Background: Few studies have simultaneously examined how blood biomarkers for inflammation, metabolic, and cardiovascular function are associated with disability incidence. This study aimed to comprehensively examine these associations. Methods: We used data from adults aged 50 and older in the Health and Retirement Study (n = 9250) and the China Health and Retirement Longitudinal Study (n = 6844), with biennial follow-up over a 4-year period. We defined abnormal biomarker values using standard clinical cut-off points for three biological systems. Disability burden was quantified as the cumulative number of impairments in basic and instrumental activities of daily living. Multivariate linear mixed-effects models were used to analyze the associations. Results: At baseline, 42% of participants had abnormal biomarker values in at least one system, 28% in two systems, and 7% in all three. A dose–response relationship was observed between the rate of disability accumulation and the number of systems with abnormal biomarker values. Compared to individuals with normal values across all systems, those with abnormalities in two systems had a significantly faster annual increase in disability burden (β = 0.06, 95% CI: 0.02–0.09), while those with abnormalities in all three systems exhibited an even steeper increase (β = 0.1, 95% CI: 0.05–0.16). Conclusions: The presence of abnormal levels in any two or all three of the systems significantly accelerated the rate of disability accumulation over a 4-year period. These findings highlight the importance of integrated biomarker monitoring for early identification of individuals at risk and inform the development of targeted preventive strategies.

The causal association between chronic diseases and depression remains unclear. This study aimed to explore the effects of types and number of chronic diseases on the risk of depression using data from the Survey of Health, Ageing and Retirement in Europe (SHARE). A self-admitted questionnaire was used to obtain data on 14 predefined chronic diseases and the European-Depression Scale (EURO-D) was used to assess depression. Among the 16,080 baseline depression-free participants aged 50+, 31.29% (5032) developed depression over 13 years. Multivariate Cox regression models showed that individuals with any chronic diseases were at higher risk of new onset depression compared to disease-free participants. The risk of new onset depression increased with an increasing number of diseases among both younger (50–64) and older (65+) adults. Individuals with heart attack, stroke, diabetes, chronic lung disease, and arthritis were at increased risk of depression across age groups. However, some age-specific associations were observed, with cancer increasing depression risk among younger- and peptic ulcer, Parkinson's disease and cataracts increasing depression risk among older adults. These findings highlight the importance of managing chronic diseases, especially among those with more than two diseases, to prevent the development of depression among middle-aged and older adults.

Objective: Given the importance of sleep in maintaining neurocognitive health, both sleep duration and quality might be component causes of dementia. However, the possible role of insomnia symptoms as risk factors for dementia remain uncertain.

Methods: We prospectively studied 22,078 participants in the Swedish National March Cohort who were free from dementia and stroke at baseline. Occurrence of dementia was documented by national registers during a median follow-up period of 19.2 years. Insomnia symptoms and sleep duration were ascertained by Karolinska Sleep Questionnaire. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI).

Results: Compared to participants without insomnia at baseline, those who reported any insomnia symptom experienced a greater incidence of dementia during follow-up (HR 1.08, 95% CI: 1.03, 1.35). Difficulty initiating sleep versus non-insomnia (HR 1.24, 95% CI: 1.02, 1.52), but not difficulty maintaining sleep or early morning awakening was associated with an increased risk of dementia. Short sleep duration was associated with increased risk of dementia (6 h vs. 8 h, HR 1.29, 95% CI: 1.11–1.51; 5 h vs. 8 h, HR 1.26, 95% CI: 1.00–1.57). Stratified analyses suggested that insomnia symptoms increased the risk of dementia only amongst participants with ≥7 h sleep (vs. non-insomnia HR 1.24, 95% CI: 1.00–1.54, P = 0.05), but not amongst short sleepers (<7 h). Short sleep duration also did not further inflate the risk of dementia amongst insomniacs.

Conclusion: Insomnia and short sleep duration increase the risk of dementia amongst middle-aged to older adults.

Objective: The aim of the study is to investigate the influence of work-related psychological and physical stresses on risk of cardiovascular disease (CVD). Methods : A total of 5651 CVD-free participants older than 50 years from the Survey of Health, Ageing and Retirement in Europe were followed up for 13 years to detect incident CVD. Work-related stress was assessed using job strain and job reward questionnaire. Cox regression model was used to estimate the association. Results: High physical demands (hazard ratio [HR], 1.30) and low reward (HR, 1.19) compared with their counterparts, as well as active physical jobs (HR, 1.41) and high physical strain (HR, 1.45) in comparison with low physical strain were associated with higher risk of incident CVD after adjusting for confounders. However, combining physically stressful jobs with low reward did not further increase the CVD risk. Conclusions: Avoiding physically stressful jobs or providing appropriate reward may reduce the occurrence of CVD.

Background. Depressive symptoms and cognitive impairment often coexisted in the elderly. This study investigates the effect of late-life depressive symptoms on risk of mild cognitive impairment (MCI).

Methods. A total of 14,231 dementia- and MCI free participants aged 60+ from the Survey of Health, Ageing, and Retirement in Europe were followed-up for 10 years to detect incident MCI. MCI was defined as 1.5 standard deviation (SD) below the mean of the standardized global cognition score. Depressive symptoms were assessed by a 12-item Europe-depression scale (EURO-D). Severity of depressive symptoms was grouped as: no/minimal (score 0–3), moderate (score 4–5), and severe (score 6–12). Significant depressive symptoms (SDSs) were defined as EURO-D score ≥ 4.

Results. During an average of 8.2 (SD = 2.4)-year follow-up, 1,352 (9.50%) incident MCI cases were identified. SDSs were related to higher MCI risk (hazard ratio [HR] = 1.26, 95% confidence intervals [CI]: 1.10–1.44) in total population, individuals aged 70+ (HR = 1.35, 95% CI: 1.14–1.61) and women (HR = 1.28, 95% CI: 1.08–1.51) in Cox proportional hazard model adjusting for confounders. In addition, there was a dose–response association between the severity of depressive symptoms and MCI incidence in total population, people aged ≥70 years and women (p-trend <0.001).

Conclusions. Significant depressive symptoms were associated with higher incidence of MCI in a dose–response fashion, especially among people aged 70+ years and women. Treating depressive symptoms targeting older population and women may be effective in preventing MCI.

Background: Evidence of the association between common chronic diseases and depression is sparse.

Methods: Totally 7819 participants aged 45+ without depression at baseline were followed-up (2011-2015) to detect incident depression. Chronic diseases and depression were defined by self-reported diagnosis and the Center for Epidemiological Studies Depression Scale (CES-D10), respectively. Cox proportional hazards model was used to explore the association between chronic diseases and depression adjusting for age, gender, education, marital/living conditions, area, smoking, drinking, economic status, BMI and health insurance.

Results: During an average of 3.42 years follow-up, 2271 participants developed depression (85 per 1000 person-year). Chronic diseases were related to significantly higher risk of depression (HR = 1.38). A higher risk of depression was also associated with specific diseases: stomach/other digestive diseases (HR = 1.19), diabetes (HR = 1.22), arthritis/rheumatism (HR = 1.30), and kidney diseases (HR = 1.34) (P < 0.05). The risk of depression increased with increasing in the number of chronic diseases (1: HR = 1.27, 2: HR = 1.49, and 3+: HR = 1.51, P-trend < 0.001). No significant difference was observed across age, gender, education, and area.

Limitations: Chronic diseases and depression were based on self-reported diagnosis and measurement scale, respectively, which could lead to information bias. Some unmeasured confounders might have biased the results.

Conclusions: The occurrence of depression in people aged 45+ is associated with number of chronic diseases in a dose-response fashion. These results may provide guidance on preventing depression and improving the quality of life in middle and late adulthood.

Background: To examine the association of job strain with cognitive ability and the influence of life-course job strain on later life cognitive decline.

Methods: Data were derived from six waves of the Survey of Health, Aging, and Retirement in Europe. The study sample consists of 13349 participants aged 50 to 98 years at wave 2 and has been followed up for 12-years. Job strain status across working life was assessed using a short demand-control job strain model containing two core dimensions: job demands and job control collected in wave 3. Cognitive abilities concerning episodic memory was assessed by immediate recall and delayed recall tests, executive function was evaluated by verbal fluency test collected in all waves (waves 2–7) except wave 3. Mixed-effects model was used to estimate working life job strain and its cumulative effect on cognitive decline.

Results: Both passive and high strain jobs were associated with lower levels of cognitive ability (episodic memory and verbal fluency) in comparison with active job. Long exposure to active- or low strain-job was associated with higher cognitive ability whereas long exposure to passive job or moderate duration of high strain job was associated with lower cognitive ability. The rate of memory decline was positively related to moderate duration of passive job and negatively related to long-term exposure to low strain job.

Limitations: Information on working conditions was based on self-reported recollections.

Conclusions: Working life variation in job strain status and their duration may explain individual differences in cognitive ability in later life.

Background: Evidence of the association between effort reward imbalance (ERI) and suicidal ideation is sparse. This study examined the influence of ERI at work on suicidal ideation and the mediating effect of depressive symptoms. Methods: There were 4963 workers aged 50 + without suicidal ideation at baseline in the Survey of Health, Aging and Retirement in Europe, these workers were followed-up for 8-years to detect incident suicidal ideation. ERI was measured by a short ERI questionnaire. Suicidal ideation was evaluated by one item derived from the 12-item Europe-depression scale, and depressive symptoms were assessed by the remaining 11 items in the scale. Cox models were employed to explore the relationship adjusting for potential confounders. Mediation analysis was used to test the mediating effect of depressive symptoms. Results: A significantly higher incidence of suicidal ideation was related with high effort (HR = 1.51) and low reward (HR = 1.42), respectively. A high effort-low reward imbalance was associated with even higher risk of suicidal ideation (HR = 1.96) as compared to low effort-high reward combination. The association was varied by gender, region, education and household income. Depressive symptoms mediated a modest proportion (natural indirect effect 14.4%) of the total association between ERI and suicidal ideation. Limitation: Suicidal ideation definition based on self-administered questionnaires which could lead to false negatives. And some unmeasured confounders might have biased the results. Conclusions: Efforts in promoting balanced effort-reward at work may reduce suicidal ideation among working population aged 50+. Avoiding depressive symptoms may further enhance such efforts.

Background: Depression is the most common mental health problem and often co-occurs with dementia in old age. This study investigates the in fluence of late-life depression on risk of dementia.

Methods: A total of 16210 dementia-free participants aged 60+ from the Survey of Health, Aging, and Retirement in Europe were followed up for 10 years to detect incident dementia. Depression was assessed by a 12-item Europe-depression scale, dementia was determined by physician diagnosis reported by the participants and their informants. Fine and Gray model was performed to explore the association between depression and incident dementia taking into account competing risk of death.

Results: During an average of 8 years follow-up, 1030 (6.35%) incident dementia were identi fied. Late-life depression was related to higher subdistribution hazard ratio (sHR) of dementia (sHR=1.52, 95%CI: 1.32-1.75) after adjusting for age, gender, country, education, smoking, drinking, living arrangement, BMI, chronic disease, and physical activity. Further, the risk was only existed in those below age of 80 (sHR=1.75, 95%CI: 1.47-2.07). In addition, a dose-response association was observed between the severity of depression and dementia risk (p for trend<0.001).

Limitation: The ascertainment of depression and dementia was based on information reported by the participants and/or their informants, which might result in information bias. The causal relationship could not be determined because limited follow-up time.

Conclusions: Late-life depression is associated with higher incidence of dementia in a dose-response fashion. Interventions targeting depression patients aged 60-79 years and those with severe depression may be e ffective strategies to prevent dementia.

Alzheimer's disease (AD) is a neurodegenerative disease that mainly occurs in old age and involves progressive cognitive impairment. AD has become a major global issue for public health, with approximately 24 million people currently affected by the disease. Estimates indicted that this number will quadruple by 2050. Because of the high incidence of AD, there is an urgent need to develop new strategies to diagnose and treat AD. Many recent studies have indicated the multiple, yet somewhat controversial, roles of exosomes in AD. Although the underlying mechanisms by which exosomes play a role in AD are still unknown, current evidence suggests that exosomes can carry and spread toxic amyloid-beta, and hyperphosphorylated tau, between cells, and then induce apoptosis, thus contributing to the loss of neurons. In addition, exosomes appear to possess the ability to reduce brain amyloid-beta, and tau hyperphosphorylation, and transfer neuroprotective substances between neural cells. The accumulating data brings hope that the application of exosomes may be helpful for early diagnostics and the identification of new therapeutic targets for AD. Here, we summarized the various roles of exosomes, and how they might relate to the pathogenesis of AD. We also highlight the potential application of exosomes as a therapeutic option in AD therapy.