Genetic Predisposition for White Matter Hyperintensities and Risk of Mild Cognitive Impairment and Alzheimer's Disease: Results from the HELIAD Study.

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.

Eating Frequency, Timing, and Duration in Relation to Cognitive Performance and Alzheimer Disease Biomarkers in Adults.

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 ß (Αß42), 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.

Genetic risk for Alzheimer's disease and adherence to the Mediterranean diet: results from the HELIAD study.

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.

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

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.

Genetically downregulated Interleukin-6 signalling is associated with a lower risk of frailty.

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

Cognitive trajectories preluding the imminent onset of Alzheimer's disease dementia in individuals with normal cognition: results from the HELIAD cohort.

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.

Application of Machine Learning Techniques in the HELIAD Study Data for the Development of Diagnostic Models in MCI and Dementia.

The increase in the population's life expectancy leads to an increase in the incidence of dementia and, therefore, in diseases such as Alzheimer's. Towards this direction, the HELIAD1 study is the first large-scale epidemiological study aimed at assessing epidemiological data on dementia, mild mental decline, and other neuropsychiatric disorders associated with old age. This is a huge study with several computational challenges, most of which can be addressed by machine learning processes. The objectives of this study were to detect patterns in the HELIAD clinical data that classify with high accuracy various levels of cognitive impairment by training ML algorithms and hence apply derived model on future clinical data to predict with the same accuracy the class variable. We propose a machine learning method based on RUSBoost classifier to identify a critical subset of biomarkers that classify accurately between neurological patients with mild cognitive impairment (MCI) or dementia of the Alzheimer's type (DAT) and the cognitively healthy control (CHC) group. In this study we used a highly skewed (imbalanced) dataset with most observations (majority class) belonging to the CHC group. The method proposed predicts accurately the clinical diagnosis label and effectively classifies the neurological patients from the CHC class. In particular, the classification accuracy (actual vs predicted) for the three classes of the clinical diagnosis was 97%, 78%, and 91% for control, MCI, and dementia class, respectively.

Simulating the multicausality of Alzheimer's disease with system dynamics.

INTRODUCTION: In Alzheimer's disease (AD), cognitive decline is driven by various interlinking causal factors. Systems thinking could help elucidate this multicausality and identify opportune intervention targets. METHODS: We developed a system dynamics model (SDM) of sporadic AD with 33 factors and 148 causal links calibrated with empirical data from two studies. We tested the SDM's validity by ranking intervention outcomes on 15 modifiable risk factors to two sets of 44 and 9 validation statements based on meta-analyses of observational data and randomized controlled trials, respectively. RESULTS: The SDM answered 77% and 78% of the validation statements correctly. Sleep quality and depressive symptoms yielded the largest effects on cognitive decline with which they were connected through strong reinforcing feedback loops, including via phosphorylated tau burden. DISCUSSION: SDMs can be constructed and validated to simulate interventions and gain insight into the relative contribution of mechanistic pathways.

Genetic propensity for cerebral amyloidosis and risk of mild cognitive impairment and Alzheimer's disease within a cognitive reserve framework.

INTRODUCTION: We constructed a polygenic risk score (PRS) for ß-amyloid (PRSAß42) 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 PRSAß42 and AD/aMCI risk. METHODS: A total of 618 cognitive-normal participants were followed-up for 2.92 years. The association of PRSAß42 and CR with AD/aMCI incidence was examined with COX models. Then we examined the additive interaction between PRSAß42 and CR and the CR effect across participants with different PRSAß42 levels. RESULTS: Higher PRSAß42 and CR were associated with a 33.9% higher risk and 8.3% less risk for AD/aMCI, respectively. An additive interaction between PRSAß42 and CR was observed. High CR was associated with 62.6% less risk of AD/aMCI incidence only in the high-PRSAß42 group. DISCUSSION: A super-additive effect of PRSAß42 and CR on AD/aMCI risk was observed. CR influence was evident in participants with high PRSAß42.

Objective Physical Function in the Alzheimer's Disease Continuum: Association with Cerebrospinal Fluid Biomarkers in the ALBION Study.

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 Aß42, 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 Aß42 (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.

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.

Plasma Glutathione and Prodromal Parkinson's Disease Probability.

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.

The factors associated with the presence of psychotic symptoms in the HELIAD Greek community study of older adults.

BACKGROUND: The prevalence and associated factors related to psychotic symptoms in older adults are understudied. The objectives were to assess the prevalence, incidence and factors associated with psychotic symptoms in a representative Greek sample of community living older adults. METHODS: The sample includes n = 1,904 residents of the cities of Larissa and Maroussi in Greece participating in the Hellenic Longitudinal Investigation of Aging and Diet study with available data at baseline and n = 947 individuals at the 3-year follow-up. Past-month presence of delusions and hallucinations was assessed on the grounds of the 17 symptoms of the Columbia University Scale for Psychopathology in Alzheimer's Disease and 14 symptoms of the Neuropsychiatric Inventory Questionnaire. A comprehensive neuropsychological assessment for probable diagnosis of dementia and physical comorbidity was carried out by neurologists. Penalized logistic regression analyses were used to assess the socio-economic and clinical factors associated with psychotic symptoms. RESULTS: Past-month prevalence of psychotic symptoms was 1.9% and 1.0% when excluding cases of dementia. The prevalence of any delusion and hallucination was 0.8% and 0.3% when excluding dementia. The incidence of psychotic symptoms without dementia was 1.3%. Recent widows and farmers/breeders/craftsmen, versus public servants/teachers/executives, had both six times the odds of experiencing psychotic symptoms without dementia. Hearing impairment and the number of health conditions also increased the odds while increased age was protective. CONCLUSION: Psychotic symptoms unrelated to dementia constitute a considerable mental health problem in old age. Paranoid delusions were the most prevalent. Socio-economic and health status factors are significant predictors of psychotic symptoms.

Initial Data and a Clinical Diagnosis Transition for the Aiginition Longitudinal Biomarker Investigation of Neurodegeneration (ALBION) Study.

Background and Objectives: This article presents data from the ongoing Aiginition Longitudinal Biomarker Investigation of Neurodegeneration study (ALBION) regarding baseline clinical characterizations and CSF biomarker profiles, as well as preliminary longitudinal data on clinical progression. Materials and Methods: As of March 2022, 138 participants who either were cognitively normal (CN, n = 99) or had a diagnosis of mild cognitive impairment (MCI, n = 39) had been recruited at the specialist cognitive disorders outpatient clinic at Aiginition Hospital. Clinical characteristics at baseline were provided. These patients were followed annually to determine progression from CN to MCI or even dementia. CSF biomarker data (amyloid ß1-42, phosphorylated tau at threonine 181, and total tau) collected using automated Elecsys® assays (Roche Diagnostics) were available for 74 patients. These patients were further sorted based on the AT(N) classification model, as determined by CSF Aß42 (A), CSF pTau (T), and CSF tTau (N). Results: Of the 49 CN patients with CSF biomarker data, 21 (43%) were classified as exhibiting "Alzheimer's pathologic change" (A+Τ− (Ν)−) and 6 (12%) as having "Alzheimer's disease" (A+T−(N)+, A+T+(N)−, or A+T+(N)+). Of the 25 MCI patients, 8 (32%) displayed "Alzheimer's pathologic change", and 6 (24%) had "Alzheimer's disease". A total of 66 individuals had a mean follow-up of 2.1 years (SD = 0.9, min = 0.8, max = 3.9), and 15 of those individuals (22%) showed a clinical progression (defined as a worsening clinical classification, i.e., from CN to MCI or dementia or from MCI to dementia). Overall, participants with the "AD continuum" AT(N) biomarker profile (i.e., A+T−(N)−, A+T−(N)+, A+T+(N)−, and A+T+(N)+) were more likely to clinically progress (p = 0.04). Conclusions: A CSF "AD continuum" AT(N) biomarker profile is associated with an increased risk of future clinical decline in CN or MCI subjects.

The impact of COVID-19 pandemic on people with mild cognitive impairment/dementia and on their caregivers.

BACKGROUND: The novel coronavirus disease (COVID-19) was first detected in Mainland China in December 2019, and soon it spread throughout the world, with multiple physical and psychological consequences across the affected populations. AIMS: The aim of the current study was to analyze the impact of COVID-19 pandemic on older adults with mild cognitive impairment (MCI)/dementia and their caregivers as well. MATERIALS AND METHODS: Two hundred and four caregivers took part in the study, completing a self-reported questionnaire about the person with MCI/dementia and their own, since the lockdown period which started in February and ended in May of 2020 in Greece. RESULTS: Results indicated a significant overall decline of the people with MCI/dementia. Further, the domains in which people with MCI/dementia were mostly affected were: communication, mood, movement and compliance with the new measures. Caregivers also reported a great increase in their psychological and physical burden during this period, where the available support sources were limited. DISCUSSION: The pandemic threatens to disrupt the basic routines that promote mental and physical health of both people with MCI/dementia and t heir caregivers. CONCLUSION: Further measures to protect and provide support to people who suffer and their families are needed.

A Prospective Validation of the Updated Movement Disorders Society Research Criteria for Prodromal Parkinson's Disease.

OBJECTIVE: The objective of this study was to validate the recently updated research criteria for prodromal Parkinson's disease (pPD) proposed by the International Parkinson's Disease and Movement Disorders Society. METHODS: A total of 16 of 21 markers of pPD were ascertained in the Hellenic Longitudinal Investigation of Aging and Diet cohort composed of community-dwelling individuals aged ≥65 years. The probability of pPD was calculated for 961 individuals without Parkinson's disease (PD) or dementia with Lewy bodies at baseline who were followed-up for a median of 3 years. The ability of the criteria to predict conversion to PD/dementia with Lewy bodies was assessed by estimating their sensitivity and specificity, plotting receiver operating characteristics curves, and using logistic regression. These analyses were repeated using the original criteria. RESULTS: No incident PD/dementia with Lewy bodies case had probable pPD at baseline (ie, ≥80% pPD probability). At cut-offs of 10%, 30%, and 50% probability of pPD, the sensitivity and specificity of the criteria ranged from 4.5% to 27.3%, and 85.7% to 98.3% respectively. The area under the receiver operating characteristics curve was 0.691 (95% confidence intervals, 0.605-0.777). In logistic regression models, the criteria-derived posttest odds of pPD were a significant predictor of conversion at follow-up. The updated criteria performed similarly to the original but showed a slight increase in sensitivity. CONCLUSIONS: The new criteria demonstrated suboptimal sensitivity in our random sample of community-dwelling individuals. The absence of specialized assessments with high likelihood ratios in our cohort could be hindering the demonstration of higher sensitivities. Such assessments should be a part of future validation attempts. © 2020 International Parkinson and Movement Disorder Society.

Prevalence of Mild Cognitive Impairment in the Elderly Population in Greece: Results From the HELIAD Study.

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-ε4) 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.

Exploring the association between subjective cognitive decline and frailty: the Hellenic Longitudinal Investigation of Aging and Diet Study (HELIAD).

Background: Subjective cognitive decline (SCD) refers to self-evaluations of impairment in cognitive functions in the absence of objective deficits. Frailty is a multidimensional syndrome that results in increased vulnerability. Both terms are associated with cognitive decline and increased incidence of dementia. The aim of this study was to explore potential associations between SCD and frailty in elderly individuals.Methods: In this cross-sectional study, we included 1454 participants aged 65 and older from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) study. Individuals with a diagnosis of dementia, mild cognitive impairment, severe anxiety or depression were excluded. SCD were assessed with eighteen questions categorized into cognitive domains. Frailty was assessed according to the Fried definition, the Frailty Index (FI) and the Tilburg Frailty Indicator (TFI). Logistic regression analysis was used to investigate the association.Results: Lower educational level, female sex and low socioeconomic status were found to be associated with frailty and more SCD complaints. Having two or more types of SCD complaints was significantly associated with frailty according to all frailty definitions. All types of SCD complaints were significantly associated with the FI and the TFI. In addition, SCD complaints concerning problems requiring mathematical reasoning had the strongest association with frailty.Conclusion: We found that SCD complaints may be a valid indicator of frailty in cognitively unimpaired older people. We believe that SCD may provide a crucial proactive assessment to detect frailty and to implement programs that will help maintain good health and quality of life during aging.

Prevalence and determinants of subjective cognitive decline in a representative Greek elderly population.

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.

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

BACKGROUND: Results from studies to date, regarding the role of chronic pesticide exposure on cognitive function remain contradictory. OBJECTIVE: To investigate the relationship between self-reported pesticide exposure and cognitive function. METHODS: Data 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. RESULTS: Non-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. CONCLUSION: Self-reported exposure to pesticides was negatively associated with cognitive performance.