PDE10A Mutation as an Emerging Cause of Childhood-Onset Hyperkinetic Movement Disorders: A Review of All Published Cases.

Cyclic nucleotide phosphodiesterase (PDE) enzymes catalyze the breakdown of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which act as intracellular second messengers for signal transduction pathways and modulate various processes in the central nervous system. Recent discoveries that mutations in genes encoding different PDEs, including PDE10A, are responsible for rare forms of chorea in children led to the recognition of an emerging role of PDEs in the field of pediatric movement disorders. A comprehensive literature review of all reported cases of PDE10A mutations in PubMed and Web of Science was performed in English. We included eight studies, describing 31 patients harboring a PDE10A mutation and exhibiting a hyperkinetic movement disorder with onset in infancy or childhood. Mutations in both GAF-A, GAF-B regulatory domains and outside the GAF domains of the PDE10A gene have been reported to cause hyperkinetic movement disorders. In general, patients with homozygous mutations in either GAF-A domain of PDE10A present with a more severe phenotype and at an earlier age but without any extensive abnormalities of the striata compared with patients with dominant variants in GAF-B domain, indicating that dominant and recessive mutations have different pathogenic mechanisms. PDE10A plays a key role in regulating control of striato-cortical movement. Comprehension of the molecular mechanisms within the cAMP and cGMP signaling systems caused by PDE10A mutations may inform novel therapeutic strategies that could alleviate symptoms in young patients affected by these rare movement disorders.

Primary Sjögren syndrome-related peripheral neuropathy: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Primary Sjögren syndrome (pSS) is a chronic, systemic, autoimmune disorder characterized by lymphocytic infiltrates of the exocrine organs, leading to sicca symptoms and parotid enlargement. pSS has been linked to various neurological manifestations, including peripheral neuropathy (PN). We aimed to provide a comprehensive analysis of the currently available evidence regarding pSS-related PN. METHODS: A literature search in the PubMed database was performed, and 49 papers were eligible to be included in this systematic review and meta-analysis. RESULTS: The pooled prevalence of PN in pSS is estimated to be 15.0% (95% confidence interval = 10.7%-20.7%). The mean age of pSS patients at PN diagnosis is 59 years. Among the patients with pSS and PN, 83% are females. Neuropathic symptoms usually precede or lead to the pSS diagnosis at a 2:1 ratio in patients with pSS-related PN. The commonest type of pSS-related PN is distal axonal polyneuropathy (80% of patients with pSS-related PN), followed by sensory ganglionopathy. Peripheral and cranial mononeuropathies-particularly trigeminal-are also frequent. Risk factors for developing PN include increasing age and presence of vasculitis. Immune-mediated pathogenetic mechanisms are discussed. Glucocorticoids are the most commonly used treatment option for managing pSS-related PN, when associated with vasculitis, followed by the use of intravenous immunoglobulin. CONCLUSIONS: PN is very common in pSS patients. Evidence on long-term prognosis of PN in pSS is limited, and further research is needed. Research into the use of immunosuppressive medication in nonvasculitic neuropathies in the context of pSS merits further consideration.

Mediterranean diet is associated with a lower probability of prodromal Parkinson's disease and risk for Parkinson's disease/dementia with Lewy bodies: A longitudinal study.

BACKGROUND AND PURPOSE: Lifestyle factors have been implicated in the long-lasting neurodegenerative process in prodromal Parkinson's disease (pPD). The aim was to investigate the associations between adherence to a Mediterranean diet (MeDi) and longitudinal changes of pPD probability and the development of Parkinson's disease (PD) or pPD in a Mediterranean older population. METHODS: Data from the Hellenic Longitudinal Investigation of Aging and Diet cohort (community-dwelling individuals, aged ≥ 65 years) were used. A detailed food frequency questionnaire was used to evaluate dietary intake and calculate MeDi adherence score, ranging from 0 to 55, with higher scores indicating higher adherence. The probability of pPD was calculated according to the updated Movement Disorder Society research criteria. RESULTS: In all, 1047 non-PD/dementia with Lewy bodies (DLB) participants were followed for 3 ± 1 years. MeDi adherence was associated with lower increase in pPD probability over time (b = -0.003, 95% confidence interval -0.006 to -0.001, p = 0.010). Forty-nine participants had incident possible/probable pPD (i.e., pPD probability ≥ 30%). Compared to the participants in the lowest quartile of MeDi adherence, those in the higher quartiles had an approximately 60%-70% lower risk for possible/probable pPD (p for trend 0.003). MeDi-pPD associations were driven by both motor and non-motor pPD markers and not from risk markers. Also, 21 participants were diagnosed with PD/DLB at follow-up. For each unit increase in the MeDi score, there was a 9%-10% lower risk for PD/DLB (hazard ratio 0.906 [95% confidence interval 0.823-0.997], p = 0.044). CONCLUSIONS: Mediterranean diet adherence is associated with lower increase in pPD probability over time and lower possible/probable pPD and PD/DLB incidence in older Mediterranean people. More studies are needed to confirm our results in other populations.

Pesticides and tremor: An overview of association, mechanisms and confounders.

Pesticides are a heterogeneous class of chemicals mainly used for the protection of crops from pests. Because of their very widespread use, acute or/and chronic exposure to these chemicals can lead to a plethora of sequelae inflicting diseases, many of which involve the nervous system. Tremor has been associated with pesticide exposure in human and animal studies. This review is aimed at assessing the studies currently available on the association between the various types of pesticides/insecticides and tremor, while also accounting for potential confounding factors. To our knowledge, this is the first coherent review on the subject. After appraising the available evidence, we call for more intensive research on this topic, as well as intonate the need of implementing future preventive measures to protect the exposed populations and to reduce potential disabilities and social drawbacks.

Prevalence and Determinants of Restless Legs Syndrome (Willis-Ekbom Disease) in an Older Greek Population.

OBJECTIVES: The present study aimed to explore the descriptive and analytic epidemiology of restless legs syndrome (RLS) in the older Greek population, with a specific focus on lifestyle indicators. METHODS: Baseline data from the randomly selected non-demented older participants of the population-based HELIAD cohort were analyzed. Multivariable binary logistic regression with RLS diagnosis as the dichotomous dependent outcome was performed. Demographic, socioeconomic, anthropometric, dietary, sleep-related and psychological parameters, physical activity, use of psychoactive substances and personal medical history were investigated for potential associations. RESULTS: A total of 133 from the eligible sample of 1,838 participants were diagnosed with RLS. The mean age-sex standardized prevalence of RLS among the elderly was estimated at 6.1% (95%CI = 5.0-7.2), with a female (8.0%, 95%CI = 6.4-9.6) to male (3.7%, 95%CI = 2.4-5.1) ratio of 2.1. The prevalence of RLS peaked during the 8th decade of life and diminished thereafter. The positive associations of RLS with female sex [OR = 2.06, 95%CI = (1.19-3.57)], anxiety levels [assessed by the 22-point HADS scale, OR = 1.08, 95%CI = (1.03-1.13)] and traumatic brain injury [OR = 2.22, 95%CI = (1.37-3.62)] were reproduced. Good sleep quality was related to 55% [95%CI~(24-83%)] lower odds of having RLS in comparison with both poor and moderate quality. Adherence to the Mediterranean dietary pattern [assessed by a 55-point scale, OR = 1.06, 95%CI = (1.01-1.11)], and low daily energy intake [low-moderate vs. low: OR = 0.45, 95%CI = (0.26-0.79)]; [moderate-high vs. low: OR = 0.69, 95%CI = (0.40-1.22)]; [high vs. low: OR = 0.31, 95%CI = (0.13-0.69)] were related to RLS for the first time. CONCLUSIONS: More emphasis should be placed on the dietary-nutritional aspects of RLS.

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.

Lack of Association between CD33 rs3865444 and Amyotrophic Lateral Sclerosis: A Case-Control Study.

BACKGROUND: Microglial activation is considered to assume a role in the pathogenesis of Amyotrophic Lateral Sclerosis (ALS). To date, the relationship between ALS and the rs3865444 polymorphism of the cluster of differentiation 33 (CD33) has not been explored. The current report aimed to investigate the potential connection between CD33 rs3865444 and ALS. METHODS: Patients diagnosed with sporadic ALS according to the revised El Escorial criteria, as well as age and sex matched community controls, were enrolled. Two evenly numbered, age and sex matched groups of 155 participants each were genotyped. RESULTS: No association was found between rs3865444 and ALS [log-additive odds ratio (OR) = 0.83 (0.57, 1.22), over-dominant OR = 0.86 (0.55, 1.36), recessive OR = 0.73 (0.25, 2.17), dominant OR = 0.82 (0.52, 1.29), co-dominant OR1 = 0.68 (0.23, 2.05) and co-dominant OR2 = 0.84 (0.53, 1.33)]. Moreover, no relationship was established between rs3865444 and the age of ALS onset based on both unadjusted and sex adjusted Cox-proportional hazards models. Finally, no association between rs3865444 and ALS was found in subgroup analyses based on the site of ALS onset (bulbar or spinal) and sex. CONCLUSIONS: The current analysis is the first to report that rs3865444 is not linked to ALS. Larger multi-racial studies are required to confirm these findings.

Restless legs syndrome due to brainstem stroke: A systematic review.

Restless Legs Syndrome (RLS) is a sleep-related movement disorder, which can also result from brainstem pathology. A systematic review of articles published in the electronic databases PubMed and Web of Science was conducted to summarize the existent literature on RLS associated with a brainstem stroke. We identified eight articles including 19 subjects with RLS due to brainstem ischemic lesion. The symptoms occurred simultaneously with the infarction (66.7%) or few days after (33.3%). The most common location of infarction was pons and less commonly medulla. In most cases (68.4%), symptoms were unilateral. In the majority of those cases (92.3%), the contralateral limb was affected due to a lateral pons infarction. RLS symptoms after infarction improved or resolved in almost 90% of cases within a few days up to 3 months. In almost all patients who received dopaminergic treatment (11 out of 13, 91.7%), the symptoms improved significantly or resolved completely. Screening for RLS has to be considered in patients suffering a brainstem stroke, particularly anteromedial pontine infarction. The appearance of acute unilateral RLS symptoms, usually in association with other sensorimotor deficits, should prompt the clinician to consider a vascular event in the brainstem. RLS in these cases seem to have a favorable outcome and respond well to dopaminergic treatment.

Myelin-associated oligodendrocyte basic protein rs616147 polymorphism as a risk factor for Parkinson's disease.

BACKGROUND: The rs616147 polymorphism of the myelin-associated oligodendrocyte basic protein (MOBP) gene locus has been associated with amyotrophic lateral sclerosis (ALS). ALS and Parkinson's disease (PD) are two common neurodegenerative disorders that share features regarding their etiology, pathophysiology, and genetic backgrounds. While the MOBP rs616147 polymorphism has been associated with ALS, little is known about its role in PD. OBJECTIVE: To assess the role of MOBP rs616147 on PD risk. METHODS: This case-control comparison study consists of 358 PD-affected cases and 358 controls from the Neurology Clinic of the University Hospital of Larissa, University of Thessaly, Faculty of Medicine, in Greece. The diagnosis of PD was made by a specialist neurologist according to the UK Parkinson's Disease Society Brain Bank's clinical criteria. All the participants were genotyped for the MOBP rs616147. Furthermore, in order to validate our results, we genotyped 327 patients with Alzheimer's disease (AD) for MOBP rs616147 and compared them with the control group. RESULTS: According to the univariate analysis, there was a significant association between rs616147 and PD in the dominant (OR [95% C.I.] = 0.70 [0.52-0.94], p = .018), the overdominant (OR [95% C.I.] = 0.68 [0.50-0.92], p = .011), and in the codominant (G/A VS G/G; OR [95% C.I.] = 0.66 [0.48-0.91], p = .035) modes of inheritance. In contrast, there was no association between the MOBP rs616147 polymorphism and AD. CONCLUSIONS: We provide preliminary results associating MOBP rs616147 genetic variant with PD.

TREM2 R47H variant and risk for Alzheimer's disease: assessment in a Greek population and updated meta-analysis.

INTRODUCTION: Rare coding variants in TREM2 and their association with the susceptibility towards Alzheimer's disease (AD) were recently studied in various ethnic groups with contradictory results. The T allele of the rs75932628 (p.R47H variant) has shown a positive risk association with AD in several studies; however, neither a study in Greece nor an updated meta-analysis have been conducted. OBJECTIVE: To assess the association between TREM2 rs75932628 and late-onset (sporadic) AD in a Greek population, and perform a meta-analysis of current data. MATERIALS AND METHODS: The rs75932628 was genotyped in a total of 327 patients with AD and 700 cognitively healthy controls. A systematic search and meta-analyses of studies presenting data regarding rs75932628 in AD cases and controls were also performed. RESULTS: Three patients vs. none of the controls were found to carry the heterozygous risk allele of the rs75932628, yielding a significant association (p = 0.032), in the Greek sample. In the meta-analysis, the overall odds ratio (OR) under a fixed-effects model was 2.98 (Confidence Interval (CI):2.52-3.53) showing a significant association of the rs75932628-T allele with AD in the overall dataset, based on data from 27 studies (26200 AD cases and 142084controls). Caucasian population-only studies (n = 16) revealed a similar OR of 2.93 (CI:2.45-3.51), whereas Asian population-only studies (n = 5) had a non-significant OR of 0.84 (CI:0.19-3.74). CONCLUSION: The rs75932628 was associated with AD in the Greek sample. Our meta-analysis, covering a total population of over 168,000 people, also showed a significant association of the allele with AD in Caucasian populations.

Identification of a novel de novo KMT2B variant in a Greek dystonia patient via exome sequencing genotype-phenotype correlations of all published cases.

Mutations in Lysine-Specific Histone Methyltransferase 2B gene (KMT2B) have been reported to be associated with isolated and complex early-onset generalized dystonia. We describe clinico-genetic features on a Greek patient with a novel de novo variant and demonstrate the phenotypic spectrum of KMT2B variants. We performed whole exome sequencing (WES), in a Greek patient with sporadic generalized dystonia. Additionally, we performed a systematic review of all published cases with KMT2B variants. The patient presented with isolated and mild generalized dystonia. We identified a novel splice site variant that was confirmed by Sanger sequencing and was not found in parents. This is the first reported KMT2B variant, in the Greek population. This case report further highlights the growing trend of identifying genetic diseases previously restricted to few cases in many different ethnic groups worldwide via exome sequencing. In the systematic review, we evaluated the mutation pathogenicity in all previously reported cases to investigate possible phenotype-genotype correlations. Greater mutation numbers in different populations will be important and mutation-specific functional studies will be essential to identify the pathogenicity of the various KMT2B variants.

Lack of association between TREM2 rs75932628 variant and amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative disease. Inflammatory processes are among the mechanisms that are implicated in ALS pathogenesis. The TREM2 rs75932628 T variant may influence the regulatory effect of TREM2 on inflammation. Studies regarding the role of the rs75932628 variant in ALS have yielded inconsistent results, so far. To assess the role of TREM2 rs75932628 on ALS risk. We genotyped 155 patients with sporadic ALS and 155 healthy controls for TREM2 rs75932628. We also merged and meta-analyzed our data with data from previous studies (with a total of 7524 ALS cases and 14,675 controls), regarding TREM2 rs75932628 and ALS. No ALS or healthy subjects carried the TREM2 rs75932628-T variant. Results from meta-analyses (overall approach and sensitivity analyses) yielded no significant results for possible connection between TREM2 rs75932628-T variant and ALS. Based on our results, TREM2 rs75932628 does not seem to play a determining role to the pathophysiology of ALS.

CYP1A2 rs762551 polymorphism and risk for amyotrophic lateral sclerosis.

BACKGROUND: Genetic variability is considered to confer susceptibility to amyotrophic lateral sclerosis (ALS). Oxidative stress is a significant contributor to ALS-related neurodegeneration, and it is regulated by cytochromes P450 (CYPs), such as CYP1A2; these are responsible for the oxidative metabolism of both exogenous and endogenous substrates in the brain, subsequently impacting ALS. The function of CYP1A2 is largely affected by genetic variability; however, the impact of CYP1A2 polymorphisms in ALS remains underinvestigated. OBJECTIVE: This study aims to examine the possible association of ALS with the CYP1A2 rs762551 polymorphism, which codes for the high inducibility form of the enzyme. METHODS: One hundred and fifty-five patients with sporadic ALS and 155 healthy controls were genotyped for the CYP1A2 rs762551. Statistical testing for the association of CYP1A2 rs762551 with risk for ALS was performed using SNPstats. RESULTS: The CYP1A2 rs762551 C allele was associated with a decreased risk of ALS development. In the subgroup analysis according to the ALS site of onset, an association between CYP1A2 rs762551 and limb and bulbar onset of ALS was shown. Cox proportional-hazard regression analyses revealed a significant effect of the CYP1A2 rs762551 on the age of onset of ALS. CONCLUSIONS: Based on our results, a primarily potential link between the CYP1A2 rs762551 polymorphism and ALS risk could exist.

Assessment of TREM2 rs75932628 variant's association with Parkinson's disease in a Greek population and Meta-analysis of current data.

BACKGROUND: Α number of genetic variants are considered to confer susceptibility to Parkinson's disease (PD). Rs75392628 (R47H), a rare variant of TREM2 gene, has been linked to PD, although its role on PD remains conflicting. OBJECTIVE: Detection of a possible contribution of rs75392628 variant of TREM2 gene to PD risk. METHODS: A total of 358 PD patients and 358 healthy controls genotyped for rs75392628. In addition, a meta-analysis was performed by merging our results with those from previous studies. RESULTS: The rare variant of rs75932628 (47H) of TREM2 gene was not detected on cohort. Meta-analysis of a total of 9271 PD cases and 9777 controls across 14 independent PD data sets from 9 studies, including the present study, did not show any statistically significant effect of rs75392628 on PD risk (ORFE:1.54 95% CI:0.87-2.73. ORRE: 1.54, 95%CI: 0.71-3.32). CONCLUSIONS: Rs75392628 TREM2 variant is rather unlikely to be a major genetic risk contributor of PD.

Τhe Greek Variant in APP Gene: The Phenotypic Spectrum of APP Mutations.

Mutations in the gene encoding amyloid precursor protein (APP) cause autosomal dominant inherited Alzheimer's disease (AD). We present a case of a 68-year-old female who presented with epileptic seizures, neuropsychiatric symptoms and progressive memory decline and was found to carry a novel APP variant, c.2062T>G pLeu688Val. A comprehensive literature review of all reported cases of AD due to APP mutations was performed in PubMed and Web of Science databases. We reviewed 98 studies with a total of 385 cases. The mean age of disease onset was 51.3 ± 8.3 (31-80 years). Mutations were most often located in exons 17 (80.8%) and 16 (12.2%). The most common symptoms were dementia, visuospatial symptoms, aphasia, epilepsy and psychiatric symptoms. Mutations in the ß-amyloid region, and specifically exon 17, were associated with high pathogenicity and a younger age of disease onset. We describe the second reported APP mutation in the Greek population. APP mutations may act variably on disease expression and their phenotype is heterogeneous.

MOBP rs616147 Polymorphism and Risk of Amyotrophic Lateral Sclerosis in a Greek Population: A Case-Control Study.

Background and Objectives: To date, only one study has investigated the association between the rs616147 polymorphism of the Myelin-associated Oligodendrocyte Basic Protein (MOBP) locus and Amyotrophic Lateral Sclerosis (ALS). Materials and Methods: A case-control study was performed. Patients with definite sporadic ALS were prospectively and consecutively recruited from the inpatient and outpatient clinics of the Neurology Department of the General University Hospital of Larissa, Central Greece. Community based, age and sex matched healthy individuals with a free personal and family history constituted the control group. Results: A total of 155 patients with definite sporadic ALS and an equal number of healthy controls were genotyped. The power of our sample size was slightly above 80% and MOBP rs616147 was determined to be in Hardy-Weinberg Equilibrium among healthy participants (p = 1.00). According to the univariate analysis, there was no significant relationship between rs616147 and ALS [log-additive OR = 0.85 (0.61, 1.19), over-dominant OR = 0.73 (0.46, 1.15), recessive OR = 1.02 (0.50, 2.09), dominant OR = 0.74 (0.47, 1.16), co-dominant OR1 = 0.71 (0.44, 1.14) and co-dominant OR2 = 0.88 (0.42, 1.84). Additionally, the effect of rs616147 on the age of ALS onset was determined insignificant using both unadjusted and adjusted (sex, site of onset) cox-proportional models. Finally, rs616147 was not related to the site of ALS onset. Conclusions: Our study is the first to report the absence of an association between MOBP rs616147 and ALS among individuals of Greek ancestry. Additional, larger nationwide and multi-ethnic studies are warranted to shed light on the connection between rs616147 and ALS.

Association between Helicobacter pylori infection and Guillain-Barré Syndrome: A meta-analysis.

BACKGROUND: Helicobacter pylori (H pylori) is a Gram-negative bacterium, considered to trigger autoimmune gastrointestinal disorders. This pathogen has also been linked to the autoimmune sequelae in extra-gastrointestinal diseases and peripheral neuropathies. Guillain-Barré syndrome (GBS) is a serious autoimmune demyelinating disorder of peripheral nerves, usually with a post-infectious onset. About 30% of cases of GBS attributed to by Campylobacter jejuni, so, H pylori, could be also involved. Growing evidence suggests the likely involvement of H pylori infection in the development of GBS. The aim of the current study was to therefore estimate the prevalence of H pylori antibodies in GBS. METHODS: A search of the literature was performed, using the PUBMED database, until December 2018. Data were extracted from six case-control studies, and a stratification analysis was conducted according to cerebrospinal fluid (CSF) or serum detection material. RESULTS: Among 29 records found, 6 studies met in the inclusion criteria for the meta-analysis. In the CSF subgroup, 105 participants were involved (40 GBS patients and 65 controls), while the serum subgroup included 325 participants (152 GBS and 173 controls). Data were combined using a fixed-effects model. Anti-H pylori IgG were significantly more prevalent in GBS patients compared to controls, in both CSF (95% CI: 9.66-186.56, OR: 42.45, Pz < .00001) and serum (95% CI: 1.30-4.11, OR: 2.31, Pz: .004) subgroups. CONCLUSION: The present meta-analysis showed a strong association between GBS and the presence of H pylori antibodies, especially in CSF, thereby suggesting a role of H pylori infection in the pathophysiology of GBS.

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.

Social life characteristics in relation to adherence to the Mediterranean diet in older adults: findings from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) study.

OBJECTIVE: The present study aimed to explore the associations between social life and adherence to a healthy dietary pattern, the Mediterranean diet (MD), in a population-representative cohort of older people. DESIGN: Cross-sectional study. Adherence to the MD was evaluated by an a priori score; tertiles of the score, indicating low, medium and high adherence, were used in the analyses. Social life was assessed by a questionnaire evaluating participation in leisure-time activities and the number of social contacts; primary occupation was also recorded and job characteristics were further explored. SETTING: Community-dwelling older adults. PARTICIPANTS: Adults from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) study (n 1933; age range 65-99 years). RESULTS: Each unit increase in the number of social contacts/month and in the frequency score of intellectual, social and physical activities was associated with a 1·6, 6·8, 4·8 and 13·7 % increase in the likelihood of a participant being in the high MD adherence group, respectively. The analysis by age group revealed that younger elderly participants had a 1·4, 8·4 and 11·3 % higher likelihood to be in the high adherence group for each unit increase in the number of social contacts/month and in the frequency score of engagement in intellectual and physical activities, respectively. Similar associations were found for older elderly participants with high compared with low MD adherence, except for the intellectual activities. CONCLUSIONS: The present results suggest that high MD adherence is associated with good social life, suggesting a clustering of health-promoting lifestyle factors in older adults.

Neurodegeneration and Inflammation-An Interesting Interplay in Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder, caused by, so far, unknown pathogenetic mechanisms. There is no doubt that pro-inflammatory immune-mediated mechanisms are pivotal to the pathogenicity and progression of the disease. In this review, we highlight the binary role of microglia activation in the pathophysiology of the disorder, both neuroprotective and neuromodulatory. We present how the expression of several cytokines implicated in dopaminergic neurons (DA) degeneration could be used as biomarkers for PD. Viral infections have been studied and correlated to the disease progression, usually operating as trigger factors for the inflammatory process. The gut-brain axis and the possible contribution of the peripheral bowel inflammation to neuronal death, mainly dopaminergic neurons, seems to be a main contributor of brain neuroinflammation. The role of the immune system has also been analyzed implicating a-synuclein in the activation of innate and adaptive immunity. We also discuss therapeutic approaches concerning PD and neuroinflammation, which have been studied in experimental and in vitro models and data stemming from epidemiological studies.