associations with Other Fatty Acids and Sex.

BACKGROUND: Omega-3 (n-3) PUFAs are suggested to play a role in the prevention of cognitive decline. The evidence may be inconsistent due to methodologic issues, including interrelations with other long-chain (14 or more carbons) fatty acids (LCFAs) and use of sex as a confounding factor rather than an effect modifier. OBJECTIVES: This study evaluated the association between serum n-3 PUFAs and performance across 4 cognitive domains, overall and by sex, while controlling for other LCFAs. METHODS: In total, 386 healthy older adults (aged 77.4 ± 3.8 y; 53% females) from the Quebec Longitudinal Study on Nutrition and Successful Aging underwent a cognitive evaluation and blood sampling. Verbal and nonverbal episodic memory, executive functioning, and processing speed were evaluated. Serum LCFA concentrations were measured by gas chromatography. LCFAs were grouped according to standard fatty acid classes and factor analysis using principal component analysis (FA-PCA). Multivariate linear regression models were performed, including unadjusted and adjusted models for other LCFAs. RESULTS: Higher n-3 PUFA concentrations were associated with better nonverbal memory and processing speed in fully adjusted models not including other LCFAs (ßs of 0.21 and 0.19, respectively). The magnitude of these associations varied when other LCFAs were entered in the model (ßs of 0.27 and 0.32, respectively) or when FA-PCA factors were considered (ßs of 0.27 and 0.21, respectively). Associations with verbal episodic memory were limited to higher concentrations of EPA, whereas there was no association between n-3 PUFAs and executive functioning. Higher n-3 PUFAs were associated with better verbal and nonverbal episodic memory in females and with better executive functioning and processing speed in males. CONCLUSIONS: These results suggest that other LCFAs should be considered when evaluating the association between n-3 PUFAs and cognitive performance in healthy older adults. Sex differences across cognitive domains warrant further investigation.

The impact of adjusting for pure predictors of exposure, mediator, and outcome on the variance of natural direct and indirect effect estimators.

It is now well established that adjusting for pure predictors of the outcome, in addition to confounders, allows unbiased estimation of the total exposure effect on an outcome with generally reduced standard errors (SEs). However, no analogous results have been derived for mediation analysis. Considering the simplest linear regression setting and the ordinary least square estimator, we obtained theoretical results showing that adjusting for pure predictors of the outcome, in addition to confounders, allows unbiased estimation of the natural indirect effect (NIE) and the natural direct effect (NDE) on the difference scale with reduced SEs. Adjusting for pure predictors of the mediator increases the SE of the NDE's estimator, but may increase or decrease the variance of the NIE's estimator. Adjusting for pure predictors of the exposure increases the variance of estimators of the NIE and NDE. Simulation studies were used to confirm and extend these results to the case where the mediator or the outcome is binary. Additional simulations were conducted to explore scenarios featuring an exposure-mediator interaction as well as the relative risk and odds ratio scales for the case of binary mediator and outcome. Both a regression approach and an inverse probability weighting approach were considered in the simulation study. A real-data illustration employing data from the Canadian Study of Health and Aging is provided. This analysis is concerned with the mediating effect of vitamin D in the effect of physical activity on dementia and its results are overall consistent with the theoretical and empirical findings.

Cumulative exposure to psychosocial stressors at work and global cognitive function: the PROspective Quebec Study on Work and Health.

OBJECTIVES: Psychosocial stressors at work have been proposed as modifiable risk factors for mild cognitive impairment (MCI). This study aimed to evaluate the effect of cumulative exposure to psychosocial stressors at work on cognitive function. METHODS: This study was conducted among 9188 white-collar workers recruited in 1991-1993 (T1), with follow-ups 8 (T2) and 24 years later (T3). After excluding death, losses to follow-up and retirees at T2, 5728 participants were included. Psychosocial stressors at work were measured according to the Karasek's questionnaire. Global cognitive function was measured with the Montreal Cognitive Assessment. Cumulative exposures to low psychological demand, low job control, passive job and high strain job were evaluated using marginal structural models including multiple imputation and inverse probability of censoring weighting. RESULTS: In men, cumulative exposures (T1 and T2) to low psychological demand, low job control or passive job were associated with higher prevalences of more severe presentation of MCI (MSMCI) at T3 (Prevalence ratios (PRs) and 95% CIs of 1.50 (1.16 to 1.94); 1.38 (1.07 to 1.79) and 1.55 (1.20 to 2.00), respectively), but not with milder presentation of MCI. In women, only exposure to low psychological demand or passive job at T2 was associated with higher prevalences of MSMCI at T3 (PRs and 95% CI of 1.39 (0.97 to 1.99) and 1.29 (0.94 to 1.76), respectively). CONCLUSIONS: These results support the deleterious effect of a low stimulating job on cognitive function and the cognitive reserve theory. Psychosocial stressors at work could be part of the effort for the primary prevention of cognitive decline.

Is Benzodiazepine Use Associated With the Risk of Dementia and Cognitive Impairment-Not Dementia in Older Persons? The Canadian Study of Health and Aging.

Background: The use of benzodiazepines in relation to cognitive decline remains an area of controversy in aging populations. Objective: This study aims to evaluate the risk of cognitive impairment-not dementia (CIND), Alzheimer disease (AD), and all-cause dementia with benzodiazepine use. The effect modification by sex was also investigated. Methods: Data come from the Canadian Study of Health and Aging, a 10-year multicentric study involving 10 263 participants randomly selected, 65 years and older, living in the community and in institutions. Current exposure to benzodiazepines was assessed in a face-to-face interview or self-reported in a questionnaire. Cox proportional hazard regression models, using age as time scale, were conducted to estimate hazard ratios, with adjustment for sex, education, smoking, alcohol intake, depression, physical activity, nonsteroidal anti-inflammatory drug use, and vascular comorbidities. Results: Data sets included 5281 participants for dementia as the outcome, 5015 for AD, and 4187 for CIND. Compared with nonusers, current use of benzodiazepines was associated with an increased risk of CIND (hazard ratio = 1.36; 95% CI = 1.08-1.72) in the simplest model. Results remained similar in the fully adjusted model (hazard ratio = 1.32; 95% CI = 1.04-1.68). There was no association between benzodiazepine use and the risk of dementia or AD. All these effects were similar between men and women. Conclusion and Relevance: Benzodiazepine use in older people from the general population is related to subsequent occurrence of cognitive dysfunction but not implicated in the pathogenesis of dementia or AD. Caution should be exercised when prescribing benzodiazepines to preserve global cognitive function.

Sex differences in the relationship between dietary pattern adherence and cognitive function among older adults: findings from the NuAge study.

BACKGROUND: Consumption of a prudent dietary pattern rich in healthy nutrients is associated with enhanced cognitive performance in older adulthood, while a Western dietary pattern low in healthy nutrients is associated with poor age-related cognitive function. Sex differences exist in dietary intake among older adults; however, there is a paucity of research examining the relationship between sex-specific dietary patterns and cognitive function in later life. METHODS: The current study aimed to investigate sex differences in the relationship between sex-specific dietary pattern adherence and global cognitive function at baseline and over a 3-year follow-up in 1268 community-dwelling older adults (Mage = 74 years, n = 664 women, n = 612 men) from the Quebec Longitudinal Study on Nutrition and Successful Aging (NuAge). A 78-item Food Frequency Questionnaire was used to estimate dietary intake over the previous year. Sex-specific dietary pattern scores were derived using principal component analysis. Global cognition was assessed using the Modified Mini-Mental State Examination (3MS). RESULTS: Adjusted linear mixed effects models indicated that a healthy, prudent dietary pattern was not associated with baseline cognitive performance in men or women. No relationship was found between Western dietary pattern adherence and baseline cognitive function in women. Among men, adherence to an unhealthy, Western dietary pattern was associated with poorer baseline cognitive function (ß = - 0.652, p = 0.02, 95% CI [- 1.22, - 0.65]). No association was found between prudent or Western dietary patterns and cognitive change over time in men or women. CONCLUSIONS: These findings highlight the importance of conducting sex-based analyses in aging research and suggest that the relationship between dietary pattern adherence and cognitive function in late life may be sex-dependent.

Exposure to polychlorinated biphenyls and organochlorine pesticides and risk of dementia, Alzheimer's disease and cognitive decline in an older population: a prospective analysis from the Canadian Study of Health and Aging.

BACKGROUND: Little attention has been paid to neurotoxicants on the risk of dementia. Exposure to known neurotoxicants such as polychlorinated biphenyls (PCBs) and organochlorine (OC) pesticides is suspected to have adverse cognitive effects in older populations. OBJECTIVE: To assess whether plasma concentrations of PCBs and OC pesticides are associated with the risk of cognitive decline, Alzheimer's disease (AD) and of all-cause dementia in the Canadian older population. METHODS: Analyses were based on data from the Canadian Study of Health and Aging, a 3-phase, 10-year population-based study of individuals aged 65+ years. Analyses included 669 clinically assessed subjects, of which 156 developed dementia including 108 incident cases of AD. Subjects were screened at each phase with the 100-point Modified Mini-Mental State Examination (3MS), a measurement of global cognitive function. Statistical analyses included Cox proportional hazards model when the outcome was dementia or AD, and a repeated-measure mixed model when the outcome was the 3MS score. RESULTS: No association of PCB and OC pesticides with the risk of dementia and AD was observed. Elevated concentrations of PCB congeners nos 118, 153, 156, 163, and OC pesticides 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT) and its metabolite 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) were significantly associated with cognitive decline as assessed with the 3MS. A posteriori analyses suggested that only p,p'-DDE was significantly related to a higher cognitive decline in time based on the 3MS among incident cases of dementia compared to subjects remaining nondemented. CONCLUSION: PCB and OC pesticide plasma concentrations were not related to the incident diagnosis of neither dementia, nor AD. Using the 3MS scores as the outcome, higher concentrations of four PCB congeners and two OC pesticides were associated with lower cognitive performances in subjects. The association of p,p'-DDE with cognitive decline in time in incident cases of dementia merits further investigation.

Use of Vitamin E and C Supplements for the Prevention of Cognitive Decline.

BACKGROUND: There are few studies of the association between the use of antioxidant vitamin supplements and the risk of Alzheimer's disease (AD). Cognitive decline is generally viewed as part of the continuum between normal aging and AD. OBJECTIVE: To evaluate whether the use of vitamin E and C supplements is associated with reduced risks of cognitive impairment, not dementia (CIND), AD, or all-cause dementia in a representative sample of older persons ≥65 years old. METHODS: Data from the Canadian Study of Health and Aging (1991-2002), a cohort study of dementia including 3 evaluation waves at 5-yearly intervals, were used. Exposure to vitamins E and C was self-reported at baseline in a risk factor questionnaire and/or in a clinical examination. RESULTS: The data set included 5269 individuals. Compared with those not taking vitamin supplements, the age-, sex-, and education-adjusted hazard ratios of CIND, AD, and all-cause dementia were, respectively, 0.77 (95% CI = 0.60-0.98), 0.60 (95% CI = 0.42-0.86), and 0.62 (95% CI = 0.46-0.83) for those taking vitamin E and/or C supplements. Results remained significant in fully adjusted models except for CIND. Similar results were observed when vitamins were analyzed separately. CONCLUSIONS: This analysis suggests that the use of vitamin E and C supplements is associated with a reduced risk of cognitive decline. Further investigations are needed to determine their value as a primary prevention strategy.

Immune checkpoint inhibitors and risk of immune-mediated adverse events: a cohort study comparing extended versus standard interval administration.

The COVID-19 pandemic precipitated the implementation of extended interval immune checkpoint inhibitors (ICIs) in an effort to limit hospital visits, but few studies have examined their safety. This study aimed to compare in oncology outpatients, immune-mediated adverse events (IMAEs) in terms of total number, incidence, severity, and time to occurrence, based on exposure to standard or extended interval ICIs. A retrospective cohort study was conducted in patients who received at least one dose of an ICI between 2015 and 2021. Data were collected from patient records and pharmacy software. Adjusted logistic, Poisson, and Cox regression models were estimated. A total of 310 patients with a mean age of 67.1 years were included, 130 of whom had the extended interval. No statistically significant differences were observed between the groups. With the standard and extended intervals, the mean total number of IMAE per participant was 1.02 and 1.18, respectively; the incidence of an IMAE was 62% and 64%. Of the 147 IMAE episodes in the standard interval group, 14 (9.5%) were grade 3 or higher, while there were 15 (12.4%) among the 121 IMAE episodes in the extended interval group. Compared with standard interval, the use of extended interval did not increase the risk of having a first IMAE (adjusted hazard ratio 0.92 (95% CI 0.67-1.26)). This study suggests that the administration of an ICI according to extended interval is as safe as the administration according to standard interval in oncology outpatients.

Implication of Circulating Extracellular Vesicles-Bound Amyloid-ß42 Oligomers in the Progression of Alzheimer's Disease.

BACKGROUND: The perplex interrelation between circulating extracellular vesicles (cEVs) and amyloid-ß (Aß) deposits in the context of Alzheimer's disease (AD) is poorly understood. OBJECTIVE: This study aims to 1) analyze the possible cross-linkage of the neurotoxic amyloid-ß oligomers (oAß) to the human cEVs, 2) identify cEVs corona proteins associated with oAß binding, and 3) analyze the distribution and expression of targeted cEVs proteins in preclinical participants converted to AD 5 years later (Pre-AD). METHODS: cEVs were isolated from 15 Pre-AD participants and 15 healthy controls selected from the Canadian Study of Health and Aging. Biochemical, clinical, lipid, and inflammatory profiles were measured. oAß and cEVs interaction was determined by nanoparticle tracking analysis and proteinase K digestion. cEVs bound proteins were determined by ELISA. RESULTS: oAß were trapped by cEVs and were topologically bound to their external surface. We identified surface-exposed proteins functionally able to conjugate oAß including apolipoprotein J (apoJ), apoE and RAGE, with apoJ being 30- to 130-fold higher than RAGE and apoE, respectively. The expression of cEVs apoJ was significantly lower in Pre-AD up to 5 years before AD onset. CONCLUSION: Our findings suggest that cEVs might participate in oAß clearance and that early dysregulation of cEVs could increase the risk of conversion to AD.

Nutrition risk and cognitive performance in community-living older adults without cognitive impairment: a cross-sectional analysis of the Canadian Longitudinal Study on Aging.

Malnutrition is correlated with poor cognition; however, an understanding of the association between nutrition risk, which precedes malnutrition, and cognition is lacking. This study aimed to determine if nutrition risk measured with the SCREEN-8 tool is associated with cognitive performance among cognitively healthy adults aged 55+, after adjusting for demographic and lifestyle covariates. Sex- and age-stratified analyses were also explored. Baseline data from the Canadian Longitudinal Study on Aging was used. Cognition was determined using a 6-measure composite score based on four executive functions and two memory tasks, taking into account age, sex, and education. Multivariable linear regression was performed while adjusting for body mass index (BMI), lifestyle, and health covariates in the entire sample (n = 11 378) and then stratified by sex and age. Approximately half of participants were female (54.5%) aged 65+ (54.1%). Greater nutrition risk was associated with poorer cognitive performance in the entire sample (F[1, 11 368] = 5.36, p = 0.021) and among participants aged 55-64 (n = 5227; F[1, 5217] = 5.45, p = 0.020). Sex differences in lifestyle and health factors associated with cognition were apparent, but nutrition risk was not associated with cognition in sex-stratified models. Based on this analysis, there may be an association between nutrition risk and cognitive performance in older adults. When screening for either cognitive impairment or nutrition risk, complementary assessments for these conditions is warranted, as early intervention may provide benefit.

Psychosocial Stressors at Work and Coronary Heart Disease Risk in Men and Women: 18-Year Prospective Cohort Study of Combined Exposures.

BACKGROUND: Psychosocial stressors at work, like job strain and effort-reward imbalance (ERI), can increase coronary heart disease (CHD) risk. ERI indicates an imbalance between the effort and received rewards. Evidence about the adverse effect of combined exposure to these work stressors on CHD risk is scarce. This study examines the separate and combined effect of job strain and ERI exposure on CHD incidence in a prospective cohort of white-collar workers in Quebec, Canada. METHODS: Six thousand four hundred sixty-five white-collar workers without cardiovascular disease (mean age, 45.3±6.7) were followed for 18 years (from 2000 to 2018). Job strain and ERI were measured with validated questionnaires. CHD events were retrieved from medico-administrative databases using validated algorithms. Marginal Cox models were used to calculate hazard ratios (HR) stratified by sex. Multiple imputation and inverse probability weights were applied to minimize potential threats to internal validity. RESULTS: Among 3118 men, 571 had a first CHD event. Exposure to either job strain or ERI was associated with an adjusted 49% CHD risk increase (HR, 1.49 [95% CI, 1.07-2.09]). Combined exposure to job strain and ERI was associated with an adjusted 103% CHD risk increase (HR, 2.03 [95% CI, 1.38-2.97]). Exclusion of early CHD cases and censoring at retirement did not alter these associations. Among 3347 women, 265 had a first CHD event. Findings were inconclusive (passive job HR, 1.24 [95% CI, 0.80-1.91]; active job HR, 1.16 [95% CI, 0.70-1.94]; job strain HR, 1.08 [95% CI, 0.66-1.77]; ERI HR, 1.02 [95% CI, 0.72-1.45]). CONCLUSIONS: In this prospective cohort study, men exposed to job strain or ERI, separately and in combination, were at increased risk of CHD. Early interventions on these psychosocial stressors at work in men may be effective prevention strategies to reduce CHD burden. Among women, further investigation is required.

Associations between circulating cardiovascular disease risk factors and cognitive performance in cognitively healthy older adults from the NuAge study.

Introduction: Cardiovascular disease risk factors (CVRFs) contribute to the development of cognitive impairment and dementia. Methods: This study examined the associations between circulating CVRF biomarkers and cognition in 386 cognitively healthy older adults (mean age = 78 ± 4 years, 53% females) selected from the Quebec Longitudinal Study on Nutrition and Successful Aging (NuAge). Memory, executive function, and processing speed were assessed at baseline and 2-year follow-up. CVRF biomarkers included total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglycerides, glucose, insulin, high sensitivity C-reactive protein (hs-CRP), homocysteine, protein carbonyls, and cortisol. Linear mixed models were used to determine associations between individual CVRF biomarkers and cognition at both time points. Results: HDL-C was most consistently associated with cognition with higher values related to better performance across several domains. Overall, stronger and more consistent relationships between CVRF biomarkers and cognition were observed in females relative to males. Discussion: Findings suggest that increases in the majority of circulating CVRFs are not associated with worse cognition in cognitively healthy older adults.

Work-Related Psychosocial Factors and Global Cognitive Function: Are Telomere Length and Low-Grade Inflammation Potential Mediators of This Association?

The identification of modifiable factors that could maintain cognitive function is a public health priority. It is thought that some work-related psychosocial factors help developing cognitive reserve through high intellectual complexity. However, they also have well-known adverse health effects and are considered to be chronic psychosocial stressors. Indeed, these stressors could increase low-grade inflammation and promote oxidative stress associated with accelerated telomere shortening. Both low-grade inflammation and shorter telomeres have been associated with a cognitive decline. This study aimed to evaluate the total, direct, and indirect effects of work-related psychosocial factors on global cognitive function overall and by sex, through telomere length and an inflammatory index. A random sample of 2219 participants followed over 17 years was included in this study, with blood samples and data with cognitive function drawn from a longitudinal study of 9188 white-collar workers (51% female). Work-related psychosocial factors were evaluated according to the Demand-Control-Support and the Effort-Reward Imbalance (ERI) models. Global cognitive function was evaluated with the validated Montreal Cognitive Assessment (MoCA). Telomere length and inflammatory biomarkers were measured using standardised protocols. The direct and indirect effects were estimated using a novel mediation analysis method developed for multiple correlated mediators. Associations were observed between passive work or low job control, and shorter telomeres among females, and between low social support at work, ERI or iso-strain, and a higher inflammatory index among males. An association was observed with higher cognitive performance for longer telomeres, but not for the inflammatory index. Passive work overall, and low reward were associated with lower cognitive performance in males; whereas, high psychological demand in both males and females and high job strain in females were associated with a higher cognitive performance. However, none of these associations were mediated by telomere length or the inflammatory index. This study suggests that some work-related psychosocial factors could be associated with shorter telomeres and low-grade inflammation, but these associations do not explain the relationship between work-related psychosocial factors and global cognitive function. A better understanding of the biological pathways, by which these factors affect cognitive function, could guide future preventive strategies to maintain cognitive function and promote healthy aging.

Nonsteroidal anti-inflammatory drug use and the risk of cognitive impairment and Alzheimer's disease.

BACKGROUND: Some observational studies have established an association between exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) and a decreased risk of subsequently developing Alzheimer's disease (AD). Mild cognitive impairment or cognitive impairment, not dementia (CIND) is more likely to convert to AD, and no specific preventive method is currently available. The objective of this study was to determine the association of NSAID use in 5276 cognitively normal subjects of the Canadian Study of Health and Aging, a 10-year population-based cohort study, with the incidence of CIND, AD, and all-cause dementia. METHODS: Hazard ratios were calculated from Cox proportional hazards models with age as the time scale according to three study samples including 824 cases of dementia (563 cases of AD), 630 cases of dementia (435 cases of AD), and 883 cases of CIND, respectively. Adjustments were made for gender, education, lifestyle factors, comorbid diseases, and vascular risk factors. RESULTS: Lower risks for AD and all-cause dementia were significantly associated with the use of any NSAIDs and the salicylates without barbiturates subgroup in the study sample including subjects with CIND at baseline. There was a weak association between any NSAIDs and the risk of CIND (hazard ratio, 0.87; 95% confidence interval, 0.76-1.00). CONCLUSION: These results suggest that there is an association between NSAID use and a lower incidence of AD and, to a lesser extent, of CIND.

An exploratory identification of biological markers of chronic musculoskeletal pain in the low back, neck, and shoulders.

OBJECTIVES: This study was an in-depth exploration of unique data from a nationally representative sample of adults living in the United States to identify biomarkers associated with musculoskeletal pain. METHODS: We performed secondary analyses of 2003-2004 NHANES data. After a first screening of 187 markers, analyses of 31 biomarkers were conducted on participants aged ≥20 years identified in all counties using the 2000 Census Bureau data (n = 4,742). To assess the association of each biomarker with each pain outcome (acute, subacute and chronic low back, neck, and shoulder pain), analyses were carried out using multivariable logistic regression with adjustments for sex, age and body mass index. Biomarkers were considered as continuous variables and categorized at the median of their distributions. RESULTS: Pain at any site for ≥24 hours during the past month was reported by 1,214 participants. Of these, 779 mentioned that the pain had lasted for ≥3 months ("chronic pain"). α-carotene, ascorbic acid, ß-carotene, mercury and total protein had a statistically significant, inverse association with ≥2 chronic pain sites. Acrylamide, alkaline phosphatase, cadmium, cotinine, glycidamide, homocysteine, retinol, triglycerides and white blood cell count were positively associated with ≥2 chronic pain sites. Few biological markers were associated with acute and subacute pain. CONCLUSIONS: This study identified some biomarkers that were strongly and consistently associated with musculoskeletal pain. These results raise new hypotheses and could have tremendous implications for advancing knowledge in the field. Research on musculoskeletal pain needs to put more effort on the biological dimension of the biopsychosocial model of pain.

The Association Between Self-Reported Cigarette Smoking and Spinal Pain is Not Explained by Serum Cotinine Levels.

PURPOSE: The aim of this study was to check if self-reported smoking is still associated with back pain above and beyond its association with cotinine, to test the hypothesis that the association of self-reported cigarette smoking with back pain is due to residual confounding. METHODS: Secondary analyses of population-based cross-sectional data pertaining to 4470 adults were conducted. In multivariate analyses examining the associations of self-reported smoking with several spinal pain outcomes (neck pain, low back pain, low back pain with pain below knee, self-reported diagnosis of arthritis/rheumatism, and related limitations), further adjustment for serum cotinine concentrations was made. RESULTS: Self-reported cigarette smoking was associated with neck pain (adjusted Odds Ratio (aOR) Regular smokers vs. Non-smokers: 1.44; 95% Confidence Interval (CI): 1.14-1.82), low back pain (aOR: 1.48; 95% CI: 1.24-1.78), low back pain with pain below knee (aOR: 1.98; 95% CI: 1.42-2.76), as well as arthritis/rheumatism (aOR: 1.33; 95% CI: 1.03-1.71), and related functional limitations (P < .05). Further adjustment for serum cotinine concentrations brought about little change in the ORs or beta coefficients. CONCLUSIONS: These results do not support the hypothesis that serum cotinine concentrations explain the well-known relationship between cigarette smoking and spinal pain.