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Estrogen exposure during menstrual years has been associated with late-life neuroprotection. We explored the presence of an age-sensitive menarche window for cognition in old age and the impact of socioeconomic status and education. We compared neuropsychological performance of 1082 older women [Mean AGE = 72.69 (5.48)] with menarche in childhood, early-, mid-, and late-adolescence and dementia prevalence, severity, and type, including the effects of education and socioeconomic status. Adjusting for covariates, menarche at 11-14 years of age was associated with better memory, executive and global cognitive functioning in old age, and stronger positive effects of education and socioeconomic status on cognition than those with menarche at 15-17 years. We found a critical age window for the neuroprotective effects of estrogens during early adolescence, putting women with later menarche at higher risk for cognitive decline. Effects of socioeconomic status and education in adulthood should be a focus of future research.

Importance: Depressive symptoms are associated with cognitive decline in older individuals. Uncertainty about underlying mechanisms hampers diagnostic and therapeutic efforts. This large-scale study aimed to elucidate the association between depressive symptoms and amyloid pathology., Objective: To examine the association between depressive symptoms and amyloid pathology and its dependency on age, sex, education, and APOE genotype in older individuals without dementia., Design, Setting, and Participants: Cross-sectional analyses were performed using data from the Amyloid Biomarker Study data pooling initiative. Data from 49 research, population-based, and memory clinic studies were pooled and harmonized. The Amyloid Biomarker Study has been collecting data since 2012 and data collection is ongoing. At the time of analysis, 95 centers were included in the Amyloid Biomarker Study. The study included 9746 individuals with normal cognition (NC) and 3023 participants with mild cognitive impairment (MCI) aged between 34 and 100 years for whom data on amyloid biomarkers, presence of depressive symptoms, and age were available. Data were analyzed from December 2022 to February 2024., Main Outcomes and Measures: Amyloid-β1-42 levels in cerebrospinal fluid or amyloid positron emission tomography scans were used to determine presence or absence of amyloid pathology. Presence of depressive symptoms was determined on the basis of validated depression rating scale scores, evidence of a current clinical diagnosis of depression, or self-reported depressive symptoms., Results: In individuals with NC (mean [SD] age, 68.6 [8.9] years; 5664 [58.2%] female; 3002 [34.0%] APOE ε4 carriers; 937 [9.6%] had depressive symptoms; 2648 [27.2%] had amyloid pathology), the presence of depressive symptoms was not associated with amyloid pathology (odds ratio [OR], 1.13; 95% CI, 0.90-1.40; P = .29). In individuals with MCI (mean [SD] age, 70.2 [8.7] years; 1481 [49.0%] female; 1046 [44.8%] APOE ε4 carriers; 824 [27.3%] had depressive symptoms; 1668 [55.8%] had amyloid pathology), the presence of depressive symptoms was associated with a lower likelihood of amyloid pathology (OR, 0.73; 95% CI 0.61-0.89; P = .001). When considering subgroup effects, in individuals with NC, the presence of depressive symptoms was associated with a higher frequency of amyloid pathology in APOE ε4 noncarriers (mean difference, 5.0%; 95% CI 1.0-9.0; P = .02) but not in APOE ε4 carriers. This was not the case in individuals with MCI., Conclusions and Relevance: Depressive symptoms were not consistently associated with a higher frequency of amyloid pathology in participants with NC and were associated with a lower likelihood of amyloid pathology in participants with MCI. These findings were not influenced by age, sex, or education level. Mechanisms other than amyloid accumulation may commonly underlie depressive symptoms in late life.

Depressive symptoms are common in mild cognitive impairment (MCI), dementia caused by Alzheimer's disease (AD dementia) and in cognitively unimpaired older adults. However, it is unclear whether they could contribute to the identification of cognitive impairment in ageing. To assess the potential utility of depressive symptoms to distinguish between healthy cognitive ageing and MCI and AD dementia. The diagnostic workup of the cognitive function of 1737 older cognitively unimpaired individuals, 334 people with MCI and 142 individuals with AD dementia relied on a comprehensive neuropsychiatric assessment, including the Mini Mental State Examination (MMSE). Depressive symptoms were tapped with the 15-item Geriatric Depression Scale (GDS). Proportional odds logistic regression (POLR) models and the machine learning technique Adaptive Boosting algorithm (AdaBoost) were employed. Stratified repeated random subsampling (stratified bootstrap resampling) was used to recursive partitioning to training- and validation set (70/30 ratio). The average accuracy of the POLR models for the GDS total score in distinguishing between cognitive impairment and healthy cognitive ageing exceeded 78% and was inferior to that of MMSE. Of note, the sensitivity of GDS total score was very low. By employing the AdaBoost algorithm and considering GDS items separately, the average accuracy was higher than 0.72 and comparable to that of the MMSE, while sensitivity- and specificity values were more balanced. The findings of the study provide initial evidence that depressive symptoms may contribute to distinguishing between cognitive impairment and cognitively healthy ageing., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Despite the well-known benefits of the Mediterranean diet (MD), low adherence is observed globally, highlighting the need to investigate the underlying causes of this trend. Large-scale, periodically repeated surveys, such as the European Health Interview Survey (EHIS), could be useful for the investigation of the factors that influence adherence to healthy dietary patterns. National EHIS-3 in Greece was designed to collect data on the consumption of all food groups, making it possible to determine adherence to MD., Methodology: This study aimed to investigate the socioeconomic factors that influence MD adherence by conducting a secondary data analysis from 7706 participants aged 15-85 years who participated in the 2019 national EHIS. MD adherence was evaluated by MedDietScore. Bivariate comparisons between the score tertiles and socioeconomic groups were performed. Logistic regression analyses were used to estimate the association between MedDietScore tertiles and demographic and socioeconomic factors, using high adherence as the reference category. Finally, cluster analysis was applied to identify the most significant factors in relation to the classification of the participants in MD adherence groups., Results: Educational level, followed by income status, emerged as the most significant factor associated with adherence to MD. Individuals who have attained only primary education had a 3.80 times higher likelihood of presenting low MD adherence instead of high MD adherence compared to persons with tertiary education. Individuals in the lower income group had 2.53 times higher odds of being in the low MD adherence instead of high MD adherence than individuals in the higher income group. These relationships remained statistically significant after adjusting for confounding factors. The group that most frequently adhered to high MD (53.4%) comprised individuals who had tertiary education, higher income, and were couples without children. Conversely, those with primary or secondary education who are single parents or live in one-person households and fall into the lower and medium income groups are most likely to have low MD adherence (44.8%)., Conclusions: Public policies to promote MD adherence should consider socioeconomic factors. Integrating questions to evaluate adherence to dietary patterns into EHIS would allow for future intercountry and longitudinal comparisons., (© 2025 The Author(s). Journal of Human Nutrition and Dietetics published by John Wiley & Sons Ltd on behalf of British Dietetic Association.)

In the present study, we investigated the association of genetic predisposition with specific dimensions of dementia pathophysiology for global and domain-specific cognitive decline in older adults. The sample was drawn from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) study, comprising 512 cognitively normal individuals over 64 years of age, with a mean follow-up of 2.9 years. Cognitive function was evaluated through a neuropsychological test battery, while genetic predisposition was assessed based on two distinct Polygenic Risk Scores (PRS) for amyloid-beta 42 (Aβ 42 ) and white matter hyperintensities (WMH). The association of each PRS with the cognitive decline rate was examined using generalized estimating equation models. In the whole sample, higher PRSs Aβ 42 (β = -0.042) and WMH (β =-0.029) were associated with a higher rate of global cognitive decline per year, an association which remained significant in age, sex, and education subgroups. Moreover, higher PRSs Aβ 42 and WMH were related to significant memory decline only in females, older, and highly educated participants. Thus, while the association of both PRSs with global cognitive decline over time was independent of age, sex, or education, the relationship of the specific PRSs with the memory decline rate appeared to vary depending on these factors.

Objective: Sleep disturbance is considered a risk factor for cognitive decline in elderly individuals. Our aim in the current study was to investigate whether baseline sleep parameters can predict the conversion from normal cognition to mild cognitive impairment or dementia at follow-up. The Hellenic Longitudinal Investigation of Aging and Diet is a longitudinal population-based study designed to estimate the prevalence and incidence of cognitive decline and dementia in the older Greek population., Methods: A total of 955 cognitively normal older adults (aged ≥65 y) were drawn from the Hellenic Longitudinal Investigation of Aging and Diet study. A comprehensive neurological and neuropsychological assessment was conducted at baseline and a mean of 3.1 (SD = 0.85) years later, resulting in 160 individuals diagnosed with mild cognitive impairment and 34 with dementia at follow-up, whereas 761 remained cognitively normal., Results: Using Cox regression analyses, no sleep parameters increased the risk of conversion status adjusting for demographics and clinical factors. Napping, however, decreased this risk by 19.3% (P < 0.001)., Conclusions: As several previous studies have proposed, napping constitutes a protective factor against cognitive decline. Thus, clinicians should encourage their elderly patients to adopt this healthy habit., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Background: There is a paucity of evidence on the association between genetic propensity for hippocampal atrophy with cognitive outcomes. Therefore, we examined the relationship of the polygenic risk score for hippocampal atrophy (PRShp) with the incidence of amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) as well as the rates of cognitive decline., Methods: Participants were drawn from the population-based HELIAD cohort. Comprehensive neuropsychological assessments were performed at baseline and at follow-up. PRShp was derived from the summary statistics of a large genome-wide association study for hippocampal volume. Cox proportional hazards models as well as generalized estimating equations (GEEs) were used to evaluate the association of PRShp with the combined incidence of aMCI/AD and cognitive changes over time, respectively. All models were adjusted for age, sex, education, and apolipoprotein E (APOE) genotype., Results: Our analysis included 618 older adults, among whom 73 developed aMCI/AD after an average follow-up of 2.96 ± 0.8 years. Each additional SD of PRShp elevated the relative hazard for incident aMCI/AD by 46%. Participants at the top quartile of PRShp had an almost three times higher risk of converting to aMCI/AD compared to the lowest quartile group. Higher PRShp scores were also linked to steeper global cognitive and memory decline. The impact of PRShp was greater among women and younger adults., Conclusions: Our findings support the association of PRShp with aMCI/AD incidence and with global cognitive and memory decline over time. The PRS association was sex- and age-dependent, suggesting that these factors should be considered in genetic modelling for AD.

Importance: Aging is accompanied by immune dysregulation, which has been implicated in Alzheimer's disease (AD) pathogenesis. Individuals who are genetically predisposed to elevated levels of proinflammatory mediators might be at increased risk for AD., Objective: To investigate whether genetic propensity for higher circulating levels of interleukin 6 (IL-6) is associated with AD risk., Design: We analyzed data from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD). Mean follow-up was 2.9 (SD, 0.8) years. Baseline assessment was from 11/2009 to 11/2016, and cognitive follow-up from 01/2013 to 07/2019. Associations of interest were also examined in the UK Biobank (UKB) for replication purposes (mean follow-up was 12.9 (SD, 2.4) years; baseline assessment was from 12/2006 to 10/2010)., Setting: Population-based study., Participants: The HELIAD sample included 622 participants ≥65 years of age without baseline dementia or amnestic mild cognitive impairment (aMCI-the prodromal stage of AD). The UKB sample included 142,637 participants ≥60 years of age without prevalent dementia., Exposures: Genetic predisposition to elevated circulating levels of IL-6 was estimated using a polygenic risk score (PRS), calculated based on the summary statistics of a current GWAS meta-analysis., Main Outcomes and Measures: AD and MCI diagnoses were based on standard clinical criteria [HELIAD], or hospital records and death registry data [UKB]. Associations with AD or aMCI incidence [HELIAD] and AD incidence [UKB] were examined with Cox regression models., Results: In HELIAD, mean age was 73.4 (SD, 5.0) years; 363 (58%) women. An increase in IL-6 PRS by 1 standard deviation unit (SDU) was associated with up to a 43% increase in the risk for incident AD/aMCI (HR GWAS significance threshold of 0.01, 1.43 [95%CI, 1.14 - 1.80]). In UKBB, mean age was 64.2 (SD, 2.8) years; 73,707 (52%) women. A 1 SDU increase in IL-6 PRS was associated with up to an 8% increase in the risk for incident AD (HR GWAS significance threshold of 0.2 , 1.08 [95%CI, 1.04 - 1.12])., Conclusions and Relevance: Genetic predisposition to higher circulating levels of IL-6 was associated with an increased risk for AD, supporting the role of IL-6-related pathways in AD pathogenesis, and suggesting that genetic predisposition to proinflammatory states might trigger or accelerate AD-related neuropathology., Competing Interests: Conflict of interest statement Dr. Scarmeas reports personal fees from Merck Consumer Health, Eisai, and personal fees from NIH unrelated to this manuscript. Dr. Seshadri reports consulting for Eisai and Biogen unrelated to this manuscript. On behalf of all authors, the corresponding author states that there is no conflict of interest., (Copyright © 2024. Published by Elsevier Masson SAS.)

Diet is a modifiable lifestyle factor with a proven role in cardiovascular disease risk reduction that might also play an important part in cognitive health. Evidence from observational studies has linked certain healthy dietary patterns to cognitive benefits. However, clinical trials of diet interventions have demonstrated either null or, at best, small effects on cognitive outcomes. In this Review, we summarize the currently available evidence from observational epidemiology and clinical trials regarding the potential role of diet in the prevention of cognitive decline and dementia. We further discuss possible methodological limitations that might have hindered the ability of previous diet intervention trials to capture potential neuroprotective effects. Considering the overwhelming and continuously expanding societal, economic and health-care burden of Alzheimer disease and other dementias, future nutritional research must address past methodological challenges to accurately and reliably inform clinical practice guidelines and public health policies. Within this scope, we provide a roadmap for future diet intervention trials for dementia prevention. We discuss study designs involving both intensive personalized interventions - to evaluate pharmacokinetic and pharmacodynamic properties, establish neuroprotective thresholds, and test hypothesized biological mechanisms and effects on brain health and cognition through sensitive and precise biomarker measures - and large-scale, pragmatic public health interventions to study population-level benefits., Competing Interests: Competing interests: N.S. has received grants from European Union Horizon Projects, the Hellenic Foundation for Research & Innovation, and Novo Nordisk during the conduct of the study, all outside the submitted work. S.C. and M.Y. declare no competing interests., (© 2024. Springer Nature Limited.)

Objective: Our study aimed to explore whether physical condition might affect the association between genetic predisposition for Alzheimer's Disease (AD) and AD incidence. Methods: The sample of participants consisted of 561 community-dwelling adults over 64 years old, without baseline dementia (508 cognitively normal and 53 with mild cognitive impairment), deriving from the HELIAD, an ongoing longitudinal study with follow-up evaluations every 3 years. Physical condition was assessed at baseline through walking time (WT), while a Polygenic Risk Score for late onset AD (PRS-AD) was used to estimate genetic predisposition. The association between WT and PRS-AD with AD incidence was evaluated with Cox proportional hazard models adjusted for age, sex, education years, global cognition score and APOE ε-4 genotype. Then, the association between WT and AD incidence was investigated after stratifying participants by low and high PRS-AD. Finally, we examined the association between PRS-AD and AD incidence after stratifying participants by WT. Results: Both WT and PRS-AD were connected with increased AD incidence ( p  < 0.05), after adjustments. In stratified analyses, in the slow WT group participants with a greater genetic risk had a 2.5-fold higher risk of developing AD compared to participants with lower genetic risk ( p  = 0.047). No association was observed in the fast WT group or when participants were stratified based on PRS-AD. Conclusions: Genetic predisposition for AD is more closely related to AD incidence in the group of older adults with slow WT. Hence, physical condition might be a modifier in the relationship of genetic predisposition with AD incidence.

Background & Aims: The ingestion of macronutrients triggers the release of several incretin peptides from the gastrointestinal system, which have both insulinotropic and satiety-inducing properties. The effect of the meal's macronutrient content on the secretion of these peptides has not been adequately studied, particularly concerning the secretion of the newly characterized proglucagon-derived peptides (PGDPs). We aimed to examine the effect of a meal's macronutrient content, specifically its protein versus carbohydrate content, on postprandial PGDPs responses in healthy men., Methods: Ten apparently healthy, normal-weight males completed a trial consisting of two interventions in a randomized, double-blind, crossover design. In one intervention, participants consumed an isocaloric high-protein breakfast (65 g of glucose, 60 g of protein), while in the other, participants consumed a carbohydrate-rich breakfast (125 g of glucose). Levels of all seven PGDPs, namely glucagon-like peptide-1 and -2 (GLP-1 and GLP-2), oxyntomodulin, glicentin, major pro-glucagon fragment (MPGF), glucagon and proglucagon, as well as glucose-dependent insulinotropic polypeptide/gastric inhibitory polypeptide total and total plus (GIP total and GIP total plus) levels were measured at baseline, every 15 minutes for the first hour and every 30 minutes for the second and third hours after each meal., Results: The two interventions produced similar glycemic and insulinemic responses, while total amino acids increased more over time in response to protein administration. Levels of proglucagon (F(8) = 4.114, p = 0.001) and the primarily pancreas-secreted glucagon and MPGF (F(8) = 3.088, p = 0.005) rose significantly during the protein intervention. GIP total and GIP total plus increased in response to carbohydrate ingestion. No major overall differences were observed for the primarily intestinally secreted GLP-1, oxyntomodulin and glicentin between the two arms of the trial, although their levels tended to increase earlier in response to carbohydrates and later in response to protein administration, especially in the case of GLP-2 levels., Conclusions: The carbohydrate vs. protein content of a meal differentially increases the levels of GIP and PGDPs during the postprandial period. Dose-response studies and comparisons with lipid intake may further advance our knowledge of the physiology of these clinically important molecules and their implications in energy homeostasis., Competing Interests: Conflict of interest I.S., A.V., M.Y. and C.A.A. have no conflicts of interest to disclose. CSM reports grants through his institution from Merck, Abbott, Esperion, Massachusetts Life Sciences Center and Boehringer Ingelheim, he reports personal consulting fees and support through his institution from Ansh Inc., collaborative research support from LabCorp Inc., reports personal consulting fees from Ansh Inc., Nestle, Olympus, Genfit, Laekna, Guidepoint, Lumos, Novo Nordisk, Amgen, Corcept, Intercept, 89 Bio, Madrigal, Aligos, Esperion, Biodexa and Regeneron, reports shares with Coherus and AltrixBio, educational activity meals through his institution or national conferences from Esperion, Merck, Boehringer Ingelheim and travel support and fees from UptoDate, TMIOA, Elsevier, and the Cardio Metabolic Health Conference. None is related to this manuscript., (Published by Elsevier Ltd.)

Introduction: Adjustable lifestyle factors, such as diet, are associated with cognitive functions, structural and functional brain measures, but the association between the functional connectivity (FC) and the Mediterranean Diet (Medicine) in population without dementia is yet to be explored., Methods: The association between MeDi and brain FC in 105 individuals without dementia aged 63 (SD ± 8.72) years old who underwent brain MRI including resting-state (rs) functional MRI (fMRI) was examined. Dietary intake was evaluated through four 24-h recalls using the multiple-pass method and adherence to the MeDi was estimated using the MedDietScore, with higher values indicating greater adherence to MeDi. Multivariable linear regression models were used to investigate the associations between FC (both positive and negative associations) and MedDietScore., Results: Rs-fMRI analysis revealed significant associations between FC and MedDietScore. The FC between the medial prefrontal cortex and a cluster located in left postcentral gyrus and in the left supramarginal gyrus was positively associated with MedDietScore. On the other hand, the FC between medial visual and right posterior division of both middle and superior temporal gyrus was negatively associated with MedDietScore. Of note, a temporal negative correlation was detected between above-mentioned FC networks. The FC between superior temporal gyrus and occipital regions was associated with participants' attention, executive functions, and memory scores. Furthermore, the associations for attention and executive functions were pronounced in participants with high adherence to MeDi compared to those with low adherence to MeDi., Discussion: In conclusion, our study documented an association between higher adherence to MeDi and rs-FC in fronto-parietal and temporo-occipital regions, particularly in areas that are involved in cognitive processes altered across normal and pathological aging. From a clinical point of view, our findings support a favorable role of MeDi on FC which may have significant clinical implications in the rapidly aging population. Rs-fMRI is also proposed as a useful tool in the emerging field of nutritional neuroscience and a candidate non-invasive biomarker of brain aging., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Karavasilis, Balomenos, Christidi, Velonakis, Angelopoulou, Yannakoulia, Mamalaki, Drouka, Brikou, Tsapanou, Gu and Scarmeas.)

Background: Adoption of allergen avoidance diets may increase the risk of nutritional deficiencies and affect growth in children with food allergy (FA). How these dietary restrictions have an impact on diet diversity, a health-promoting eating behavior, remains unclear., Objective: To evaluate diet diversity, dietary intake, and weight status of children with FA., Design: Observational study., Participants/setting: One hundred children with immunoglobulin E (IgE)-mediated milk, egg, or nut FA or multiple FAs and 60 children with perennial respiratory allergies (RA) matched as controls, aged 3 to 18 years, were consecutively recruited into the study., Main Outcome Measures: Dietary intake and diet diversity (number of different foods consumed/day) were assessed through 4 24-hour recalls. Weight status (underweight, healthy weight, overweight, or obesity) was also evaluated., Statistical Analyses Performed: Chi-squared test and 2-sample independent t test were used to test differences between groups. Adjustment for sex, age, and energy intake was made using linear regression., Results: The percentage of underweight was higher in children with FA (19.6%) compared with children in the control group (5.1%). Children with FA compared with children in the control group consumed more servings of meat (1.7, 95% CI, 1.6, 1.9 vs. 1.5, 95% CI, 1.3, 1.7 servings/day [Padj = 0.031]). No difference was observed in the diet diversity between the 2 groups (11-12 different foods/day). Within the FA group, children with allergy to milk proteins had lower energy intake from protein, lower intake of calcium, lower consumption of commercially prepared sweets, and higher consumption of eggs, compared with children with nut or egg allergy, but no difference in diet diversity was observed., Conclusions: Diet diversity did not differ between children with FA and children with no FA, despite some differences in the intake from specific food groups. However, the higher percentage of underweight in children with FA suggests the need for targeted nutrition intervention as early as possible after FA diagnosis., (Copyright © 2024 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Fermented dairy products have recently gained popularity due to their purported health benefits, nevertheless, their role in ageing remains uncertain. This narrative review aims to evaluate evidence from observational (prospective) and interventional studies on the potential benefits of fermented dairy product consumption for musculoskeletal and mental health in older adults. Additionally, it seeks to determine whether any observed benefits surpass those of non-fermented dairy products and to identify directions for future research. Prospective studies support either favourable or neutral associations of fermented dairy products with outcomes of musculoskeletal health or neutral associations with mental health outcomes, whilst it remains unclear if the benefits observed with fermented dairy products go beyond those of the non-fermented dairy foods. Few interventional studies suggest overall favourable effects of yogurt and cheese on musculoskeletal health in older adults but given their small number (N = 6) and heterogeneity, they do not allow a clear assessment or definitive recommendations for fermented dairy intake. Interventional studies reporting mental health outcomes are largely lacking for this age group (N = 1). Given the very limited evidence for the effectiveness of fermented dairy products, future well-designed prospective and randomized controlled trials are needed to better understand their benefits (especially compared to those of non-fermented dairy foods), their characteristics and the quantities required to offer protection against musculoskeletal and/or mental health ageing., (© 2024. The Author(s).)

The prevalence of food insecurity in Cyprus and the socio-demographic factors that are related to this public health problem are unknown. Data used in this cross-sectional study were collected between 1 June 2022 and 21 May 2023 using a self-reported method. Food insecurity was evaluated using the Greek version of Adult Food Security Survey Module. The data regarding socio-demographic and socio-economic characteristics along with body weight and height measurements were collected through self-administered questionnaire. A representative sample of n=1255 adults, ≥18 years old living in the five different districts of the Republic of Cyprus, was recruited. Prevalence of food insecurity in Cypriot population was 12.6%. Prevalence was higher in females, in older adults, in adults living in Paphos, in individuals who were separated, divorced, or widowed, in retired people, in people living with children, and in people with low income and education. Based on multivariable analysis, income was the strongest socio-demographic factor independently associated with food security (€ 6,500-€ 19,500: AOR: 0.49, 95% CI 0.28, 0.86 and >€ 19,500: AOR: 0.15, 95% CI 0.73, 0.31). Food insecurity is a global problem that need further examination. The association between food insecurity and socio-demographic characteristics needs to be highlighted in order for each country to develop specific public health policies (e.g. financial support to low income people) to decrease food insecurity and improve people's overall health and quality of life., Competing Interests: None., (© The Author(s) 2024.)

Background and Objectives: Previous randomized controlled trials and longitudinal studies have indicated that ongoing antihypertensive use in late life reduces all-cause dementia risk, but the specific impact on Alzheimer dementia (AD) and non-AD risk remains unclear. This study investigates whether previous hypertension or antihypertensive use modifies AD or non-AD risk in late life and the ideal blood pressure (BP) for risk reduction in a diverse consortium of cohort studies., Methods: This individual participant data meta-analysis included community-based longitudinal studies of aging from a preexisting consortium. The main outcomes were risk of developing AD and non-AD. The main exposures were hypertension history/antihypertensive use and baseline systolic BP/diastolic BP. Mixed-effects Cox proportional hazards models were used to assess risk and natural splines were applied to model the relationship between BP and the dementia outcomes. The main model controlled for age, age 2 , sex, education, ethnoracial group, and study cohort. Supplementary analyses included a fully adjusted model, an analysis restricting to those with >5 years of follow-up and models that examined the moderating effect of age, sex, and ethnoracial group., Results: There were 31,250 participants from 14 nations in the analysis (41% male) with a mean baseline age of 72 (SD 7.5, range 60-110) years. Participants with untreated hypertension had a 36% (hazard ratio [HR] 1.36, 95% CI 1.01-1.83, p = 0.0406) and 42% (HR 1.42, 95% CI 1.08-1.87, p = 0.0135) increased risk of AD compared with "healthy controls" and those with treated hypertension, respectively. Compared with "healthy controls" both those with treated (HR 1.29, 95% CI 1.03-1.60, p = 0.0267) and untreated hypertension (HR 1.69, 95% CI 1.19-2.40, p = 0.0032) had greater non-AD risk, but there was no difference between the treated and untreated groups. Baseline diastolic BP had a significant U-shaped relationship ( p = 0.0227) with non-AD risk in an analysis restricted to those with 5-year follow-up, but otherwise there was no significant relationship between baseline BP and either AD or non-AD risk., Discussion: Antihypertensive use was associated with decreased AD but not non-AD risk throughout late life. This suggests that treating hypertension throughout late life continues to be crucial in AD risk mitigation. A single measure of BP was not associated with AD risk, but DBP may have a U-shaped relationship with non-AD risk over longer periods in late life.

Childhood overweight/obesity (OV/OB) is a major public health problem in Western countries, often accompanied with comorbidities (e.g., hypertension and insulin resistance) (i.e., metabolically unhealthy obesity-MUO). Among diet-related risk factors of OV/OB risk and MUO, meal patterns remain limitedly studied. The aim of this systematic review was to explore associations between meal patterns and the risk of childhood OV/OB and MUO in children/adolescents aged 2-19 years. Longitudinal studies and randomised controlled trials from PUBMED and Scopus published between January 2013 and April 2024 were retrieved. Twenty-eight studies were included, all of which reported on OV/OB risk, with none on MUO risk. Regular consumption of breakfast ( n = 3) and family meals ( n = 4) and avoiding dining while watching TV ( n = 4) may be protective factors against childhood OV/OB, whereas meal skipping (primarily breakfast; n = 4) may be a detrimental factor. Mixed effects of meal frequency on OV/OB risk were observed; no effects of frequency of lunch or of fast-food consumption and of meals served at school were found. There was insufficient evidence to support the role of other patterns (meal timing, eating in other social contexts). Meals were mainly participant-identified, leading to increased heterogeneity. Research focusing on childhood MUO and the use of harmonised definitions regarding the assessment of meal patterns are highly warranted.

Background: Sleep patterns often shift as people age, a phenomenon frequently associated with the onset of neurodegenerative conditions. Additionally, distinct alterations occur in brain structure as individuals grow older, particularly within the hippocampus, a region known for its role in cognition and sleep regulation. Yet, how exactly do changes in sleep relate to specific subfields within the hippocampus is still unclear., Methods: We conducted a study involving non-demented healthy adults from the Aiginition Longitudinal Biomarker Investigation Of Neurodegeneration (ALBION) cohort. Participants underwent objective sleep measurements using wrist Actiwatch and WatchPAT devices. Further, all participants underwent the same Magnetic Resonance Imaging (MRI) protocol, including a 3D high resolution T1-weighted sequence, on the same 3.0 Tesla MRI scanner using an eight-channel head coil. The study aimed to examine the relationship between objectively measured sleep metrics and the morphology of twenty-two distinct hippocampal subregions., Results: In total, 75 non-demented participants with 63 mean years of age were included in the study. Results indicated that a higher frequency of awakenings during sleep was associated with increased volume in the right presubiculum body (beta = 0.630, p False Discovery Rate (FDR) <0.036). Longer sleep duration showed a tendency to be associated with smaller volumes of the right presubiculum body, hinting at a possible negative impact of prolonged sleep on this brain region. Similar trends were observed regarding sleep apnea and the presubiculum body volume. Further analysis based on age stratification revealed that in younger participants, longer sleep duration was linked to decreased volume of the presubiculum body, while a greater number of awakenings was correlated with increased volume of the same region. Among older participants, higher frequencies of awakenings were associated with larger volumes in various hippocampal subfields., Conclusions: These findings shed light on the complex relationship between sleep characteristics and brain structure, highlighting potential age-related differences. The study provides valuable insights into how sleep disruptions may impact hippocampal morphology and cognitive function of cognitively healthy adults. Further research is warranted to elucidate the underlying mechanisms and implications for neurodegenerative diseases., Competing Interests: The authors declare no conflict of interest. Foteini Christidi and Efstratios Karavasilis are serving as the Guest editors of this journal. We declare that Foteini Christidi and Efstratios Karavasilis had no involvement in the peer review of this article and have no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Igor Timofeev., (© 2024 The Author(s). Published by IMR Press.)

(1) Background: Many studies link food intake with clinical cognitive outcomes, but evidence for brain biomarkers, such as memory-related limbic white matter (WM) tracts, is limited. We examined the association between food groups, limbic WM tracts integrity, and memory performance in community-dwelling individuals. (2) Methods: We included 117 non-demented individuals (ALBION study). Verbal and visual episodic memory tests were administered, and a composite z-score was calculated. Diffusion tensor imaging tractography was applied for limbic WM tracts (fornix-FX, cingulum bundle-CB, uncinate fasciculus-UF, hippocampal perforant pathway zone-hPPZ). Food intake was evaluated through four 24-h recalls. We applied linear regression models adjusted for demographics and energy intake. (3) Results: We found significant associations between (a) higher low-to-moderate alcohol intake and higher FX fractional anisotropy (FA), (b) higher full-fat dairy intake and lower hPPZ FA, and (c) higher red meat and cold cuts intake and lower hPPZ FA. None of the food groups was associated with memory performance. (4) Conclusions: Despite non-significant associations between food groups and memory, possibly due to participants' cognitive profile and/or compensatory mechanisms, the study documented a possible beneficial role of low-to-moderate alcohol and a harmful role of full-fat dairy and red meat and cold cuts on limbic WM tracts.

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], I 2  = 4 %). No association was found between vegetable intake and incident depression (HR 0.93, 95%CI [0.84, 1.04], I 2  = 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., Competing Interests: Declaration of competing interest Henry Brodaty is or has been an advisory board member or consultant to Biogen, Eisai, Eli Lilly, Roche and Skin2Neuron. He is a Medical/Clinical Advisory Board member for Montefiore Homes and Cranbrook Care., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: This study aimed to examine the relationship between family history of diabetes, irrational beliefs, and health anxiety in the development of type 2 diabetes mellitus (T2DM)., Method: ATTICA is a prospective, cohort study (2002-2012). The working sample included 845 participants (18-89 years), free of diabetes at baseline. Α detailed biochemical, clinical, and lifestyle evaluation was performed, while participants' irrational beliefs and health anxiety were assessed through the Irrational Beliefs Inventory and the Whiteley index scale, respectively. We evaluated the association between the participants' family history of diabetes mellitus with the 10-year risk of diabetes mellitus, both in the total study's sample and separately according to their levels of health anxiety and irrational beliefs., Results: The crude 10-year risk of T2DM was 12.9% (95%CI: 10.4, 15.4), with 191 cases of T2DM. Family history of diabetes was associated with 2.5 times higher odds (2.53, 95%CI 1.71, 3.75) of T2DM compared to those without family history. Among participants with family history of diabetes, the highest likelihood of developing T2DM, regarding their tested psychological features (i.e., low/high irrational beliefs in the entire group, low/high health anxiety in the entire group, and low/high irrational beliefs, low/high healthy anxiety), had people with high irrational beliefs, low health anxiety (OR 3.70, 95%CI 1.83, 7.48)., Conclusions: The findings underline the important moderating role of irrational beliefs and health anxiety in the prevention of T2DM, among participants at increased risk of T2DM., (© 2023. The Author(s).)

Background: The potential association between temporal dimensions of eating and cognition/cognitive declines has been poorly investigated so far., Objectives: The aim of this study was to examine relationships among eating frequency, timing and time window, and cognitive performance and novel Alzheimer disease (AD) biomarkers in cognitively healthy and mildly cognitively impaired middle-aged and older adults., Methods: Cross-sectional data were derived from the Aiginition Longitudinal Biomarker Investigation of Neurodegeneration (ALBION) cohort study, including people aged 40 y or older who have a positive family history of cognitive disorder or cognition-related concerns. Cognitive performance was assessed by a battery of neuropsychological tests. Amyloid β (Αβ42), a biomarker of AD-related pathology, was measured in cerebrospinal fluid. Eating frequency, timing, and the eating time window between the first and the last meal were estimated using time-related information recorded in four 24-h recalls., Results: Study participants had, on average, 5.3 ± 1.2 eating episodes per day, consumed at 8:20 ± 1.3 and 21:14 ± 1.3 h their first and their last eating episode, respectively, while their eating time window was 12.9 ± 1.6 h. Eating frequency, but not eating time window, was positively associated with global cognition, executive and language performance even after controlling for age, sex, education, BMI, and Mediterranean diet. Increasing eating frequency by 1 eating episode per day was associated with 0.169 higher global z-score. Furthermore, compared with ≤4, having 5-6 or >6 eating episodes per day was associated with better global and memory z-scores. Time of last eating episode was also positively associated with language performance. No associations were detected among eating frequency, timing and window, and AD pathology., Conclusions: An eating pattern characterized by less frequent eating and/or by earlier times is present in individuals with worse cognitive performance. Our results shed light on the relevance of temporal eating patterns as potential early markers of behavioral or metabolic changes related to AD pathology., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Objective: Normative data for older adults may be tainted by inadvertent inclusion of undiagnosed individuals at the very early stage of a neurodegenerative process. To avoid this pitfall, we developed norms for a cohort of older adults without MCI/dementia at 3-year follow-up., Methods: A randomly selected sample of 1041 community-dwelling individuals (age ≥ 65) received a full neurological and neuropsychological examination on two occasions [mean interval = 3.1 (SD = 0.9) years]., Results: Of these, 492 participants (Group 1; 65-87 years old) were without dementia on both evaluations (CDR=0 and MMSE ≥ 26); their baseline data were used for norms development. Group 2 ( n = 202) met the aforementioned criteria only at baseline, but not at follow-up. Multiple linear regressions included demographic predictors for regression-based normative formulae and raw test scores as dependent variables for each test variable separately. Standardized scaled scores and stratified discrete norms were also calculated. Group 2 performed worse than Group 1 on most tests ( p -values < .001-.021). Education was associated with all test scores, age with most, and sex effects were consistent with the literature., Conclusions: We provide a model for developing sound normative data for widely used neuropsychological tests among older adults, untainted by potential early, undiagnosed cognitive impairment, reporting regression-based, scaled, and discrete norms for use in clinical settings to identify cognitive decline in older adults. Additionally, our co-norming of a variety of tests may enable intra-individual comparisons for diagnostic purposes. The present work addresses the challenge of developing robust normative data for neuropsychological tests in older adults.

Background & Aims: Low-grade systemic inflammation (LGSI) is critical to developing many chronic diseases. In turn, it has been shown that the diet can modulate favorably or unfavorably the inflammatory status. Thus, evaluating the diet from appropriate approaches is fundamental; to do so, there are different proposals for dietary indexes. We aimed to: (i) investigate the association between three well-known dietary indexes and LGSI biomarkers; (ii) test these associations individually or in combination with an indicator of ultra-processed foods (UFPs) intake. (iii) as an additional aim, hypothesizing that all the indexes should be capable of identifying the inflammatory potential of diet, we tested the hypothesis that these indexes agree and correlate with each other., Methods: Cross-sectional population-based data of adults and older persons (n = 583). Dietary data were obtained through two non-consecutive 24-h dietary recalls (24HDR) and calculated for Dietary Inflammatory Index (DII), Mediterranean-Style Dietary Pattern Score (MSDPS); Brazilian Healthy Eating Index - Revised (BHEI-R) and energy ingested from UPFs (UPFs ratio). An LGSI score was created from some plasma inflammatory biomarkers [C-Reactive Protein (CRP), tumor necrosis factor-alpha (TNF-α), and adiponectin]. Logistic and linear regression models tested the associations between dietary indexes and LGSI score., Results: The MSDPS and DII were significantly associated with our inflammatory score, but the BHEI-R did not. Including UPFs in regression models did not increase the strength of these associations., Conclusions: From the three scores, the dietary inflammatory index and the Mediterranean-style dietary pattern score (MSDPS) were the ones that showed significant association with the inflammatory biomarker. The combination of the indexes with a ratio of UPF intake did not increase the significance of our analyses. The best agreement between the indexes was found between MSDPS and UPFs ratio; the only pair of indexes considered concordant and correlated was the BHEI-R and DII., Competing Interests: Conflict of interest The authors report the non-existence of any conflict of interest., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Introduction: The LIfestyle for BRAin Health (LIBRA) index yields a dementia risk score based on modifiable lifestyle factors and is validated in Western samples. We investigated whether the association between LIBRA scores and incident dementia is moderated by geographical location or sociodemographic characteristics., Methods: We combined data from 21 prospective cohorts across six continents (N = 31,680) and conducted cohort-specific Cox proportional hazard regression analyses in a two-step individual participant data meta-analysis., Results: A one-standard-deviation increase in LIBRA score was associated with a 21% higher risk for dementia. The association was stronger for Asian cohorts compared to European cohorts, and for individuals aged ≤75 years (vs older), though only within the first 5 years of follow-up. No interactions with sex, education, or socioeconomic position were observed., Discussion: Modifiable risk and protective factors appear relevant for dementia risk reduction across diverse geographical and sociodemographic groups., Highlights: A two-step individual participant data meta-analysis was conducted. This was done at a global scale using data from 21 ethno-regionally diverse cohorts. The association between a modifiable dementia risk score and dementia was examined. The association was modified by geographical region and age at baseline. Yet, modifiable dementia risk and protective factors appear relevant in all investigated groups and regions., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

The possible relationship between Subjective Cognitive Decline (SCD) and dementia needs further investigation. In the present study, we explored the association between specific biomarkers of Alzheimer's Disease (AD), amyloid-beta 42 (Aβ 42 ) and Tau with the odds of SCD using data from two ongoing studies. In total, 849 cognitively normal (CN) individuals were included in our analyses. Among the participants, 107 had available results regarding cerebrospinal fluid (CSF) Aβ 42 and Tau, while 742 had available genetic data to construct polygenic risk scores (PRSs) reflecting their genetic predisposition for CSF Aβ 42 and plasma total Tau levels. The associations between AD biomarkers and SCD were tested using logistic regression models adjusted for possible confounders such as age, sex, education, depression, and baseline cognitive test scores. Abnormal values of CSF Aβ 42 were related to 2.5-fold higher odds of SCD, while higher polygenic loading for Aβ 42 was associated with 1.6-fold higher odds of SCD. CSF Tau, as well as polygenic loading for total Tau, were not associated with SCD. Thus, only cerebral amyloidosis appears to be related to SCD status, either in the form of polygenic risk or actual CSF measurements. The temporal sequence of amyloidosis being followed by tauopathy may partially explain our findings.

The Mediterranean dietary pattern (MPD) has shown promise in preventing low-grade systemic inflammation (LGSI). This study tested if a high adherence to the MDP by younger and older Brazilian adults is associated with lower LGSI and investigated which Mediterranean food components may contribute to these associations. We performed a secondary study on 2015 ISA-Nutrition (290 younger adults (20-59 years old) and 293 older adults (≥60 years old)), a cross-sectional population-based study in São Paulo, SP, Brazil. The adherence to the MDP was assessed using the Mediterranean Diet Score (MedDietScore), obtained from two non-consecutive 24 h dietary recalls (24HDRs). The LGSI score (from plasma CRP, TNF-α, and adiponectin) identified the inflammatory status. Linear regression models assessed the association between LGSI and the MedDietScore. In older adults only, a high adherence to the MDP signified an 11.5% lower LGSI score. Older adults, classified with high adherence to the MDP, differed by consuming lower meat intake and full-fat dairy. Between older adults, the intake of vegetables and olive oil was inversely associated with the levels of LGSI. Thus, among older adults, the intake of some specific Mediterranean food determined high adherence to the MDP and was associated with decreased LGSI.

Background : Restless legs syndrome/Willis-Ekbom disease (RLS/WED) has occasionally but not consistently been associated with cognitive and most notably language and executive impairment. The present study was conducted to investigate the cognitive trajectories of older individuals with RLS/WED. Methods : Participants were drawn from the randomly selected, older (>64 years), population-based HELIAD cohort. Individuals without dementia and with available neuropsychological evaluations at baseline and follow-up were considered for potential eligibility. A comprehensive assessment examining five principal components of cognition (memory, visuo-spatial ability, attention, executive function, and language) was administered to the participants. Generalized estimating equation analyses were used to examine the unadjusted and adjusted (for critical factors and covariates) effects of RLS/WED on cognition over time. Results : A total of 1003 predominantly female (59.5%), older (72.9 ± 4.9 years) participants with follow-up evaluations after a mean of 3.09 ± 0.85 years and without dementia at baseline and follow-up were included in the present study. Among them, 81 were diagnosed with RLS/WED at baseline. Global cognition, memory, attention, and executive and visuo-perceptual skills did not differ between those with and without RLS/WED. However, the RLS/WED group performed worse on language at baseline by a standard deviation of 0.249, while demonstrating a mitigated language decline over time, by a standard deviation of 0.063. The unadjusted models yielded similar results. Conclusions : Our findings were indicative of a baseline language disadvantage among older individuals with RLS/WED, but the initial discrepancy tends to dissolve over time.

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.

Objectives: To study (i) the prevalence of mild and moderate-to-severe depressive symptoms in the entire spectrum of cognitive ageing in Greece and (ii) the relationship between these symptoms and demographic and clinical data., Methods: The study was based on the randomly selected cohort of the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD). Depressive symptoms were assessed with the 15-item version of the Geriatric Depression Scale. Participants also received a comprehensive neuropsychological assessment, while the clinical diagnoses of dementia and mild cognitive impairment were established according to international diagnostic criteria. Statistical analyses relied on comparison tests and a logistic (proportional odds) ordinal regression model., Results: Depressive symptoms were detected in 19.5% of the 1936 study participants, while 11.3% of both people with MCI and dementia had moderate-to-severe depressive symptoms. The regression model revealed that older adults with more severe depressive symptoms were more likely female, cognitively impaired, less educated, were treated with psychotropic medication and lived in Attica versus Thessaly., Conclusions: Since depressive symptoms were detected in almost one in five older adults, healthcare professionals in Greece should safeguard the timely detection and effective treatment of such symptoms and the post-diagnostic care of older adults with depression.

This study aimed to evaluate the association between irrational beliefs and the 10-year cardiovascular disease (CVD) incidence among apparently healthy adults. The ATTICA study is a population-based, prospective cohort (2002-2012) consisting of 853 participants without evidence of CVD (453 men and 400 women) who underwent psychological evaluations. Participants completed the Irrational Beliefs Inventory (IBI, range 0-88), a self-reported measure consistent with the Ellis model of psychological disturbance. We conducted a factor analysis to develop irrational beliefs factors to evaluate the association between subcategories of irrational beliefs and CVD incidence. Demographic characteristics, detailed medical history, other psychological factors, and dietary and other lifestyle habits were also evaluated. The incidence of CVD was defined according to the International Coding Diseases (ICD)-10 criteria. The identified dominant irrational beliefs factor, "cognitive vulnerability to anxiety," consisted of demandingness, perfectionism, emotional irresponsibility, anxious overconcern, dependence on others, and overconcern for the welfare of others, was strongly associated with an increased 10-year CVD risk. Nested multi-adjusted regression analysis revealed that anxiety, as well as negative physical well-being, mediated this relationship, and subset of irrational beliefs predicted CVD risk directly and indirectly through anxiety and negative physical well-being. These findings further map the path through which irrational beliefs can contribute to CVDs and provide insights in favor of preventive healthcare., (© 2023 The Authors. Applied Psychology: Health and Well-Being published by John Wiley & Sons Ltd on behalf of International Association of Applied Psychology.)

The present study investigated the association of genetic predisposition for white matter hyperintensities (WMHs) with incident amnestic mild cognitive impairment (aMCI) or Alzheimer's disease (AD), as well as whether such an association was influenced by age, sex, and cognitive reserve. Overall, 537 individuals without aMCI or dementia at baseline were included. Among them, 62 individuals developed aMCI/AD at follow up. Genetic propensity to WMH was estimated using a polygenic risk score for WMHs (PRS WMH). The association of PRS WMH with aMCI/AD incidence was examined using COX models. A higher PRS WMH was associated with a 47.2% higher aMCI/AD incidence ( p = 0.015) in the fully adjusted model. Subgroup analyses showed significant results in the older age group, in which individuals with a higher genetic predisposition for WMHs had a 3.4-fold higher risk for developing aMCI/AD at follow up ( p < 0.001), as well as in the lower cognitive reserve (CR, proxied by education years) group, in which individuals with a higher genetic predisposition for WMHs had an over 2-fold higher risk ( p = 0.013). Genetic predisposition for WMHs was associated with aMCI/AD incidence, particularly in the group of participants with a low CR. Thus, CR might be a modifier in the relationship between genetic predisposition for WMHs and incident aMCI/AD.

Background: The aim of the present study was to investigate the association of prodromal PD (pPD) with trajectories of healthy aging, according to its latest definition by the WHO. Methods: In a sample of 1,226 older adults (704 women), PD diagnosis was reached through standard clinical research procedures. Probability of pPD was calculated according to the International Parkinson and Movement Disorder Society's research criteria for PD-free participants. A healthy aging metric was introduced using an item response theory approach (IRT) based on information from validated questionnaires assessing functionality. 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. Results: 34.3% 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. Participants with possible/probable pPD were 78% less likely to belong in High-High trajectory of healthy aging as compared to those without pPD (OR = 0.22, 95%CI 0.06-0.79, p -value = 0,02). Conclusion: Our findings suggest an inverse association of pPD probability with healthy aging among older adults; Further research is needed to investigate the clinical implications of this association.

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.

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 having a confidante was associated with reduced risk of dementia and mortality., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background and Objectives: The present study explored the utilization of verbal fluency (VF) cognitive strategies, including clustering, switching, intrusions, and perseverations, within both semantic (SVF) and phonemic (PVF) conditions, across a continuum of neurocognitive decline, spanning from normal cognitive ageing (NC) to mild cognitive impairment (MCI) and its subtypes, amnestic (aMCI) and non-amnestic (naMCI), as well as AD. Materials and Methods: The study sample was derived from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) cohort. The sample included 1607 NC individuals, 146 with aMCI (46 single-domain and 100 multi-domain), 92 with naMCI (41 single-domain and 51 multi-domain), and 79 with AD. Statistical analyses, adjusting for sex, age, and education, employed multivariate general linear models to probe differences among these groups. Results: Results showed that AD patients exhibited poorer performance in switching in both VF tasks and SVF clustering compared to NC. Similarly, the aMCI group performed worse than the NC in switching and clustering in both tasks, with aMCI performing similarly to AD, except for SVF switching. In contrast, the naMCI subgroup performed similarly to those with NC across most strategies, surpassing AD patients. Notably, the aMCI subgroup's poor performance in SVF switching was mainly due to the subpar performance of the multi-domain aMCI subgroup. This subgroup was outperformed in switching in both VF tasks by the single-domain naMCI, who also performed better than the multi-domain naMCI in SVF switching. No significant differences emerged in terms of perseverations and intrusions. Conclusions: Overall, these findings suggest a continuum of declining switching ability in the SVF task, with NC surpassing both aMCI and AD, and aMCI outperforming those with AD. The challenges in SVF switching suggest executive function impairment associated with multi-domain MCI, particularly driven by the multi-domain aMCI.

The objective of this narrative review was to summarize existing literature on the effectiveness of school-based interventions, implemented in Europe, under the aim of promoting healthy lifestyle behaviors in children (6-10 years old). A search of PubMed, Scopus, EFSA and Google Scholar databases was performed for studies published from January 2016 to June 2022. Specific search terms and exclusion criteria were used. Based on the results, diet and physical activity interventions had favorable effects on a series of health outcomes, including anthropometric parameters, biomarkers, eating behavior and self-efficacy. Diet-only interventions had a positive impact specifically on eating habits, mostly on water consumption. Most successful interventions lasted for 1 school year, and they were characterized by parental involvement and teachers' training.

Objective: Nutritional status and growth is well associated with disease outcomes and lung function in patients with cystic fibrosis (CF). Current dietary guidelines for the management of CF suggest a high-calorie, high-fat diet. Pancreatic insufficiency (PI) is present in most patients and contributes to malabsorption and malnutrition, but a considerable number of patients have pancreatic sufficiency (PS). The aim of this study was to compare weight status, clinical characteristics, and dietary intake of children with CF, with PS or PI., Methods: Patients with a diagnosis of CF (sweat test ≥60 mmol/L) and/or two known mutations for CF, ages 1 to 19 y were included in the study. Weight status, pulmonary characteristics, and blood lipid concentrations were evaluated. Dietary intake was evaluated through four 24-h recalls and energy, macronutrient intake, and intake in terms of food groups were assessed., Results: Included in the present analyses were 134 patients with CF (30 with PS and 104 with PI). The percentage of overweight/obesity (47%) was higher in children with PS than in those with PI (22%). Overall, children with PS had higher body mass index, blood lipid levels, and pulmonary function levels than those with PI (all P < 0.05). Total energy intake was lower in children with PS than in those with PI (P < 0.001), even after adjustment for age and sex (P adj < 0.001)., Conclusions: Weight status, dietary intake, pulmonary function, and lipid profile differed significantly in children with CF by pancreatic status. Nevertheless, the percentage of overweight and obesity was higher in children with PS than in those with PI. To avoid obesity, dietary recommendations for a high-calorie, high-fat diet should be reconsidered in patients with CF regarding their pancreatic status., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Cognitive and physical decline, both indicators of aging, seem to be associated with each other. The aim of the present study was to investigate whether physical function parameters (walking time and handgrip strength) are related to cerebrospinal fluid (CSF) biomarkers (amyloid-beta Aβ 42 , Tau, PhTau) in individuals in the Alzheimer's disease (AD) continuum. The sample was drawn from the Aiginition Longitudinal Biomarker Investigation of Neurodegeneration study, comprising 163 individuals aged 40-75 years: 112 cognitively normal (CN) and 51 with mild cognitive impairment (MCI). Physical function parameters were measured at baseline, a lumbar puncture was performed the same day and CSF biomarkers were analyzed using automated methods. The association between walking time, handgrip strength and CSF biomarkers was evaluated by linear correlation, followed by multivariate linear regression models adjusted for age, sex, education and APOEe4 genotype. Walking time was inversely related to CSF Aβ 42 (lower CSF values correspond to increased brain deposition) in all participants ( p < 0.05). Subgroup analysis showed that this association was stronger in individuals with MCI and participants older than 60 years old, a result which remained statistically significant after adjustment for the aforementioned confounding factors. These findings may open new perspectives regarding the role of mobility in the AD continuum.

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 with 34 519 community dwelling older adults (20 160 [58.4%] female) with a mean (SD) age of 72.5 (7.5) years and a mean (SD) follow-up of 4.3 (4.3) years. In the main, partially adjusted analysis including 14 studies, individuals with untreated hypertension had a 42% increased risk of dementia compared with healthy controls (hazard ratio [HR], 1.42; 95% CI 1.15-1.76; P = .001) and 26% increased risk compared with individuals with treated hypertension (HR, 1.26; 95% CI, 1.03-1.53; P = .02). Individuals with treated hypertension had no significant increased dementia risk compared with healthy controls (HR, 1.13; 95% CI, 0.99-1.28; P = .07). The association of antihypertensive use or hypertension status with dementia did not vary with baseline BP. There was no significant association of baseline SBP or DBP with dementia risk in any of the analyses. There were no significant interactions with age, sex, or racial group for any of the analyses., Conclusions and Relevance: This individual patient data meta-analysis of longitudinal cohort studies found that antihypertensive use was associated with decreased dementia risk compared with individuals with untreated hypertension through all ages in late life. Individuals with treated hypertension had no increased risk of dementia compared with healthy controls.

Introduction: We constructed a polygenic risk score (PRS) for β-amyloid (PRSAβ42) to proxy AD pathology and investigated its association with incident Alzheimer's disease (AD)/amnestic mild cognitive impairment (aMCI) and the influence of cognitive reserve (CR), proxied by educational years, on the relationship between PRSAβ42 and AD/aMCI risk., Methods: A total of 618 cognitive-normal participants were followed-up for 2.92 years. The association of PRSAβ42 and CR with AD/aMCI incidence was examined with COX models. Then we examined the additive interaction between PRSAβ42 and CR and the CR effect across participants with different PRSAβ42 levels., Results: Higher PRSAβ42 and CR were associated with a 33.9% higher risk and 8.3% less risk for AD/aMCI, respectively. An additive interaction between PRSAβ42 and CR was observed. High CR was associated with 62.6% less risk of AD/aMCI incidence only in the high-PRSAβ42 group., Discussion: A super-additive effect of PRSAβ42 and CR on AD/aMCI risk was observed. CR influence was evident in participants with high PRSAβ42., (© 2023 the Alzheimer's Association.)

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: Diet is a critical component of healthy lifestyle, especially in cardiac rehabilitation. Psychological interventions, as well as mix-treatment interventions, such as psychological components, appear promising approaches in the adoption and maintenance of a healthy diet in patients with cardiovascular disease (CVD). Given the variety of clinical intervention programmes available, we aimed to determine whether psychological interventions and interventions that incorporate psychological components provide better lifestyle outcomes than traditional care, specifically targeting dietary outcomes, and what types of psychological or mix-treatment interventions are more likely to benefit patients with CVD., Methods: A systematic literature search was performed using MEDLINE (PubMed), Scopus, Cochrane Library and PsycINFO to identify interventional studies, published from 2012 to 2022, written in English, evaluating psychological and mix-treatment intervention programmes for dietary outcomes in patients with CVD. In total, 33 intervention studies (n = 5644 patients) were retrieved and analysed using fixed and random effects models., Results: No significant effect of the psychological intervention was observed regarding fruit and vegetable intake (Hedge's g = +1.06, p = 0.766), whereas a significant reduction was observed in alcoholic beverage consumption in the intervention group, as compared to the control group (Hedge's g = -7.33, p < 0.001). However, based on both our qualitative and quantitative analyses, psychological and mix-treatment interventions were more effective than traditional models in dietary modification. Also, the majority of effective interventions were psychological over mixed-treatment interventions., Conclusions: Findings add to the growing evidence suggesting that specific psychological interventions may be effective approaches in dietary modification for patients with CVD, potentially forming part of public health agenda., (© 2023 The Authors. Journal of Human Nutrition and Dietetics published by John Wiley & Sons Ltd on behalf of British Dietetic Association.)

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.)

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 8 th 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.

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.