Co-occurrence of depressive and anxious symptoms and their influence on self-rated health: a national representative survey among Chinese older adults.

OBJECTIVES: The prevalence of the co-occurrence of depressive and anxious symptoms (CO) and their influence on perceived overall health were not clear in community dwelling Chinese older adults. The aims of the study were to investigate the prevalence of CO and to explore its influence on self-rated health (SRH). METHOD: This study included 12301 individuals aged ≥65 years from the 2018 wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS), a nationally representative survey of older adults in mainland China. Participants received face-to-face interviews and assessments of depressive symptoms and anxious symptoms via 10-item of the Center for Epidemiologic Studies Depression Scale (CES-D-10) and 7-item Generalized Anxiety Disorder Questionnaire (GAD-7), respectively. SRH was measured by self-reported. A logistic regression model was used to examine the association between CO and SRH after adjusting for confounding variables. RESULTS: The average age was 83.4 (SD: 11.0) years and there were 6576 (53.5%) females. The age- and sex-standardized prevalence of depressive symptoms only (DSO) was 38.6%, anxious symptoms only (ASO) was 1.5%, and CO was 10.8%. Compared with those without depressive and anxious symptoms, the older adults with DSO or ASO were more likely to have significant influence on SRH. And particularly, CO was likely to produce the greatest decrement in the level of SRH. CONCLUSION: CO was not rare in Chinese older adults nationwide. The older adults having CO had increased risk for lower level of SRH than having DSO or ASO. More attention should be given to CO among the older adults.

Sex differences in cognitive function trajectories and their determinants in older adults: Evidence from the Chinese longitudinal healthy longevity survey.

OBJECTIVES: To examine sex differences in the cognitive trajectories of a nationally representative sample of older people living in China and to explore potential determinants of these trajectories. METHODS: The study included 2230 women and 2171 men who were cognitively healthy and aged over 60 at the first observation from the Chinese Longitudinal Healthy Longevity Survey based on the 2008-2018 cohort. Cognitive function was measured using the Chinese version of the Mini-Mental State Examination (MMSE). Group-based trajectory modeling was used to identify potential heterogeneity of longitudinal changes over the 10 years in each gender. Logistic regression was used to investigate associations between baseline characteristics (age, education, fertility history, sleep length, physical activity, and health status and behaviors) and trajectory classes. RESULTS: Three trajectories (labeled stable, slow decline, and rapid decline) were identified according to the changes in MMSE scores for both women and men. For the women, both the slow and rapid decline groups accounted for a larger proportion (14.7% and 11.0%, respectively) than the male decline groups (8.1% and 6.6%, respectively), and the women had a lower baseline MMSE score with a faster decline. In the multivariable logistic regression analyses, older age, less education, older age at first birth, poorer functional abilities, hearing impairment, and lower baseline MMSE scores were significantly associated with cognitive decline in both the female and male groups compared to the stable group. For the women, sleeping over 9 h was also associated with a rapid cognitive decline trajectory, while current exercise and being overweight/obese were protective factors against cognitive decline. CONCLUSIONS: The women had an overall more serious cognitive decline than men. The potential determinants of cognitive decline identified in this study could be considered for developing specific intervention strategies aimed at promoting a healthy brain and preventing cognitive decline in different sexes, especially in low-income and developing countries.

Genetic associations with longevity are on average stronger in females than in males.

It is long observed that females tend to live longer than males in nearly every country. However, the underlying mechanism remains elusive. In this study, we discovered that genetic associations with longevity are on average stronger in females than in males through bio-demographic analyses of genome-wide association studies (GWAS) dataset of 2178 centenarians and 2299 middle-age controls of Chinese Longitudinal Healthy Longevity Study (CLHLS). This discovery is replicated across North and South regions of China, and is further confirmed by North-South discovery/replication analyses of different and independent datasets of Chinese healthy aging candidate genes with CLHLS participants who are not in CLHLS GWAS, including 2972 centenarians and 1992 middle-age controls. Our polygenic risk score analyses of eight exclusive groups of sex-specific genes, analyses of sex-specific and not-sex-specific individual genes, and Genome-wide Complex Trait Analysis using all SNPs all reconfirm that genetic associations with longevity are on average stronger in females than in males. Our discovery/replication analyses are based on genetic datasets of in total 5150 centenarians and compatible middle-age controls, which comprises the worldwide largest sample of centenarians. The present study's findings may partially explain the well-known male-female health-survival paradox and suggest that genetic variants may be associated with different reactions between males and females to the same vaccine, drug treatment and/or nutritional intervention. Thus, our findings provide evidence to steer away from traditional view that "one-size-fits-all" for clinical interventions, and to consider sex differences for improving healthcare efficiency. We suggest future investigations focusing on effects of interactions between sex-specific genetic variants and environment on longevity as well as biological function.

Development and validation of a stacking ensemble model for death prediction in the Chinese Longitudinal Healthy Longevity Survey (CLHLS).

OBJECTIVE: This study aimed to develop and validate a mortality risk prediction model for older people based on the Chinese Longitudinal Healthy Longevity Survey using the stacking ensemble strategy. MATERIAL AND METHODS: A total of 12,769 participants aged 65 or more at baseline were included. Ensemble machine learning models were applied to develop a mortality prediction model. We selected three base learners, including logistic regression, eXtreme Gradient Boosting, and Categorical + Boosting, and used logistic regression as the meta-learner. The primary outcome was five-year survival. Variable importance was evaluated by the SHapley Additive exPlanations method. RESULTS: The mean age at baseline was 88, and 57.8 % of participants were women. The CatBoost model performed the best among the three base learners, the area under the receiver operating characteristics curve (AUC) reached 0.8469 (95%CI: 0.8345-0.8593), and the stacking ensemble model further improved the discrimination ability (AUC = 0.8486, 95%CI: 0.8367-0.8612, P = 0.046). Conventional logistic regression had comparable performance (AUC = 0.8470, 95 % CI: 0.8346-0.8595). Older age, higher scores for self-care activities of daily living, being male, higher objective physical performance capacity scores, not undertaking housework, and lower scores on the Mini-Mental State Examination contributed to higher risk. CONCLUSIONS: We successfully constructed and validated a few death risk prediction models for a Chinese population of older adults. While the stacking ensemble approach had the best prediction performance, the improvement over conventional logistic regression was insubstantial.

Self- and interviewer-reported cognitive problems in relation to cognitive decline and dementia: results from two prospective studies.

BACKGROUND: Little is known regarding the association of interviewer-reported cognitive problems (ICP) with age-related cognitive decline. We aimed to investigate the independent associations of ICP and the combined associations of ICP and self-reported cognitive problems (SCP) with subsequent cognitive decline and dementia in two prospective cohort studies. METHODS: We included 10,976 Chinese (age = 57.7 ± 8.7) and 40,499 European (age = 64.6 ± 9.4) adults without dementia from the China Health and Retirement Longitudinal Study (CHARLS) and the Survey of Health, Ageing, and Retirement in Europe (SHARE). Self-rated memory (5-point scale) and interviewer-rated frequencies of asking for clarification (6-point scale) were used to define SCP and ICP (dichotomized). Outcomes included objective cognitive test scores (z-score transformation) and incident dementia. Generalized estimating equation models were performed to evaluate mean differences in objective cognitive decline. Logistic and Cox regression models were used to estimate the relative risk of dementia. Results from two cohorts were pooled using the random-effects models. RESULTS: ICP was associated with faster cognitive decline in CHARLS (ßCHARLS = -0.025 [-0.044, -0.006] z-score/year). ICP and SCP were also independently associated with higher risk of dementia in two cohorts (pooled relative risk for SCP = 1.73 [1.30, 2.29]; pooled relative risk for ICP = 1.40 [1.10, 1.79]). In the joint analysis, participants with coexistence of SCP and ICP had the fastest cognitive decline (ßCHARLS = -0.051 [-0.080, -0.021]; ßSHARE = -0.024 [-0.043, -0.004]; pooled ß = -0.035 [-0.061, -0.009] z-score/year) and highest risk of dementia (ORCHARLS = 1.77 [1.42, 2.20]; HRSHARE = 2.94 [2.42, 3.59]; pooled relative risk = 2.29 [1.38, 3.77]). CONCLUSIONS: The study suggested that interviewer-reported cognitive problems may be early indicators of cognitive decline and dementia in middle-aged and older adults. A combination of self- and interviewer-reported cognitive problems showed the strongest associations with cognitive decline and dementia.

Dietary factors in relation to the risk of cognitive impairment and physical frailty in Chinese older adults: a prospective cohort study.

PURPOSE: The study aimed to investigate the independent associations of dietary factors with cognitive impairment (CI) and physical frailty (PF) among Chinese older adults. METHODS: This study included 10,734 participants (mean age = 78.7 years) free of CI and PF at baseline from the Chinese Longitudinal Health Longevity Survey. Dietary intake was collected using a simplified food frequency questionnaire every 3-4 years. The Chinese version Mini-Mental State Examination was used to assess cognition function, participants with a score below 18 were defined as CI. PF was defined using the activities of daily living, instrumental activities of daily living, and functional limitation-related questions. The outcome was defined as the first onset of either CI or PF. Competing risk models were used to estimate the corresponding hazard ratios (HRs) and the 95% confidence intervals (95% CIs). RESULTS: During the study follow-up (mean = 8.1 years), a total of 1220 CI cases and 1451 PF cases were newly identified. Higher frequency of fruits intake was associated with a lower hazard of CI (HR = 0.75, 95% CI 0.58-0.97), whereas higher intake of preserved vegetables demonstrated an opposite association (HR = 1.23, 95% CI 1.07-1.42). In terms of PF, we observed a lower risk associated with higher meat and poultry intake (HR = 0.72, 95% CI 0.61-0.88). In particular, a significant protective association of fish and aquatic products intake with PF was observed among participants with ≥ 28 natural teeth (HR = 0.52, 95% CI 0.27-0.99). CONCLUSION: Our findings suggest divergent roles of major dietary factors in the development of CI and PF among Chinese older adults.

A Stable and Scalable Digital Composite Neurocognitive Test for Early Dementia Screening Based on Machine Learning: Model Development and Validation Study.

BACKGROUND: Dementia has become a major public health concern due to its heavy disease burden. Mild cognitive impairment (MCI) is a transitional stage between healthy aging and dementia. Early identification of MCI is an essential step in dementia prevention. OBJECTIVE: Based on machine learning (ML) methods, this study aimed to develop and validate a stable and scalable panel of cognitive tests for the early detection of MCI and dementia based on the Chinese Neuropsychological Consensus Battery (CNCB) in the Chinese Neuropsychological Normative Project (CN-NORM) cohort. METHODS: CN-NORM was a nationwide, multicenter study conducted in China with 871 participants, including an MCI group (n=327, 37.5%), a dementia group (n=186, 21.4%), and a cognitively normal (CN) group (n=358, 41.1%). We used the following 4 algorithms to select candidate variables: the F-score according to the SelectKBest method, the area under the curve (AUC) from logistic regression (LR), P values from the logit method, and backward stepwise elimination. Different models were constructed after considering the administration duration and complexity of combinations of various tests. Receiver operating characteristic curve and AUC metrics were used to evaluate the discriminative ability of the models via stratified sampling cross-validation and LR and support vector classification (SVC) algorithms. This model was further validated in the Alzheimer's Disease Neuroimaging Initiative phase 3 (ADNI-3) cohort (N=743), which included 416 (56%) CN subjects, 237 (31.9%) patients with MCI, and 90 (12.1%) patients with dementia. RESULTS: Except for social cognition, all other domains in the CNCB differed between the MCI and CN groups (P<.008). In feature selection results regarding discrimination between the MCI and CN groups, the Hopkins Verbal Learning Test-5 minutes Recall had the best performance, with the highest mean AUC of up to 0.80 (SD 0.02) and an F-score of up to 258.70. The scalability of model 5 (Hopkins Verbal Learning Test-5 minutes Recall and Trail Making Test-B) was the lowest. Model 5 achieved a higher level of discrimination than the Hong Kong Brief Cognitive test score in distinguishing between the MCI and CN groups (P<.05). Model 5 also provided the highest sensitivity of up to 0.82 (range 0.72-0.92) and 0.83 (range 0.75-0.91) according to LR and SVC, respectively. This model yielded a similar robust discriminative performance in the ADNI-3 cohort regarding differentiation between the MCI and CN groups, with a mean AUC of up to 0.81 (SD 0) according to both LR and SVC algorithms. CONCLUSIONS: We developed a stable and scalable composite neurocognitive test based on ML that could differentiate not only between patients with MCI and controls but also between patients with different stages of cognitive impairment. This composite neurocognitive test is a feasible and practical digital biomarker that can potentially be used in large-scale cognitive screening and intervention studies.

Proinflammatory phenotype in major depressive disorder with adulthood adversity: In line with social signal transduction theory of depression.

BACKGROUND: The social signal transduction theory of depression proposes that life stress can be transformed into inflammatory signals, and ultimately lead to the development of major depressive disorder (MDD). The hypotheses of this study were: (1) The pro-inflammatory effect of life stress was only seen in patients with MDD, but not in healthy controls (HCs); (2) Inflammation can mediate the relationship between life stress and depressive symptoms. METHODS: This study included 170 MDD patients and 196 HCs, and 13 immune-inflammatory biomarkers closely related to MDD were measured, principal component analysis (PCA) was adopted to extract the inflammatory index. Life stress was assessed by Life Event Scale (LES), a total score of >32 points on the LES was considered as adulthood adversity (AA). Path analyses were used to explore the relationship among adulthood stress, inflammatory index, and severity of depression. RESULTS: Among MDD patients, α2M, CXCL-1, IL-1ß, and TLR-1 levels were higher in patients with AA than non-AA group (all FDR-adjusted P values <0.05), meanwhile, the levels of CCL-2 and IL-18 were lower. Path analyses suggested that pro- and anti-inflammatory index could mediate the association between AA and severity of depression in MDD patients. CONCLUSION: This study found that inflammatory signals can mediate the relationship between adulthood adversity and depression, however, the causal relationship need to be further confirmed. These findings shed light on further understanding the theory of social signal transduction in MDD and provide clues for stress management and controlling inflammation strategies in depression. CLINICAL TRIALS: NCT02023567.

Characteristics and Potential Neural Substrates of Encoding and Retrieval During Memory Binding in Amnestic Mild Cognitive Impairment.

BACKGROUND: Whether encoding or retrieval failure contributes to memory binding deficit in amnestic mild cognitive impairment (aMCI) has not been elucidated. Also, the potential brain structural substrates of memory binding remained undiscovered. OBJECTIVE: To investigate the characteristics and brain atrophy pattern of encoding and retrieval performance during memory binding in aMCI. METHODS: Forty-three individuals with aMCI and 37 cognitively normal controls were recruited. The Memory Binding Test (MBT) was used to measure memory binding performance. The immediate and delayed memory binding indices were computed by using the free and cued paired recall scores. Partial correlation analysis was performed to map the relationship between regional gray matter volume and memory binding performance. RESULTS: The memory binding performance in the learning and retrieval phases was worse in the aMCI group than in the control group (F = 22.33 to 52.16, all p < 0.001). The immediate and delayed memory binding index in the aMCI group was lower than that in the control group (p < 0.05). The gray matter volume of the left inferior temporal gyrus was positively correlated with memory binding test scores (r = 0.49 to 0.61, p < 0.05) as well as the immediate (r = 0.39, p < 0.05) and delayed memory binding index (r = 0.42, p < 0.05) in the aMCI group. CONCLUSION: aMCI may be primarily characterized by a deficit in encoding phase during the controlled learning process. Volumetric losses in the left inferior temporal gyrus may contribute to encoding failure.

Adverse effects of 21 antidepressants on sleep during acute-phase treatment in major depressive disorder: a systemic review and dose-effect network meta-analysis.

STUDY OBJECTIVES: Sleep-related adverse effects during acute treatment with antidepressants undermine adherence and impede remission. We aimed to address subtypes of sleep-related adverse effects and depict the relationship between dose and sleep-related adverse events. METHODS: We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science for double-blind randomized controlled trials of depression published before April 30th, 2023. Eligible studies reporting sleep-related adverse effects during short-term monotherapy were included. The odds ratios (ORs) for sleep-related adverse effects were addressed with network meta-analysis. A Bayesian approach was used to depict the dose-effect relationship. Heterogeneity among studies was assessed using the τ2 and I2 statistics. Sensitivity analyses were performed without studies featuring high risk of bias. RESULTS: Studies with 64 696 patients were examined from 216 trials. Compared to placebo, 13 antidepressants showed higher ORs for somnolence, of which fluvoxamine (OR = 6.32; 95% CI: 3.56 to 11.21) ranked the top. Eleven had higher risks for insomnia, reboxetine ranked the top (OR = 3.47; 95% CI: 2.77 to 4.36). The dose-effect relationships curves between somnolence or insomnia and dose included linear shape, inverted U-shape, and other shapes. There was no significant heterogeneity among individual studies. The quality of evidence for results in network meta-analyses was rated as very low to moderate by Grading of Recommendations Assessment, Development, and Evaluation. CONCLUSIONS: Most antidepressants had higher risks for insomnia or somnolence than placebo. The diverse relationship curves between somnolence or insomnia and dose of antidepressants can guide clinicians to adjust the doses. These findings suggest clinicians pay more attention to sleep-related adverse effects during acute treatment with antidepressants.

Characteristics of Odor Identification and Hedonics and Their Association with Piriform Cortex-Based Resting-State Functional Connectivity in Amnestic Mild Cognitive Impairment.

BACKGROUND: Olfactory identification dysfunction (OID) might be an early sign of amnestic mild cognitive impairment (aMCI). However, odor hedonics, the ability to perceive odor pleasantness, is neglected. Also, the neural substrate of OID remains unclear. OBJECTIVE: To explore the characteristics of odor identification and hedonics in aMCI and examine the potential neural correlates of OID by analyzing olfactory functional connectivity (FC) patterns in MCI. METHODS: Forty-five controls and 83 aMCI patients were examined. The Chinese smell identification test was used to assess olfaction. Global cognition, memory, and social cognition were assessed. Resting-state functional networks associated with olfactory cortex seeds were compared between the cognitively normal (CN) and aMCI groups, as well as between aMCI subgroups by the degree of OID. RESULTS: Compared to controls, aMCI patients had a significant deficit in olfactory identification, mainly reflected in the identification of pleasant and neutral odors. aMCI patients also rated pleasant and neutral odors much lower than controls. A positive correlation between olfaction and social cognition was found in aMCI. The seed-based FC analysis found that aMCI patients had higher FC between the right orbitofrontal cortex and right frontal lobe/middle frontal gyrus than controls. Subgroup analysis showed that, compared to aMCI without OID, aMCI with severe OID had abnormal FC in the bilateral piriform region. CONCLUSION: Our results suggest that OID in aMCI primarily refers to the identification of pleasant and neutral odors. The FC alterations in bilateral orbitofrontal cortex and piriform cortices might contribute to the impairment in odor identification.

Prevalence and Correlates of Risky Drinking Among the Oldest-Old in China: A National Community-Based Survey.

Aims: To investigate the prevalence and correlates of risky drinking in Chinese elderly people aged 80 and over. Methods: Data were obtained from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) conducted in 2018. A total of 10,141 respondents aged 80 years or older were included in this analysis. Risky drinking was defined as drinking > 2 drinks per day. The participants were divided into no risky drinking, past risky drinking, and current risky drinking groups. The prevalence of risky drinking, daily dosage, and type of alcohol beverages were assessed. The correlates of risky drinking were analyzed using logistic regression. Results: The prevalence of past and current risky drinking was 6.2 and 4.4%, respectively. A total of 12.2% of males and 2.1% of females reported past risky drinking, and 8.9% of males and 1.4% of females reported current risky drinking. The median of the daily dosage of the past risky drinking group was 4.5 and 4 drinks in males and females, respectively, and were 4 and 3.3, respectively, of the current risky drinking group. Strong liquor was the most popular alcohol beverage in all groups. Men who were older or had white-collar work were less likely to be past risky drinkers, while those with smoking in past or current or heart disease were more likely to be past risky drinkers. Women who smoked in the past were more likely to be past risky drinkers. Men with older age or living in the urban areas or with heart disease were less likely to be current risky drinkers. Women with higher education or with heart disease were less likely to be current risky drinkers. Women with current smoking were more likely to have current risky drinking. Conclusions: Our findings indicated that risky drinking among the oldest-old was not rare in China. The correlates of past and current risky drinking were different. Men and women had various correlates of risky drinking as well. Those with higher socioeconomic status seemed less likely to be risky drinking. More attention should be given to risky drinking among the oldest old, and sex-specific intervention may be needed.

Long-term Weight Change and its Temporal Relation to Later-life Dementia in the Health and Retirement Study.

CONTEXT: Weight loss among middle-aged and older adults has been associated with a higher risk of subsequent dementia. However, most studies have limited follow-up durations or suboptimal control for the potential influence of physical frailty (PF). OBJECTIVE: Our study aimed to investigate the long-term and temporal relations of weight change to risk of dementia among middle-aged and older adults in the United States. METHODS: A total of 5985 participants aged 65 years and older were included from the Health and Retirement Study. History of long-term weight change was calculated using 9 repeated body mass index measurements during 1992-2008. We then followed participants' dementia status from 2008 to 2018. Multivariable Cox proportional hazard models were used. RESULTS: During the study follow-up period (mean = 7.54 years), a total of 682 (11.40%) dementia cases were documented. After adjustment for basic demographic and lifestyle factors, participants with weight loss (median: -0.23 kg/m2 per year) were at a significantly higher risk of dementia (HR = 1.60; 95% CI, 1.33, 1.92), compared with the stable weight group (median: 0.11 kg/m2 per year). This association was attenuated but remained strong and significant after further adjustment for PF (HR = 1.57; 95% CI, 1.30, 1.89). Significant association was observed for weight loss assessed approximately 14 to 18 years preceding dementia diagnosis (HR = 1.30; 95% CI, 1.07, 1.58), and was consistent closer to diagnosis. CONCLUSION: Both recent and remote weight loss were associated with a higher risk of later-life dementia among middle-aged and older adults independent of PF status.

Features of cognitive impairment and related risk factors in patients with major depressive disorder: A case-control study.

BACKGROUND: Cognitive impairment (CI) is a common symptom contributing to functional loss in major depressive disorder (MDD). However, the features of CI and its related risk factors in young and middle-aged MDD patients remain unclear. METHODS: In this case-control study, 18- to 55-year-old acute-onset MDD patients and healthy controls (HCs) were recruited from nine centers in China. MDD patients were diagnosed based on the DSM-IV, the Mini-International Neuropsychiatric Interview, and a 17-item Hamilton Rating Scale for Depression score ≥ 14. Cognitive function, including attention/vigilance, learning, memory, processing speed and executive function, was assessed with a neuropsychological battery and compared between MDD patients and HCs. MDD patients scoring 1.5 SDs below the mean HC score in at least 2 domains were defined as having CI. Logistic regression analysis was used to identify risk factors for CI in MDD patients. RESULTS: Compared with HCs (n = 302), MDD patients (n = 631) showed significant impairment in all cognitive domains (P < 0.001); 168 MDD patients (26.6%) had CI. Male sex (OR: 1.712; 95% CI: 1.165-2.514; P < 0.01) was positively correlated with CI; age of first onset (OR: 0.974; 95% CI: 0.957-0.991; P < 0.05) and comorbid anxiety disorders (OR: 0.514; 95% CI: 0.332-0.797; P < 0.01) were negatively correlated with CI. LIMITATIONS: Biomarkers and neuroimaging were not used to investigate the possible biological mechanism and neural basis of CI in MDD. CONCLUSIONS: CI was prominent in adults with acute-onset MDD; male sex and younger age of first onset were independent risk factors, and comorbid anxiety disorders were a protective factor.

Major depressive disorder comorbid with general anxiety disorder: Associations among neuroticism, adult stress, and the inflammatory index.

Accumulating evidence shows that higher neuroticism and adult stress may be potential risk factors for major depressive disorder (MDD) comorbid with generalized anxiety disorder (GAD). Studies have shown that anxious and depressed patients have significantly more neurobiological abnormalities than non-anxious depressed patients. However, the biological mechanism of comorbidity remains unknown. A study of serum markers allows a better understanding of the mechanism. This was a multi-centre, cross-sectional study. A total of 169 MDD patients (42 MDD patients with comorbid GAD and 127 MDD patients without comorbid GAD) were studied to analyse the risk factors for MDD with comorbid GAD. Twenty-four peripheral serum markers were measured. Path analysis was applied to test the association among neuroticism, adult stress, inflammatory markers, and psychopathology. After Bonferroni correction, MDD patients with comorbid GAD had lower levels of CCL2 (P = 0.001) and higher levels of α2M (P < 0.001) and TLR-1 (P = 0.001) than MDD patients without comorbid GAD (adjusted P < 0.002). In the path analyses of the association among adult stress, the inflammatory index, and psychopathology, neuroticism had a direct effect (ß = 0.238, P = 0.003) and an indirect effect (ß = 0.068, P = 0.004) on MDD and GAD comorbidity through adult stress and the inflammatory index. Our results suggest that MDD with comorbid GAD is associated with higher levels of inflammatory markers, stress factors and personality traits, which may provide some cues for early identification or more tailored and comprehensive treatment for MDD with comorbid GAD.

The effect of China's Clean Air Act on cognitive function in older adults: a population-based, quasi-experimental study.

BACKGROUND: Air pollution might accelerate cognitive ageing; it is unclear whether large-scale interventions, such as China's Clean Air Act (CCAA), can mitigate cognitive deterioration. We aimed to evaluate the effect of CCAA on changes in cognitive function in older adults. METHODS: In this population-based, quasi-experimental study, we did a difference-in-differences analysis of the data collected during the 2014 and 2018 waves of the Chinese Longitudinal Healthy Longevity Survey (CLHLS). The study design used a counterfactual analysis feature by dividing CLHLS participants into two groups. The intervention group included participants who lived in areas where the provincial government set a target of reducing particulate matter (PM) by at least 5% annually from 2014 onward, whereas the control group consisted of individuals who lived in areas without a PM reduction target. Global cognitive function was measured using the Mini-Mental State Examination (MMSE). We used fixed-effects models to examine the between-group differences in MMSE score changes before and after CCAA implementation. We associated longitudinal changes in MMSE scores with changes in concentrations of PM with a diameter of less than 2·5 µm (PM2·5) concentration and other regulated pollutants. We used alternative models and sensitivity analyses to evaluate the robustness of the results from the main models. FINDINGS: 2812 individuals participated in the 2014 and 2018 surveys (mean age 81·0 years [SD 9·3] in 2014; 1408 [50·1%] female and 1404 [49·9%] male). 2251 (80·0%) were included in the intervention group and 561 (20·0%) in the control group. After controlling for potential confounders, the intervention group had a significantly smaller decline in MMSE scores from 2014 to 2018 compared with the control group: the mean between-group difference was 2·45 points (95% CI 1·32-3·57). Interquartile increases in PM2·5 were associated with a significant MMSE score decline of 0·83 points (95% CI 0·24-1·42); similarly, increases in SO2 were also associated with a significant MMSE score decline of 0·80 points (0·32-1·29). INTERPRETATION: Implementing stringent clean air policies might mitigate the risk of air pollutant-associated cognitive ageing in older people. FUNDING: National Natural Sciences Foundation of China, National Key R&D Program of China, China Postdoctoral Science Foundation funded project, the Duke/Duke-National University of Singapore Collaboration Pilot Project, the National Institute on Aging and Peking University-Baidu Fund, Energy Foundation, and the Fundamental Research Funds for the Central Universities.

Childhood adversity, adulthood adversity and suicidal ideation in Chinese patients with major depressive disorder: in line with stress sensitization.

The stress sensitization model indicates that early adversity (e.g., childhood stress) sensitizes individuals to subsequent proximal stress (e.g., stressful life events in adult life), thereby increasing their vulnerability to psychiatric disorders. However, the effect of stress sensitization on suicidality in patients with major depressive disorder (MDD) has not been previously investigated. Data for the present study were derived from the Objective Diagnostic Markers and Personalized Intervention in MDD Patients (ODMPIM) study. The psychiatric diagnosis and suicidal ideation were evaluated by the Mini-International Neuropsychiatric Interview (M.I.N.I.). We used a multiple logistic analysis to examine the association among childhood adversity (CA), adulthood adversity (AA) and suicidal ideation. Among 1084 MDD patients, 48.6% had suicidal ideation and 65.6% experienced life adversity during their childhood or adulthood. Patients who reported suicidal ideation were more likely to report CA (46.7% vs. 38.7%, P = 0.008) or AA (49.5% vs. 40.9%, P = 0.004) than patients without suicidal ideation. Patients who experienced two waves of adversity (both CA and AA) were associated with higher rates of suicidal ideation (odds ratio = 1.68, 95% CI = 1.19-2.37, P = 0.003); however, neither CA nor AA alone was associated with suicidal ideation. This study first verifies the hypothesis of stress sensitization on suicidal ideation in patients with MDD. Focusing on stress sensitization may enhance the early identification of MDD patients at suicidal risk and the ability to provide timely and appropriate intervention. Clinicaltrials.gov identifier: NCT02023567.

Prescription Patterns of Antidementia and Psychotropic Drugs in People Living With Dementia: Findings From the Clinical Pathway Study of Alzheimer's Disease in China.

OBJECTIVES: Evidence about prescribing patterns of dementia medication in China is lacking. This study aimed to examine prescribing rates of antidementia and psychotropic drugs and factors associated with drug prescription for dementia in China. DESIGN: A multicenter observational study. SETTING AND PARTICIPANTS: This study employed cross-sectional data from the Clinical Pathway for Alzheimer's Disease in China study that was conducted in 28 memory clinics at tertiary hospitals across 14 provinces between 2012 and 2013. Patients aged ≥45 years with a diagnosis of dementia were included. METHODS: Antidementia and psychotropic drugs were classified according to the Anatomical Therapeutic Chemical codes. Odds ratios (ORs) of putative factors associated with prescription patterns were estimated using logistic regressions. RESULTS: A total of 751 respondents were included in this study, 77.8% of whom were prescribed antidementia drugs, and 33.0% were prescribed at least 1 psychotropic drug. The concomitant prescription rate of antidementia and psychotropic drugs was 24.1%. Frontotemporal dementia [OR 9.92 (99.17% CI 3.08-42.70)], severe dementia [4.25 (1.88-9.79)], and apathy [1.94 (1.18-3.20)] were significantly associated with an elevated likelihood of memantine prescription. Psychotic symptoms [1.84 (1.02-3.35)], agitation [1.91 (1.08-3.40)], and depressive symptoms [2.10 (1.12-3.94)] were significantly associated with the coprescription of antidementia and psychotropic agents. CONCLUSIONS AND IMPLICATIONS: The prescribing rate of antidementia drugs in the study sample was higher, whereas the rate of coprescription of psychotropic and antidementia drugs was lower than reported in Western studies. Dementia prescription practice was generally consistent with clinical guidelines in memory clinics in China, whereas the prescription of antidementia and psychotropic medication mainly depended on patients' clinical symptoms.

Excessive sleep increased the risk of incidence of cognitive impairment among older Chinese adults: a cohort study based on the Chinese Longitudinal Healthy Longevity Survey (CLHLS).

STUDY OBJECTIVES: Based on a cohort from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), we aimed to evaluate the relationship between sleep duration and the incidence of cognitive impairment among older Chinese adults. METHODS: We conducted a prospective analysis based on 3692 participants from the CLHLS at baseline (in 2011), and as a 3-year follow-up (till 2014), 531 participants (14.4%) had cognitive impairment, which was defined as a Mini-Mental State Examination score <24. Sleep duration was classified into three groups: short (≤5 hours/day), normal (>5 but <10 hours), and long (≥10 hours/day). A logistic regression model was used to examine the association between baseline sleep duration and cognitive impairment after adjusting for sociodemographic data, living habits, and health conditions. RESULTS: Five hundred sixty-two participants (15.2%) were in the short-duration group, and 608 participants (16.5%) were in the long-duration group. After adjusting for multiple potential confounders, compared with normal sleep duration, long sleep duration was associated with the incidence of cognitive impairment (OR = 1.309, 95% CI: 1.019-1.683), especially among men (OR = 1.527, 95% CI: 1.041-2.240) and those having a primary and above education level (OR = 1.559, 95% CI: 1.029-2.361). No significant association was observed between short sleep duration and cognitive impairment (OR = 0.860, 95% CI: 0.646-1.145). CONCLUSIONS: Excessive sleep may increase the risk of cognitive impairment in older individuals. It may be a suggestive sign of early neurodegeneration and may be a useful clinical tool to identify those at a higher risk of progressing to cognitive impairment.