Hellenic Longitudinal Investigation Of Aging And Diet Research Articles

Depressive symptoms in the entire spectrum of cognitive ageing in Greece: evidence from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD)

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. Key points Depressive symptoms are present in approximately 20% of older adults. More than 10% of older individuals with dementia or mild cognitive impairment report moderate-to-severe depressive symptoms. Female sex, lower education, lower cognitive performance, living in urban areas and treatment with psychotropic medication pertain to more severe depressive symptoms in ageing. Timely detection and effective treatment of depressive symptoms are crucial in the clinical practice of the care of older adults. Further research is needed in order to elucidate the complex relationship between depressive symptoms and cognitive impairment in ageing.

Exploring Verbal Fluency Strategies among Individuals with Normal Cognition, Amnestic and Non-Amnestic Mild Cognitive Impairment, and Alzheimer's Disease.

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.

Qualitative Verbal Fluency Components as Prognostic Factors for Developing Alzheimer's Dementia and Mild Cognitive Impairment: Results from the Population-Based HELIAD Cohort.

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

Language performance as a prognostic factor for developing Alzheimer's clinical syndrome and mild cognitive impairment: Results from the population-based HELIAD cohort.

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. 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. 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. 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.

Longitudinal trajectories and normative language standards in older adults with normal cognitive status.

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).

Adherence to the Mediterranean diet and incident frailty: Results from a longitudinal study

ObjectivesThe aim of the current prospective study was to examine the relationship between adherence to the Mediterranean diet and incident frailty. Study design1075 Greek community-dwelling older adults from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) were included in the present longitudinal analysis. Main outcome measuresAdherence to the Mediterranean diet was evaluated through the MedDietScore, calculated from the information participants provided on a validated food frequency questionnaire. Frailty was assessed using two multidomain tools: the Frailty Index (FI) and the Tilburg Frailty Indicator (TFI). Analysis of the incidence of frailty as a function of the baseline MedDietScore was performed using Cox proportional hazards models. Additionally, Generalized Estimating Equations (GEE) models were used to explore whether the baseline MedDietScore was associated with the change in the total number of frailty criteria met by participants over time. In testing for a dose–response association between Mediterranean diet and frailty, the MedDietScore was treated either as a continuous variable or as tertiles of low, medium and high adherence to MeDi. Results176 and 131 participants developed incident frailty, as measured with the FI and TFI respectively. Each unit of MedDietScore was associated with a 5% (ΗR 0.95, 95% CI 0.91–0.99, p = 0.012) and 10% (ΗR 0.90, 95% CI 0.86–0.95, p ≤ 0.001) decrease in the risk of incident frailty when measured with the FI and TFI respectively. Compared with participants reporting low adherence to the Mediterranean diet (lowest tertile), those with high adherence (highest tertile) had a 41% (ΗR 0.59, 95% CI 0.38–0.91, p = 0.017) and a 57% (ΗR 0.43, 95% CI 0.27–0.70, p ≤ 0.001) lower risk of incident frailty as measured with the FI and TFI respectively. After excluding from the analyses participants diagnosed with dementia at baseline or follow-up, the same results were obtained: each unit of MedDietScore was associated with a 5% (HR 0.95 CI 0.91–0.99, p = 0.023) and a 10% (HR 0.90 CI 0.86–0.94, p ≤ 0.001) decrease in the risk of incident frailty as measured with the FI and TFI respectively. ConclusionsThe present longitudinal study showed that non-frail community-dwelling older adults with high adherence to the Mediterranean dietary pattern had a significantly lower incidence of frailty.

Editors' Note: Diet Inflammatory Index and Dementia Incidence: A Population-Based Study

Using data from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD), Charisis et al. evaluated the relationship between the validated diet inflammatory index (DII) and incident dementia. In their cohort of 1,059 patients, 62 of whom were eventually diagnosed with dementia (5.9% over a mean follow-up of 3 years), there was a strong and independent relationship between DII and eventual dementia diagnosis (HR for each DII point 1.26 [95% CI 1.05–1.52]; p = 0.013). Dr. Daly highlights an important observation regarding this study and similar observational cohorts, noting that these relationships between diet and lifestyle risk factors and later dementia diagnoses often fail to translate into meaningful interventions for at-risk patients. Specifically, there remains no proven benefit of interventions such as reducing inflammatory dietary intake at reducing the long-term risk of dementia. The HELIAD investigators emphasize that the value of their study lies in the potential to design an interventional trial that could leverage these nutritional data, but they acknowledge such a trial may be challenging to conduct. Using data from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD), Charisis et al. evaluated the relationship between the validated diet inflammatory index (DII) and incident dementia. In their cohort of 1,059 patients, 62 of whom were eventually diagnosed with dementia (5.9% over a mean follow-up of 3 years), there was a strong and independent relationship between DII and eventual dementia diagnosis (HR for each DII point 1.26 [95% CI 1.05–1.52]; p = 0.013). Dr. Daly highlights an important observation regarding this study and similar observational cohorts, noting that these relationships between diet and lifestyle risk factors and later dementia diagnoses often fail to translate into meaningful interventions for at-risk patients. Specifically, there remains no proven benefit of interventions such as reducing inflammatory dietary intake at reducing the long-term risk of dementia. The HELIAD investigators emphasize that the value of their study lies in the potential to design an interventional trial that could leverage these nutritional data, but they acknowledge such a trial may be challenging to conduct.

Sex Differences in Frailty Incidence in Greek Community-Dwelling Older People: The HELIAD Study.

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

Objective and Subjective Measurements of Motor Function: Results from the HELIAD Study.

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

Sleep Polygenic Risk Score Is Associated with Cognitive Changes over Time.

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.

Association of the Polygenic Risk Score With the Probability of Prodromal Parkinson's Disease in Older Adults.

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

Population attributable fractions for modifiable risk factors of dementia in cognitively normal and MCI populations: Data from two countries

AbstractBackgroundPrevious studies have shown that population‐wide up to 40% of all dementia cases are related to twelve modifiable risk factors, which thus calls for preventive measures. To inform health promotion strategies, it is important to know whether the risk attributable to modifiable risk factors differs in cognitively healthy persons and persons with Mild Cognitive impairment (MCI). This study analyzed associations and population attributable fractions (PAFs) of twelve modifiable risk factors with dementia in cognitively healthy and declining (MCI) adults aged ≥65 years, in two cohort studies from the US and Greece.MethodData were from the National Alzheimer’s Coordinating Centre (NACC) (n=16,147, impaired‐not‐MCI n=1007, mean age 75.2 ±6.9, 54.8% female) and the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) (n=1141, mean age 72.9 ±5.0, 58.0% female). PAFs were calculated based on hazard ratios (HRs) for the risk of dementia and risk factor prevalence in the NACC (9 risk factors) and HELIAD (10 risk factors) data. Weighted PAFs were calculated to adjust for communality between risk factors. Analyses were performed for the total samples, as well as separately for cognitively healthy participants and those with MCI at baseline.Result2,630 participants enrolled by the NACC developed MCI (25.1%) and 3,333 developed dementia (20.7%) during a mean follow‐up of 4.9 (±3.5) years. 131 participants developed MCI (11.2%) and 68 developed dementia (5.9%) during HELIAD follow‐up of on average 3.1 (±0.86) years. A relatively low weighted overall PAF of 21.4% was found in the total sample of the NACC study. The PAF was 20.8% in the cognitively normal subgroup and ‐6.17% in the MCI subgroup A relatively high weighted overall PAF of 60.7% was found for the total sample in HELIAD. The PAF was 78.4% in the cognitively normal subgroup and 80.6% in the MCI subgroup.ConclusionIn general, translating valuable global meta‐analysis data on modifiable risk factors should be carefully carried out per population before starting preventive interventions. Within each cohort, the PAFs for cognitively healthy and cognitively declining participants were in the same range, suggesting that also in persons with MCI, elimination of risk factors continues to be important.

Diet Inflammatory Index and Dementia Incidence: A Population-Based Study.

Aging 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. Individuals 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. Analyses 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). In 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.

Alcohol use and cognitive performance: a comparison between Greece and the United States

Objectives To examine associations between alcohol use and cognitive performance among older adults in Greece and the United States, and assess potential differences due to differing drinking practices in the two countries. Methods Data came from Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) and National Alzheimer’s Coordinating Center Uniform Dataset (NACC). We examined those aged 65–90 years at baseline who had no cognitive impairment and complete data for cognitive and alcohol use variables (N = 1110 from HELIAD; N = 2455 from NACC). We examined associations between current alcohol use and frequency of such use with cognitive performance on various cognitive tasks stratified by gender. Results In NACC, use of alcohol was associated with better cognitive performance. Men drinkers performed better than non-drinkers on Trail A (standardized mean 0.07 vs. −0.24, p<.001), Trail B (0.06 vs. −0.19, p=.001), and women drinkers performed better on Trail A (0.04 vs. −0.09, p=.016), Trail B (0.04 vs. −0.10, p=.005), verbal fluency (Animals: 0.05 vs. −0.13, p<.001; Vegetables: 0.04 vs. −0.09, p=.027), and MoCA (0.03 vs. −0.08, p=.039). In HELIAD, fewer differences were seen with only women drinkers exhibiting better performance than non-drinkers on the Boston Naming Task (0.11 vs. −0.05, p=.016). In general, more frequent drinkers performed better on cognitive tasks than less frequent drinkers, although this was only statistically significant in the NACC dataset. Conclusion While drinking alcohol may be associated with better cognitive performance across both the US and Greece, more research is needed to assess the cultural factors that may modify this association.

Identifying Appropriate Neuropsychological Tests for Uneducated/Illiterate Older Individuals.

We investigated the utility of traditional neuropsychological tests in older uneducated/illiterate individuals without dementia to determine the possibility that they are likely not appropriate for this group. We assessed the neuropsychological performance of 1122 older adults [≥65 years old; mean age: 74.03 (SD = 5.46); mean education: 4.76 (SD = 2.5) years; women: n = 714], in the context of the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD), a population-based study conducted in Greece. We based our analyses on three groups: high-functioning/cognitively healthy (i.e., without dementia) uneducated/illiterate individuals (n = 80), high-functioning/cognitively healthy educated/literate individuals (n = 932), and low-functioning/cognitively impaired educated/literate individuals (presumably with dementia; n = 110). We used binary regression analyses with Bonferroni correction to investigate whether test performance differentiated uneducated/illiterate from educated/literate individuals. Models were adjusted for age and sex; raw test scores were the predictor variables. The uneducated/illiterate cohort was at a disadvantage relative to the healthy educated/literate group on all variables but verbal memory recognition and consolidation, congruent motor responses, and phonological fluency clustering (p>.002). Moreover, only word list learning immediate and delayed free recall and delayed cued recall differentiated the high-functioning/cognitively healthy uneducated/illiterate from the low-functioning/cognitively impaired educated/literate group, favoring the former (p's<.002). Our findings suggest that only particular verbal memory test variables are fair in determining whether older uneducated/illiterate individuals have functional/cognitive impairment suggestive of a neurodegenerative process. On all other neuropsychological variables, this cohort was at a disadvantage. Therefore, we highlight the need for identifying appropriate methods of assessment for older uneducated/illiterate individuals.

Challenges in the development of accurate normative neuropsychological test data for older adults: Findings from the HELIAD Study

AbstractBackgroundNormative data collected from older adult cohorts may be tainted by the inadvertent inclusion of undiagnosed individuals at the very early stage of a dementia process or Mild Cognitive Impairment (MCI). To avoid this pitfall, we developed normative data from an older adult group who remained cognitively intact at follow‐up examination. The present work addresses the challenge and the absence of appropriate normative data for a range of neuropsychological tests in older adults in Greece.Method1031 community dwelling participants (age≥65) underwent neurological and neuropsychological assessment on two occasions with a mean interval of 2.8 years (range:1.2‐5.2; SD:0.8) for the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD). A value of 0 or 0.5 for the Clinical Dementia Rating (CDR) and a threshold value of ≥ 26 on the Mini Mental State Examination (MMSE) were used as clinical diagnostic criteria to determine the cognitive status of the participants. Based on these criteria, 750 individuals were cognitively intact in both evaluations and their data were used for norms development. Participants received a comprehensive neuropsychological assessment encompassing five cognitive domains: memory, language, attention/speed, executive and visual‐spatial functioning. Multiple linear regression models were performed, with age at baseline (years), education (years) and sex as the demographic predictors for regression‐based normative formulae, and raw test scores as the dependent variables. The effects of age, education and sex were investigated for each test and subtest separately. Discrete norms were also derived, stratified by four age strata (64‐69, 70‐74, 75‐79, 80‐89) and by three education strata (0, 1‐9, 10+).ResultRegression analyses revealed that education was associated with all test scores, whereas age was an important predictor of all but a few visuoperceptual, executive functioning and memory variables. Women outperformed men on verbal memory, attention/information processing speed and subtests of executive functioning. Men, however, outperformed women on visual memory recall and visuospatial perception.ConclusionThe current study provides sound normative data for widely‐used neuropsychological tests among older adults, untainted by potential early and undiagnosed cognitive impairment. We report both discrete and regression‐based norms for use in clinical settings to identify cognitive decline in older adults.

Plasma GSH levels and Alzheimer's disease. A prospective approach.: Results from the HELIAD study

BackgroundPotential 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. MethodsParticipants 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 and longitudinal follow-up. 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. ResultsA 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. ConclusionIn 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.

Association Between Sleep Disturbances and Frailty: Evidence From a Population-Based Study

ObjectiveTo explore the association between both self-reported quality and quantity sleep characteristics and frailty status in a large non–sex-specific population of older individuals in Greece. DesignCross-sectional study. Setting and ParticipantsIn total, 1984 older individuals (≥65 years old) were drawn from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD). MeasuresFrailty was assessed using 3 different definitions, the Frailty Index (FI), the Tilburg Frailty Indicator (TFI), and the Groningen Frailty Indicator (GFI). Sleep quality was evaluated through the Sleep Index II, which includes 9 of the 12 self-reported items of the Medical Outcomes Study-Sleep Scale. To examine sleep duration, participants were asked to report on how many hours they slept each night during the past 4 weeks. Logistic regression models adjusted for multiple covariates were explored. Additional analyses, stratified by gender, adjusting for sleep-related medications and excluding participants diagnosed with dementia, were also performed. ResultsIn total, 389 (20%), 619 (31.9%), and 608 (31.3%) participants were categorized as frail according to the FI, the TFI, and the GFI respectively. Sleep quality was significantly associated with frailty in all models. Even after adjusting for subjective sleep duration, compared with participants who subjectively reported high sleep quality, those with low sleep quality had 3.7, 2.6, and 2.5 more times to be frail as measured with FI, TFI, and GFI respectively. Regarding the associations between frailty and self-reported sleep duration, sex-specific associations were observed: prolonged sleep duration was associated with frailty in the subsample of male participants. Conclusions and ImplicationsThe present study shows a strong correlation between subjective sleep quality and frailty status, contributing substantial information to the growing literature demonstrating that sleep is associated with older people's overall health. Sleep complaints should not be underestimated, and older individuals who self-report sleep disorders should be further assessed for frailty.

Pesticide exposure and cognitive function: Results from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD)

BackgroundResults from studies to date, regarding the role of chronic pesticide exposure on cognitive function remain contradictory. ObjectiveTo investigate the relationship between self-reported pesticide exposure and cognitive function. MethodsData from a population-based cohort study of older adults (HEllenic Longitudinal Investigation of Aging and Diet) in Greece was used. Pesticide exposure classification was based on 1) living in areas that were being sprayed; 2) application of spray insecticides/pesticides in their gardens; and 3) occupational application of sprays. Associations between z-scores of cognitive performance and self-reported pesticide exposure were examined with linear regression analyses. Adjusted models were applied, for all analyses. ResultsNon-demented individuals who reported that they had been living in areas near sprayed fields, had poorer neuropsychological performance, compared to those who had never lived in such areas. Sub-analyses revealed poorer performance in language, executive and visual-spatial functioning, and attention. These associations remained after a sensitivity analysis excluding subjects with mild cognitive impairment. ConclusionSelf-reported exposure to pesticides was negatively associated with cognitive performance.

Dementia Prevalence in Greece: The Hellenic Longitudinal Investigation of Aging and Diet (HELIAD).

Study of the epidemiology of dementia to gain insight into putative predisposing and prophylactic factors is the first step toward establishing effective preventive and therapeutic strategies for this ever-growing public health problem. Relevant data in Greece are scattered and outdated. We investigated dementia prevalence as part of a population-representative epidemiological study [Hellenic Longitudinal Investigation of Aging and Diet (HELIAD)] in 2 Greek regions. Our sample comprised 1792 adults 65 years of age or older, who received a full neurological and neuropsychological evaluation that led to a consensus diagnosis. The overall prevalence of dementia was 5.0%, with 75.3% of the cases attributed to Alzheimer disease. Dementia odds were 15.8% higher for every year of advancing age and 9.4% lower for every additional year of education. Carrying at least 1 APOE-ε4 allele doubled the risk of dementia, whereas sex did not exert a statistically significant effect. Our results are consistent with previous research in Southern European countries; dementia prevalence in Greece is in the lower range of what has been reported globally.