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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.

To determine the longitudinal trajectories and normative standards of language in older adults.Participants were drawn from the cognitively normal (CN) subgroup of the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) cohort, a fairly representative cohort of the older Greek population. Language was assessed via semantic (SVF) and phonemic verbal fluency (PVF), Boston Naming Test-short form (BNT-sf), verbal comprehension and repetition, and a composite language z-score. Both baseline and longitudinal associations of language performance with age, sex, and education were explored with linear regression and generalized estimated equations.A total of 1,607 individuals (73.82 years ± 5.43, 60% women), with a mean educational attainment of 8.17 years (± 4.86) were CN at baseline. Baseline analysis revealed a continuum of language decline with higher age and lower educational attainment. Women performed better in composite and SVF tasks. A subgroup of 761 participants with available assessments after 3.07 years remained CN at follow-up. Each additional year of education mitigated composite language decline by .004 of a SD per year. Education additionally mitigated yearly reductions in SVF (by .049) and repetition (by .018) totals. Intriguingly, educational attainment was inversely related to the rate of PVF decline over time (β = -.063). Women exhibited a more precipitous course of decline in SVF totals (.355 per year). Age was not related to differential rates of language decline in any measure. No significant longitudinal associations emerged for comprehension and BNT-sf.Lower educational attainment (but not aging) was associated with steeper language decline, mainly driven by SVF and verbal repetition. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Background: It is unclear whether the main antihypertensive medication classes (diuretics, calcium channel blockers, beta-blockers, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers (ARBs)) are associated with different risks of cognitive decline. Published evidence is conflicting and stems mainly from observational studies. Objective: To investigate the differential effects of antihypertensives on the risks of developing dementia and cognitive decline, with a specific focus on the vascular component of the mechanisms underlying these interactions. Methods: Older adults with a history of hypertension and without dementia were drawn from the population-based HELIAD cohort. Age-, gender-, education-, and antihypertensive medication- (five dichotomous exposures) adjusted Cox proportional-hazards models and generalized estimating equations were performed to appraise the associations of baseline antihypertensive therapy with dementia incidence and cognitive decline (quantified using a comprehensive neuropsychological battery). Analyses were subsequently adjusted for clinical vascular risk (dyslipidemia, diabetes mellitus, smoking, cardiovascular, and cerebrovascular history) and genetic susceptibility to stroke (using polygenic risk scores generated according to the MEGASTROKE consortium GWAS findings). Results: A total of 776 predominantly female participants (73.61±4.94 years) with hypertension and a mean follow-up of 3.02±0.82 years were analyzed. Baseline treatment was not associated with the risk of incident dementia. ARB users experienced a slower yearly global cognitive [2.5% of a SD, 95% CI = (0.1, 4.9)] and language [4.4% of a SD, 95% CI = (1.4, 7.4)] decline compared to non-users. The fully adjusted model reproduced similar associations for both global cognitive [β= 0.027, 95% CI = (–0.003, 0.057)], and language decline [β= 0.063, 95% CI = (0.023, 0.104)]. Conclusion: ARBs may be superior to other antihypertensive agents in the preservation of cognition, an association probably mediated by vascular-independent mechanisms.

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.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.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 8More emphasis should be placed on the dietary-nutritional aspects of RLS.

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.

Backgroundnumerous studies point towards a critical role of Interleukin 6 (IL-6) pathway in frailty pathogenesis yet the causal relationship between the two remains elusive.Methodswe 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.Resultsgenetic 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.Conclusionour 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.

Very few data are available regarding the association of adherence to the Mediterranean Diet (MeDi) with Subjective Cognitive Decline (SCD) evolution over time. A cohort of 939 cognitively normal individuals reporting self-experienced, persistent cognitive decline not attributed to neurological, psychiatric or medical disorders from the Hellenic Epidemiological Longitudinal Investigation of Aging and Diet (HELIAD study) was followed-up for a mean period of 3·10 years. We defined our SCD score as the number of reported SCD domains (memory, language, visuoperceptual and executive), ranging from 0 to 4. Dietary intake at baseline was assessed through a food frequency questionnaire; adherence to the MeDi pattern was evaluated through the Mediterranean Diet Score (MDS) that ranged from 0 to 55, with higher values indicating greater adherence to the MeDi. The mean SCD score in our cohort increased by 0·20 cognitive domains during follow-up. After adjustment for multiple potential confounders, we showed that an MDS higher by 10 points was associated with a 7% reduction in the progression of SCD within one year. In terms of food groups, every additional vegetable serving consumption per day was associated with a 2·2% reduction in SCD progression per year. Our results provide support to the notion that MeDi may have a protective role against the whole continuum of cognitive decline, starting at the first subjective complaints. This finding may strengthen the role of the MeDi as a population-wide, cost-effective preventive strategy targeting the modifiable risk factors for cognitive decline.

Background and ObjectivesAging is characterized by a functional shift of the immune system toward a proinflammatory phenotype. This derangement has been associated with cognitive decline and has been implicated in the pathogenesis of dementia. Diet can modulate systemic inflammation; thus, it may be a valuable tool to counteract the associated risk for cognitive impairment and dementia. The present study aimed to explore the associations between the inflammatory potential of diet, assessed with an easily applicable, population-based, biomarker-validated diet inflammatory index (DII), and the risk for dementia in community-dwelling older adults.MethodsIndividuals from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) were included in the present cohort study. Participants were recruited through random population sampling and were followed up for a mean of 3.05 (standard deviation 0.85) years. Dementia diagnosis was based on standard clinical criteria. Those with baseline dementia or missing cognitive follow-up data were excluded from the analyses. The inflammatory potential of diet was assessed through a DII score that considers literature-derived associations of 45 food parameters with levels of proinflammatory and anti-inflammatory cytokines in the blood; higher values indicated a more proinflammatory diet. Consumption frequencies were derived from a detailed food frequency questionnaire and were standardized to representative dietary intake normative data from 11 different countries. Analysis of dementia incidence as a function of baseline DII scores was performed by Cox proportional hazards models.ResultsAnalyses included 1,059 individuals (mean age 73.1 years, 40.3% male, mean education 8.2 years), 62 of whom developed incident dementia. Each additional unit of DII score was associated with a 21% increase in the risk for dementia incidence (hazard ratio 1.21 [95% confidence interval 1.03–1.42]; p = 0.023). Compared to participants in the lowest DII score tertile, participants in the highest one (maximal proinflammatory diet potential) were 3 (95% confidence interval 1.2–7.3; p = 0.014) times more likely to develop incident dementia. The test for trend was also significant, indicating a potential dose-response relationship (p = 0.014).DiscussionIn the present study, higher DII scores (indicating greater proinflammatory diet potential) were associated with an increased risk for incident dementia. These findings might avail the development of primary dementia preventive strategies through tailored and precise dietary interventions.

BACKGROUND A decrease in glutathione (GSH) levels is considered one of the earliest biochemical changes in Parkinson's disease (PD). OBJECTIVE The authors explored the potential role of plasma GSH as a risk/susceptibility biomarker for prodromal PD (pPD) by examining its longitudinal associations with pPD probability trajectories. METHODS A total of 405 community-dwelling participants (median age [interquartile range] = 73.2 [7.41] years) without clinical features of parkinsonism were followed for a mean (standard deviation) of 3.0 (0.9) years. RESULTS A 1 μmol/L increase in plasma GSH was associated with 0.4% (95% confidence interval [CI], 0.1%-0.7%; P = 0.017) less increase in pPD probability for 1 year of follow-up. Compared with participants in the lowest GSH tertile, participants in the highest GSH tertile had a 12.9% (95% CI, 22.4%-2.2%; P = 0.020) slower rate of increase of pPD probability for 1 year of follow-up. CONCLUSION Plasma GSH was associated with pPD probability trajectories; therefore, it might assist in the identification of individuals who are likely to reach the threshold for pPD diagnosis more rapidly. © 2021 International Parkinson and Movement Disorder Society.

During the Covid-19 pandemic in Greece, quality and quantity of support for people with dementia and their family carers varies widely and depends on the availability of resourses in different areas. The pandemic forced an urgent transition from face-to-face to telehealth services. The Greek Dementia Helpline 1102 was launched on February 2021, as a telephone service staffed by psychologists, neurologists and social workers with expertise in dementia care and is provided by Athens Alzheimer Association. The aim of the helpline is to offer counseling about dementia, to support and guide family carers and link them with community support services and programs. Between February 2021 and October 2021, more than 8000 people have called Helpline 1102 and more than 2500 people have contacted the line via email or live webchat (68% women and 32% men). The beneficiaries of the helpline were family carers (75%), health professionals (15%) and lay people requesting information on dementia prevention, care and treatment. Especially, carers were interested in availability of dementia services in different areas of Greece, disability allowances, legal issues, and how to choose residential homes or paid caregivers. After using the Dementia Helpline, carers have reported increased sensitivity to the challenges faced by their loved ones with dementia, and more able to make the needed adjustments to their care-giving task. Dementia Helpline 1102 provides dementia carers with a reliable a framework through the implementation of appropriate counseling by trustworthy healthcare professionals. Athens Alzheimer Association offers this service free of charge.

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.

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.

Given the increase in the aging population and thus in the prevalence of dementia, the identification of protective factors against cognitive decline is necessary. In a cohort of 1076 non-demented adults ≥ 65 years old (59.7% women) from the HELIAD study, we assessed whether changes in body mass index (BMI) were associated with changes in cognition over a 3-year follow-up period separately for those ≤ 75 and >75 years old. We identified six BMI trajectory groups based on participants’ BMI status at baseline and at the first follow-up visit; normal to normal BMI was the reference group. Major cognitive domains were evaluated, and a composite index reflecting global cognition was calculated. In participants aged ≤75 years, weight loss—moving from obesity to overweight or normal BMI—was associated with less decline in the memory composite score over time (β = 0.141; p = 0.035), while 3-year maintenance of a BMI ≥ 25 kg/m2 was related to greater reduction in the visuospatial composite score over time (β = −0.093; p = 0.020). Regarding participants aged >75 years, 3-year maintenance of a BMI ≥ 30 kg/m2 contributed to a slower rate of decline in the memory composite score over time (β = 0.102; p = 0.042), whereas weight loss—from overweight to normal BMI—was associated with a decreased attention/processing speed composite score longitudinally (β = −0.275; p = 0.043). Our findings indicated that the association between changes in BMI and cognitive functioning was modified by age. Weight management may have the potential to delay cognitive decline in older adults.

Background Current evidence suggests that nutrition in general and specific dietary patterns in particular, such as the Mediterranean type diet (MeDi), can be employed as potential preventive strategies against the development of dementia and cognitive decline. However, longitudinal data exploring the applicability of these findings in populations of Mediterranean origin are limited. The aim of the present study was to explore the potential relationships of MeDi adherence with dementia incidence rates and cognitive change over time in a traditional Mediterranean population, characterized by a lifelong exposure to Mediterranean eating habits and lifestyle. Methods The sample consisted of 1046 non-demented individuals over the age of 64 (mean age = 73.1; SD = 5.0), with available baseline dietary information and longitudinal follow-up. Diagnosis of dementia was made by a full clinical and neuropsychological evaluation, while cognitive performance was assessed according to five cognitive domains (memory, language, attention-speed, executive functioning, visuospatial perception) and a global cognitive score. Adherence to MeDi was evaluated by an a priori score (range 0-55), derived from a detailed food frequency questionnaire. Results A total of 62 incident dementia cases occurred during a mean (SD) of 3.1 (0.9) years of follow-up. Individuals in the highest MeDi quartile (highest adherence to MeDi) had a 72% lower risk for development of dementia, compared to those in the lowest one (p = 0.013). In addition, analysis of cognitive performance as a function of MeDi score revealed that the biennial cognitive benefit of a 10-unit increase in MeDi score offsets the cognitive decline associated with 1 year of cognitive aging. Conclusion In the present study, higher adherence to MeDi was associated with a reduced risk for dementia and cognitive decline in a traditional Mediterranean population.

There are no published data on Mild Cognitive Impairment (MCI) incidence in people over 65 years of age in Greece, relevant literature is scarce for Southern Europe, and reported rates worldwide show great variability. To investigate the incidence and risk factors of MCI and its subtypes in the elderly population in Greece. The incidence cohort of the HELIAD study (Hellenic Epidemiological Longitudinal Investigation of Aging and Diet) comprised 955 individuals who received full neurological and neuropsychological evaluation on two separate occasions about three years apart. The MCI incidence rate in our cohort is 54.07 new cases per 1000 person-years, standardized by age and sex to 59.99. Each additional year of age over 65 raises the probability of novel MCI by 6.2%, while lower educational attainment more than doubles the risk for incident MCI. Apolipoprotein E-e4 (APOE-e4) carriage results in increased risk for MCI by more than 1.7 times. Incidence rates for amnestic MCI are slightly higher than for the non-amnestic subtype, and AD is the most common potential underlying etiology. The MCI incidence rate in the Greek population over 65 years of age is 54/1000 person-years. Advanced age and APOE-e4 carriage are predisposing factors, while higher educational attainment was found to exert a protective effect. MCI incidence in people over 65 years-old in Greece is consistent with reported rates around the world. Larger studies encompassing neuroimaging and cerebrospinal fluid biomarkers will hopefully shed more light on MCI epidemiology in Greece in the future.

Objectives Recently a declining trend in dementia incidence rates has been reported in high-income countries. We investigated dementia incidence in a representative sample of the Greek population in the age group of 65 years and above. Methods This research is part of the Hellenic Epidemiological Longitudinal Investigation of Aging and Diet (HELIAD). The incidence cohort consisted of 1072 participants who were reevaluated after a mean period of 3.09 years. Results The incidence rate of dementia was 19.0 cases per 1000 person-years (age-standardized and sex-standardized incidence: 25.4/1000 person-years), of which 16.3 per 1000 person-years were attributable to Alzheimer disease. Each additional year of age increased dementia risk by 19.3% and each additional year of education decreased dementia risk by 12.1%. Apolipoprotein E (APOE)-e4 homozygous participants were 18 times more likely to be diagnosed with dementia. A baseline diagnosis of mild cognitive decline (MCI) resulted in a risk for dementia increased by 3.7 times compared with the cognitively normal; in participants with MCI at baseline, APOE-e4 carriage increased dementia risk by 4.5 times. Conclusions The incidence rate of dementia in people 65 years and above in Greece is generally consistent with recently published rates in Europe and North America. Advancing age, baseline MCI, and APOE-e4 homozygosity are risk factors, while higher educational attainment seems protective.

Introduction Timely recognition of mild cognitive impairment (MCI) is essential in optimizing prevention and treatment for Alzheimer disease. Because of the paucity of data on MCI epidemiology in Greece and the variability of worldwide published results, we investigated the prevalence and determinants of MCI in the elderly population in Greece. Methods As part of the Hellenic Epidemiological Longitudinal Investigation of Aging and Diet (HELIAD), we randomly selected 1960 individuals 65 years and older to undergo full neurological and neuropsychological assessment by a multidisciplinary team. MCI was diagnosed according to the Petersen criteria. Results The age-standardized and gender-standardized prevalence of MCI in people aged 65 years and older in Greece is 13.11%. The amnestic and multidomain MCI subtypes are more common than their nonamnestic and single-domain counterparts, respectively. Almost two thirds of cases are because of suspected Alzheimer disease. Every additional year of age increases the odds of prevalent MCI by 7.4%, every additional year of education decreases the odds of MCI by 6.3%, and apolipoprotein E (APOE-e4) carriage increases the odds of MCI by 57.9%. Conclusions MCI prevalence in the elderly population in Greece is on par with previously reported rates. Prospective studies with robust methodology will enhance our understanding of the dementia continuum.

The COVID-19 pandemic brought into the spotlight the technological needs of carers together with accessibility and availability of disease-related web-based services. Athens Alzheimer Association undertook the cultural adaptation of the platform iSupport in Greece. The process included multiple methodological steps based on Ecological Validity Model, and the platform was pilot tested to 15 carers of people with dementia. The duration of this project lasted for one year (April 2020-March 2021). Today more than 160 carers in Greece have registered on the platform. All 23 lessons are easily accessible by the isupportdementia-greece website.

The COVID-19 pandemic brought into the spotlight the technological needs of carers together with accessibility and availability of disease-related web-based services. Athens Alzheimer Association undertook the cultural adaptation of the platform iSupport in Greece. The process included multiple methodological steps based on Ecological Validity Model, and the platform was pilot tested to 15 carers of people with dementia. The duration of this project lasted for one year (April 2020-March 2021). Today more than 160 carers in Greece have registered on the platform. All 23 lessons are easily accessible by the isupportdementia-greece website.

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.

Sleep problems have been associated with cognition, both cross-sectionally and longitudinally. Specific genes have been also associated with both sleep regulation and cognition. In a large group of older non-demented adults, we aimed to (a) validate the association between Sleep Polygenic Risk Score (Sleep PRS) and self-reported sleep duration, and (b) examine the association between Sleep PRS and cognitive changes in a three-year follow-up. Participants were drawn from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD). A structured, in-person interview, consisting of a medical history report and physical examination, was conducted for each participant during each of the visits (baseline and first follow-up). In total, 1376 participants were included, having all demographic, genetic, and cognitive data, out of which, 688 had at least one follow-up visit. In addition, an extensive neuropsychological assessment examining five cognitive domains (memory, visuo-spatial ability, attention/speed of processing, executive function, and language) was administered. A PRS for sleep duration was created based on previously published, genome-wide association study meta-analysis results. In order to assess the relationship between the Sleep PRS and the rate of cognitive change, we used generalized estimating equations analyses. Age, sex, education, ApolipoproteinE-ε4 genotype status, and specific principal components were used as covariates. On a further analysis, sleep medication was used as a further covariate. Results validated the association between Sleep PRS and self-reported sleep duration (B = 1.173, E-6, p = 0.001). Further, in the longitudinal analyses, significant associations were indicated between increased Sleep PRS and decreased visuo-spatial ability trajectories, in both the unadjusted (B = −1305.220, p = 0.018) and the adjusted for the covariates model (B = −1273.59, p = 0.031). Similarly, after adding sleep medication as a covariate (B = −1372.46, p = 0.019), none of the associations between Sleep PRS and the remaining cognitive domains were significant. PRS indicating longer sleep duration was associated with differential rates of cognitive decline over time in a group of non-demented older adults. Common genetic variants may influence the association between sleep duration and healthy aging/cognitive health.

Background: The impact of the new coronavirus disease (COVID-19) is deteriorating as time passes and the virus keeps spreading, with people with dementia and their caregivers being affected significantly. Objective: The aim of this study was to examine the effect of prolonged isolation because of the COVID-19 pandemic on people with dementia and their caregivers. Methods: Caregivers answered online questions regarding their own physical and psychological burden, and of the person they take care of. Participants were mostly members of online seminars of the Athens Alzheimer’s Association. Questions referred to their own burden, the overall decline of the persons they take care of, and changes in specific domains as well. Further, participants were asked about any changes between the two major lockdown periods. Analysis was performed including the total sample and then, by three different stages of dementia. Results: A total of 339 caregivers took part in the study. Results indicated significant decline, both in an overall aspect of the people with dementia, and in specific domains (mostly communication and mood). Regarding the caregivers, they reported having significantly increased physical and psychological burden, and also, noticing an overall change between the two lockdown periods in their own burden. Analysis by dementia-stage group indicated that significant decline occurred both in the middle-stage and the late-stage group. Conclusion: An urgency for further support of both the people with neurodegenerative disorders and their caregivers is needed. Collaboration among care workers, online programs, governmental support, and day-care centers should be planned to ensure continuity of care for those in need during the pandemic.

OBJECTIVES We studied the prevalence of subjective cognitive decline (SCD) and its determinants in a sample of 1456 cognitively normal Greek adults ≥65 years old. METHODS/DESIGN Subjects were evaluated by a multidisciplinary team on their neurological, medical, neuropsychological, and lifestyle profile to reach consensus diagnoses. We investigated various types of SCD, including single-question, general memory decline, specific subjective memory decline based on a list of questions and three types of subjective naming, orientation, and calculation decline. RESULTS In a single general question about memory decline, 28.0% responded positively. The percentage of our sample that reported at least one complaint related to subjective memory decline was 76.6%. Naming difficulties were also fairly common (26.0%), while specific deficits in orientation (5.4%) and calculations/currency handling (2.6%) were rare. The majority (84.2%) of the population reported subjective deficits in at least one cognitive domain. Genetic predisposition to dementia increased the odds for general memory decline by more than 1.7 times. For each one-unit reduction in the neuropsychological composite score (a mean of memory, executive, language, visuospatial, and attention-speed composite scores), the odds for decline in orientation increased by 40.3%. Depression/anxiety and increased cerebrovascular risk were risk factors for almost all SCD types. CONCLUSIONS SCD regarding memory is more frequent than non-memory decline in the cognitively normal Greek elderly population. Genetic predisposition to dementia, lower cognitive performance, affective symptoms, and increased cerebrovascular risk are associated with prevalent SCD. Further prospective research is needed to improve understanding of the evolution of SCD over time.

Short sleep duration and low sleep quality are negatively associated with obesity in young adults, but in older people the results are inconsistent. The aim of the present study was to examine the associations between sleep duration and quality with both body mass index (BMI) and waist circumference (WC) and to investigate sex- and age-specific associations in a population-representative cohort of older adults. 1781 participants ≥ 65 years old from the HELIAD study were included. Sleep duration and quality were based on self-report, whereas BMΙ and WC were evaluated clinically. Sleep duration was inversely related to WC, only in women, even after adjustment for age, sex, years of education, total energy intake and level of physical activity. Furthermore, sleep quality was negatively related to both BMI and WC in women. In men, however, no significant relationships were observed between these variables. Associations between sleep and weight did not differ between those aged

The aim of the present study was to investigate the association of the inflammatory potential of diet with prodromal Parkinson's disease (pPD) probability and incidence among community-dwelling older individuals without clinical features of parkinsonism at baseline. The sample consisted of 1,030 participants 65 years old or older, drawn from a population-based cohort study of older adults in Greece (Hellenic Longitudinal Investigation of Aging and Diet - HELIAD). We calculated pPD probability, according to International Parkinson and Movement Disorder Society research criteria. Dietary Inflammatory Index (DII) was used to measure the dietary inflammatory potential, with higher index score reflecting a more pro-inflammatory diet. Associations of baseline DII with pPD probability cross-sectionally, and with possible/probable pPD incidence (pPD probability ≥30%) during the follow-up period, were examined via general linear models and generalized estimating equations, respectively. Cross-sectionally, one unit increase of DII score [DII (min, max) = -5.83, 6.01] was associated with 4.9% increased pPD probability [β=0.049, 95%CI (0.025-0.090), p0.001]. Prospectively, 62 participants developed pPD during 3.1±0.9 (mean±SD) years of follow-up. One unit increase in DII was associated with 20.3% increased risk for developing pPD [RR=1.203, 95%CI (1.070-1.351), p=0.002]. Participants in the highest tertile of DII score were 2.6 times more likely to develop pPD [β=2.594, 95%CI (1.332-5.050), p=0.005], compared to those in the lowest tertile. More pro-inflammatory diet was related with higher pPD probability and pPD incidence (pPD probability ≥30%) in a community-dwelling older adult population. Further studies are needed to confirm these findings.

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.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.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.Both genetic risk and vascular burden are independently and additively associated with worse cognitive performance and higher odds of dementia.

There are no published data on Mild Cognitive Impairment (MCI) incidence in people over 65 years of age in Greece, relevant literature is scarce for Southern Europe, and reported rates worldwide show great variability.To investigate the incidence and risk factors of MCI and its subtypes in the elderly population in Greece.The incidence cohort of the HELIAD study (Hellenic Epidemiological Longitudinal Investigation of Aging and Diet) comprised 955 individuals who received full neurological and neuropsychological evaluation on two separate occasions about three years apart.The MCI incidence rate in our cohort is 54.07 new cases per 1000 person-years, standardized by age and sex to 59.99. Each additional year of age over 65 raises the probability of novel MCI by 6.2%, while lower educational attainment more than doubles the risk for incident MCI. Apolipoprotein E-ε4 (APOE-ε4) carriage results in increased risk for MCI by more than 1.7 times. Incidence rates for amnestic MCI are slightly higher than for the non-amnestic subtype, and AD is the most common potential underlying etiology.The MCI incidence rate in the Greek population over 65 years of age is 54/1000 person-years. Advanced age and APOE-ε4 carriage are predisposing factors, while higher educational attainment was found to exert a protective effect.MCI incidence in people over 65 years-old in Greece is consistent with reported rates around the world. Larger studies encompassing neuroimaging and cerebrospinal fluid biomarkers will hopefully shed more light on MCI epidemiology in Greece in the future.

Introduction Some case series have suggested that psychotic features could occur even before the onset of motor symptoms of Parkinson's Disease (PD). Our aim was to investigate a possible association between psychotic symptoms and prodromal Parkinson's disease in a population-based cohort, the Hellenic Longitudinal Investigation of Aging and Diet study. Methods This cross-sectional study included participants aged ≥65 years without dementia or PD. We defined psychotic symptoms as the presence of at least one new hallucinatory or delusional feature, assessed with the Neuropsychiatric Inventory scale and the Columbia University Scale for Psychopathology in Alzheimer's Disease, exhibited only at follow-up and not present at baseline visit. We calculated the probability of prodromal PD (pPD) for every participant, according to the 2019 International Parkinson and Movement Disorders Society research criteria for prodromal PD. Results Participants who developed psychotic manifestations over a three-year follow up (20 of 914) had 1.3 times higher probability of pPD score (β [95%CI]: 1.3 [0.9-1.5], p=0.006) compared to non-psychotic subjects. This association was driven mostly by depressive symptoms, constipation and subthreshold parkinsonism (p Conclusion Our data indicate that emerging psychotic features evolve in parallel with the probability of pPD. This is the first study that provides evidence for the presence of psychotic experiences in pPD. The association detected needs to be confirmed in longitudinal studies.

Background Potential links between oxidative stress and the pathophysiology of Alzheimer's Disease (AD) have been reported in the existing literature. Biological markers of oxidative stress, such as the reduced form of glutathione (GSH), may have a potential role as predictive biomarkers for AD development. The aim of the present study was to explore the longitudinal associations between plasma GSH and the risk of developing AD or cognitive decline, in a sample of community-dwelling, non-demented older adults. Methods Participants from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) were included in the present prospective study. The sample used in the analyses consisted of 391 non-demented individuals over the age of 64 (mean age = 73.85 years; SD=5.06), with available baseline GSH measurements. The participants were followed longitudinally until a second evaluation was performed. Plasma GSH was treated both as a continuous variable and as tertiles in our analyses. Cox proportional hazards models were used to evaluate the Hazard ratio (HR) for AD incidence as a function of baseline plasma GSH. Generalized estimating equations (GEE) models were deployed to explore the associations between baseline plasma GSH and the rate of change of performance scores on individual cognitive domains over time. Models were adjusted for age, years of education and sex. Supplementary exploratory models were also adjusted for mild cognitive impairment (MCI) at baseline, risk for malnutrition, physical activity and adherence to the Mediterranean dietary pattern. Results A total of 24 incident AD cases occurred during a mean (SD) of 2.99 (0.92) years of follow-up. Individuals in the highest GSH tertile group (highest baseline plasma GSH values) had a 70.1% lower risk for development of AD, compared to those in the lowest one [HR=0.299 (0.093 - 0.959); p=0.042], and also demonstrated a slower rate of decline of their executive functioning over time (5.2% of a standard deviation less decline in the executive composite score for each additional year of follow-up; p=0.028). The test for trend was also significant suggesting a potential dose-response relationship. Conclusion In the present study, higher baseline plasma GSH levels were associated with a decreased risk of developing AD and with a better preservation of executive functioning longitudinally.

New web-based services emerge to support carers in their role, but little is known regarding the way that carers use the internet or any related services. In an effort, to improve the health-related digital skills of carers aiming to support their caring role, we have developed eHealth Literacy Learning Skills among Carers of People with Dementia, the eLILY project. This paper presents the findings of a modified Delphi survey planned and delivered in the framework of the project as an effort to integrate stakeholders' knowledge and expertise in the proposed curriculum.