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Background: Emerging observational evidence supports a role for higher fruit and vegetable intake in protecting against the development of depression. However, there is a scarcity of research in older adults or in low- to middle-income countries (LMICs). Methods: Participants were 7801 community-based adults (mean age 68.6 ± 8.0 years, 55.8 % female) without depression, from 10 diverse cohorts, including four cohorts from LMICs. Fruit and vegetable intake was self-reported via comprehensive food frequency questionnaire, short food questionnaire or diet history. Depressive symptoms were assessed using validated measures, and depression defined applying validated cut-offs. The associations between baseline fruit and vegetable intakes and incident depression over a follow-up period of three to nine years were examined using Cox regression. Analyses were performed by cohort with results meta-analysed. Results: There were 1630 cases of incident depression (21 % of participants) over 40,258 person-years of follow-up. Higher intake of fruit was associated with a lower risk of incident depression (HR 0.87, 95%CI [0.77, 0.99], I2 = 4 %). No association was found between vegetable intake and incident depression (HR 0.93, 95%CI [0.84, 1.04], I2 = 0 %). Limitations: Diverse measures used across the different cohorts and the modest sample size of our study compared with prior studies may have prevented an association being detected for vegetable intake. Conclusions: Our study supports a role for fruit, but not vegetable intake in protecting against depression. Research investigating different types of fruits and vegetables using standardised measures in larger cohorts of older adults from low- and middle-income countries is warranted.

The original version of this Article omitted from the author list the 212th author Patrizia Mecocci, who is from the Institute of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Perugia, Italy. Consequently, the “Sample Contribution” section of Author Contributions was updated to add “P.M” between “P.D.” and “R.C.”. Additionally, the original version of this Article contained the incorrect affiliation for author Patrick Gavin Kehoe, which incorrectly read “German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany”. The correct version replaces this affiliation with “Bristol Medical School (THS), University of Bristol, Southmead Hospital, Bristol, UK”. This has been corrected in both the PDF and HTML versions of the Article.

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.

Introduction: Sex differences in dementia risk, and risk factor (RF) associations with dementia, remain uncertain across diverse ethno-regional groups. Methods: A total of 29,850 participants (58% women) from 21 cohorts across six continents were included in an individual participant data meta-analysis. Sex-specific hazard ratios (HRs), and women-to-men ratio of hazard ratios (RHRs) for associations between RFs and all-cause dementia were derived from mixed-effect Cox models. Results: Incident dementia occurred in 2089 (66% women) participants over 4.6 years (median). Women had higher dementia risk (HR, 1.12 [1.02, 1.23]) than men, particularly in low- and lower-middle-income economies. Associations between longer education and former alcohol use with dementia risk (RHR, 1.01 [1.00, 1.03] per year, and 0.55 [0.38, 0.79], respectively) were stronger for men than women; otherwise, there were no discernible sex differences in other RFs. Discussion: Dementia risk was higher in women than men, with possible variations by country-level income settings, but most RFs appear to work similarly in women and men.

Introduction: Previous meta-analyses have linked social connections and mild cognitive impairment, dementia, and mortality. However, these used aggregate data from North America and Europe and examined a limited number of social connection markers. Methods: We used individual participant data (N = 39271, Mage = 70.67 (40-102), 58.86% female, Meducation = 8.43 years, Mfollow-up = 3.22 years) from 13 longitudinal ageing studies. A two-stage meta-analysis of Cox regression models examined the association between social connection markers with our primary outcomes. Results: We found associations between good social connections structure and quality and lower risk of incident mild cognitive impairment (MCI); between social structure and function and lower risk of incident dementia and mortality. Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and having a confidante was associated with reduced risk of dementia and mortality. Discussion: Different aspects of social connections – structure, function, and quality – are associated with benefits for healthy aging internationally. Highlights: Social connection structure (being married/in a relationship, weekly community group engagement, weekly family/friend interactions) and quality (never lonely) were associated with lower risk of incident MCI. Social connection structure (monthly/weekly friend/family interactions) and function (having a confidante) were associated with lower risk of incident dementia. Social connection structure (living with others, yearly/monthly/weekly community group engagement) and function (having a confidante) were associated with lower risk of mortality. Evidence from 13 longitudinal cohort studies of ageing indicates that social connections are important targets for reducing risk of incident MCI, incident dementia, and mortality. Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and having a confi

Importance: The utility of antihypertensives and ideal blood pressure (BP) for dementia prevention in late life remains unclear and highly contested. Objectives: To assess the associations of hypertension history, antihypertensive use, and baseline measured BP in late life (age >60 years) with dementia and the moderating factors of age, sex, and racial group. Data Source and Study Selection: Longitudinal, population-based studies of aging participating in the Cohort Studies of Memory in an International Consortium (COSMIC) group were included. Participants were individuals without dementia at baseline aged 60 to 110 years and were based in 15 different countries (US, Brazil, Australia, China, Korea, Singapore, Central African Republic, Republic of Congo, Nigeria, Germany, Spain, Italy, France, Sweden, and Greece). Data Extraction and Synthesis: Participants were grouped in 3 categories based on previous diagnosis of hypertension and baseline antihypertensive use: healthy controls, treated hypertension, and untreated hypertension. Baseline systolic BP (SBP) and diastolic BP (DBP) were treated as continuous variables. Reporting followed the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data reporting guidelines. Main Outcomes and Measures: The key outcome was all-cause dementia. Mixed-effects Cox proportional hazards models were used to assess the associations between the exposures and the key outcome variable. The association between dementia and baseline BP was modeled using nonlinear natural splines. The main analysis was a partially adjusted Cox proportional hazards model controlling for age, age squared, sex, education, racial group, and a random effect for study. Sensitivity analyses included a fully adjusted analysis, a restricted analysis of those individuals with more than 5 years of follow-up data, and models examining the moderating factors of age, sex, and racial group. Results: The analysis included 17 studies

Objectives: There is limited research on the prognostic value of language tasks regarding mild cognitive impairment (MCI) and Alzheimer's clinical syndrome (ACS) development in the cognitively normal (CN) elderly, as well as MCI to ACS conversion. Methods: Participants were drawn from the population-based Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) cohort. Language performance was evaluated via verbal fluency [semantic (SVF) and phonemic (PVF)], confrontation naming [Boston Naming Test short form (BNTsf)], verbal comprehension, and repetition tasks. An additional language index was estimated using both verbal fluency tasks: SVF-PVF discrepancy. Cox proportional hazards analyses adjusted for important sociodemographic parameters (age, sex, education, main occupation, and socioeconomic status) and global cognitive status [Mini Mental State Examination score (MMSE)] were performed. Results: A total of 959 CN and 118 MCI older (>64 years) individuals had follow-up investigations after a mean of ∼3 years. Regarding the CN group, each standard deviation increase in the composite language score reduced the risk of ACS and MCI by 49% (8-72%) and 32% (8-50%), respectively; better SVF and BNTsf performance were also independently associated with reduced risk of ACS and MCI. On the other hand, using the smaller MCI participant set, no language measurement was related to the risk of MCI to ACS conversion. Conclusions: Impaired language performance is associated with elevated risk of ACS and MCI development. Better SVF and BNTsf performance are associated with reduced risk of ACS and MCI in CN individuals, independent of age, sex, education, main occupation, socioeconomic status, and MMSE scores at baseline. Copyright © INS. Published by Cambridge University Press, 2022.

Cognitive disorders have become important public health issues around the world. Studies evaluating the association between cognitive decline and food timing are lacking. The objective of this study was to examine the potential association between energy intake distribution during the day and cognitive performance in cognitively healthy and mildly cognitive impaired individuals. Data were derived from the ongoing Albion study which includes people aged 40 years or older who have a positive family history of cognitive disorder or concern about their cognitive status. A thorough dietary and cognitive assessment was performed. Participants consuming low energy intake at the beginning of the day or high energy at the end of the day had higher cognitive function compared to participants characterized by the opposite pattern. This trend remained statistically significant even after adjustment for potential confounders (p = 0.043). This study suggests that individuals with worse cognitive function may choose to eat earlier during the day, when cognitive performance is better, and it might be hypothesized that a meal pattern characterized by high energy consumption at the beginning of the day or low energy at the end of the day could be a marker of cognitive impairment. © 2023 by the authors.

Introduction: Previous meta-analyses have linked social connections and mild cognitive impairment, dementia, and mortality. However, these used aggregate data from North America and Europe and examined a limited number of social connection markers. Methods: We used individual participant data (N = 39271, Mage = 70.67 (40-102), 58.86% female, Meducation = 8.43 years, Mfollow-up = 3.22 years) from 13 longitudinal ageing studies. A two-stage meta-analysis of Cox regression models examined the association between social connection markers with our primary outcomes. Results: We found associations between good social connections structure and quality and lower risk of incident mild cognitive impairment (MCI); between social structure and function and lower risk of incident dementia and mortality. Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and having a confidante was associated with reduced risk of dementia and mortality. Discussion: Different aspects of social connections – structure, function, and quality – are associated with benefits for healthy aging internationally. Highlights: Social connection structure (being married/in a relationship, weekly community group engagement, weekly family/friend interactions) and quality (never lonely) were associated with lower risk of incident MCI. Social connection structure (monthly/weekly friend/family interactions) and function (having a confidante) were associated with lower risk of incident dementia. Social connection structure (living with others, yearly/monthly/weekly community group engagement) and function (having a confidante) were associated with lower risk of mortality. Evidence from 13 longitudinal cohort studies of ageing indicates that social connections are important targets for reducing risk of incident MCI, incident dementia, and mortality. Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and having a confi

OBJECTIVE: To investigate differences in language performance among older adults with normal cognition (CN), mild cognitive impairment (MCI), and Alzheimer's disease (ad). Owing to the conflicting literature concerning MCI, discrepancies between amnestic (aMCI) and non-amnestic MCI (naMCI) were explored in greater detail. METHOD: The study sample was drawn from the older (>64 years) HELIAD cohort. Language performance was assessed via semantic and phonemic fluency, confrontation naming, verbal comprehension, verbal repetition as well as a composite language index. Age, sex, and education adjusted general linear models were used to quantify potential pairwise differences in language performance. RESULTS: The present analysis involved 1607 participants with CN, 146 with aMCI [46 single and 100 multi-domain aMCI], 92 with naMCI [41 single and 51 multi-domain naMCI], and 79 with ad. The mean age and education of our predominantly female (60%) participants were 73.82 (±5.43) and 7.98 (±4.93) years, respectively. MCI individuals performed between those with CN and ad, whereas participants with aMCI performed worse compared to those with naMCI, especially in the semantic fluency and verbal comprehension tasks. Discrepancies between the aMCI and naMCI groups were driven by the exquisitely poor performance of multi-domain aMCI subgroup. CONCLUSIONS: Overall, individuals could be hierarchically arranged in a continuum of language impairment with the CN individuals constituting the healthy reference and naMCI, aMCI, ad patients representing gradually declining classes in terms of language performance. Exploration of language performance via separation of single from multi-domain naMCI provided a potential explanation for the conflicting evidence of previous research. © The Author(s) 2022. Published by Oxford University Press.

Background and purpose: Lifestyle factors have been implicated in the long-lasting neurodegenerative process in prodromal Parkinson's disease (pPD). The aim was to investigate the associations between adherence to a Mediterranean diet (MeDi) and longitudinal changes of pPD probability and the development of Parkinson's disease (PD) or pPD in a Mediterranean older population. Methods: Data from the Hellenic Longitudinal Investigation of Aging and Diet cohort (community-dwelling individuals, aged ≥ 65 years) were used. A detailed food frequency questionnaire was used to evaluate dietary intake and calculate MeDi adherence score, ranging from 0 to 55, with higher scores indicating higher adherence. The probability of pPD was calculated according to the updated Movement Disorder Society research criteria. Results: In all, 1047 non-PD/dementia with Lewy bodies (DLB) participants were followed for 3 ± 1 years. MeDi adherence was associated with lower increase in pPD probability over time (b = −0.003, 95% confidence interval −0.006 to −0.001, p = 0.010). Forty-nine participants had incident possible/probable pPD (i.e., pPD probability ≥ 30%). Compared to the participants in the lowest quartile of MeDi adherence, those in the higher quartiles had an approximately 60%–70% lower risk for possible/probable pPD (p for trend 0.003). MeDi–pPD associations were driven by both motor and non-motor pPD markers and not from risk markers. Also, 21 participants were diagnosed with PD/DLB at follow-up. For each unit increase in the MeDi score, there was a 9%–10% lower risk for PD/DLB (hazard ratio 0.906 [95% confidence interval 0.823–0.997], p = 0.044). Conclusions: Mediterranean diet adherence is associated with lower increase in pPD probability over time and lower possible/probable pPD and PD/DLB incidence in older Mediterranean people. More studies are needed to confirm our results in other populations. © 2023 European Academy of Neurology.

Background: Subjective cognitive decline (SCD) is a self-evaluation of cognitive impairment, in the absence of observed objective cognitive deficits on a neuropsychological assessment. Frailty refers to a multidimensional syndrome where the individual has poor health including falls, disabilities, hospitalization, and vulnerability. Both terms are associated with cognitive decline and increased incidence of dementia. The present longitudinal study explored whether the detection of SCD can predict the development of frailty over time. Methods: The Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) is an epidemiological, population-based study. From the original testing sample of 1,984 older Greek individuals (≥65 years old), 1,121 remained in the longitudinal analysis. Participants diagnosed with frailty, Mild Cognitive Impairment (MCI), dementia, severe depression, and anxiety, in the baseline assessment were excluded from the analysis (n=146), resulting in a total sample of 975 participants. The average follow-up interval was 3.1 years (SD=0.84 years). SCD was assessed in the baseline assessment with a series of eighteen questions. The questions regarding SCD were categorized according to cognitive domains. Frailty was assessed according to a phenotypic-physiologic (Fried’s definition) and a multidomain approach (Frailty Index). Univariate and multivariate Cox regression analyses were used for exploring the role of SCD in developing frailty. Results: The proportion of individuals with frailty according to Fried’s definition was greater compared to the Frailty Index. At follow-up according to Fried’s definition, a greater proportion of cases with frailty was found in those who reported SCD complaints regarding orientation (OD) (HR=3.12 95% CI:1.45–6.73 p<0.004) or in those who reported at least three SCD complaints regarding their memory performance (SMC3) (HR=1.92 95% CI:1.05–3.52 p<0.035) at the baseline assessment. Subjective complaints regardin

Obejctives: The aim of the current study was to investigate whether genetic risk factors may moderate the association between adherence to the Mediterranean diet and AD incidence. Mehtods: The sample was drawn from the HELIAD study, a longitudinal study with a follow-up interval of 3 years. In total 537 older adults without dementia or AD at baseline were included. Adherence to the Mediterranean diet was assessed at baseline and AD diagnosis was determined at both visits. A Polygenic Index for late onset AD (PGI-AD) was constructed. Cox proportional hazard models adjusted for age, sex, education, baseline Global cognition score and APOE e-4 genotype were employed to evaluate the association between PGI-AD and Mediterranean diet with AD incidence. Next, we examined the association between adherence to the Mediterranean diet and AD risk over time across participants stratified by low and high PGI-AD. Results: Twenty-eight participants developed AD at follow-up. In fully adjusted models both the PGI-AD and the adherence to the Mediterranean diet were associated with AD risk (p < 0.05 for both). In the low PGI-AD group, those with a low adherence had a 10-fold higher risk of developing AD per year of follow-up, than did the participants with a high adherence to the Mediterranean diet (p = 0.011), whereas no such association was found for participants in the high PGI-AD group. Discussion: The association of Mediterranean diet with AD risk is more prominent in the group of older adults with a low polygenic risk for developing AD. Our findings suggest that genetic risk factors should be taken into account when planning interventions aiming to improve cognitive health. © 2023 Informa UK Limited, trading as Taylor & Francis Group.

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. © 2023 The Authors. Psychiatry and Clinical Neurosciences © 2023 Japanese Society of Psychiatry and Neurology.

Objective: We investigated the diagnostic accuracy of the Clock Drawing Test (CDT) in discriminating Mild Cognitive Impairment (MCI) and dementia from normal cognition. Additionally, its clinical utility in predicting the transition from normal cognition to MCI and dementia over the course of several years was explored. Method: In total, 1037 older adults (633 women) who completed the CDT in a baseline assessment were drawn from the population-based HELIAD cohort. Among these, 848 participants were identified as cognitively normal, 142 as having MCI and 47 with dementia during the baseline assessment. Of these individuals, 565 attended the follow-up assessment (mean interval: 3.21 years). ROC curve and binary logistic regression analyses were performed. Results: The CDT exhibited good diagnostic accuracy for the discrimination between dementia and normal cognition (AUC =.879, SN =.813, SP =.778, LR+ = 3.66, LR- =.240, <.001, d = 1.655) and acceptable diagnostic accuracy for the discrimination between dementia and MCI (AUC=.761, SN=.750, SP=.689, LR+ = 2.41, LR- =.362, p <.001, d = 1.003). We found limited diagnostic accuracy, however, for the discrimination between MCI and normal cognition (AUC =.686, SN =.764, SP =.502, LR+ = 1.53, LR- =.470, p <.001, d =.685). Moreover, the CDT significantly predicted the transition from normal cognition to dementia [Exp(B)= 1.257, p =.022], as well as the transition from MCI to normal cognition [Exp(B) = 1.334, p =.023] during the longitudinal investigation. Conclusions: The CDT is a neuropsychological test with acceptable diagnostic accuracy for the discrimination of dementia from MCI and normal cognition. Furthermore, it has an important predictive value for the transition from normal cognition to dementia and from MCI to normal cognition. © 2023 Informa UK Limited, trading as Taylor & Francis Group.

Although research has generally shown a negative association between depression and adherence to the Mediterranean diet (MeDi), the literature related to older adults is controversial, perhaps partially due to the fact that cognitive status has not been considered. The aim of the current work was to investigate the association between MeDi and incident depression in a representative cohort of people, taking into account their cognitive status in multiple ways. The sample was drawn from the HELIAD study, a longitudinal study including a follow-up of 3 years after the baseline assessment. In total, 879 participants without depression at baseline were included (55.4% women, mean age ± Standard Deviation: 73.3 ± 5.0 years). Depression was determined as a score in the Geriatric depression scale ≥6 and/or antidepressant medication and/or clinical diagnosis of depression. Cox proportional hazard models adjusted for age, sex and education were employed. In the basic model, adherence to the MeDi was negatively associated with depression. In the most conservative model, excluding participants with dementia and Mild Cognitive Impairment, and after controlling for the baseline Cognitive Status, each unit (range 0–55) increase in MeDi was associated with a 6.2% decrease in the risk for depression (p < 0.001). These findings indicate that MeDi is negatively associated with depression longitudinally in older adults, above and beyond cognitive status. © 2023 by the authors.

Background: The cognitive trajectories of cognitively normal (CN) individuals rapidly progressing to Alzheimer’s disease dementia (AD) have not been investigated. Aim: To explore the preclinical pattern of cognitive performance heralding the rapid progression from normal cognition to AD. Methods: The HELIAD cohort underwent comprehensive neuropsychological assessments (memory, language, attention, executive and visuo-perceptual functions) at baseline and after approximately 3-year intervals. The cognitive trajectories of those with normal cognition at baseline were explored according to the follow-up diagnosis using adjusted generalised estimating equations analyses. Results: A total of 932 predominantly female (61%), older (72.9 ± 4.9), CN participants were followed for 3.09 (± 0.83) years. Among them, 761 individuals remained CN, 29 progressed to AD and 142 developed MCI (33 single-domain amnestic, 41 multidomain amnestic, 37 single-domain non-amnestic and 31 multidomain non-amnestic). Those progressing to AD were already performing worse than the healthy reference in every single cognitive domain at baseline. Cognitive deficits ranged between ~ 0.5SD (attention, executive function and language) and ~ 1.0SD (memory and visuo-perceptual skills). Throughout the 3-year follow-up, memory constantly exhibited the most prominent impairment compared to the remaining cognitive domains while executive function diminished in the most abrupt fashion (~ 0.19SD yearly) separating from the remaining three cognitive functions before the development of full-blown AD. Heterogeneous patterns of cognitive decline clearly differentiated those progressing to MCI from those rapidly converting to AD, as well. Discussion: Poor performance in every cognitive domain may characterise cognitively normal individuals at high risk of fast progression to AD. Conclusion: Strict neuropsychological cut-offs fail to detect a considerable number of individuals at high risk of rapid progression to AD.

Introduction: Sex differences in dementia risk, and risk factor (RF) associations with dementia, remain uncertain across diverse ethno-regional groups. Methods: A total of 29,850 participants (58% women) from 21 cohorts across six continents were included in an individual participant data meta-analysis. Sex-specific hazard ratios (HRs), and women-to-men ratio of hazard ratios (RHRs) for associations between RFs and all-cause dementia were derived from mixed-effect Cox models. Results: Incident dementia occurred in 2089 (66% women) participants over 4.6 years (median). Women had higher dementia risk (HR, 1.12 [1.02, 1.23]) than men, particularly in low- and lower-middle-income economies. Associations between longer education and former alcohol use with dementia risk (RHR, 1.01 [1.00, 1.03] per year, and 0.55 [0.38, 0.79], respectively) were stronger for men than women; otherwise, there were no discernible sex differences in other RFs. Discussion: Dementia risk was higher in women than men, with possible variations by country-level income settings, but most RFs appear to work similarly in women and men. © 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

Background: Irrational beliefs, maladaptive emotions, and unhealthy lifestyle behaviors can adversely affect health status. However, limited research has examined the association between irrational beliefs and cardiovascular disease (CVD). The aim of this study was to evaluate the association between irrational beliefs and the 10-year CVD incidence among apparently healthy adults, considering the potential moderating or mediating role of particular social and lifestyle factors. Methods: The ATTICA study is a population-based, prospective cohort (2002–2012), in which 853 participants without a history of CVD [453 men (aged 45 ± 13 years) and 400 women (aged 44 ± 18 years)] underwent psychological evaluations. Among other tools, participants completed the irrational beliefs inventory (IBI, range 0–88), a self-reported measure consistent with the Ellis model of psychological disturbance. Demographic characteristics, detailed medical history, dietary, and other lifestyle habits were also evaluated. Incidence of CVD (i.e., coronary heart disease, acute coronary syndromes, stroke, or other CVD) was defined according to the International Coding Diseases (ICD)-10 criteria. Results: Mean IBI score was 53 ± 2 in men and 53 ± 3 in women (p = 0.88). IBI score was positively associated with 10-year CVD risk (hazard ratio 1.07, 95%CI 1.04, 1.13), in both men and women, and more prominently among those with less healthy dietary habits and lower education status; specifically, higher educational status leads to lower IBI score, and in conjunction they lead to lower 10-year CVD risk (HR for interaction 0.98, 95%CI 0.97, 0.99). Conclusions: The findings of this study underline the need to build new, holistic approaches in order to better understand the inter-relationships between irrational beliefs, lifestyle behaviors, social determinants, and CVD risk in individuals. © 2022, International Society of Behavioral Medicine.

BACKGROUND: numerous studies point towards a critical role of Interleukin 6 (IL-6) pathway in frailty pathogenesis yet the causal relationship between the two remains elusive. METHODS: we selected genetic variants near the IL-6 receptor locus (IL-6R) associated with reduced C-reactive protein (CRP) levels, a downstream effector of IL-6 pathway, and we used them as genetic proxies of IL-6 signalling downregulation. We then performed a two-sample Mendelian randomisation (MR) to investigate the association with frailty status, as defined by the Frailty Index (FI) in 11,171 individuals from the Hellenic Longitudinal Investigation of Ageing and Diet (HELIAD) study. MR analysis was repeated after excluding depression or cognition-related FI items as well as following age or sex stratification. Association with frailty was also examined using an alternative instrument, weighted on s-IL-6R levels. Replication was attempted in UK Biobank dataset. RESULTS: genetic predisposition to IL-6 signalling downregulation, weighted on CRP levels, was associated with lower risk of frailty, inserted either as categorical (odds ratio [95% confidence interval] = 0.15 [-3.39, -0.40], P = 0.013) or continuous variable (beta [se] = -0.09 [0.003], P = 0.0009). Sensitivity analyses revealed similar estimates across different MR methods with no evidence for horizontal pleiotropy or heterogeneity. Results remained robust after exclusion of depression or cognition-related FI items and following sex or age stratification. Genetically increased s-IL-6R levels were negatively correlated with frailty and this finding remained significant in a meta-analysis of UK Biobank and HELIAD cohorts. CONCLUSION: our results support a potential causal effect of IL-6 signalling on frailty and further suggest that downregulation of IL-6 levels may reduce frailty risk. © The Author(s) 2023. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please

The A. G. Leventis Foundation International Conference, “Prevention of Alzheimer’s Disease and Cognitive Decline with Diet & Lifestyle”, was held on May 11–12th, 2022 in Nicosia, Cyprus. This conference examined the role of diet and lifestyle for the prevention and treatment of Alzheimer’s Disease and other forms of cognitive decline. Speakers from leading academic institutions presented evidence on healthy dietary patterns, with a particular focus on the traditional Mediterranean diet (MedDiet), in association with cognitive outcomes, mainly cognitive decline, dementia, and Alzheimer’s disease, from both observational and interventional studies. Moreover, future directions for the potential use of olive oil, rich in polyphenols, for its therapeutic use as a nutraceutical, as well as nutritional interventions with high-quality dietary patterns (i.e. MedDiet) that support existing primarily observational evidence for the prevention of cognitive decline, as well as challenges in designing rigorous clinical trials are summarized and discussed within the conference proceedings. © 2022, Serdi.

Item does not contain fulltext, INTRODUCTION: Previous meta-analyses have linked social connections and mild cognitive impairment, dementia, and mortality. However, these used aggregate data from North America and Europe and examined a limited number of social connection markers. METHODS: We used individual participant data (N = 39271, M(age) = 70.67 (40-102), 58.86% female, M(education) = 8.43 years, M(follow-up) = 3.22 years) from 13 longitudinal ageing studies. A two-stage meta-analysis of Cox regression models examined the association between social connection markers with our primary outcomes. RESULTS: We found associations between good social connections structure and quality and lower risk of incident mild cognitive impairment (MCI); between social structure and function and lower risk of incident dementia and mortality. Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and having a confidante was associated with reduced risk of dementia and mortality. DISCUSSION: Different aspects of social connections - structure, function, and quality - are associated with benefits for healthy aging internationally. HIGHLIGHTS: Social connection structure (being married/in a relationship, weekly community group engagement, weekly family/friend interactions) and quality (never lonely) were associated with lower risk of incident MCI. Social connection structure (monthly/weekly friend/family interactions) and function (having a confidante) were associated with lower risk of incident dementia. Social connection structure (living with others, yearly/monthly/weekly community group engagement) and function (having a confidante) were associated with lower risk of mortality. Evidence from 13 longitudinal cohort studies of ageing indicates that social connections are important targets for reducing risk of incident MCI, incident dementia, and mortality. Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and havin, 01 november 2023

Background and Objectives: The aim of the present study was to investigate the prognostic value of the qualitative components of verbal fluency (clustering, switching, intrusions, and perseverations) on the development of mild cognitive impairment (MCI) and dementia. Materials and Methods: Participants were drawn from the multidisciplinary, population-based, prospective HELIAD (Hellenic Longitudinal Investigation of Aging and Diet) cohort. Two participant sets were separately analysed: those with normal cognition and MCI at baseline. Verbal fluency was assessed via one category and one letter fluency task. Separate Cox proportional hazards regressions adjusted for important sociodemographic parameters were performed for each qualitative semantic and phonemic verbal fluency component. Results: There were 955 cognitively normal (CN), older (72.9 years ±4.9), predominantly female (~60%) individuals with available follow-up assessments after a mean of 3.09 years (±0.83). Among them, 34 developed dementia at follow-up (29 of whom progressed to Alzheimer’s dementia (AD)), 160 developed MCI, and 761 remained CN. Each additional perseveration on the semantic condition increased the risk of developing all-cause dementia and AD by 52% and 55%, respectively. Of note, participants with two or more perseverations on the semantic task presented a much more prominent risk for incident dementia compared to those with one or no perseverations. Among the remaining qualitative indices, none were associated with the hazard of developing all-cause dementia, AD, and MCI at follow-up. Conclusions: Perseverations on the semantic fluency condition were related to an increased risk of incident all-cause dementia or AD in older, CN individuals. © 2022 by the authors.

Purpose: The increase in cardiovascular risk after the menopausal transition remains partly explained until today. Further research is needed to identify risk factors potentially modifiable by primary prevention practices. This cross-sectional study, part of a larger prospective project, aims to investigate possible associations between dietary patterns and indices of vascular structure and function among healthy postmenopausal women. Methods: Postmenopausal women (n = 310) without clinically overt cardiovascular disease were recruited consecutively from a University Menopause Clinic over three years. Dietary intake was assessed by a validated food frequency questionnaire and the MedDietScore. In addition, we assessed anthropometric/biochemical parameters, including the Triglyceride-glucose index (TyG-Index), body fat distribution [triceps skinfold (TSF), mid-upper arm circumference (MUAC)] and physical activity. The vascular assessment included carotid-femoral pulse wave velocity (PWV), carotid and femoral-artery intima-media thickness (IMT) and atheromatous plaques presence. Results: Consumption of non-refined cereals was associated with carotid-bulb IMT (R2 = 5.5% b-coefficient = −0.142; p = 0.011), adjusting for age, physical activity, lipids, systolic blood pressure, smoking, body mass index, insulin resistance, and daily energy intake. PWV was associated with the intake of total dairy products (R2 = 27.3%, b-coefficient = −0.117; p = 0.017). Higher red meat consumption was related to a greater TyG-index (Model 1, R2 = 14.3%, b-coefficient=0.121; p = 0.048), an association mediated by total daily energy intake. Higher consumption of alcohol, as well as the MedDietScore, were inversely associated with TSF measurements, significant after Bonferroni correction. Conclusion: Dietary patterns are associated with metabolic indices and subclinical atherosclerosis in postmenopausal women independently of traditional cardiovascular risk factors, total energy intake or ph

The aim of the current study was to investigate whether a Total Lifestyle Index (TLI), including adherence to the Mediterranean diet, sleep duration, physical activity and engagement in activities of daily living, is associated with cognitive health over time and dementia risk, in a representative cohort of older people. A total of 1018 non-demented community-dwelling older adults ≥65 years old (60% women) from the HELIAD study were included. A comprehensive neurological and neuropsychological assessment was conducted at baseline and at the 3-year follow-up evaluating cognitive functioning, and a dementia diagnosis was set. Diet, physical activity, sleep duration and engagement in activities of daily living were assessed using standard, validated questionnaires at baseline. Sixty-one participants developed dementia at follow-up; participants who developed dementia were older and had fewer years of education compared with participants with normal cognition. With the exception of sleep duration, participants with normal cognition at follow-up scored higher in the individual lifestyle factors compared to those who developed dementia. Regarding TLI, values were lower for participants with dementia compared with those with normal cognition. Each additional unit of the TLI was associated with 0.5% of a standard deviation less decline per year of the Global Cognition score, whereas for each additional unit of the TLI, the risk for dementia was reduced by 0.2% per year (p < 0.05). Our results suggest that greater adherence to a healthy lifestyle pattern is associated with a slower decline of cognitive function and reduced dementia risk. © 2022 by the authors.

Cognitive impairment is a rapidly growing public health problem. As there is no curative treatment for dementia, the proactive management of modifiable risk factors and the identification of early biomarkers indicative of the cognitive decline are of great importance. Although nutrition is one of the most extensively studied lifestyle factor in relation to cognitive health, its association with brain magnetic resonance imaging (MRI) biomarkers is not well established. In the present work, we review available studies relating dietary or nutrient patterns with brain MRI biomarkers in dementia-free adults. Greater adherence to the Mediterranean diet has been associated with the preservation of structural connectivity and less brain atrophy in adults without dementia. In addi-tion, specific nutrient patterns, characterized by a high intake of antioxidant vitamins, polyphenols and unsaturated fatty acids, have been related to larger brain volume. Although the results are en-couraging regarding the role of dietary and nutrient patterns on imaging biomarkers, more well-designed observational longitudinal studies and clinical trials are needed in order to confirm po-tentially causal relationships and better understand underlying mechanisms. © 2022 by the authors. Li-censee MDPI, Basel, Switzerland.

Objectives: The present study aimed to explore the descriptive and analytic epidemiology of restless legs syndrome (RLS) in the older Greek population, with a specific focus on lifestyle indicators. Methods: Baseline data from the randomly selected non-demented older participants of the population-based HELIAD cohort were analyzed. Multivariable binary logistic regression with RLS diagnosis as the dichotomous dependent outcome was performed. Demographic, socioeconomic, anthropometric, dietary, sleep-related and psychological parameters, physical activity, use of psychoactive substances and personal medical history were investigated for potential associations. Results: A total of 133 from the eligible sample of 1,838 participants were diagnosed with RLS. The mean age-sex standardized prevalence of RLS among the elderly was estimated at 6.1% (95%CI = 5.0–7.2), with a female (8.0%, 95%CI = 6.4–9.6) to male (3.7%, 95%CI = 2.4–5.1) ratio of 2.1. The prevalence of RLS peaked during the 8th decade of life and diminished thereafter. The positive associations of RLS with female sex [OR = 2.06, 95%CI = (1.19–3.57)], anxiety levels [assessed by the 22-point HADS scale, OR = 1.08, 95%CI = (1.03–1.13)] and traumatic brain injury [OR = 2.22, 95%CI = (1.37–3.62)] were reproduced. Good sleep quality was related to 55% [95%CI~(24–83%)] lower odds of having RLS in comparison with both poor and moderate quality. Adherence to the Mediterranean dietary pattern [assessed by a 55-point scale, OR = 1.06, 95%CI = (1.01–1.11)], and low daily energy intake [low-moderate vs. low: OR = 0.45, 95%CI = (0.26–0.79)]; [moderate-high vs. low: OR = 0.69, 95%CI = (0.40–1.22)]; [high vs. low: OR = 0.31, 95%CI = (0.13–0.69)] were related to RLS for the first time. Conclusions: More emphasis should be placed on the dietary-nutritional aspects of RLS. © 2022 Taylor & Francis Group, LLC.

Both under-and over-nutrition are prevalent in patients with Crohn’s Disease (CD). The aim of the present study was to evaluate dietary intake and compare it with relevant recommendations during active disease and remission, also taking into consideration the adequacy of energy reporting. Dietary quality was assessed through adherence to the Mediterranean diet and to the European dietary guidelines for cardiovascular disease prevention (CVD-score). Malnutrition was diagnosed with the GLIM criteria. There were 237 patients evaluated (54.9% males, 41.3 ± 14.1 years and 37.6% with active disease). In the total sample, high prevalence of overweight/obesity (61.6%) and low prevalence of malnutrition (11.4%) were observed, whereas 25.5% reported low protein intake in the sub-sample of adequate energy reporters. The mean MedDietScore was 28.0 ± 5.5 and the mean CVD-score was 5.25 ± 1.36, both reflecting moderate dietary quality. Patients with active disease reported higher prevalence of low protein intake, lower carbohydrate, fibers, fruits, vegetables, legumes, and sweets consumption and a lower MedDietScore compared to patients in remission. Consumption of fibers, fruits, vegetables, and legumes while in remission did not result in reaching the recommended intakes, and dietary quality was low as reflected by the MedDietScore. In conclusion, both protein undernutrition and energy overconsumption were prevalent in the current sample and overall patients adhered to a moderate quality diet irrespective of disease stage. © 2022 by the authors.

Individual lifestyle targets have been associated with weight loss outcomes, yet few studies have examined associations of one's total lifestyle with weight loss maintenance. We aimed to examine the relationship between lifestyle patterns and weight loss outcomes in weight loss maintainers and regainers. We hypothesized that higher adherence to a broader healthy lifestyle favors maintenance (over regain). This is a cross-sectional analysis of 470 adults (62% women) with a history of overweight/obesity and significant weight loss 12 months before study entry. Participants were classified as maintainers (current weight ≤90% maximum weight) or regainers. They were asked to fill in a series of questionnaires on demographics and lifestyle habits (dietary intake and eating behaviors through two 24-hour recalls, physical activity, and sleep). A total Mediterranean Lifestyle Index (total-MLI, range 0-13) was generated by summing up ratings in the lifestyle domain quartiles (diet quality, physical activity, and sleep habits) and dietary behaviors (seasonal food and vegetable intake, intake of traditional foods, responsibility for food preparation, conviviality). Maintainers scored higher in the total-MLI than regainers (6.93 ± 2.31 vs 5.78 ± 2.49, P < .001). Adherence to the total-MLI was associated with 28% higher odds for weight loss maintenance (per unit increment) in linear analyses. Being in the highest total-MLI quartile was associated with 5.27 (95% CI, 2.77-10.02) odds for maintenance. Higher adherence to a comprehensive Mediterranean lifestyle pattern was associated with higher odds for weight loss maintenance. Our findings suggest that even modest shifts toward a healthier living may contribute to favorable weight loss outcomes. © 2022 Elsevier Inc.

Background and aims: Various bio-psychological mechanisms underlying the association between mental health problems and metabolic syndrome remain unknown. We investigated the role of irrational beliefs in conjunction with anxiety, depression and hostility in the 10-year metabolic syndrome (MetS) incidence, and the effect of biochemical and socio-behavioral factors on the aforementioned associations. Methods and results: ATTICA is a prospective, cohort study (2002–2012). The sample included 591 participants [51.3% men (aged 41.5 ± 10 years) and 48.7% women (aged 37.5 ± 11.5 years)], free of MetS at baseline. Detailed biochemical, clinical, and lifestyle evaluations were performed, while participants’ irrational beliefs, anxiety, depression and hostility were assessed using the Irrational Beliefs Inventory, the Spielberger State-Trait Anxiety Inventory, the Zung Self-Rating Depression Scale and the Hostility and Direction of Hostility Questionnaire, respectively. Multiple logistic regression was applied to estimate the odds ratio (OR) of developing MetS and to control for confounders, as well as stratified logistic regression to detect moderator effects. High irrational beliefs were associated with 1.5-times higher odds of developing MetS than low irrational beliefs. Especially, participants with high irrational beliefs and high anxiety were 96% more likely to develop MetS, compared with those with low irrational beliefs and low or high anxiety (OR = 1.96; 95% CI = 1.01, 3.80). Conclusion: The findings of the study underline the important role of irrational beliefs and anxiety in the development of MetS and the need to build new holistic approaches focused on the primary prevention of both mental health and MetS. © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University

Aims: Proglucagon-derived peptides (PGDPs) secreted by the gut and pancreas play a major role in metabolism. We measured concentrations of five PGDPs in response to per os (PO) or intravenous (IV) glucose or lipid intake and a mixed meal test (MMT) consumed by subjects with normal weight, overweight or obesity. Materials and methods: GLP-1, oxyntomodulin and glicentin (gut-secreted PGDPs) and glucagon and MPGF (pancreas-secreted PGDPs) were assessed in: (a) 32 subjects receiving PO or IV glucose, lipids or water over 6 h, (b) 33 subjects with normal weight, overweight or obesity who consumed a MMT. Results: (a) GLP-1, oxyntomodulin, glicentin and glucagon levels increase more profoundly and persistently after lipids PO (2.5 g/kg) than glucose PO (2.5 g/kg) or IV lipids (Intralipid/Liposyn II 20% at 0.35 ml/kg/h and Intralipid/Liposyn II 20% at 0.83 ml/kg/h for 6 h) or IV glucose (10% glucose at 3.6 ml/kg/h for 6 h). Oxyntomodulin and glicentin increased more than GLP-1 in response to lipids PO. MPGF levels decrease in response to glucose PO or IV indicating a shift towards preferential production of gut-secreted peptides. (b) Fasting and postprandial areas under the curve (AUCs) after MMT of GLP-1, MPGF and glucagon levels correlated positively with BMI. The fasting levels of glucagon and MPGF were elevated in obesity and remained elevated after the MMT. Conclusion: Circulating levels of PGDPs are differentially regulated by body weight, the type of macronutrients administered and the respective route of administration. Mechanistic studies are needed to define the exact mechanisms underlying this regulation. Clinical Trial Registration: Study 1 has the NCT01520454 and the NCT04888325 number in ClinicalTrials.gov. Study 2 has the number NCT01495754 in ClinicalTrials.gov. © 2022 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism

Background: Slow gait speed has recently emerged as a potential prodromal feature of cognitive decline and dementia. Besides objective measurements, subjective motor function (SMF) difficulties might be present prior to the manifestation of gait disorders. Objectives: To examine the association of walking time and the presence of SMF with future cognitive decline in cognitively normal individuals. Design: Longitudinal study. Settings: Athens and Larissa, Greece. Participants: 931 cognitively normal individuals over the age of 64 with longitudinal follow-up from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD). Measurements: We used a simple chronometer for recording objective walking time (OWT) and SMF was assessed using a self-reported physical functioning questionnaire. Generalized estimating equations (GEE) models were deployed to explore the associations between baseline OWT and SMF difficulties and the rate of change of performance scores on individual cognitive domains over time. Models were adjusted for age, years of education and sex. Results: Each additional second of OWT was associated with 1.1% of a standard deviation more decline per year in the composite z-score, 1.6% in the memory z-score, 1.1% in the executive z-score and 1.8% in the attention-speed z-score. The presence of SMF difficulties was not associated with differential rates of decline in any cognitive domain. Conclusion: Gait speed can be indicative of future cognitive decline adding credence to the notion that gait speed might serve as a simple and easily accessible clinical tool to identify a larger pool of at risk individuals and improve the detection of prodromal dementia. © 2022, Serdi.

Background: The aging of global population has increased the scientific interest in the concept of healthy aging and its determinants. Aim: The aim of this study was to investigate the association of sleep characteristics with trajectories of healthy aging. Design and Setting: Prospective observational study conducted in two cities, Maroussi and Larissa. Participants: A total of 1226 older adults (≥65 years, 704 women) were selected through random sampling. Measurements: Sleep quality was assessed with the Sleep Index II, and sleep duration was self-reported. A healthy aging metric was introduced using an Item Response Theory approach based on validated questionnaires that assessed functionality. Four healthy aging trajectories were developed based on whether the healthy aging status of the participants was above (High) or below (Low) the median at baseline and follow-up, i.e., High-High, High-Low, Low-High, and Low-Low. The association of sleep characteristics with the trajectories was investigated using a multinomial logistic regression with the Low-Low group as reference, adjusting for potential confounders. Results: 34.3% participants classified to the High-High group, 15.7% to the High-Low, 18.6% to the Low-High, and 31.4% to the Low-Low group. Better sleep quality was associated with the probability of belonging to the High-High group (p-value<0.001); while, long sleep duration was inversely associated with likelihood of being classified in the High-High group (p-value < 0.05). Conclusion: Poor sleep quality and long sleep duration seem to have a significant negative association with healthy aging. Public health policies are needed to raise awareness about the importance of sleep characteristics on human health. © 2022, Serdi and Springer Nature Switzerland AG.

Background: Previous frailty studies found higher prevalence of frailty in female than in male participants. This was mainly attributed to the fact that compared to men, women show increased longevity. Recent studies have reported that the observed difference between sexes applies irrespectively of the age of older people. Objectives: To provide data on sex differences in incident frailty by applying both phenotypic and multi-domain frailty measures in the same population of Greek community-dwelling older people. Design: Longitudinal study. Setting: Data were drawn from the Hellenic longitudinal Investigation of Aging and Diet (HELIAD), a population-based, multidisciplinary study designed to estimate the prevalence and incidence of dementia in the Greek population. Participants: 1104 participants aged 65 year and above were included in this longitudinal study. This incidence cohort was reevaluated after a mean follow-up period of 3.04±0.90 years. Measurements: Frailty was operationalized using 5 different definitions in the same population the Fried Frailty Phenotype (FFP) definition, the FRAIL Scale, the Frailty Index (FI), the Tilburg Frailty Indicator (TFI) and the Groningen Frailty Index (GFI). Frailty incidence was calculated a) for the whole sample, b) separately for men and women and c) after both age and sex stratification. Results: Age and sex stratification revealed that irrespective of age and frailty measurement, women showed higher incidence rates of frailty than men. Specifically, frailty seems to be a condition concerning women >65 years old, but when it comes to men, it is more frequent in those aged more than 75 years old. Finally, in relation to overall frailty incidence and comparing our results to previous studies, we detected a lower frailty incidence in the Greek population. Conclusions: Differences between the two sexes indicate that when exploring the factors that are related to frailty, studies should provide data disaggregated for men an

Objective: To determine the longitudinal trajectories and normative standards of episodic memory in older adults. Methods: Participants were drawn from the cognitively normal(CN) subgroup of the population-based HELIAD cohort, a fairly representative cohort of the older Greek population. Verbal and non-verbal memory were assessed using the Greek Verbal Learning Test and Medical College of Georgia-Complex Figure Test. Baseline and longitudinal associations of memory performance with age, sex and formal education were explored with linear regression analysis and generalized estimated equations. Results: A total of 1607 predominantly female (60%) individuals (73.82 ± 5.43 years), with a mean educational attainment of 8.17(±4.86) years were CN at baseline. Baseline analysis revealed a continuum of memory decline with aging and lower educational attainment. Women performed better in composite and verbal memory measures, while men performed better in non-verbal memory tasks. A subgroup of 761 participants with available assessments after 3.07(±0.82) years remained CN at follow-up. Composite memory scores yearly diminished by an additional 0.007 of a SD for each additional year of age at baseline. Regarding verbal learning, immediate free verbal recall, delayed free verbal recall and delayed cued verbal recall, an additional yearly decrease of 0.107, 0.043, 0.036 and 0.026 words were respectively recorded at follow-up, for each additional year of age at baseline. Women underwent steeper yearly decreases of 0.227 words in delayed cued verbal recall. No significant longitudinal associations emerged for immediate non-verbal memory, delayed non-verbal memory and immediate cued verbal recall. Conclusions: In the present study, aging (but not educational attainment) was consistently associated with steeper verbal memory decline. © 2022 Informa UK Limited, trading as Taylor & Francis Group.

Background and Objectives: Various bio-psychosocial mechanisms underlying the link between anxiety, depression and cardiovascular disease risk, remain unknown. We investigated the role of irrational beliefs in conjunction with anxiety and depression in the 10-year cardiovascular disease (CVD) incidence, and the effect of biochemical and socio-behavioral factors. Design: 853[453 men (45 ± 13 years) and 400 women (44 ± 18 years)] from the ATTICA study (2002–2012) and without evidence of CVD were assessed. Methods: The Irrational Beliefs Inventory (IBI), the Zung Self-Rating-Depression-Scale (ZDRS) and the State-Trait-Anxiety-Inventory (STAI) were used for the assessments. Incidence of CVD was defined according to the International Coding Diseases (ICD)−10 criteria. Results: Participants with high irrational beliefs and anxiety symptoms had a 138% greater risk of developing CVD during the 10-year follow-up (2.38; 95%CI 1.75, 3.23) as compared to those without anxiety. Among others, C-reactive protein, interleukin-6 and total antioxidant capacity were mediators in the tested association. Interaction of irrational beliefs and depression was not associated with the 10-year CVD in all models. Conclusions: Inflammation and oxidative stress, partially explained the associations between irrational beliefs and anxiety in predicting CVD risk. These findings advance psychological research in the area of primary prevention of mental health and cardiovascular diseases. © 2022 Informa UK Limited, trading as Taylor & Francis Group.

Background and purpose: Vascular risk factors may influence cognitive function and thus represent possible targets for preventive approaches against dementia. Yet it remains unknown, if they associate with cognition independently of the individual genetic risk for dementia. Methods: In a population-based study of 1172 community-dwelling individuals aged ≥65 years in Greece, we constructed a vascular burden score (VBS; based on presence of hypertension, diabetes, hyperlipidemia, heart disease, and cerebrovascular disease, range 0–5) and a polygenic risk score (PRS) for clinically-diagnosed Alzheimer's disease (AD) based on 23 genetic variants. We then explored in joint models the associations of the PRS for AD and VBS with global cognitive performance, cognitive performance across multiple cognitive domains, and odds of dementia. Results: The mean age of study participants was 73.9 ± 5.2 years (57.1% females). Both the PRS for AD and VBS were associated with worse global cognitive performance (beta per-SD-increment in PRS: -0.06, 95%CI: -0.10 to -0.02, beta per-point-increment in VBS: -0.05, 95%CI: -0.09 to -0.02), worse performance across individual cognitive domains (memory, executive function, attention, language, visuospatial ability), and higher odds of dementia (OR per-SD increment in PRS: 1.56, 95%CI: 1.17–2.09, OR per-point increment in VBS: 1.38, 95%CI: 1.05–1.81). There was no evidence of an interaction between the two scores. Higher VBS was associated with worse cognitive performance equally across tertiles of the PRS for AD, even among individuals at the highest tertile. Conclusions: Both genetic risk and vascular burden are independently and additively associated with worse cognitive performance and higher odds of dementia. © 2022

Objectives: To evaluate the association of meat consumption with prevalent depressive symptomatology and cardiovascular disease (CVD) incidence in apparently healthy individuals.Methods: ATTICA study was conducted during 2001-2012 including n = 1514 men and n = 1528 women (aged >18 years old) from the greater Athens area, Greece. At baseline, depressive symptomatology through Zung Self-Rating Depression Scale (range 20-80) and meat consumption (total meat, red, white and processed meat) through validated semi-quantitative food frequency questionnaire were assessed. Follow-up (2011-2012) was achieved in n = 2020 participants (n = 317 cases); n = 845 participants with complete psychological metrics were used for the primary analysis.Results: Ranking from 1st to 3rd total meat consumption (low to high) tertiles, participants assigned in 2nd tertile had the lowest depressive-symptomatology scoring (p<0.001). This trend was retained in multiadjusted logistic regression analysis; participants reporting moderate total and red meat consumption had ∼20% lower likelihood to be depressed (i.e. Zung scale<45) compared with their 1st tertile counterparts (Odds Ratio (OR)total meat 0.82, 95% Confidence Interval (95%CI) (0.60, 0.97) and ORred meat 0.79 95%CI (0.45, 0.96)). Non-linear associations were revealed; 2-3 serving/week total meat and 1-2 servings/week red meat presented the lowest odds of depressive symptomatology (all ps<0.05). These U-shape trends seemed to attenuate the aggravating effect of depressive symptomatology on CVD hard endpoints. All aforementioned associations were more evident in women (all ps for sex-related interaction<0.05).Discussion: The present findings generate the hypothesis that moderate total meat consumption and notably, red meat may be more beneficial to prevent depressed mood and in turn hard CVD endpoints.

Background Frailty is a complex geriatric syndrome arising from a combination of genetic and environmental factors and is associated with adverse health outcomes and mortality. A recent study reported an association between variants of the 9p21-23 locus, associated with a number of age-related disorders, including Alzheimer’s disease (AD), and frailty. Frailty has been associated with increased risk of developing AD and it has been proposed that frailty burden may modify AD clinical presentation. In view of the overlapping genetic architecture between the two disorders, it is noteworthy to conduct studies to uncover risk variants that contribute to both AD and frailty. The purpose of this study is to test the reproducibility of the association of 9p21-23 locus with frailty in a population that is ethnically different from previous work and in the context of multidimensional definitions of frailty that will allow us to examine the potential impact to domains pertaining to AD pathology. Methods We operationalized frailty according two definitions and the corresponding instruments, the Frailty Index (FI) and the Tilburg Frailty Indicator (TFI) and we determined genotypes of eight alleles previously identified as risk increasing for frailty in 1172 community-dwelling older participants (57% females) from the HELIAD study with a mean age of 74 years old. We cross-sectionally investigated the association between risk alleles and frailty, as well as with specific components of each definition using linear regression analyses adjusted for age, sex and years of education. Results Compared to non-carriers, carriers of rs7038172 C risk allele, were associated with a higher FI Score (beta=0.089, p=0.002). Similarly, we found a positive association between the presence of at least one rs7038172 C variant and TFI score (beta=0.053, p=0.04). Moreover, the rs7038172 variant was associated, irrespectively of dementia status, with the memory and psychological domain of FI and TFI, re

Background/objectives: To quantify the changes in 10-year cardiovascular disease (CVD) onset, recurrence, and mortality, in relation to transitioning from low to a higher level of adherence to the Mediterranean diet. Subjects/methods: An individual-level microsimulation was created based on ATTICA (2002–2012, n = 3042 subjects free-of-CVD) and GREECS (2004–2014, n = 2172 patients with acute coronary syndrome (ACS)) studies (in total n = 5214). Eight scenarios regarding the proportion of participants and the size of improvement of the level of adherence to the Mediterranean diet (corresponding to one to ten point increases in MedDietScore) were compared in terms of relative change in CVD incidence and mortality, as well as, the number of preventable CVD events and deaths. Results: Improving adherence to the Mediterranean diet in at least 10% of the population, a significant relative percentage reduction could be observed in 10-year CVD onset, recurrence, and mortality. At least 851 first CVD events, 374 recurrent CVD events, and 205 CVD deaths per 100,000 of the population could be averted or delayed. In addition, Mediterranean diet clustering revealed that scoring higher in fruits, vegetables, whole wheat products, and legumes was more important than achieving higher scores in low consumption of meat and full-fat dairy products against CVD (all HRs in the former cluster were lower than the latter, indicating a stronger protective effect). Conclusions: This microsimulation process confirms the added value of the Mediterranean diet in primary and secondary CVD prevention having great achievements even with modifications in a small part of the population (10%), while challenges the orientation of Mediterranean-diet interventions giving higher weights to plant-based part. © 2021, The Author(s), under exclusive licence to Springer Nature Limited.

Background: The aim of the present study was to investigate the association of adherence to the Mediterranean diet with trajectories of healthy aging. Methods: The dataset of the Hellenic Longitudinal Investigation of Aging and Diet was the basis for the present longitudinal analysis. In a sample of 1226 older (> 65 years) adults (704 women), adherence to the Mediterranean diet was assessed through the calculation of the MedDietScore. A healthy aging metric was introduced using an item response theory (IRT) approach based on information from validated questionnaires assessing functionality and cognition. Four trajectories of healthy aging were created based on whether the healthy aging status of participants was above or below the median at baseline and follow-up: High-High, High-Low, Low-High and Low-Low. The association of adherence to the Mediterranean diet with the trajectories was investigated using a multinomial logistic regression with the Low-Low group set as reference, while adjusting for potential confounders. Results: 34.3% of participants belonged to the High-High group, 15.7% to the High-Low, 18.6% to the Low-High and 31.4% to the Low-Low group. Greater adherence to the Mediterranean diet was significantly associated with the probability of having one of the healthier trajectories (i.e., Low-High or High-High). Substitution analysis revealed that substituting energy intake from proteins and lipids with carbohydrates was associated with a lower probability of having one of the favorable trajectories. Conclusion: Greater adherence to the Mediterranean diet was associated with more favorable trajectories of aging and policies to raise awareness about its significance should be implemented. © 2022

Background Frailty is a complex geriatric syndrome arising from a combination of genetic and environmental factors and is associated with adverse health outcomes and mortality. A recent study reported an association between variants of the 9p21-23 locus, associated with a number of age-related disorders, including Alzheimer's disease (AD), and frailty. Frailty has been associated with increased risk of developing AD and it has been proposed that frailty burden may modify AD clinical presentation. In view of the overlapping genetic architecture between the two disorders, it is noteworthy to conduct studies to uncover risk variants that contribute to both AD and frailty. The purpose of this study is to test the reproducibility of the association of 9p21-23 locus with frailty in a population that is ethnically different from previous work and in the context of multidimensional definitions of frailty that will allow us to examine the potential impact to domains pertaining to AD pathology. Methods We operationalized frailty according two definitions and the corresponding instruments, the Frailty Index (FI) and the Tilburg Frailty Indicator (TFI) and we determined genotypes of eight alleles previously identified as risk increasing for frailty in 1172 community-dwelling older participants (57% females) from the HELIAD study with a mean age of 74 years old. We cross-sectionally investigated the association between risk alleles and frailty, as well as with specific components of each definition using linear regression analyses adjusted for age, sex and years of education. Results Compared to non-carriers, carriers of rs7038172 C risk allele, were associated with a higher FI Score (beta=0.089, p=0.002). Similarly, we found a positive association between the presence of at least one rs7038172 C variant and TFI score (beta=0.053, p=0.04). Moreover, the rs7038172 variant was associated, irrespectively of dementia status, with the memory and psychological domain of FI and TFI, re

Several studies have investigated the association of the Parkinson’s disease (PD) polygenic risk score (PRS) with several aspects of well-established PD. We sought to evaluate the association of PRS with the prodromal stage of PD. We calculated PRS in a longitudinal sample (n = 1120) of community dwelling individuals ≥ 65 years from the HELIAD (The Hellenic Longitudinal Investigation of Aging and Diet) study in order to evaluate the association of this score with the probability of prodromal PD or any of the established risk and prodromal markers in MDS research criteria, using regression multi-adjusted models. Increases in PRS estimated from GWAS summary statistics’ ninety top SNPS with p < 5 × 10–8 was associated with increased odds of having probable/possible prodromal PD (i.e., ≥ 30% probability, OR = 1.033, 95%CI: 1.009–1.057 p = 0.006). From the prodromal PD risk markers, significant association was found between PRS and global cognitive deficit exclusively (p = 0.003). To our knowledge, our study is the first population based study investigating the association between PRS scores and prodromal markers of Parkinson’s disease. Our results suggest a strong relationship between the accumulation of many common genetic variants, as measured by PRS, and cognitive deficits. Copyright © 2021 Maraki, Hatzimanolis, Mourtzi, Stefanis, Yannakoulia, Kosmidis, Dardiotis, Hadjigeorgiou, Sakka, Ramirez, Grenier-Boley, Lambert, Heilmann-Heimbach, Stamelou, Scarmeas and Xiromerisiou.