Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.

We assessed 300 healthy adults in Greece on measures of semantic and phonemic verbal fluency in order to develop norms for the Greek population. We also evaluated the strategies that the participants used spontaneously in order to maximize word production, namely clustering and switching techniques. Our tasks comprised three semantic and three phonemic categories. Consistent with previous investigations of English-speaking samples, we found a contribution of demographic variables to word fluency. Specifically, level of education contributed to total word production, number of switches, and number of repetitive responses on both semantic and phonemic tasks, and the average cluster size only on the phonemic task. Age contributed to total word production and cluster size on the semantic task, and to number of switches on both semantic and phonemic tasks. Sex contributed only to total word production on the semantic task. In our sample, clustering and switching strategies were related to total word production on both tasks, suggesting that these strategies were used effectively. We present tables of normative data stratified by age and level of education. We have also included detailed guidelines for scoring clusters relevant to the Greek population.

Illiterates represent a significant proportion of the world's population. Written language not only plays a role in mediating cognition, but also extends our knowledge of the world. Two major reasons for illiteracy can be distinguished, social (e.g., absence of schools), and personal (e.g., learning difficulties). Without written language, our knowledge of the external world is partially limited by immediate sensory information and concrete environmental conditions. Literacy is significantly associated with virtually all neuropsychological measures, even though the correlation between education and neuropsychological test scores depends on the specific test. The impact of literacy is reflected in different spheres of cognitive functioning. Learning to read reinforces and modifies certain fundamental abilities, such as verbal and visual memory, phonological awareness, and visuospatial and visuomotor skills. Functional imaging studies are now demonstrating that literacy and education influence the pathways used by the brain for problem-solving. The existence of partially specific neuronal networks as a probable consequence of the literacy level supports the hypothesis that education impacts not only the individual's day-to-day strategies, but also the brain networks. A review of the issues related to dementia in illiterates is presented, emphasizing that the association between the education level and age-related cognitive changes and education remains controversial. The analysis of the impact of illiteracy on neuropsychological test performance represents a crucial approach to understanding human cognition and its brain organization under normal and abnormal conditions.

BackgroundThe Mediterranean dietary pattern has been associated with a decreased risk of many degenerative diseases and cognitive function in particular; however, relevant information from Mediterranean regions, where the prototype Mediterranean diet is typically adhered to, have been very limited. Additionally, predefined Mediterranean diet (MeDi) scores with use of a priori cut-offs have been used very rarely, limiting comparisons between different populations and thus external validity of the associations. Finally, associations between individual components of MeDi (i.e., food groups, macronutrients) and particular aspects of cognitive performance have rarely been explored. We evaluated the association of adherence to an a priori defined Mediterranean dietary pattern and its components with dementia and specific aspects of cognitive function in a representative population cohort in Greece.MethodsParticipants from the Hellenic Longitudinal Investigation of Ageing and Diet (HELIAD), an on-going population-based study, exploring potential associations between diet and cognitive performance in a representative sample from Greek regions, were included in this analysis. 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 composite cognitive score. Adherence to MeDi was evaluated by an a priori score (range 0–55), derived from a detailed food frequency questionnaire.ResultsAmong 1,865 individuals (mean age 73±6 years, 41% male), 90 were diagnosed with dementia and 223 with mild cognitive impairment. Each unit increase in the Mediterranean dietary score (MedDietScore) was associated with a 10% decrease in the odds for dementia. Adherence to the MeDi was also associated with better performance in memory, language, visuospatial perception and the composite cognitive score; the associations were strongest for memory. Fish consumption was negatively associated with dementia and cognitive performance positively associated with non-refined cereal consumption.ConclusionsOur results suggest that adherence to the MeDi is associated with better cognitive performance and lower dementia rates in Greek elders. Thus, the MeDi in its a priori constructed prototype form may have cognitive benefits in traditional Mediterranean populations.

Background The International Parkinson and Movement Disorder Society recently introduced a methodology for probability score calculation for prodromal PD. Objectives To assess the probability of prodromal PD in an older population and investigate its possible association with Mediterranean diet adherence. Methods Data from a population‐based cohort study of older adults (HEllenic Longitudinal Investigation of Aging and Diet) in Greece were used. Probability of prodromal PD was calculated according to International Parkinson and Movement Disorder Society research criteria. A detailed food frequency questionnaire was used to evaluate dietary intake and calculate Mediterranean diet adherence score, ranging from 0 to 55, with higher scores indicating higher adherence. Results Median probability of prodromal PD was 1.9%, ranging from 0.2 to 96.7% in 1,731 PD‐free individuals aged ≥ 65 (41% male). Lower probability for prodromal PD (P < 0.001) in the higher Mediterranean diet adherence groups was noted, driven mostly by nonmotor markers of prodromal PD, depression, constipation, urinary dysfunction, and daytime somnolence. Each unit increase in Mediterranean diet score was associated with a 2% decreased probability for prodromal PD (P < 0.001). Compared to participants in the lowest quartile of Mediterranean diet adherence, those in the highest quartile were associated with a ∼21% lower probability for prodromal PD. Conclusions Adherence to the Mediterranean diet is associated with lower probability of prodromal PD in older people. Further studies are needed to elucidate the potential causality of this association, potential relation of the Mediterranean diet to delayed onset or lower incidence of PD, as well as the underlying neurobiological mechanisms. © 2018 International Parkinson and Movement Disorder Society

Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease.

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Background: Accumulating epidemiological evidence from several populations supports the important role of the Mediterranean-type diet (MeDi) in reducing the risk for age-related diseases such as Alzheimer's disease (AD). However, the relevant literature is clearly deficient for most Mediterranean countries that more closely adhere to the originally described MeDi. Greece resides in the Mediterranean basin, and older generations traditionally adhere to a MeDi. Methods: We here present the design and the preliminary baseline characteristics of the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD). The HELIAD is a population-based, multidisciplinary, collaborative study designed to estimate the prevalence and incidence of AD, other dementias, mild cognitive impairment, and other neuropsychiatric conditions of aging in the Greek population and to investigate associations between nutrition and cognitive dysfunction/age-related neuropsychiatric diseases in this Mediterranean population. The study also ascertains several demographic, medical, social, environmental, clinical, nutritional, and neuropsychological determinants and lifestyle activities. Results: In total, 1,050 participants of a random sample have already completed the initial evaluation. The subjects were, on average, 73.4 (SD = 6.0) years old, 60% of the sample were female, and most of the participants were poorly educated with an average of 5.41 (SD = 3.5) years of education. The performance on the neuropsychological tests was equivalent to the average scores of previous normative Greek samples. More than one third of the population under investigation was considered to be at high risk for malnutrition. Conclusions: The HELIAD may provide important data for expanding our knowledge regarding the prevalence, incidence, and risk factors of AD and several other neuropsychiatric diseases in the Mediterranean region.