A multidomain intervention against cognitive decline in an at-risk-population in Germany: Results from the cluster-randomized AgeWell.de trial.

INTRODUCTION: We investigated the effectiveness of a multidomain intervention to preserve cognitive function in older adults at risk for dementia in Germany in a cluster-randomized trial. METHODS: Individuals with a Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) risk score ≥ 9 aged 60 to 77 years were recruited. After randomization of their general practitioner (GP), patients received a multidomain intervention (including optimization of nutrition and medication, and physical, social, and cognitive activity) or general health advice and GP treatment as usual over 24 months. Primary outcome was global cognitive performance (composite z score, based on domain-specific neuropsychological tests). RESULTS: Of 1030 participants at baseline, n = 819 completed the 24-month follow-up assessment. No differences regarding global cognitive performance (average marginal effect = 0.010, 95% confidence interval: -0.113, 0.133) were found between groups at follow-up. Perceived restrictions in intervention conduct by the COVID-19 pandemic did not impact intervention effectiveness. DISCUSSION: The intervention did not improve global cognitive performance. HIGHLIGHTS: Overall, no intervention effects on global cognitive performance were detected. The multidomain intervention improved health-related quality of life in the total sample. In women, the multidomain intervention reduced depressive symptoms. The intervention was completed during the COVID-19 pandemic.

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.

Effects of APOE e4-allele and mental work demands on cognitive decline in old age: Results from the German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe).

OBJECTIVES: Previous studies have observed protective effects of high mental demands at work on cognitive functioning and dementia risk. However, it is unclear what types of demands drive this effect and whether this effect is subject to a person's genetic risk. We investigated to what extent eight different types of mental demands at work together with the APOE e4 allele, a major risk gene for late-onset Alzheimer's disease, affect cognitive functioning in late life. METHODS/DESIGN: The population-based German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe, n = 2 154) followed cognitively healthy individuals aged 75 years and older in seven assessment waves. Cognitive functioning was assessed via the mini-mental status examination. RESULTS: Mixed-effects modeling (adjusted for education, gender, marital status, stroke, depression, and diabetes) indicated that participants who had an occupational history of working in jobs with high compared to low demands in "Language & Knowledge", "Pattern detection", "Information processing", and "Service" had a slower cognitive decline. APOE e4-allele carriers had an accelerated cognitive decline, but this decline was significantly smaller if they had a medium compared to a low level of demands in contrast to non-carriers. CONCLUSIONS: Our longitudinal observations suggest that cognitive decline could be slowed by an intellectually enriched lifestyle even in risk gene carriers. Fostering intellectual engagement throughout the life-course could be a key prevention initiative to promote better cognitive health in old age.

Help-seeking for psychological distress and its association with anxiety in the oldest old - results from the AgeQualiDe cohort study.

Objectives: This study aimed to examine aspects of help-seeking for psychological distress and its association with increased anxiety symptoms in the oldest old.Method: Baseline data from AgeQualiDe, a multicenter cohort study of people aged 85 and over recruited in primary care, were analyzed. Help-seeking for psychological distress (items from the Camberwell Assessment of Need for the Elderly) was analyzed using ordinal and logistic regression models as a function of increased anxiety symptoms (Geriatric Anxiety Inventory-Short Form ≥ 3), as well as relevant socio-demographic and health-related covariates.Results:N = 155 (18.1% of the sample) reported having experienced psychological distress recently and were thus included in the analysis. Among those, 26.5% reported experiencing increased anxiety symptoms. On a descriptive level, 76.8% sought informal, 29.0% sought formal, and 18.1% sought no help for psychological distress. In covariate-adjusted regression models, increased anxiety was significantly associated with increased use of informal support (OR: 2.92, 95% CI: 1.31-6.48), but was neither associated with formal (OR: 0.72, 95% CI: 0.26-1.97) nor no help-seeking (OR: 0.28, 95% CI: 0.08-1.05).Conclusion: A large proportion of those experiencing psychological distress sought support from informal sources in this study. Anxiety symptoms in the oldest old were associated with the increased use of informal support, but not formal support or no help-seeking. Training and support for people providing informal help to those with mental health problems should be promoted to reduce a possible burden. However, future research addressing underlying mechanisms is needed.

Does parity matter in women's risk of dementia? A COSMIC collaboration cohort study.

BACKGROUND: Dementia shows sex difference in its epidemiology. Childbirth, a distinctive experience of women, is associated with the risk for various diseases. However, its association with the risk of dementia in women has rarely been studied. METHODS: We harmonized and pooled baseline data from 11 population-based cohorts from 11 countries over 3 continents, including 14,792 women aged 60 years or older. We investigated the association between parity and the risk of dementia using logistic regression models that adjusted for age, educational level, hypertension, diabetes mellitus, and cohort, with additional analyses by region and dementia subtype. RESULTS: Across all cohorts, grand multiparous (5 or more childbirths) women had a 47% greater risk of dementia than primiparous (1 childbirth) women (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.10-1.94), while nulliparous (no childbirth) women and women with 2 to 4 childbirths showed a comparable dementia risk to primiparous women. However, there were differences associated with region and dementia subtype. Compared to women with 1 to 4 childbirths, grand multiparous women showed a higher risk of dementia in Europe (OR = 2.99, 95% CI = 1.38-6.47) and Latin America (OR = 1.49, 95% CI = 1.04-2.12), while nulliparous women showed a higher dementia risk in Asia (OR = 2.15, 95% CI = 1.33-3.47). Grand multiparity was associated with 6.9-fold higher risk of vascular dementia in Europe (OR = 6.86, 95% CI = 1.81-26.08), whereas nulliparity was associated with a higher risk of Alzheimer disease (OR = 1.91, 95% CI 1.07-3.39) and non-Alzheimer non-vascular dementia (OR = 3.47, 95% CI = 1.44-8.35) in Asia. CONCLUSION: Parity is associated with women's risk of dementia, though this is not uniform across regions and dementia subtypes.

Mild cognitive impairment and quality of life in the oldest old: a closer look.

PURPOSE: Mild cognitive impairment (MCI) is a widespread phenomenon, especially affecting older individuals. We will analyze in how far MCI affects different facets of quality of life (QOL). METHODS: We used a sample of 903 participants (110 with MCI) from the fifth follow-up of the German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe), a prospective longitudinal study, to analyze the effects of MCI on different facets of the WHOQOL-OLD. We controlled for age, gender, marital status, education, living situation, daily living skills, and the ability to walk, see, and hear. RESULTS: Univariate analyses showed that individuals with MCI exhibited lower QOL with regard to the facets autonomy; past, present, and future activities; social participation; and intimacy, but less fears related to death and dying. No significant difference was shown with regard to the facet sensory abilities. In multivariate analyses controlling for age, gender, marital status, education, living situation, daily living skills, and the ability to walk, see and hear, MCI-status was significantly associated with QOL in the facet autonomy. CONCLUSION: Effects of MCI go beyond cognition and significantly impact the lives of those affected. Further research and practice will benefit from utilizing specific facets of QOL rather than a total score.

Determinants of incident dementia in different old age groups: results of the prospective AgeCoDe/AgeQualiDe study.

OBJECTIVES: To examine the impact of determinants of incident dementia in three different old age groups (75-79, 80-84, 85+years) in Germany. DESIGN: Multicenter prospective AgeCoDe/AgeQualiDe cohort study with baseline and nine follow-up assessments at 1.5-year intervals. SETTING: Primary care medical record registry sample. PARTICIPANTS: General practitioners' (GPs) patients aged 75+years at baseline. MEASUREMENTS: Conduction of standardized interviews including neuropsychological assessment and collection of GP information at each assessment wave. We used age-stratified competing risk regression models (accounting for the competing event of mortality) to assess determinants of incident dementia and age-stratified ordinary least square regressions to quantify the impact of identified determinants on the age at dementia onset. RESULTS: Among 3027 dementia-free GP patients, n = 704 (23.3%) developed dementia during the 13-year study period. Worse cognitive performance and subjective memory decline with related worries at baseline, and the APOE ε4 allele were associated independently with increased dementia risk in all three old age groups. Worse cognitive performance at baseline was also associated with younger age at dementia onset in all three age groups. Other well-known determinants were associated with dementia risk and age at dementia onset only in some or in none of the three old age groups. CONCLUSIONS: This study provides further evidence for the age-specific importance of determinants of incident dementia in old age. Such specifics have to be considered more strongly particularly with regard to potential approaches of early detection and prevention of dementia.

The association between mental demands at the workplace and cognitive functioning: the role of the big five personality traits.

Objectives: Mental demands at the workplace can be preventive against cognitive decline. However, personality shapes the way information is processed and we therefore assume that Neuroticism, Extraversion, Openness, Agreeableness and Conscientiousness, would moderate the beneficial effects of workplace stimulation on cognitive outcomes.Methods: We analyzed data from the population-based LIFE-Adult-Study (n = 6529). Cognitive outcomes were assessed via the Trail-Making Test (TMTA, TMTB) and the Verbal Fluency Test. Personality was assessed via the Personality Adjective List (16 AM). Mental demands were classified with the indices Verbal and Executive based on the O*NET database.Results: Multivariate regression analyses showed only two significant moderation effects of personality, i.e. in individuals with low scores on Conscientiousness/Openness, index Verbal was connected to better TMTB performance, while this effect disappeared for individuals with high values on the personality trait. However, the additional explained variance remained marginal.Conclusion: The findings suggest that personality does not modify associations between high mental demands at work and better cognitive functioning in old age; however, there is a tendency that high levels of Openness and Conscientiousness may offset effects of mental demands.

Prediction of dementia of Alzheimer type by different types of subjective cognitive decline.

INTRODUCTION: Subjective cognitive decline (SCD) is a risk condition for dementia, including dementia of Alzheimer type (DAT). METHODS: We report sensitivity, specificity, positive and negative predictive values (PPV, NPV) for conversion to all-cause dementia, and DAT in different SCD types (decline in memory, assocated worries, longitudinal consitency, of the AgeCoDe study (n = 2.402, 12 years follow-up). RESULTS: 82.7% of those converting to any dementia and 84.4% of those converting with DAT at follow-up, reported memory decline and fulfilled criteria of SCD at least at one time point before. SCD with worries at two consecutive time points showed a specificity of 92.2% for any dementia and also for DAT as well as a PPV of 44.3% for any dementia and of 36.9% for DAT at follow-up at the expense of low sensitivity. DISCUSSION: Different SCD subtypes were either sensitive or specific for future all-cause dementia and DAT in cognitively unimpaired individuals. Modest PPV of the most specific SCD subtypes were achieved in this low prevalence population.

A cross-national study of depression in preclinical dementia: A COSMIC collaboration study.

INTRODUCTION: Depression commonly accompanies Alzheimer's disease, but the nature of this association remains uncertain. METHODS: Longitudinal data from the COSMIC consortium were harmonized for eight population-based cohorts from four continents. Incident dementia was diagnosed in 646 participants, with a median follow-up time of 5.6 years to diagnosis. The association between years to dementia diagnosis and successive depressive states was assessed using a mixed effect logistic regression model. A generic inverse variance method was used to group study results, construct forest plots, and generate heterogeneity statistics. RESULTS: A common trajectory was observed showing an increase in the incidence of depression as the time to dementia diagnosis decreased despite cross-national variability in depression rates. DISCUSSION: The results support the hypothesis that depression occurring in the preclinical phases of dementia is more likely to be attributable to dementia-related brain changes than environment or reverse causality.

Determinants of cognitive performance and decline in 20 diverse ethno-regional groups: A COSMIC collaboration cohort study.

BACKGROUND: With no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups. METHODS AND FINDINGS: We harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54-105 (mean = 72.7) years and without dementia at baseline. Studies had 2-15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E ε4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = -0.1, SE = 0.01), APOE*4 carriage (B = -0.31, SE = 0.11), depression (B = -0.11, SE = 0.06), diabetes (B = -0.23, SE = 0.10), current smoking (B = -0.20, SE = 0.08), and history of stroke (B = -0.22, SE = 0.09) were independently associated with poorer cognitive performance (p < 0.05 for all), and higher levels of education (B = 0.12, SE = 0.02) and vigorous physical activity (B = 0.17, SE = 0.06) were associated with better performance (p < 0.01 for both). Age (B = -0.07, SE = 0.01), APOE*4 carriage (B = -0.41, SE = 0.18), and diabetes (B = -0.18, SE = 0.10) were independently associated with faster cognitive decline (p < 0.05 for all). Different effects between Asian people and white people included stronger associations for Asian people between ever smoking and poorer cognition (group by risk factor interaction: B = -0.24, SE = 0.12), and between diabetes and cognitive decline (B = -0.66, SE = 0.27; p < 0.05 for both). Limitations of our study include a loss or distortion of risk factor data with harmonization, and not investigating factors at midlife. CONCLUSIONS: These results suggest that education, smoking, physical activity, diabetes, and stroke are all modifiable factors associated with cognitive decline. If these factors are determined to be causal, controlling them could minimize worldwide levels of cognitive decline. However, any global prevention strategy may need to consider ethno-regional differences.

Is function in instrumental activities of daily living a useful feature in predicting Alzheimer's disease dementia in subjective cognitive decline?

OBJECTIVE: Subjective cognitive decline (SCD), the earliest symptom in preclinical Alzheimer's disease (AD), is insufficient to identify individuals at risk for AD dementia. Therefore, we aimed to investigate whether function in instrumental activities of daily living (IADL) contributes to identification. METHODS: We analysed data of cognitively unimpaired participants of the prospective German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe) and its extension, the Study on Needs, Health Service Use, Costs and Health-related Quality of Life in a Large Sample of Oldest-old Primary Care Patients (AgeQualiDe), collected over 10.5 years. Development of AD dementia was quantified as incidence rates (IRs) per 1000 person-years. Cox regression was used to assess the association of SCD and IADL function in regard to incident AD dementia. RESULTS: Of 1467 included individuals, 792 (54.0%) reported SCD at baseline. Impaired IADL were present in 50 (3.4%) individuals. IR for AD dementia was highest in individuals with SCD and impaired IADL (49.7; 95% CI, 24.8-99.3). Unadjusted and adjusted Cox analyses revealed an increased AD dementia risk for individuals with SCD and impaired IADL (uHR = 6.1; 95% CI, 2.9-13.0; P < 0.001; aHR = 2.5; 95% CI, 1.1-5.7; P < 0.05). CONCLUSIONS: Consistent with the SCD concept, IADL function was largely well preserved in the majority of individuals with SCD. However, if difficulties in IADL were present, risk for AD dementia was increased. Therefore, screening for IADL impairment could serve as an economically viable indicator to assess AD dementia risk above and beyond SCD.

HELP@APP: development and evaluation of a self-help app for traumatized Syrian refugees in Germany - a study protocol of a randomized controlled trial.

BACKGROUND: Syrians represent the largest group among refugees in Germany. Many of them were exposed to sequential traumatizing events including war, escape and post-migration stressors, which significantly increase the risk to develop symptoms of posttraumatic stress and other mental disorders. However, there is a lack of adequate treatment options for traumatized refugees in Germany. Moreover, their access to psychosocial care is often restricted due to legal regulation, language barriers, and unclear cost coverage. We therefore aim to develop a low-threshold supportive self-help app for Syrian refugees with posttraumatic stress symptoms. By conducting a randomized controlled trial, we further aim to evaluate the apps' efficacy, usability, acceptance, and economic health benefit/cost-effectiveness. METHODS: We will develop a modular, interactive self-help app in Arabic, which will be grounded on cognitive-behavioral models for the treatment of posttraumatic stress. Subsequently, screened positive (i.e., Syrian refugees, 18-65 years old, mild to moderate posttraumatic stress symptomatology as quantified by the Posttraumatic Stress Diagnostic Scale for DSM-5/PDS-5) participants (ideally up to n = 234) will be randomly allocated to an intervention (IG) and control group (CG), respectively. Participants in the IG will gain access to the self-help app for one month, while participants in the CG will receive psychoeducational reading material in form of a comprehensive brochure on traumatization and posttraumatic stress. Measurements are scheduled before the intervention (T0), directly after the intervention (T1, one month later) and three months after the intervention (T2). Using linear mixed effect models, we will investigate change in posttraumatic symptomatology. We will also test for changes in secondary outcomes such as depression, anxiety, and quality of life. Moreover, we will inspect the usability and user acceptance of the app. To evaluate the app in terms of its economic health benefit, the incremental cost-effectiveness ratio will be calculated. DISCUSSION: We plan to make the app freely available to the general public after evaluation. Thus, the app can help to add-on to routine care, which currently lacks sufficient and appropriate treatment options for Syrian refugees. TRIAL REGISTRATION: German Clinical Trials Register/Deutsches Register Klinischer Studien (DRKS). Registration ID: DRKS00013782 . Registered: 06th of July 2018.

Subjective cognitive decline and rates of incident Alzheimer's disease and non-Alzheimer's disease dementia.

INTRODUCTION: In this multicenter study on subjective cognitive decline (SCD) in community-based and memory clinic settings, we assessed the (1) incidence of Alzheimer's disease (AD) and non-AD dementia and (2) determinants of progression to dementia. METHODS: Eleven cohorts provided 2978 participants with SCD and 1391 controls. We estimated dementia incidence and identified risk factors using Cox proportional hazards models. RESULTS: In SCD, incidence of dementia was 17.7 (95% Poisson confidence interval 15.2-20.3)/1000 person-years (AD: 11.5 [9.6-13.7], non-AD: 6.1 [4.7-7.7]), compared with 14.2 (11.3-17.6) in controls (AD: 10.1 [7.7-13.0], non-AD: 4.1 [2.6-6.0]). The risk of dementia was strongly increased in SCD in a memory clinic setting but less so in a community-based setting. In addition, higher age (hazard ratio 1.1 [95% confidence interval 1.1-1.1]), lower Mini-Mental State Examination (0.7 [0.66-0.8]), and apolipoprotein E ε4 (1.8 [1.3-2.5]) increased the risk of dementia. DISCUSSION: SCD can precede both AD and non-AD dementia. Despite their younger age, individuals with SCD in a memory clinic setting have a higher risk of dementia than those in community-based cohorts.

[Strategies to Recruit Refugees for Intervention Studies: Lessons Learned from the "Sanadak" Trial]. / Strategien zur Rekrutierung von Geflüchteten für Interventionsstudien: Erkenntnisse aus dem "Sanadak"-Trial.

OBJECTIVE: Recruitment of so called rare populations, including refugees, for participation in research studies is challenging. We aim to share our lessons learned regarding recruitment strategies used in the "Sanadak" trial, a randomized controlled trial for the evaluation of a self-help app for Syrian refugees with posttraumatic stress. METHODS: We conducted an interim evaluation of our recruitment strategies. A quantitative analysis addressed how potential study participants first learned about "Sanadak" and in which way they made first contact with us. A qualitative part included problem-centered interviews with our Syrian study nurses (n=3) regarding the success of various recruitment strategies and perceived barriers. RESULTS: Data were available for the recruitment of 140 Syrian refugees. Almost half of the sample (44%) was recruited via personal contact, about another third (36%) by means of study promotion (e. g. Facebook ads), and about a fifth (19%) through multipliers. Typical barriers were concerns regarding data protection, anonymity and stigmatization. DISCUSSION: Snowball sampling was an effective recruitment strategy in our trial. This is also the most acknowledged recruitment strategy for rare populations. In addition, other strategies were useful to increase sample variance. The interim evaluation helped to direct efforts towards effective recruitment strategies and to identify and address barriers. CONCLUSION: Multi-strategic recruitment with a focus on snowball sampling, multiple options to make contact with the study team, and having culturally sensitive members in the study team contributed towards successful recruitment in the "Sanadak"-trial.

Subjective cognitive decline is longitudinally associated with lower health-related quality of life.

BACKGROUND: Subjective cognitive decline (SCD), the potentially earliest notable manifestation of preclinical Alzheimer's disease and other dementias, was consistently associated with lower quality of life in cross-sectional studies. The aim of this study was to investigate whether such an association persists longitudinally - particularly with health-related quality of life (HRQoL) in older individuals without cognitive impairment. METHODS: Data were derived from follow-up 2-6 of the prospective Germany Study on Ageing, Cognition and Dementia in Primary Care (AgeCoDe) covering a total six-year observation period. We used linear mixed effects models to estimate the effect of SCD on HRQoL measured by the EQ-5D visual analogue scale (EQ VAS). RESULTS: Of 1,387 cognitively unimpaired individuals aged 82.2 years (SD = 3.2) on average, 702 (50.6%) reported SCD and 230 (16.6%) with SCD-related concerns. Effect estimates of the linear mixed effects models revealed lower HRQoL in individuals with SCD (unadjusted: -3.7 points on the EQ VAS, 95%CI = -5.3 to -2.1; SE = 0.8; p < 0.001; adjusted: -2.9 points, 95%CI = -3.9 to -1.9; SE = 0.5; p < 0.001) than in individuals without SCD. The effect was most pronounced in SCD with related concerns (unadjusted: -5.4, 95%CI = -7.6 to -3.2; SE = 1.1; p < 0.001; adjusted: -4.3, 95%CI = -5.8 to -2.9, SE = 0.7; p < 0.001). CONCLUSION: SCD constitutes a serious issue to older cognitively unimpaired individuals that is depicted in persisting lower levels of HRQoL beyond depressive symptoms and functional impairment. Therefore, SCD should be taken seriously in clinical practice.

Outcomes of stable and unstable patterns of subjective cognitive decline - results from the Leipzig Longitudinal Study of the Aged (LEILA75+).

BACKGROUND: Subjective cognitive decline (SCD), i.e., the self-perceived feeling of worsening cognitive function, may be the first notable syndrome of preclinical Alzheimer's disease and other dementias. However, not all individuals with SCD progress. Stability of SCD, i.e., repeated reports of SCD, could contribute to identify individuals at risk, as stable SCD may more likely reflect the continuous neurodegenerative process of Alzheimer's and other dementias. METHODS: Cox regression analyses were used to assess the association between stability of SCD and progression to MCI and dementia in data derived from the population-based Leipzig Longitudinal Study of the Aged (LEILA75+). RESULTS: Of 453 cognitively unimpaired individuals with a mean age of 80.5 years (SD = 4.2), 139 (30.7 %) reported SCD at baseline. Over the study period (M = 4.8 years, SD = 2.2), 84 (18.5 %) individuals had stable SCD, 195 (43.1 %) unstable SCD and 174 (38.4 %) never reported SCD. Stable SCD was associated with increased risk of progression to MCI and dementia (unadjusted HR = 1.8, 95 % CI = 1.2-2.6; p < .01), whereas unstable SCD yielded a decreased progression risk (unadjusted HR = 0.5, 95 % CI = 0.4-0.7; p < .001) compared to no SCD. When adjusted for baseline cognitive functioning, progression risk in individuals with stable SCD was significantly increased in comparison to individuals with unstable SCD, but not compared to individuals without SCD. CONCLUSIONS: Our results, though preliminary, suggest that stable SCD, i.e., repeated reports of SCD, may yield an increased risk of progression to MCI and dementia compared to unstable SCD. Baseline cognitive scores, though within a normal range, seem to be a driver of progression in stable SCD. Future research is warranted to investigate whether stability could hold as a SCD research feature.

Independent and joint associations of cardiometabolic multimorbidity and depression on cognitive function: findings from multi-regional cohorts and generalisation from community to clinic.

Background: Cardiometabolic multimorbidity (CMM) and depression are often co-occurring in older adults and associated with neurodegenerative outcomes. The present study aimed to estimate the independent and joint associations of CMM and depression on cognitive function in multi-regional cohorts, and to validate the generalizability of the findings in additional settings, including clinical. Methods: Data harmonization was performed across 14 longitudinal cohort studies within the Cohort Studies of Memory in an International Consortium (COSMIC) group, spanning North America, South America, Europe, Africa, Asia, and Australia. Three external validation studies with distinct settings were employed for generalization. Participants were eligible for inclusion if they had data for CMM and were free of dementia at baseline. Baseline CMM was defined as: 1) CMM 5, ≥2 among hypertension, hyperlipidemia, diabetes, stroke, and heart disease and 2) CMM 3 (aligned with previous studies), ≥2 among diabetes, stroke, and heart disease. Baseline depression was primarily characterized by binary classification of depressive symptom measurements, employing the Geriatric Depression Scale and the Center for Epidemiological Studies-Depression scale. Global cognition was standardized as z-scores through harmonizing multiple cognitive measures. Longitudinal cognition was calculated as changes in global cognitive z-scores. A pooled individual participant data (IPD) analysis was utilized to estimate the independent and joint associations of CMM and depression on cognitive outcomes in COSMIC studies, both cross-sectionally and longitudinally. Repeated analyses were performed in three external validation studies. Findings: Of the 32,931 older adults in the 14 COSMIC cohorts, we included 30,382 participants with complete data on baseline CMM, depression, and cognitive assessments for cross-sectional analyses. Among them, 22,599 who had at least 1 follow-up cognitive assessment were included in the longitudinal analyses. The three external studies for validation had 1964 participants from 3 multi-ethnic Asian older adult cohorts in different settings (community-based, memory clinic, and post-stroke study). In COSMIC studies, each of CMM and depression was independently associated with cross-sectional and longitudinal cognitive function, without significant interactions between them (Ps > 0.05). Participants with both CMM and depression had lower cross-sectional cognitive performance (e.g. ß = -0.207, 95% CI = (-0.255, -0.159) for CMM5 (+)/depression (+)) and a faster rate of cognitive decline (e.g. ß = -0.040, 95% CI = (-0.047, -0.034) for CMM5 (+)/depression (+)), compared with those without either condition. These associations remained consistent after additional adjustment for APOE genotype and were robust in two-step random-effects IPD analyses. The findings regarding the joint association of CMM and depression on cognitive function were reproduced in the three external validation studies. Interpretation: Our findings highlighted the importance of investigating age-related co-morbidities in a multi-dimensional perspective. Targeting both cardiometabolic and psychological conditions to prevent cognitive decline could enhance effectiveness. Funding: Natural Science Foundation of China and National Institute on Aging/National Institutes of Health.

Gender-specific design and effectiveness of non-pharmacological interventions against cognitive decline and dementia-protocol for a systematic review and meta-analysis.

INTRODUCTION: Dementia is a public health priority with projected increases in the number of people living with dementia worldwide. Prevention constitutes a promising strategy to counter the dementia epidemic, and an increasing number of lifestyle interventions has been launched aiming at reducing risk of cognitive decline and dementia. Gender differences regarding various modifiable risk factors for dementia have been reported, however, evidence on gender-specific design and effectiveness of lifestyle trials is lacking. Therefore, we aim to systematically review evidence on gender-specific design and effectiveness of trials targeting cognitive decline and dementia. METHODS AND ANALYSIS: We will conduct a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases MEDLINE (PubMed interface), PsycINFO, Web of Science Core Collection, Cochrane Central Register of Controlled Trials (CENTRAL) and ALOIS will be searched for eligible studies using a predefined strategy, complemented by searches in clinical trials registers and Google for grey literature. Studies assessing cognitive function (overall measure or specific subdomains) as outcome in dementia-free adults will be included, with analyses stratified by level of cognitive functioning at baseline: a) cognitively healthy b) subjective cognitive decline 3) mild cognitive impairment. Two reviewers will independently evaluate eligible studies, extract data and determine methodological quality using the Scottish Intercollegiate Guidelines Network (SIGN)-criteria. If sufficient data with regards to quality and quantity are available, a meta-analysis will be conducted. ETHICS AND DISSEMINATION: No ethical approval will be required as no primary data will be collected. PROSPERO REGISTRATION NUMBER: CRD42021235281.

Social isolation, mental health, and use of digital interventions in youth during the COVID-19 pandemic: A nationally representative survey.

BACKGROUND: Public health measures to curb SARS-CoV-2 transmission rates may have negative psychosocial consequences in youth. Digital interventions may help to mitigate these effects. We investigated the associations between social isolation, COVID-19-related cognitive preoccupation, worries, and anxiety, objective social risk indicators, and psychological distress, as well as use of, and attitude toward, mobile health (mHealth) interventions in youth. METHODS: Data were collected as part of the "Mental Health And Innovation During COVID-19 Survey"-a cross-sectional panel study including a representative sample of individuals aged 16-25 years (N = 666; Mage = 21.3; assessment period: May 5, 2020 to May 16, 2020). RESULTS: Overall, 38% of youth met criteria for moderate or severe psychological distress. Social isolation worries and anxiety, and objective risk indicators were associated with psychological distress, with evidence of dose-response relationships for some of these associations. For instance, psychological distress was progressively more likely to occur as levels of social isolation increased (reporting "never" as reference group: "occasionally": adjusted odds ratio [aOR] 9.1, 95% confidence interval [CI] 4.3-19.1, p < 0.001; "often": aOR 22.2, CI 9.8-50.2, p < 0.001; "very often": aOR 42.3, CI 14.1-126.8, p < 0.001). There was evidence that psychological distress, worries, and anxiety were associated with a positive attitude toward using mHealth interventions, whereas psychological distress, worries, and anxiety were associated with actual use. CONCLUSIONS: Public health measures during pandemics may be associated with poor mental health outcomes in youth. Evidence-based digital interventions may help mitigate the negative psychosocial impact without risk of viral infection given there is an objective need and subjective demand.