Type I interferon signaling, cognition and neurodegeneration following COVID-19: update on a mechanistic pathogenetic model with implications for Alzheimer's disease.

COVID-19's effects on the human brain reveal a multifactorial impact on cognition and the potential to inflict lasting neuronal damage. Type I interferon signaling, a pathway that represents our defense against pathogens, is primarily affected by COVID-19. Type I interferon signaling, however, is known to mediate cognitive dysfunction upon its dysregulation following synaptopathy, microgliosis and neuronal damage. In previous studies, we proposed a model of outside-in dysregulation of tonic IFN-I signaling in the brain following a COVID-19. This disruption would be mediated by the crosstalk between central and peripheral immunity, and could potentially establish feed-forward IFN-I dysregulation leading to neuroinflammation and potentially, neurodegeneration. We proposed that for the CNS, the second-order mediators would be intrinsic disease-associated molecular patterns (DAMPs) such as proteopathic seeds, without the requirement of neuroinvasion to sustain inflammation. Selective vulnerability of neurogenesis sites to IFN-I dysregulation would then lead to clinical manifestations such as anosmia and cognitive impairment. Since the inception of our model at the beginning of the pandemic, a growing body of studies has provided further evidence for the effects of SARS-CoV-2 infection on the human CNS and cognition. Several preclinical and clinical studies have displayed IFN-I dysregulation and tauopathy in gene expression and neuropathological data in new cases, correspondingly. Furthermore, neurodegeneration identified with a predilection for the extended olfactory network furthermore supports the neuroanatomical concept of our model, and its independence from fulminant neuroinvasion and encephalitis as a cause of CNS damage. In this perspective, we summarize the data on IFN-I as a plausible mechanism of cognitive impairment in this setting, and its potential contribution to Alzheimer's disease and its interplay with COVID-19.

Revolutionizing Stroke Recovery: Unveiling the Promise of Stem Cell Therapy.

Stem cells, renowned for their unique regenerative capabilities, present significant hope in treating stroke, a major cause of disability globally. This review offers a detailed analysis of stem cell applications in stroke (ischemic and hemorrhagic) recovery. It examines therapies based on autologous (patient-derived), allogeneic (donor-derived), and Granulocyte-Colony Stimulating Factor (G-CSF) based stem cells, focusing on cell types such as Mesenchymal Stem/Stromal Cells (MSCs), Bone Marrow Mononuclear Stem Cells (BMMSCs), and Neural Stem/Progenitor Cells (NSCs). The paper compiles clinical trial data to evaluate their effectiveness and safety and addresses the ethical concerns of these innovative treatments. By explaining the mechanisms of stem cell-induced neurological repair, this review underscores stem cells' potential in revolutionizing stroke rehabilitation and suggests avenues for future research.

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.

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.

Development of robust normative data for the neuropsychological assessment of Greek older adults.

OBJECTIVE: Normative data for older adults may be tainted by inadvertent inclusion of undiagnosed individuals at the very early stage of a neurodegenerative process. To avoid this pitfall, we developed norms for a cohort of older adults without MCI/dementia at 3-year follow-up. METHODS: A randomly selected sample of 1041 community-dwelling individuals (age ≥ 65) received a full neurological and neuropsychological examination on two occasions [mean interval = 3.1 (SD = 0.9) years]. RESULTS: Of these, 492 participants (Group 1; 65-87 years old) were without dementia on both evaluations (CDR=0 and MMSE ≥ 26); their baseline data were used for norms development. Group 2 (n = 202) met the aforementioned criteria only at baseline, but not at follow-up. Multiple linear regressions included demographic predictors for regression-based normative formulae and raw test scores as dependent variables for each test variable separately. Standardized scaled scores and stratified discrete norms were also calculated. Group 2 performed worse than Group 1 on most tests (p-values < .001-.021). Education was associated with all test scores, age with most, and sex effects were consistent with the literature. CONCLUSIONS: We provide a model for developing sound normative data for widely used neuropsychological tests among older adults, untainted by potential early, undiagnosed cognitive impairment, reporting regression-based, scaled, and discrete norms for use in clinical settings to identify cognitive decline in older adults. Additionally, our co-norming of a variety of tests may enable intra-individual comparisons for diagnostic purposes. The present work addresses the challenge of developing robust normative data for neuropsychological tests in older adults.

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.

Trajectories of healthy aging and their association with prodromal parkinson disease: The HELIAD study.

Background: The aim of the present study was to investigate the association of prodromal PD (pPD) with trajectories of healthy aging, according to its latest definition by the WHO.Methods: In a sample of 1,226 older adults (704 women), PD diagnosis was reached through standard clinical research procedures. Probability of pPD was calculated according to the International Parkinson and Movement Disorder Society's research criteria for PD-free participants. A healthy aging metric was introduced using an item response theory approach (IRT) based on information from validated questionnaires assessing functionality. Four trajectories of healthy aging were created based on whether the healthy aging status of participants was above or below the median at baseline and follow up: High-High, High-Low, Low-High and Low-Low.Results: 34.3% belonged to the High-High group, 15.7% to the High-Low, 18.6% to the Low-High and 31.4% to the Low-Low group. Participants with possible/probable pPD were 78% less likely to belong in High-High trajectory of healthy aging as compared to those without pPD (OR = 0.22, 95%CI 0.06-0.79, p-value = 0,02).Conclusion: Our findings suggest an inverse association of pPD probability with healthy aging among older adults; Further research is needed to investigate the clinical implications of this association.

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

OBJECTIVES: To study (i) the prevalence of mild and moderate-to-severe depressive symptoms in the entire spectrum of cognitive ageing in Greece and (ii) the relationship between these symptoms and demographic and clinical data. METHODS: The study was based on the randomly selected cohort of the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD). Depressive symptoms were assessed with the 15-item version of the Geriatric Depression Scale. Participants also received a comprehensive neuropsychological assessment, while the clinical diagnoses of dementia and mild cognitive impairment were established according to international diagnostic criteria. Statistical analyses relied on comparison tests and a logistic (proportional odds) ordinal regression model. RESULTS: Depressive symptoms were detected in 19.5% of the 1936 study participants, while 11.3% of both people with MCI and dementia had moderate-to-severe depressive symptoms. The regression model revealed that older adults with more severe depressive symptoms were more likely female, cognitively impaired, less educated, were treated with psychotropic medication and lived in Attica versus Thessaly. CONCLUSIONS: Since depressive symptoms were detected in almost one in five older adults, healthcare professionals in Greece should safeguard the timely detection and effective treatment of such symptoms and the post-diagnostic care of older adults with depression.Key pointsDepressive symptoms are present in approximately 20% of older adults.More than 10% of older individuals with dementia or mild cognitive impairment report moderate-to-severe depressive symptoms.Female sex, lower education, lower cognitive performance, living in urban areas and treatment with psychotropic medication pertain to more severe depressive symptoms in ageing.Timely detection and effective treatment of depressive symptoms are crucial in the clinical practice of the care of older adults.Further research is needed in order to elucidate the complex relationship between depressive symptoms and cognitive impairment in ageing.

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

Background and Objectives: The present study explored the utilization of verbal fluency (VF) cognitive strategies, including clustering, switching, intrusions, and perseverations, within both semantic (SVF) and phonemic (PVF) conditions, across a continuum of neurocognitive decline, spanning from normal cognitive ageing (NC) to mild cognitive impairment (MCI) and its subtypes, amnestic (aMCI) and non-amnestic (naMCI), as well as AD. Materials and Methods: The study sample was derived from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) cohort. The sample included 1607 NC individuals, 146 with aMCI (46 single-domain and 100 multi-domain), 92 with naMCI (41 single-domain and 51 multi-domain), and 79 with AD. Statistical analyses, adjusting for sex, age, and education, employed multivariate general linear models to probe differences among these groups. Results: Results showed that AD patients exhibited poorer performance in switching in both VF tasks and SVF clustering compared to NC. Similarly, the aMCI group performed worse than the NC in switching and clustering in both tasks, with aMCI performing similarly to AD, except for SVF switching. In contrast, the naMCI subgroup performed similarly to those with NC across most strategies, surpassing AD patients. Notably, the aMCI subgroup's poor performance in SVF switching was mainly due to the subpar performance of the multi-domain aMCI subgroup. This subgroup was outperformed in switching in both VF tasks by the single-domain naMCI, who also performed better than the multi-domain naMCI in SVF switching. No significant differences emerged in terms of perseverations and intrusions. Conclusions: Overall, these findings suggest a continuum of declining switching ability in the SVF task, with NC surpassing both aMCI and AD, and aMCI outperforming those with AD. The challenges in SVF switching suggest executive function impairment associated with multi-domain MCI, particularly driven by the multi-domain aMCI.

Secondary Central Nervous System Demyelinating Disorders in the Elderly: A Narrative Review.

Secondary demyelinating diseases comprise a wide spectrum group of pathological conditions and may either be attributed to a disorder primarily affecting the neurons or axons, followed by demyelination, or to an underlying condition leading to secondary damage of the myelin sheath. In the elderly, primary demyelinating diseases of the central nervous system (CNS), such as multiple sclerosis, are relatively uncommon. However, secondary causes of CNS demyelination may often occur and in this case, extensive diagnostic workup is usually needed. Infectious, postinfectious, or postvaccinal demyelination may be observed, attributed to age-related alterations of the immune system in this population. Osmotic disturbances and nutritional deficiencies, more commonly observed in the elderly, may lead to conditions such as pontine/extrapontine myelinolysis, Wernicke encephalopathy, and demyelination of the posterior columns of the spinal cord. The prevalence of malignancies is higher in the elderly, sometimes leading to radiation-induced, immunotherapy-related, or paraneoplastic CNS demyelination. This review intends to aid clinical neurologists in broadening their diagnostic approach to secondary CNS demyelinating diseases in the elderly. Common clinical conditions leading to secondary demyelination and their clinical manifestations are summarized here, while the current knowledge of the underlying pathophysiological mechanisms is additionally presented.

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.

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.

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.

Olfactory schwannomas - an enigmatic clinical entity.

Olfactory Schwannomas (OS) are a rare, benign tumour entity. Throughout literature, only few cases have been reported. We describe here a case of a 75-year-old female with a contrast enhanced mass lesion in the anterior fossa, who underwent a surgical removal and its histopathological analysis was consistent with a schwannoma. The description of the origin of this tumour is intriguing and enigmatic. Although rare, this type of tumour should always be included in the differential diagnosis of anterior fossa lesions. Further research on the pathogenesis and the natural course of OS is needed.

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.

Selenium, Stroke, and Infection: A Threefold Relationship; Where Do We Stand and Where Do We Go?

Stroke is currently the second most common cause of death worldwide and a major cause of serious long-term morbidity. Selenium is a trace element with pleotropic effects on human health. Selenium deficiency has been associated with a prothrombotic state and poor immune response, particularly during infection. Our aim was to synthesize current evidence on the tripartite interrelationship between selenium levels, stroke, and infection. Although evidence is contradictory, most studies support the association between lower serum selenium levels and stroke risk and outcomes. Conversely, limited evidence on the role of selenium supplementation in stroke indicates a potentially beneficial effect of selenium. Notably, the relationship between stroke risk and selenium levels is bimodal rather than linear, with higher levels of serum selenium linked to disturbances of glucose metabolism and high blood pressure, morbidities which are, in turn, substrates for stroke. Another such substrate is an infection, albeit forming a bidirectional relationship with both stroke and the consequences of impaired selenium metabolism. Perturbed selenium homeostasis leads to impaired immune fitness and antioxidant capacity, which both favor infection and inflammation; specific pathogens may also contend with the host for transcriptional control of the selenoproteome, adding a feed-forward loop to this described process. Broader consequences of infection such as endothelial dysfunction, hypercoagulation, and emergent cardiac dysfunction both provide stroke substrates and further feed-forward feedback to the consequences of deficient selenium metabolism. In this review, we provide a synthesis and interpretation of these outlined complex interrelationships that link selenium, stroke, and infection and attempt to decipher their potential impact on human health and disease. Selenium and the unique properties of its proteome could provide both biomarkers and treatment options in patients with stroke, infection, or both.

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.