Updating the evidence for an association between anxiety and risk of Alzheimer's disease: A meta-analysis of prospective cohort studies.

OBJECTIVES: Anxiety is postulated to be a modifiable risk factor for Alzheimer's disease (AD). Our primary aim was to conduct a meta-analysis of prospective cohort studies investigating the association between anxiety and AD risk. DESIGN: We searched multiple scientific databases to identify relevant papers published up to March 2019. Inclusion criteria were: prospective cohort studies with a minimum follow-up period of 1 year, baseline anxiety assessment, absence of dementia at baseline, investigated the association between anxiety and AD incidence, and reporting Relative Risks (RRs), or equivalents (HRs and SHRs), for the association between anxiety and AD risk. We excluded studies that: focused on subjective memory or mild cognitive impairment samples, review and meta-analyses, not reporting original, published peer-reviewed results. We used a random-effects model that accommodated the differences in association statistics. RESULTS: 7 prospective cohorts (reported in 6 studies), with a total of 24,528 participants, were included in our meta-analysis. A marginally significant association between anxiety and AD risk was found, with a pooled RR of 1.45 (95% CI: 1.00-2.12), and a population attributable fraction for AD of 2.8% (95% CI: 1.2%-4.3%). LIMITATIONS: There was a high level of heterogeneity across the studies, which may be associated with differences in the covariates adjusted for. Studies also differed considerably in how they measured anxiety. CONCLUSION: Anxiety is marginally associated with an increased risk of AD in this meta-analysis. Future research is needed to determine the extent to which anxiety might be a cause of AD rather than a prodrome or marker.

[Clinically relevant late-life depression as risk factor of dementia: a systematic review and meta-analysis of prospective cohort studies]. / Depresion tardia clinicamente relevante y riesgo de demencia: revision sistematica y metaanalisis de estudios prospectivos de cohortes.

AIM: To carry out a meta-analysis of population-based prospective cohort studies to investigate the risk of dementia and Alzheimer's disease (AD) according to clinically relevant depression, assessed with Geriatric Mental State (GMS) criteria. PATIENTS AND METHODS: A systematic literature search of the studies published in PubMed and Web of Science up to January 2018 was performed to identify all longitudinal studies on the association between clinically relevant depression (diagnosed with GMS criteria) and risk of dementia in the elderly. We calculated pooled relative risks to examine depression as a possible risk factor for dementia in community studies, as well as to compute population attributable fraction (PAF). RESULTS: Six studies met inclusion criteria for the systematic review. All of them provided enough information to perform a meta-analysis. Participants with clinically relevant depression had a 54% higher risk of dementia (p = 0.026) with a PAF attributable to clinically relevant depression of 8.6%. The numbers for AD were 50% higher risk (p = 0.038) and a PAF of 10.8%. CONCLUSION: Clinically relevant depression is associated with an increased risk for dementia and AD in the community, with a potential impact higher than other known/recognized risk factors. Future studies should explore the mechanisms linking depression and dementia and AD as well as whether an effective treatment of clinically significant depression could prevent dementia and AD development.

TITLE: Depresion tardia clinicamente relevante y riesgo de demencia: revision sistematica y metaanalisis de estudios prospectivos de cohortes.Objetivo. Realizar un metaanalisis de estudios de cohortes prospectivos, con base poblacional, que investiguen el riesgo de demencia y enfermedad de Alzheimer (EA) segun la depresion clinicamente relevante, diagnosticada con criterios del Geriatric Mental State (GMS). Pacientes y metodos. Se realizo una busqueda sistematica de los estudios publicados en PubMed y Web of Science hasta enero de 2018 para identificar todos los estudios longitudinales sobre la asociacion entre la depresion clinicamente relevante (diagnosticada con criterios del GMS) y el riesgo de demencia y EA en los ancianos. Se calculo el riesgo relativo agrupado para examinar la depresion como un posible factor de riesgo para la demencia en estudios comunitarios, asi como la fraccion poblacional de demencia y EA atribuible a la depresion. Resultados. Seis estudios cumplieron los criterios de inclusion para la revision sistematica. Todos ellos proporcionaron suficiente informacion para realizar un metaanalisis. Los participantes con depresion clinicamente relevante tuvieron un riesgo un 54% mas elevado de demencia (p = 0,026) y una fraccion atribuible poblacional del 8,6%. Los pacientes con EA tuvieron un riesgo un 50% mas alto (p = 0,038) y una fraccion atribuible poblacional del 10,8%. Conclusion. La depresion clinicamente relevante se asocia con un mayor riesgo de demencia y EA en la comunidad, con un impacto potencial mayor que otros factores de riesgo conocidos. Los estudios futuros deben explorar los mecanismos que vinculan la depresion con la demencia y la EA, asi como si un tratamiento eficaz de la depresion clinicamente relevante podria prevenir la demencia y el desarrollo de la EA.

Clinically relevant anxiety and risk of Alzheimer's disease in an elderly community sample: 4.5 years of follow-up.

OBJECTIVES: To investigate whether clinically relevant anxiety increased the risk for developing Alzheimer's disease (AD) while controlling for the presence of depression and other confounders; and to report the population attributable fraction (PAF) associated with anxiety disorder. METHOD: We used data from the longitudinal, community-based Zaragoza Dementia and Depression (ZARADEMP) study. A random sample of 4057 dementia-free community dwellers aged ≥55 years were followed for 4.5 years. The Geriatric Mental State-Automated Geriatric Examination for Computer Assisted Taxonomy package was used for the diagnosis of clinically significant cases and subcases of anxiety; and AD was diagnosed by a panel of research psychiatrists according to DSM-IV criteria. Multivariate survival analysis with competing risk regression model was performed. RESULTS: We observed a significant association between anxiety cases at baseline and AD risk in the univariate analysis that persisted in the fully adjusted model (SHR: 3.90; 95% CI: 1.59-9.60; p = 0.003), with a PAF for AD of 6.11% (95% CI: 1.30%-16.17%). No significant association between 'subcases' of anxiety at baseline and AD risk was found. LIMITATIONS: Data on apolipoprotein E were not available. The hospital-based diagnosis was not completed in all cases of dementia. CONCLUSION: Late-life, clinically significant anxiety (but not subclinical anxiety) seems to increase the risk of AD, independently of the effect of several confounders, including depression. Taking into account the high prevalence of anxiety among the elderly, future studies are warranted to determine potential risk reduction of AD.

Prevalence of anxiety disorder among older adults in Spain: A meta-analysis.

BACKGROUND: Anxiety disorders are recognized as one of the most prevalent mental disorders in late-life. However, the prevalence of anxiety disorders in older Spanish people has not yet been determined. The aim was to review epidemiological studies systematically to calculate the overall prevalence of anxiety in Spanish older adults by using meta-analytic techniques. METHODS: We searched relevant published studies in electronic databases up to January 2018 providing data on the prevalence of anxiety among people aged 65+  years in Spain. Overall anxiety prevalence estimates were calculated using random-effects models. Sources of heterogeneity were explored by means of univariate meta-regressions. RESULTS: A total of 9 studies were included in the meta-analysis (N = 12,577). Pooled overall prevalence of anxiety was 11% (95% confidence interval (CI): 6%-18%) representing 1958,471 people aged 65+  (95%CI: 1068,257-3204,771). Point, 12-month and lifetime prevalence of anxiety disorders were 12%, 6% and 19%, respectively. LIMITATIONS: We detected a small publication bias effect for life-time prevalence of anxiety. The use of different diagnostic methods across the studies would have required separate analyzes. CONCLUSION: Some heterogeneity was found across studies, probably due to different methodological issues. Overall, the pooled prevalence of anxiety disorders in Spanish older adults was lower than that observed in other countries. Due to the negative consequences of anxiety disorders in older adults, detection and treatment should be a priority in this population.

Clinically significant anxiety as a risk factor for dementia in the elderly community.

OBJECTIVE: To evaluate whether clinically significant anxiety is an independent risk factor for dementia, taking into account both depression among potentially confounding factors and the competing risk of death. METHOD: During the Zaragoza Dementia and Depression (ZARADEMP) study, a random sample of community dwellers aged 55 years or older was assessed (n = 4803), and a two-wave, 4.5-year follow-up was completed. Geriatric Mental State (GMS)-AGECAT criteria were used to diagnose anxiety and DSM-IV criteria were applied to diagnose incident dementia. The multivariate Fine and Gray regression model was implemented to calculate dementia risk. RESULTS: Compared with non-cases (GMS-AGECAT criteria), the incidence rate of dementia was significantly higher in subcases of anxiety, and particularly significant in the cases of anxiety (incidence rate ratio (IRR): 2.77; P = 0.010). Cases of anxiety, but not subcases, at baseline were significantly associated with dementia risk (adjusted subdistribution hazard ratio (SHR): 2.7; P = 0.019). CONCLUSION: Clinically significant anxiety is associated with an almost threefold increase in the risk of dementia in the population, even when controlling for depression and considering mortality in the competing risks model.

Disability in a memory clinic: Frequency and associations with low cognitive performance

BACKGROUND AND OBJECTIVE: To document the frequency of disability in a Psychiatry Memory Clinic (MC); to test the conjecture that there is an association between low cognitive performance and disability, even when controlling by dementia and clinically significant depression. METHODS: A sample of 158 individuals referred to a Psychiatry MC were assessed with a full clinical protocol. Instruments used: Mini-Mental Status Examination (MMSE); Semantic verbal fluency; the Clock Drawing test; Katz Index; Lawton and Brody Scale. DSM-IV criteria were used for diagnosing depression and dementia. The statistical analysis included logistic regression models. RESULTS: The frequency of disability was 71.6%. MMSE score was significantly associated with moderate-severe disability on instrumental activities of daily living (ADL's) (OR 0.83; 95%CI 0.72-0.96) and with social ADL's (OR 0.87; 95%CI 0.79-0.95)). Orientation, attention and language MMSE subscores were the cognitive domains most significantly associated with disability. CONCLUSIONS: Disability in patients referred to a Psychiatry MC with a heterogeneous clinical population is associated with low cognitive performance. The probability of having moderate-severe disability is related to the degree of impairment on MMSE global scores

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Different subpopulations of mild cognitive impairment are identified by using Petersen's or DSM-5 criteria

OBJECTIVES: In view of differences in the prevalence and conversion rate to dementia of Petersen's (P-MCI) and DSM-5's (DSM-5-MCI) categories of mild cognitive impairment, this paper is intended to examine the diagnostic agreement between the categories and to analyze clinical factors related to the potential discrepancies. METHOD: A representative population cohort of 4580 dementia-free individuals 55+ years of age was examined in Zaragoza, Spain (ZARADEMP). Validated Spanish versions of instruments, including the Geriatric Mental State-AGECAT, were used for assessment. Research psychiatrists diagnosed DSM-5-MCI and P-MCI following operationalized criteria. Between-category differences were analyzed, and the statistical methods included the calculation of Cohen's Kappa coefficients of agreement, and the McNemar's test to compare the performance of the intermediate cognitive definitions. RESULTS: Diagnostic concordance in the classification of MCI cases was very limited. In the total sample, 2.7% of individuals did not meet the P-MCI criteria but met the DSM-5-MCI criteria; and 6.4% met the P-MCI criteria, but not the DSM-5-MCI criteria. Overlap of both categories was observed in only 0.6%. The overall Kappa (agreement between both MCI categories) was 0.08 (95% CI: 0.04-0.12; p < 0.001). While no between-category significant differences was observed in cognitive scores, relevant differences in the populations identified had to do with demographic, non-cognitive psychopathological factors, activities of daily living and general health factors. CONCLUSIONS: This study shows 'poor' diagnostic agreement between the P-MCI and the DSM-5-MCI categories. The non-cognitive factors should receive special attention when trying to improve the validity of the MCI construct

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Conversion to dementia in mild cognitive impairment diagnosed with DSM-5 criteria and with Petersen's criteria.

OBJECTIVE: In a background of revision of criteria for states of increased risk for progression to dementia, we compare the conversion rate to dementia and Alzheimer's disease (AD) of mild cognitive impairment (MCI) as diagnosed using DSM-5 (DSM-5-MCI) and Petersen's (P-MCI) criteria. METHOD: A population representative cohort of 4057 dementia-free individuals 55+ years of age was followed up at 2.5 and 4.5 years in Zaragoza, Spain (ZARADEMP). Using the Geriatric Mental State- AGECAT for assessment, research psychiatrists diagnosed DSM-5-MCI and P-MCI following operationalized criteria. 'Conversion rate' (CR), 'annual conversion rate' (ACR), and incidence rate (IR) were calculated along with incidence rate ratio (IRR) to compare the performance of the intermediate cognitive definitions. RESULTS: At 4.5-year follow-up, in individuals aged 65+ years, ACRs for non-cases, P-MCI, and DSM-5-MCI were 0.8, 1.9 and 3.4, respectively, for global dementia. The IRRs were 2.9 and 5.3 for P-MCI and DSM5-MCI, respectively, being the non-cases the reference category. The corresponding values were slightly lower for AD. CONCLUSION: Conversion rate to dementia and AD was higher using DSM-5-MCI criteria than using Petersen's criteria. However, prediction of the construct still has some way to go, as most MCI individuals did not convert at 4.5-year follow-up.

Behavioral predictors of attrition in adolescents participating in a multidisciplinary obesity treatment program: EVASYON study.

The aims of this study were to identify the cognitive and behavioral predictors of dropping out and to estimate the attrition rate during different phases of an intervention program to treat overweight and obesity in adolescents. Overweight/obese adolescents (n=156, aged: 13-16 years; 71 male and 85 female subjects) were included in a multicomponent (diet, physical activity and psychological support) family-based group treatment program. At baseline and after 2 months (intensive phase) and 13 months (extensive phase) of follow-up, we measured adolescents' cognitive and behavioral dimensions, together with the parents' perception of their child's behavior. Of the 156 adolescents selected, 112 completed the full program (drop-out rate of 28.2%). The risk of dropping out during the extensive phase increased by 20% for each unit increase in the adolescent's social insecurity score (odds ratio=1.20, 95% confidence interval=1.07-1.34, P=0.002). The adolescents who had a high interoceptive awareness showed a significant decrease of 13.0% in the probability of dropping out (odds ratio=0.87, 95% confidence interval=0.77-0.99, P=0.040). Adolescents' social insecurity was the main predictor of drop-out in a multicomponent family-group-based obesity treatment program. To reduce attrition rates in these programs, the individual's social insecurity level needs to be reduced, whereas the family's awareness of eating-related behavior needs adjustment.

Staging cognitive impairment and incidence of dementia.

AIMS: In a background of interest in staging models in psychiatry, we tested the validity of a simple staging model of cognitive impairment to predict incident dementia. METHOD: A large community sample of adults aged ≥55 years (N = 4803) was assessed in the baseline of a longitudinal, four-wave epidemiological enquiry. A two-phase assessment was implemented in each wave, and the instruments used included the Mini-Mental Status Examination (MMSE); the History and Aetiology Schedule and the Geriatric Mental State-AGECAT. For the standardised degree of cognitive impairment Perneczky et al's MMSE criteria were applied. A panel of psychiatrists diagnosed cases of dementia according to DSM-IV criteria, and cases and sub-cases of dementia were excluded for the follow-up waves. Competing risk regression models, adjusted by potential confounders, were used to test the hypothesised association between MMSE levels and dementia risk. RESULTS: Out of the 4057 participants followed up, 607 (14.9%) were classified as 'normal' (no cognitive impairment), 2672 (65.8%) as 'questionable' cognitive impairment, 732 (18.0%) had 'mild' cognitive impairment, 38 (0.9%) had 'moderate' cognitive impairment and eight (0.2%) had 'severe' impairment. Cognitive impairment was associated with risk of dementia, the risk increasing in parallel with the level of impairment (hazard ratio: 2.72, 4.78 and 8.38 in the 'questionable', 'mild' and 'moderate' level of cognitive impairment, respectively). CONCLUSIONS: The documented gradient of increased risk of dementia associated with the severity level of cognitive impairment supports the validity of the simple staging model based on the MMSE assessment.

The MCCB impairment profile in a Spanish sample of patients with schizophrenia: Effects of diagnosis, age, and gender on cognitive functioning.

The MATRICS Consensus Cognitive Battery (MCCB) was administered to 293 schizophrenia outpatients and 210 community residents in Spain. Our first objective was to identify the age- and gender-corrected MCCB cognitive profile of patients with schizophrenia. The profile of schizophrenia patients showed deficits when compared to controls across the seven MCCB domains. Reasoning and Problem Solving and Social Cognition were the least impaired, while Visual Learning and Verbal Learning showed the greatest deficits. Our second objective was to study the effects on cognitive functioning of age and gender, in addition to diagnosis. Diagnosis was found to have the greatest effect on cognition (Cohen's d>0.8 for all MCCB domains); age and gender also had effects on cognitive functioning, although to a lesser degree (with age usually having slightly larger effects than gender). The effects of age were apparent in all domains (with better performance in younger subjects), except for Social Cognition. Gender had effects on Attention/Vigilance, Working Memory, Reasoning and Problem Solving (better performance in males), and Social Cognition (better performance in females). No interaction effects were found between diagnosis and age, or between diagnosis and gender. This lack of interactions suggests that age and gender effects are not different in patients and controls.

Mild cognitive impairment diagnosed with the new DSM-5 criteria: prevalence and associations with non-cognitive psychopathology.

OBJECTIVE: To contrast the prevalence of mild cognitive impairment (MCI) as diagnosed using DSM-5 criteria (DSM5-MCI) with MCI as diagnosed using Petersen's criteria (P-MCI) and to explore the association of both with non-cognitive psychopathological symptoms (NCPS). METHOD: A two-phase epidemiological screening was implemented in a population-based sample of individuals aged 55+ (n = 4803). The Geriatric Mental State (GMS) was the main psychopathological instrument used, and AGECAT was used to make psychiatric diagnoses. Research psychiatrists diagnosed DSM5-MCI and P-MCI using operational criteria. Logistic regression models were then used to investigate the association of MCI with anxiety and depression and with NCPS. RESULTS: Weighted prevalence of DSM5-MCI and P-MCI was, respectively, 3.72% and 7.93% for the aged 65+. NCPS were common in both MCI categories, but negative-type symptoms such as 'anergia' and 'observed slowness' were considerably more frequent among persons with DSM5-MCI. Anxiety and depression diagnostic categories were associated with both P-MCI and DSM5-MCI, but affective-type symptoms were mainly associated with P-MCI. Some negative-type symptoms were inversely associated with P-MCI, and no association was observed with DSM5-MCI. CONCLUSION: The prevalence of DSM5-MCI was half that of P-MCI. Negative-type NCPS were more frequently and typically associated with DSM5-MCI.

Degree of cognitive impairment and mortality: a 17-year follow-up in a community study.

BACKGROUND: To test the hypothesis that cognitive impairment in older adults is associated with all-cause mortality risk and the risk increases when the degree of cognitive impairment augments; and then, if this association is confirmed, to report the population-attributable fraction (PAF) of mortality due to cognitive impairment. METHOD: A representative random community sample of individuals aged over 55 was interviewed, and 4557 subjects remaining alive at the end of the first year of follow-up were included in the analysis. Instruments used in the assessment included the Mini-Mental Status Examination (MMSE), the History and Aetiology Schedule (HAS) and the Geriatric Mental State (GMS)-AGECAT. For the standardised degree of cognitive impairment Perneczky et al's MMSE criteria were applied. Mortality information was obtained from the official population registry. Multivariate Cox proportional hazard models were used to test the association between MMSE degrees of cognitive impairment and mortality risk. We also estimated the PAF of mortality due to specific MMSE stages. RESULTS: Cognitive impairment was associated with mortality risk, the risk increasing in parallel with the degree of cognitive impairment (Hazard ratio, HR: 1.18 in the 'mild' degree of impairment; HR: 1.29 in the 'moderate' degree; and HR: 2.08 in the 'severe' degree). The PAF of mortality due to severe cognitive impairment was 3.49%. CONCLUSIONS: A gradient of increased mortality-risk associated with severity of cognitive impairment was observed. The results support the claim that routine assessment of cognitive function in older adults should be considered in clinical practice.

High-vacuum annealing reduction of Co/CoO nanoparticles.

Porous films of Co/CoO magnetic nanoparticles have been obtained by inert gas condensation and partially oxidized in situ in the deposition chamber. These nanoparticle films were subjected to thermal treatments in high vacuum and the chemical and structural changes monitored by x-ray diffraction, transmission electron microscopy, transport and magnetic measurements (with a focus on the exchange-bias phenomenon), which evidence that for vacuum annealing temperatures above 360 °C, most of the CoO phase is reduced to metallic Co without requiring the presence of an external reducing agent (e.g., H2) or a plasma. Additionally, there is a certain degree of particle coalescence resulting in the formation of greater nanoparticles as the annealing temperature increases. This yields a smaller proportion of CoO compared to metallic Co and a reduction of the Co/CoO interface density, pinpointed by a drastic decrease of the exchange-bias field. The crucial roles of the vacuum level and the surface-to-volume ratio are evidenced by magnetic measurements, highlighting the potential of magnetometry as a probe for the reduction/oxidation of composite nanostructures.

The MATRICS consensus cognitive battery (MCCB): co-norming and standardization in Spain.

The MATRICS Consensus Cognitive Battery (MCCB), developed by the National Institute of Mental Health (NIMH) Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative, has been recommended as the standard battery for clinical trials of cognition-enhancing interventions for schizophrenia. Normative data for the MCCB has been previously obtained in the U.S. Extrapolation of these normative data to different countries may be problematic due to the translation of the different tests, as well as potential cultural influences. We present the process of obtaining normative data for the MCCB in Spain with administration of the battery to a general community standardization sample. In addition, we examine the influence of age, gender, and educational level on test performance. The MCCB was administered to a total sample of 210 healthy volunteers, at three Spanish sites. For each site, recruitment of the sample was stratified according to age, gender, and educational level. Our findings indicate significant age, gender, and education effects on the normative data for the MCCB in Spain, which are comparable to those effects described for the original standardized English version in the U.S. The fact that the normative data are comparable, and that the variables age, gender, and education have a similar influence on performance, supports the robustness of the MCCB for use in different countries.

Incidence and lifetime risk of dementia and Alzheimer's disease in a Southern European population.

OBJECTIVE: To calculate both the incidence rates and the lifetime risk (LTR) of dementia and Alzheimer's disease (AD). METHODS: A two-phase case-finding procedure was implemented in a cohort of 4057 cognitively intact individuals 55+ years of age living in Zaragoza, Spain, and followed-up at 2.5 and 4.5 years. Age- and sex-specific incidence rates were calculated. A mortality-adjusted, multivariate model was used to document LTRs. RESULTS: The incidence rate of dementia continued to rise after the age of 90 years, but was slightly lower than in North and West European studies. Only a tendency for an increased LTR with age was observed. Thus, LTR was 19.7% for a 65-year-old woman and 20.4% at the age of 85 years, the corresponding figures for AD being 16.7% and 17.6%. The LTR of AD was higher in women and was about twice as high among illiterate individuals when compared with individuals with higher educational levels. CONCLUSIONS: The incidence rate of dementia in this Southern European city was slightly lower than in previous studies in North-West Europe. LTR of dementia and AD seems to be slightly increased with age. The association of illiteracy with higher LTR of AD is intriguing.

Diseño metodológico del proyecto ZARADEMP / No disponible

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Riesgo de depresión incidente y ACV en el estudio ZARADEMP / No disponible

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Incidencia de demencia en el estudio ZARADEMP / No disponible

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