Association of Body Mass Index and Parkinson Disease: A Bidirectional Mendelian Randomization Study.

BACKGROUND AND OBJECTIVES: The role of body mass index (BMI) in Parkinson disease (PD) is unclear. Based on the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in PD (Courage-PD) consortium, we used 2-sample Mendelian randomization (MR) to replicate a previously reported inverse association of genetically predicted BMI with PD and investigated whether findings were robust in analyses addressing the potential for survival and incidence-prevalence biases. We also examined whether the BMI-PD relation is bidirectional by performing a reverse MR. METHODS: We used summary statistics from a genome-wide association study (GWAS) to extract the association of 501 single-nucleotide polymorphisms (SNPs) with BMI and from the Courage-PD and international Parkinson Disease Genomics Consortium (iPDGC) to estimate their association with PD. Analyses are based on participants of European ancestry. We used the inverse-weighted method to compute odds ratios (ORIVW per 4.8 kg/m2 [95% CI]) of PD and additional pleiotropy robust methods. We performed analyses stratified by age, disease duration, and sex. For reverse MR, we used SNPs associated with PD from 2 iPDGC GWAS to assess the effect of genetic liability toward PD on BMI. RESULTS: Summary statistics for BMI are based on 806,834 participants (54% women). Summary statistics for PD are based on 8,919 (40% women) cases and 7,600 (55% women) controls from Courage-PD, and 19,438 (38% women) cases and 24,388 (51% women) controls from iPDGC. In Courage-PD, we found an inverse association between genetically predicted BMI and PD (ORIVW 0.82 [0.70-0.97], p = 0.012) without evidence for pleiotropy. This association tended to be stronger in younger participants (≤67 years, ORIVW 0.71 [0.55-0.92]) and cases with shorter disease duration (≤7 years, ORIVW 0.75 [0.62-0.91]). In pooled Courage-PD + iPDGC analyses, the association was stronger in women (ORIVW 0.85 [0.74-0.99], p = 0.032) than men (ORIVW 0.92 [0.80-1.04], p = 0.18), but the interaction was not statistically significant (p-interaction = 0.48). In reverse MR, there was evidence for pleiotropy, but pleiotropy robust methods showed a significant inverse association. DISCUSSION: Using an independent data set (Courage-PD), we replicate an inverse association of genetically predicted BMI with PD, not explained by survival or incidence-prevalence biases. Moreover, reverse MR analyses support an inverse association between genetic liability toward PD and BMI, in favor of a bidirectional relation.

Sex hormone binding globulin (SHBG) serum levels and insulin resistance in men on chronic hemodialysis.

BACKGROUND: In males with end stage renal disease biochemical hypogonadism is a frequent finding. Testosterone and sex hormone binding globulin (SHBG) have been associated with insulin resistance, a well-known condition in uremia. The aim of the present study was to investigate in males on chronic hemodialysis the relationship of testosterone and SHBG serum levels with insulin resistance. METHODS: In a cross-sectional study we enrolled men treated with chronic hemodialysis who did not suffer from an acute illness or other endocrinopathy, as well as primary hypogonadism, and were not hospitalised. Diabetes mellitus, diabetic nephropathy or previous transplantation were not exclusion criteria. As controls we used a community-based group of healthy males matched for age and Body Mass Index (BMI). We assessed the BMI (kg/m2) from body weight and height, the body fat content (%) by bioelectrical impedance and serum testosterone (ng/ml), SHBG (nmol/L) and estradiol (pg/ml) by standard methods. Testosterone < 3.25 ng/ml defined biochemical hypogonadism. In non-diabetic males, we calculated the homeostasis model assessment index (HOMA-R), an estimate of insulin resistance, from serum fasting insulin and glucose. RESULTS: 27 men (age 54.4 ± 19 years) on chronic hemodialysis (treatment duration 29.1 ± 14.4 months) and 51 healthy men (age 47.1 ± 9.6 years) were included. In men on hemodialysis vs. healthy men there were increased serum levels of SHBG (40.9 ± 26.9 vs. 27.6 ± 11.9 nmol/L; p = 0.031) and a significantly enhanced frequency of biochemical hypogonadism (22.2 vs. 3.9%; p = 0.011). In cases without diabetes (n = 22) a significant correlation was observed between the HOMA-R (r = -0.586, p = 0.004) and the fasting insulin levels (r = -0.650, p = 0.001) on the one hand and the serum SHBG levels on the other. CONCLUSIONS: Our findings confirm enhanced prevalence of biochemical hypogonadism in males on chronic hemodialysis. In non-diabetic cases the serum levels of SHBG correlated with serum insulin and insulin resistance.

Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction.

Restless legs syndrome (RLS) affects up to 10% of older adults. Their healthcare is impeded by delayed diagnosis and insufficient treatment. To advance disease prediction and find new entry points for therapy, we performed meta-analyses of genome-wide association studies in 116,647 individuals with RLS (cases) and 1,546,466 controls of European ancestry. The pooled analysis increased the number of risk loci eightfold to 164, including three on chromosome X. Sex-specific meta-analyses revealed largely overlapping genetic predispositions of the sexes (rg = 0.96). Locus annotation prioritized druggable genes such as glutamate receptors 1 and 4, and Mendelian randomization indicated RLS as a causal risk factor for diabetes. Machine learning approaches combining genetic and nongenetic information performed best in risk prediction (area under the curve (AUC) = 0.82-0.91). In summary, we identified targets for drug development and repurposing, prioritized potential causal relationships between RLS and relevant comorbidities and risk factors for follow-up and provided evidence that nonlinear interactions are likely relevant to RLS risk prediction.

Longitudinal Cognitive Trajectories in Older Adults with Restless Legs Syndrome or Willis-Ekbom Disease.

Background: Restless legs syndrome/Willis-Ekbom disease (RLS/WED) has occasionally but not consistently been associated with cognitive and most notably language and executive impairment. The present study was conducted to investigate the cognitive trajectories of older individuals with RLS/WED. Methods: Participants were drawn from the randomly selected, older (>64 years), population-based HELIAD cohort. Individuals without dementia and with available neuropsychological evaluations at baseline and follow-up were considered for potential eligibility. A comprehensive assessment examining five principal components of cognition (memory, visuo-spatial ability, attention, executive function, and language) was administered to the participants. Generalized estimating equation analyses were used to examine the unadjusted and adjusted (for critical factors and covariates) effects of RLS/WED on cognition over time. Results: A total of 1003 predominantly female (59.5%), older (72.9 ± 4.9 years) participants with follow-up evaluations after a mean of 3.09 ± 0.85 years and without dementia at baseline and follow-up were included in the present study. Among them, 81 were diagnosed with RLS/WED at baseline. Global cognition, memory, attention, and executive and visuo-perceptual skills did not differ between those with and without RLS/WED. However, the RLS/WED group performed worse on language at baseline by a standard deviation of 0.249, while demonstrating a mitigated language decline over time, by a standard deviation of 0.063. The unadjusted models yielded similar results. Conclusions: Our findings were indicative of a baseline language disadvantage among older individuals with RLS/WED, but the initial discrepancy tends to dissolve over time.

Adult Neoneurogenesis and Oligodendrogenesis in Multiple Sclerosis: A Systematic Review of Human and Animal Studies.

Introduction: The subventricular zone promotes remyelination through activation differentiation of oligodendroglial precursor cells (OPCs) and neural stem cells (NSCs) into mature oligodendrocytes and thus in the adult brain. In multiple sclerosis (MS) this regenerative capability is halted resulting in neurodegeneration. We aimed to systematically search and synthesize evidence on mechanisms and phenomena associated with subventricular zone (SVZ) dysfunction in MS. Materials and Methods: Our systematic review was reported according to the PRISMA-ScR statement. MEDLINE, SCOPUS, ProQuest, and Google Scholar were searched using the terms "subventricular zone" and "multiple sclerosis," including English-written in vivo and postmortem studies. Results: Twenty studies were included. Thirteen studies on models of experimental autoimmune encephalomyelitis (EAE) reported among others strong stathmin immunoreactivity in the SVZ of EAE models, the role of MOG immunization in neurogenesis impairment, the effect of parenchymal OPCs and NSCs in myelin repair, and the importance of ependymal cells (E1/E2) and ciliated B1 cells in SVZ stem cell signaling. CXCR4 signaling and transcriptional profiles of SVZ microglia, Gli1 pathway, and galactin-3 were also explored. Studies in humans demonstrated microstructural SVZ damage in progressive MS and the persistence of black holes near the SVZ, whereas postmortem confirmed the generation of polysialic acid-neural cell adhesion molecule and NG2-positive progenitors through SVZ activation, SVZ stathmin immunoreactivity, Shh pathway, and Gal-3 upregulation. Discussion: Oligodendrogenesis defects translate to reduced remyelination, a hallmark of MS that determines its end-phenotype and disease course. Conclusion: The role of inflammation and subsequent SVZ microenvironment disruption is evident in MS pathology.

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.

Miller Fischer syndrome after COVID-19 infection and vaccine: a systematic review.

BACKGROUND: COVID-19 (CoranaVirus disease 2019) is an ongoing infectious disease caused by the RNA SARS-CoV-2 virus (Severe Acute Respiratory Syndrome CoronaVirus-2). The virus mainly causes respiratory symptoms, but neurological symptoms have also been reported to be part of the clinical manifestations of the disease. The aim of this study was to systematically review Miller fisher syndrome (MFS) published cases, in the context of COVID-19 infection or vaccination. METHODS: A systematic literature review on Medline was performed. A total of 21 papers were included in the present review. RESULTS: Twenty-two MFS cases (77% males) were identified, 14 related to COVID-19 infection and 8 to vaccination against COVID-19. The median age of the adult patients was 50 years (interquartile range 36-63 years). Sixteen patients (73%) had the classic triad of MFS (ophthalmoplegia, ataxia, areflexia), four (18%) had acute ophthalmoplegia and one other characteristic symptom and two patients (9%) had only one other characteristic symptom, but they tested positive for GQ1b antibodies. Nine (41%) patients had positive GQ1b antibodies and were classified as "definite" MFS. Albuminocytologic dissociation was found in half of the cases. The outcome was favourable in the majority of cases (86%) whereas one patient, despite the initial improvement, died because of a cardiac arrest, after cardiac arrythmia. CONCLUSIONS: MFS after COVID-19 infection/vaccination was found to have the typical epidemiological characteristics of classic MFS; being rare, occurring more often after infection than vaccination, affecting mainly middle-aged males usually within 3 weeks after the event and having an excellent prognosis after treatment with IVIG or even with no treatment at all. We found no evidence that MFS after COVID-19 infection was different from MFS after COVID-19 vaccination, although the former tended to occur earlier.

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.

A case of unusual presentation with anti-glycine receptor (GlyR) and myelin oligodentrocyte glycoprotein (MOG) antibody.

Movement disorders can be a prominent feature in autoimmune encephalitis. Here we present a rare case of a 73-year-old woman, who presented with a complex phenotype with encephalopathy, parkinsonism, cervical dystonia, left-sided hemidystonia and hemifacial spasm of subacute onset and was found to have breast cancer and positive anti-Glycine Receptor (GlyR) and Myelin Oligodentrocyte Glycoprotein (MOG) antibodies.

Longitudinal Examination of Body Mass Index and Cognitive Function in Older Adults: The HELIAD Study.

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

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.

Predictive ability of the clock drawing test to detect mild cognitive impairment and dementia over time: Results from the HELIAD study.

Objective: We investigated the diagnostic accuracy of the Clock Drawing Test (CDT) in discriminating Mild Cognitive Impairment (MCI) and dementia from normal cognition. Additionally, its clinical utility in predicting the transition from normal cognition to MCI and dementia over the course of several years was explored. Method: In total, 1037 older adults (633 women) who completed the CDT in a baseline assessment were drawn from the population-based HELIAD cohort. Among these, 848 participants were identified as cognitively normal, 142 as having MCI and 47 with dementia during the baseline assessment. Of these individuals, 565 attended the follow-up assessment (mean interval: 3.21 years). ROC curve and binary logistic regression analyses were performed. Results: The CDT exhibited good diagnostic accuracy for the discrimination between dementia and normal cognition (AUC = .879, SN = .813, SP = .778, LR+ = 3.66, LR- = .240, < .001, d = 1.655) and acceptable diagnostic accuracy for the discrimination between dementia and MCI (AUC=.761, SN= .750, SP= .689, LR+ = 2.41, LR- = .362, p < .001, d = 1.003). We found limited diagnostic accuracy, however, for the discrimination between MCI and normal cognition (AUC = .686, SN = .764, SP = .502, LR+ = 1.53, LR- = .470, p < .001, d = .685). Moreover, the CDT significantly predicted the transition from normal cognition to dementia [Exp(B)= 1.257, p = .022], as well as the transition from MCI to normal cognition [Exp(B) = 1.334, p = .023] during the longitudinal investigation. Conclusions: The CDT is a neuropsychological test with acceptable diagnostic accuracy for the discrimination of dementia from MCI and normal cognition. Furthermore, it has an important predictive value for the transition from normal cognition to dementia and from MCI to normal cognition.

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.

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.

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.

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.

Anti-MOG Positive Bilateral Optic Neuritis and Brainstem Encephalitis Secondary to COVID-19 Infection: A Case Report.

(1) Introduction: There have been numerous reports on the neuroinvasive competence of SARS-CoV-2. Here, we present a case with anti-MOG positive bilateral optic neuritis and brainstem encephalitis secondary to COVID-19 infection. Additionally, we present a review of the current literature regarding the manifestation of anti-MOG positive optic neuritis as well as anti-MOG positive encephalitis after COVID-19 infection. (2) Case Report: A 59-year-old female patient, with a recent history of COVID-19 infection, presented a progressive reduction of visual acuity and bilateral retrobulbar pain for the last 20 days. An ophthalmological examination revealed a decreased visual acuity (counting fingers) and a bilateral papilledema. An MRI scan of the brain revealed a mild thickening of the bilateral optic nerves and high-intensity lesions in the medial and right lateral pons. A high titer of IgG and IgM antibodies against SARS-CoV-2 in serum and antibodies against myelin oligodendrocyte glycoprotein (anti-MOG) in serum and CSF were revealed. The diagnosis of anti-MOG brainstem encephalitis and optic neuritis was set. (3) Conclusions: The history of COVID-19 infection should raise awareness about these autoimmune and infection-triggered diseases, such as anti-MOG antibody disease.

Vascular burden and genetic risk in association with cognitive performance and dementia in a population-based study.

Background and purpose: Vascular risk factors may influence cognitive function and thus represent possible targets for preventive approaches against dementia. Yet it remains unknown, if they associate with cognition independently of the individual genetic risk for dementia. Methods: In a population-based study of 1172 community-dwelling individuals aged ≥65 years in Greece, we constructed a vascular burden score (VBS; based on presence of hypertension, diabetes, hyperlipidemia, heart disease, and cerebrovascular disease, range 0-5) and a polygenic risk score (PRS) for clinically-diagnosed Alzheimer's disease (AD) based on 23 genetic variants. We then explored in joint models the associations of the PRS for AD and VBS with global cognitive performance, cognitive performance across multiple cognitive domains, and odds of dementia. Results: The mean age of study participants was 73.9 ± 5.2 years (57.1% females). Both the PRS for AD and VBS were associated with worse global cognitive performance (beta per-SD-increment in PRS: -0.06, 95%CI: -0.10 to -0.02, beta per-point-increment in VBS: -0.05, 95%CI: -0.09 to -0.02), worse performance across individual cognitive domains (memory, executive function, attention, language, visuospatial ability), and higher odds of dementia (OR per-SD increment in PRS: 1.56, 95%CI: 1.17-2.09, OR per-point increment in VBS: 1.38, 95%CI: 1.05-1.81). There was no evidence of an interaction between the two scores. Higher VBS was associated with worse cognitive performance equally across tertiles of the PRS for AD, even among individuals at the highest tertile. Conclusions: Both genetic risk and vascular burden are independently and additively associated with worse cognitive performance and higher odds of dementia.

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.