Sex Differences in Longitudinal Trajectories of Cognitive Aging in Zaragoza, Spain.

OBJECTIVES: The objective of this study was to document the longitudinal trajectories of cognitive aging in a sample of cognitively healthy subjects of 55 years or older. The following differences between men and women were hypothesized: 1) in the cognitive loss through aging, 2) in the distinct trajectories identified; and 3) in the predictors associated with the identified trajectories. DESIGN AND SETTING: A 4-wave, population-based study in Zaragoza, Spain (1994-2006). PARTICIPANTS: A total of 2,403 individuals aged 55+ years, cognitively healthy at baseline. MEASUREMENTS: All participants had at least three measurements with the Mini-Mental State Examination (MMSE). Validated Spanish versions of international instruments were used for assessment. Random effects linear panel regression model for analyzing differences by sex in MMSE scores through aging were performed, and growth mixture models (GMM) applied independently for each sex for modeling the longitudinal cognitive trajectories. RESULTS: Women showed lower mean MMSE scores in all phases and significantly higher loss in the MMSE from phases 2 to 3 and 3 to 4. The best fitting age-adjusted model of the cognitive trajectories was a 4-class GMM in men and a 3-class in women. Education was a predictor of cognitive trajectories in both men and women. Dependence on iADLs and alcohol status were predictors only for men, and depression and diabetes only for women. CONCLUSIONS: The identified differences by sex in cognitive trajectories and their associated factors suggest that men and women may require a different strategy when addressing cognitive aging.

Parental history of dementia and the risk of dementia: A cross-sectional analysis of a global collaborative study.

BACKGROUND: Parental history of dementia appears to increase the risk of dementia, but there have been inconsistent results. We aimed to investigate whether the association between parental history of dementia and the risk of dementia are different by dementia subtypes and sex of parent and offspring. METHODS: For this cross-sectional study, we harmonized and pooled data for 17,194 older adults from nine population-based cohorts of eight countries. These studies conducted face-to-face diagnostic interviews, physical and neurological examinations, and neuropsychological assessments to diagnose dementia. We investigated the associations of maternal and paternal history of dementia with the risk of dementia and its subtypes in offspring. RESULTS: The mean age of the participants was 72.8 ± 7.9 years and 59.2% were female. Parental history of dementia was associated with higher risk of dementia (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.15-1.86) and Alzheimer's disease (AD) (OR = 1.72, 95% CI = 1.31-2.26), but not with the risk of non-AD. This was largely driven by maternal history of dementia, which was associated with the risk of dementia (OR = 1.51, 95% CI = 1.15-1.97) and AD (OR = 1.80, 95% CI = 1.33-2.43) whereas paternal history of dementia was not. These results remained significant when males and females were analyzed separately (OR = 2.14, 95% CI = 1.28-3.55 in males; OR = 1.68, 95% CI = 1.16-2.44 for females). CONCLUSIONS: Maternal history of dementia was associated with the risk of dementia and AD in both males and females. Maternal history of dementia may be a useful marker for identifying individuals at higher risk of AD and stratifying the risk for AD in clinical trials.

Reliability and validity of the Spanish version of the IDEAL Schedule for assessing care needs in dementia: Cross-sectional, multicenter study.

OBJECTIVE: The IDEAL Schedule was developed for staging "care needs" in patients with dementia. We here aim to validate the Spanish version, further test its psychometric properties and explore a latent construct for "care needs". METHODS: A multicenter study was done in 8 dementia care facilities across Spain. Patients referred with a reliable ICD-10 diagnosis of dementia (n = 151) were assessed with the IDEAL Schedule by pairs of raters. Inter-rater reliability (intra-class correlation [ICC] coefficients), internal consistency (Cronbach's alpha), and factor analysis were calculated. Convergent validity for individual items was tested against validated Spanish versions of international instruments. RESULTS: Pilot testing with numerical scales supported the feasibility, face, and content validity of the schedule. The psychometric coefficients were good/clinically acceptable: inter-rater reliability (mean ICC = 0.861; 85% of the ICCs > 0.8), internal consistency (global alpha coefficient = 0.74 in 5 nuclear items), and concurrent validity (global score against the Clinical Dementia Rating schedule, r = 0.63; coefficients for individual items ranging from 0.40 to 0.84, all statistically significant, p < 0.05). Internal consistency was low for the "nonprofessional care" and "social support" dimensions. Factor analysis supported a unidimensional solution, suggesting a latent "care needs" construct. CONCLUSION: The Spanish version of the IDEAL Schedule confirms the main psychometric properties of the original version and documents for the first time the convergent validity of individual items. Factor analysis identified a latent construct consistent with the concept "care needs" although 2 dimensions need further psychometric research.

Age-related cognitive decline and associations with sex, education and apolipoprotein E genotype across ethnocultural groups and geographic regions: a collaborative cohort study.

BACKGROUND: The prevalence of dementia varies around the world, potentially contributed to by international differences in rates of age-related cognitive decline. Our primary goal was to investigate how rates of age-related decline in cognitive test performance varied among international cohort studies of cognitive aging. We also determined the extent to which sex, educational attainment, and apolipoprotein E ε4 allele (APOE*4) carrier status were associated with decline. METHODS AND FINDINGS: We harmonized longitudinal data for 14 cohorts from 12 countries (Australia, Brazil, France, Greece, Hong Kong, Italy, Japan, Singapore, Spain, South Korea, United Kingdom, United States), for a total of 42,170 individuals aged 54-105 y (42% male), including 3.3% with dementia at baseline. The studies began between 1989 and 2011, with all but three ongoing, and each had 2-16 assessment waves (median = 3) and a follow-up duration of 2-15 y. We analyzed standardized Mini-Mental State Examination (MMSE) and memory, processing speed, language, and executive functioning test scores using linear mixed models, adjusted for sex and education, and meta-analytic techniques. Performance on all cognitive measures declined with age, with the most rapid rate of change pooled across cohorts a moderate -0.26 standard deviations per decade (SD/decade) (95% confidence interval [CI] [-0.35, -0.16], p < 0.001) for processing speed. Rates of decline accelerated slightly with age, with executive functioning showing the largest additional rate of decline with every further decade of age (-0.07 SD/decade, 95% CI [-0.10, -0.03], p = 0.002). There was a considerable degree of heterogeneity in the associations across cohorts, including a slightly faster decline (p = 0.021) on the MMSE for Asians (-0.20 SD/decade, 95% CI [-0.28, -0.12], p < 0.001) than for whites (-0.09 SD/decade, 95% CI [-0.16, -0.02], p = 0.009). Males declined on the MMSE at a slightly slower rate than females (difference = 0.023 SD/decade, 95% CI [0.011, 0.035], p < 0.001), and every additional year of education was associated with a rate of decline slightly slower for the MMSE (0.004 SD/decade less, 95% CI [0.002, 0.006], p = 0.001), but slightly faster for language (-0.007 SD/decade more, 95% CI [-0.011, -0.003], p = 0.001). APOE*4 carriers declined slightly more rapidly than non-carriers on most cognitive measures, with processing speed showing the greatest difference (-0.08 SD/decade, 95% CI [-0.15, -0.01], p = 0.019). The same overall pattern of results was found when analyses were repeated with baseline dementia cases excluded. We used only one test to represent cognitive domains, and though a prototypical one, we nevertheless urge caution in generalizing the results to domains rather than viewing them as test-specific associations. This study lacked cohorts from Africa, India, and mainland China. CONCLUSIONS: Cognitive performance declined with age, and more rapidly with increasing age, across samples from diverse ethnocultural groups and geographical regions. Associations varied across cohorts, suggesting that different rates of cognitive decline might contribute to the global variation in dementia prevalence. However, the many similarities and consistent associations with education and APOE genotype indicate a need to explore how international differences in associations with other risk factors such as genetics, cardiovascular health, and lifestyle are involved. Future studies should attempt to use multiple tests for each cognitive domain and feature populations from ethnocultural groups and geographical regions for which we lacked data.

Mortality in Mild Cognitive Impairment Diagnosed with DSM-5 Criteria and with Petersen's Criteria: A 17-Year Follow-Up in a Community Study.

OBJECTIVE: To explore the possibility that the mortality risk of mild cognitive impairment (MCI) as diagnosed using Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria (DSM-5-MCI) will be higher than using Petersen's criteria (P-MCI) and to report the population-attributable fraction (PAF) of mortality due to MCI. METHODS: A representative community sample of 4,803 individuals aged 55 or more years was interviewed and then followed for 17 years. Standardized instruments were used in the assessment, including the Geriatric Mental State-AGECAT, and research psychiatrists diagnosed P-MCI and DSM-5-MCI cases following operationalized criteria. Mortality information was obtained from the official population registry. Kaplan-Meier age-adjusted survival curves were built for the MCI diagnostic groups, and Cox proportional hazards regression models were used to calculate the hazard ratio of death in participants with MCI relative to those without. We also estimated the PAF of mortality due to specific MCI diagnostic groups. RESULTS: Compared with noncases, the mortality rate ratio was approximately double in DSM-5-MCI individuals (2.3) than in P-MCI individuals (1.2). In the multivariate statistical analysis, a significant association between each diagnostic category and mortality was observed but was only maintained in the final model in DSM-5-MCI cases (hazard ratio: 1.24). The PAF of mortality due to MCI was approximately 1% in both MCI categories. CONCLUSION: The mortality risk in comparison with noncases was higher in DSM-5-MCI than in P-MCI. The PAF of mortality in DSM-5-MCI individuals was ~ 1% over a 17-year period.

Depression and incident Alzheimer disease: the impact of disease severity.

OBJECTIVES: To test the hypothesis that clinically significant depression (particularly severe depression) increases the risk of Alzheimer's disease (AD). METHODS: A longitudinal, three-wave epidemiologic study was implemented in a sample of individuals aged 55 years and older (n = 4,803) followed up at 2.5 years and 4.5 years. This was a population-based cohort drawn from the Zaragoza Dementia and Depression (ZARADEMP) Project, in Zaragoza, Spain. Participants included individuals cognitively intact at baseline (n = 3,864). The main outcome measures were depression as assessed by using the diagnostic interview Geriatric Mental State- Automated Geriatric Examination for Computer Assisted Taxonomy package; and AD diagnosed by a panel of research psychiatrists according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. The Fine and Gray multivariate regression model was used in the analysis, accounting for mortality. RESULTS: At baseline, clinically significant depression was diagnosed in 452 participants (11.7%); of these, 16.4% had severe depression. Seventy incident cases of AD were found at follow-up. Compared with nondepressed individuals, the incidence rate of AD was significantly higher in the severely depressed subjects (incidence rate ratio: 3.59 [95% confidence interval: 1.30-9.94]). A consistent, significant association was observed between severe depression at baseline and incident AD in the multivariate model (hazard ratio: 4.30 [95% CI: 1.39-13.33]). Untreated depression was associated with incident AD in the unadjusted model; however, in the final model, this association was attenuated and nonsignificant. CONCLUSIONS: Severe depression increases the risk of AD, even after controlling for the competing risk of death.

COSMIC (Cohort Studies of Memory in an International Consortium): an international consortium to identify risk and protective factors and biomarkers of cognitive ageing and dementia in diverse ethnic and sociocultural groups.

BACKGROUND: A large number of longitudinal studies of population-based ageing cohorts are in progress internationally, but the insights from these studies into the risk and protective factors for cognitive ageing and conditions like mild cognitive impairment and dementia have been inconsistent. Some of the problems confounding this research can be reduced by harmonising and pooling data across studies. COSMIC (Cohort Studies of Memory in an International Consortium) aims to harmonise data from international cohort studies of cognitive ageing, in order to better understand the determinants of cognitive ageing and neurocognitive disorders. METHODS/DESIGN: Longitudinal studies of cognitive ageing and dementia with at least 500 individuals aged 60 years or over are eligible and invited to be members of COSMIC. There are currently 17 member studies, from regions that include Asia, Australia, Europe, and North America. A Research Steering Committee has been established, two meetings of study leaders held, and a website developed. The initial attempts at harmonising key variables like neuropsychological test scores are in progress. DISCUSSION: The challenges of international consortia like COSMIC include efficient communication among members, extended use of resources, and data harmonisation. Successful harmonisation will facilitate projects investigating rates of cognitive decline, risk and protective factors for mild cognitive impairment, and biomarkers of mild cognitive impairment and dementia. Extended implications of COSMIC could include standardised ways of collecting and reporting data, and a rich cognitive ageing database being made available to other researchers. COSMIC could potentially transform our understanding of the epidemiology of cognitive ageing, and have a world-wide impact on promoting successful ageing.

The effect of occupation on the incidence of vascular dementia: A 12-year follow-up cohort study.

INTRODUCTION: Vascular dementia (DV) is the second cause of dementia with 15.8-20% of cases. Previous studies of the effect of occupation in DV do not show conclusive results, therefore, the objective was to analyze if the type of occupation can vary the risk of developing DV in those older than 55 years. MATERIAL AND METHODS: In the ZARADEMP project, a community sample of 4,803 individuals were followed longitudinally in four waves. The occupation was classified following the National Classification of Occupations (CNO-11) and the International Standard Classification of Occupations (ISCO-08). Different standardized instruments were used: the medical and psychiatric histories (History and Aetiology Schedule) and other risk factors (Mini-Mental Status Examination, Geriatric Mental State-AGECAT). For this study, we calculated incidence rates, incidence rate ratios and hazard ratios in multivariate Cox regression models, stratified by gender. For this study, we included 3,883 participants. RESULTS: In women, the risk of DV was doubled in Blue-collar workers, with a moderate effect (Cohen's d=0.54) and multiplying by 2.7 in Homeworks respect to White Collar with a moderate effect (Cohen's d=0.77), although they did not reach statistical significance. We did not observe the effect of occupation on the risk of DV in men. CONCLUSIONS: We have found a moderate but non-significant effect between occupation and DV risk in women. We found no effect of occupation on the risk of VD in males while other clinical factors (age, diabetes or body mass index) presented a clearer effect than the occupation.

Psychosomatic response to acute emotional stress in healthy students.

The multidimensionality of the stress response has shown the complexity of this phenomenon and therefore the impossibility of finding a unique biomarker among the physiological variables related to stress. An experimental study was designed and performed to guarantee the correct synchronous and concurrent measure of psychometric tests, biochemical variables and physiological features related to acute emotional stress. The population studied corresponds to a group of 120 university students between 20 and 30 years of age, with healthy habits and without a diagnosis of chronic or psychiatric illnesses. Following the protocol of the experimental pilot, each participant reached a relaxing state and a stress state in two sessions of measurement for equivalent periods. Both states are correctly achieved evidenced by the psychometric test results and the biochemical variables. A Stress Reference Scale is proposed based on these two sets of variables. Then, aiming for a non-invasive and continuous approach, the Acute Stress Model correlated to the previous scale is also proposed, supported only by physiological signals. Preliminary results support the feasibility of measuring/quantifying the stress level. Although the results are limited to the population and stimulus type, the procedure and methodological analysis used for the assessment of acute stress in young people can be extrapolated to other populations and types of stress.

Education, Occupational Complexity, and Incident Dementia: A COSMIC Collaborative Cohort Study.

BACKGROUND: Education and occupational complexity are main sources of mental engagement during early life and adulthood respectively, but research findings are not conclusive regarding protective effects of these factors against late-life dementia. OBJECTIVE: This project aimed to examine the unique contributions of education and occupational complexity to incident dementia, and to assess the mediating effects of occupational complexity on the association between education and dementia across diverse cohorts. METHOD: We used data from 10,195 participants (median baseline age = 74.1, range = 58∼103), representing 9 international datasets from 6 countries over 4 continents. Using a coordinated analysis approach, the accelerated failure time model was applied to each dataset, followed by meta-analysis. In addition, causal mediation analyses were performed. RESULT: The meta-analytic results indicated that both education and occupational complexity were independently associated with increased dementia-free survival time, with 28%of the effect of education mediated by occupational complexity. There was evidence of threshold effects for education, with increased dementia-free survival time associated with 'high school completion' or 'above high school' compared to 'middle school completion or below'. CONCLUSION: Using datasets from a wide range of geographical regions, we found that both early life education and adulthood occupational complexity were independently predictive of dementia. Education and occupational experiences occur during early life and adulthood respectively, and dementia prevention efforts could thus be made at different stages of the life course.

Prevalence of depression during the COVID-19 outbreak: A meta-analysis of community-based studies.

Introduction: COVID-19 pandemic, declared on March 11, 2020, constitute an extraordinary health, social and economic global challenge. The impact on people's mental health is expected to be high. This paper sought to systematically review community-based studies on depression conducted during the COVID-19 and estimate the pooled prevalence of depression. Method: We searched for cross-sectional, community-based studies listed on PubMed or Web of Science from January 1, 2020 to May 8, 2020 that reported prevalence of depression. A random effect model was used to estimate the pooled proportion of depression. Results: A total of 12 studies were included in the meta-analysis, with prevalence rates of depression ranging from 7.45% to 48.30%. The pooled prevalence of depression was 25% (95% CI: 18% - 33%), with significant heterogeneity between studies (I 2  = 99.60%, p < .001). Conclusions: Compared with a global estimated prevalence of depression of 3.44% in 2017, our pooled prevalence of 25% appears to be 7 times higher, thus suggesting an important impact of the COVID-19 outbreak on people's mental health. Addressing mental health during and after this global health crisis should be placed into the international and national public health agenda to improve citizens' wellbeing.

Introducción: La pandemia de COVID-19, declarada el 11 de marzo de 2020, representa un reto global extraordinario a nivel sanitario, social y económico. Se espera un impacto alto en la salud mental de las personas. Este artículo tiene como objetivo realizar una revisión sistemática de estudios transversales basados en muestras comunitarias que proporcionaban la prevalencia de depresión durante la crisis del COVID-19. Método: Se realizó una búsqueda de estudios comunitarios publicados en Pubmed y Web of Science desde el 1 de enero del 2020 al 8 de mayo del 2020 y que informaron sobre la prevalencia de depresión. Se usó un modelo de efectos aleatorios para estimar la proporción agrupada de depresión. Resultados: Un total de 12 estudios fueron incluidos en el meta-análisis, con prevalencias de depresión que oscilaban entre 7,45% y 48,30%. La prevalencia agrupada de depresión fue de 25% (95% CI: 18%-33%), con heterogeneidad significativa entre estudios (I 2  = 99,60%, p < 0,001). Conclusiones: En comparación con una estimación global de depresión en 2017 del 3,44%, nuestra prevalencia agrupada del 25% es 7 veces mayor, sugiriendo un impacto importante del brote de COVID-19 en la salud mental de las personas. El abordaje de la salud mental durante y después de esta crisis global sanitaria debe ser parte de las agendas de salud pública nacionales e internacionales para mejorar el bienestar de los ciudadanos.

Anhedonia as a Potential Risk Factor of Alzheimer's Disease in a Community-Dwelling Elderly Sample: Results from the ZARADEMP Project.

(1) Introduction: Dementia is a major public health problem, and Alzheimer's disease (AD) is the most frequent subtype. Clarifying the potential risk factors is necessary in order to improve dementia-prevention strategies and quality of life. Here, our purpose was to investigate the role of the absence of hedonic tone; anhedonia, understood as the reduction on previous enjoyable daily activities, which occasionally is underdetected and underdiagnosed; and the risk of developing AD in a cognitively unimpaired and non-depressed population sample. (2) Method: We used data from the Zaragoza Dementia and Depression (ZARADEMP) project, a longitudinal epidemiological study on dementia and depression. After excluding subjects with dementia, a sample of 2830 dwellers aged ≥65 years was followed for 4.5 years. The geriatric mental state examination was used to identify cases of anhedonia. AD was diagnosed by a panel of research psychiatrists according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. A multivariate survival analysis and Cox proportional hazards regression model were performed, and the analysis was controlled by an analysis for the presence of clinically significant depression. (3) Results: We found a significant association between anhedonia cases and AD risk in the univariate analysis (hazard ratio (HR): 2.37; 95% CI: 1.04-5.40). This association persisted more strongly in the fully adjusted model. (4) Conclusions: Identifying cognitively intact individuals with anhedonia is a priority to implement preventive strategies that could delay the progression of cognitive and functional impairment in subjects at risk of AD.

Cognition and daily activities in a general population sample aged +55.

Objective: We tested the association of individual cognitive domains measured with the Mini-Mental State Examination (MMSE) and disability. Method: Cross-sectional study in a population-based cohort aged ≥55 years (n = 4,803). Sample was divided into two groups: individuals with cognition within the normal range (CNR) (n = 4,057) and those with cognitive impairment (CI) (n = 746). Main outcome measures: The MMSE, the Katz Index (Basic Activities of Daily Living, bADL), the Lawton and Brody Scale (Instrumental Activities of Daily Living, iADL), and the Geriatric Mental State (GMS-AGECAT). Results: MMSE-orientation was associated with disability in bADL, iADL and a decrease in social participation, regardless of cognitive status. MMSE-attention was associated with disability in iADL, but only in CNR. MMSE-language was associated with disability in bADL, iADL and with reduced social participation, but only in CI. Conclusions: The associations observed between disability and orientation may have clinical and public health implications.

A Novel Score for Predicting Alzheimer's Disease Risk from Late Life Psychopathological and Health Risk Factors.

With the increasing size of the aging population, dementia risk reduction has become a main public health concern. Dementia risk models or indices may help to identify individuals in the community at high risk to develop dementia. We have aimed to develop a novel dementia risk index focused on the late-life (65 years or more) population, that addresses risk factors for Alzheimer's disease (AD) easily identifiable at primary care settings. These risk factors include some shown to be associated with the risk of AD but not featured in existing indices, such as hearing loss and anxiety. Our index is also the first to account for the competing risk of death. The Zaragoza Dementia and Depression Project (ZARADEMP) Alzheimer Dementia Risk Score predicts an individual´s risk of developing AD within 5 years. The probability of late onset AD significantly increases in those with risk scores between 21 and 28 and, furthermore, is almost 4-fold higher for those with risk scores of 29 or higher. Our index may provide a practical instrument to identify subjects at high risk of AD and to design preventive strategies targeting the contributing risk factors.

Prevalence of anxiety in the COVID-19 pandemic: An updated meta-analysis of community-based studies.

BACKGROUND: The unprecedented worldwide crisis caused by the rapid spread of COVID-19 and the restrictive public health measures enforced by some countries to slow down its transmission have severely threatened the physical and mental wellbeing of communities globally. METHODS: We conducted a systematic review and meta-analysis to determine the prevalence of anxiety in the general population during the COVID-19 pandemic. Two researchers independently searched for cross-sectional community-based studies published between December 1, 2019 and August 23, 2020, using PubMed, WoS, Embase, and other sources (e.g., grey literature, manual search). RESULTS: Of 3049 records retrieved, 43 studies were included. These studies yielded an estimated overall prevalence of anxiety of 25%, which varied significantly across the different tools used to measure anxiety. Consistently reported risk factors for the development of anxiety included initial or peak phase of the outbreak, female sex, younger age, marriage, social isolation, unemployment and student status, financial hardship, low educational level, insufficient knowledge of COVID-19, epidemiological or clinical risk of disease and some lifestyle and personality variables. CONCLUSIONS: As the overall global prevalence of anxiety disorders is estimated to be 7.3% normally, our results suggest that rates of anxiety in the general population could be more than 3 times higher during the COVID-19 pandemic. These findings suggest a substantial impact on mental health that should be targeted by individual and population-level strategies.

Anxiety and Risk of Vascular Dementia in an Elderly Community Sample: The Role of Sex.

Background: To assess the association between anxiety and risk of vascular dementia (VaD), as well as potential sex differences, in a community-based cohort. Methods: A random sample of 4057 dementia-free community participants aged 55 or older, from the longitudinal, community-based Zaragoza Dementia and Depression Project (ZARADEMP) study were followed for 4.5 years. Geriatric Mental State B (GMS)-Automated Geriatric Examination for Computer Assisted Taxonomy (AGECAT) was used for the assessment and diagnosis of anxiety, and a panel of research psychiatrists diagnosed the incident cases of VaD according to DSM-IV (Diagnostic and Statistical Manual of mental disordes). Multivariate survival analysis with competing risk regression model was performed. Results: In men, the incidence rate of VaD was significantly higher among anxiety subjects compared with non-anxiety subjects (incidence rate ratio (IRR) (95% confidence interval (CI)): 3.24 (1.13-9.35); p = 0.029), and no difference was observed in women (IRR (95%CI): 0.68 (0.19-2.23); p = 0.168). In the multivariate model, for men, cases of anxiety had 2.6-fold higher risk of VaD (subdistribution hazard ratio (SHR): 2.61; 95%CI: 0.88-7.74) when all potential confounding factors were controlled, with no statistical significance (p = 0.084), but a clinically relevant effect (Cohen's d: 0.74). No association was found in women. Conclusions: In men, but not in women, risk of VaD was higher among individuals with anxiety, with a clinically relevant effect. Potential anxiety-related preventive interventions for VaD might be tailored to men and women separately.

Association between Anxiety and Vascular Dementia Risk: New Evidence and an Updated Meta-Analysis.

The association between anxiety and vascular dementia (VaD) is unclear. We aimed to reliably estimate the association between anxiety and VaD risk using meta-analysis to pool new results from a large community-based cohort (Zaragoza Dementia and Depression (ZARADEMP) study) and results from previous studies. ZARADEMP participants (n = 4057) free of dementia were followed up on for up to 12 years. Cases and subcases of anxiety were determined at baseline. A panel of four psychiatrists diagnosed incident cases of VaD by consensus. We searched for similar studies published up to October 2019 using PubMed and Web of Science. Observational studies reporting associations between anxiety and VaD risk, and adjusting at least for age, were selected. Odds ratios (ORs) from each study were combined using fixed-effects models. In the ZARADEMP study, the risk of VaD was 1.41 times higher among individuals with anxiety (95% CI: 0.75-2.68) compared with non-cases (p = 0.288). Pooling this result with results from two previous studies yielded an OR of 1.65 (95% CI: 1.07-2.53; p = 0.022). These findings indicate that anxiety is associated with an increased risk of VaD. Taking into account that anxiety is commonly observed in the elderly, treating and preventing it might reduce the prevalence and incidence of VaD. However, whether anxiety is a cause of a prodrome of VaD is still unknown, and future research is needed to clarify this.

The effect of occupation on the incidence of vascular dementia: A 12-year follow-up cohort study. / El efecto de la ocupación laboral en la incidencia de demencia vascular: un estudio de cohortes de 12 años de seguimiento.

INTRODUCTION: Vascular dementia (DV) is the second cause of dementia with 15.8-20% of cases. Previous studies of the effect of occupation in DV do not show conclusive results, therefore, the objective was to analyze if the type of occupation can vary the risk of developing DV in those older than 55 years. MATERIAL AND METHODS: In the ZARADEMP project, a community sample of 4,803 individuals were followed longitudinally in 4 waves. The occupation was classified following the National Classification of Occupations of 2011 and the International Standard Classification of Occupations of 2008. Different standardized instruments were used: the medical and psychiatric histories (History and Aetiology Schedule) and other risk factors (Mini-Mental Status Examination, Geriatric Mental State-AGECAT). For this study, we calculated incidence rates, incidence rate ratios and hazard ratios in multivariate Cox regression models, stratified by gender. For this study, we included 3,883 participants. RESULTS: In women, the risk of DV was doubled in blue-collar workers, with a moderate effect (Cohen's d=0.54), and multiplying by 2.7 in homeworks respect to white-collar with a moderate effect (Cohen's d=0.77), although they did not reach statistical significance. We did not observe the effect of occupation on the risk of DV in men. CONCLUSIONS: We have found a moderate but non-significant effect between occupation and DV risk in women. We found no effect of occupation on the risk of VD in males while other clinical factors (age, diabetes or body mass index) presented a clearer effect than the occupation.

Does Anxiety Increase the Risk of All-Cause Dementia? An Updated Meta-Analysis of Prospective Cohort Studies.

Background: Anxiety has been suggested as a potentially modifiable risk factor for dementia, but results are still controversial. Our main objectives are to develop an updated meta-analysis of prospective population-based studies on the relationship between anxiety and risk of dementia, and to estimate the population fraction of dementia attributable to anxiety (PAF). Methods: We searched for cohort studies listed on PubMed or Web of Science from January 2018 to January 2020 that reported risk estimates for the association between anxiety and incident dementia. These were added to cohort studies published before January 2018 that were used in a previously published meta-analysis. Fully adjusted RRs were pooled using random effects models. We estimated the proportion of incident dementia attributable to anxiety by using PAF. Results: The meta-analysis included nine prospective cohorts from eight studies, representing 29,608 participants. The overall relative risk (RR) of dementia was 1.24 (95% CI: 1.06-1.46) and the PAF of dementia due to anxiety was 3.9%. Conclusions: Anxiety is significantly associated with an increased risk of all-cause dementia. The treatment or prevention of anxiety might help to reduce dementia incidence rates, but more research is needed to clarify whether anxiety is a cause of dementia rather than a prodrome.

Prevalence of Anxiety in Medical Students during the COVID-19 Pandemic: A Rapid Systematic Review with Meta-Analysis.

The novel coronavirus disease (COVID-19) pandemic has brought a great deal of pressure for medical students, who typically show elevated anxiety rates. Our aim is to investigate the prevalence of anxiety in medical students during this pandemic. This systematic review and mini meta-analysis has been conducted following the PRISMA guidelines. Two researchers independently searched PubMed on 26 August 2020 for cross-sectional studies on medical students during the COVID-19 outbreak, with no language restrictions applied. We then performed a manual search to detect other potentially eligible investigations. To the 1361 records retrieved in the initial search, 4 more were added by manual search on medRxiv. Finally, eight studies were finally included for qualitative and quantitative analysis, which yielded an estimated prevalence of anxiety of 28% (95% CI: 22-34%), with significant heterogeneity between studies. The prevalence of anxiety in medical students is similar to that prior to the pandemic but correlates with several specific COVID-related stressors. While some preventive and risk factors have been previously identified in a non-pandemic context, knowledge and cognitions on COVID-19 transmission, treatment, prognosis and prevention negatively correlate with anxiety, emerging as a key preventive factor that may provide a rationale for why the levels of anxiety have remained stable in medical students during the pandemic while increasing in their non-medical peers and the general population. Other reasons for the invariability of anxiety rates in this population are discussed. A major limitation of our review is that Chinese students comprised 89% the total sample, which could compromise the external validity of our work.