AIM:The apolipoprotein E ε4 (APOE ε4) allele is a well-established genetic risk factor for Alzheimer's disease (AD), with a gene-dose effect, but its prevalence and clinical correlates in remain underexplored in South Asians. We examined APOE ε4 homozygosity and its clinical correlates in Indian cohort. PATIENTS AND METHODS:We analyzed APOE genotype data from 393 patients with AD and 850 age-matched healthy controls from India. Variables included family history of dementia, age at onset, behavioral and psychological symptoms of dementia (BPSD), comorbidities (Diabetes and Hypertension), and severity on the Hindi Mental Status Examination (HMSE) and Clinical Dementia Rating (CDR) scale. RESULTS:APOE ε4 allele frequency was higher in patients with AD (25%) than controls (9%); homozygosity was also more frequent among patients (5% vs 1%; X2 = 103.48, p < 0.001). Homozygosity was associated with family history of dementia, [Odds Ratio (OR) 4.03, 95% CI 1.46-11.10, p = 0.007], consistent on Firth analysis, but not with age at onset, duration, severity, BPSD, or comorbidities. CONCLUSION:In this Indian cohort, APOE ε4 homozygosity reflects increased susceptibility and familial aggregation of AD but does not confer a more severe or distinct phenotype, suggesting ancestry- specific expression of APOE ε4 gene-dose effects.
OBJUECTIVE:This study aimed to determine the prevalence of polypharmacy among patients with Multiple Sclerosis (MS) registered in the MS registry system of Gilan Province, Iran, and to analyze the relationships between polypharmacy and various demographic, clinical, and disease-related factors. METHODS:This was a cross-sectional analytical study conducted on 1,282 MS patients registered in Gilan's MS registry system. Data were collected using a researcher-developed questionnaire that included questions on age, gender, marital status, education, occupation, smoking habits, comorbidities, family history of MS, and medication use. RESULTS:The study found that 92.4% of patients used MS-related medications, and 65.5% used at least one non-MS medication. Polypharmacy was significantly associated with age, occupation, history of preexisting illnesses, comorbidities, number of coexisting diseases, and symptoms such as balance and urinary control disorders. Younger patients and those with multiple comorbidities were more likely to engage in polypharmacy. CONCLUSIONS:The results emphasize the high prevalence of polypharmacy in MS patients, underscoring the need for personalized treatment strategies. Educating patients about managing the risks of drug interactions and improving treatment adherence is crucial. The findings can inform healthcare policies to optimize the management of MS in similar regions.
AIMS:Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder. Understanding the underlying causes would help further studies on the pathogenesis and treatments. Recent interest has emerged in evaluating whether the COVID-19 pandemic and vaccination have any influence on the epidemiological patterns of ALS. MATERIALS & METHODS:To assess this association in Isfahan, Iran, during the post-COVID-19 era, we conducted this retrospective study. Newly diagnosed ALS cases were identified, and demographic data, environmental exposures, comorbidities, vaccination history, and other aspects were collected. RESULTS:A total of 63 patients were diagnosed with definite ALS, yielding an incidence rate of 0.74 per 100,000 person-years (95% CI: 0.57-0.94). The mean age was 59.7 ± 11.6 years, and cases were predominantly male (73%). Of the 63 new ALS-diagnosed cases, 45% of patients reported probable prior COVID-19 infection, and 95.3% mentioned at least one dose of COVID-19 vaccination. Bulbar signs, including facial muscle weakness, tongue atrophy, and fasciculation, were present in 46% of cases, and emotional lability and cognitive decline were observed in 20.6%. CONCLUSION:We showed a probable relation between COVID-19 infection and the epidemiology of ALS in post-COVID era. However, our results and symptom alterations require further investigation.
INTRODUCTION:Current Parkinson's disease (PD) treatments offer limited, temporary relief. Fecal microbiota transplantation (FMT) is a potential therapy, but its safety and efficacy remain unclear. METHODS:PubMed, Scopus, Cochrane Library, and Web of Science were searched on 20 July 2026. Eligible studies included adults with PD receiving FMT reporting motor and non-motor outcomes. Study quality was assessed using Joanna Briggs Institute checklists and Cochrane RoB 2. Due to heterogeneity, results were synthesized narratively. RESULTS:Fourteen studies (nine trials, three case series, two case reports; 369 participants) were included. FMT protocols varied in stool preparation, delivery route, regimen, and follow-up (3-12 months). Four of six trials reported modest, short-term motor improvements. Non-motor benefits, mainly gastrointestinal function, sleep, and mood, were inconsistent. Microbiota analyses showed partial or temporary restoration toward healthy profiles. FMT was generally safe, with mainly mild, transient adverse events. Risk of bias varied: two high, four some concerns, one low. CONCLUSIONS:FMT appears safe and may provide short-term improvements in select motor and gastrointestinal outcomes in PD. Evidence is limited by small samples, heterogeneity, and methodological weaknesses. Well-designed, adequately powered RCTs with standardized protocols are needed to determine its therapeutic and disease-modifying potential. REGISTRATION:PROSPERO (CRD42024508462).
AIMS:The primary aim was to explore the relationship between neck weakness in people with motor neurone disease (MND) and their respiratory function. The secondary aim was to identify whether neck weakness can be a prognostic factor. METHODS:This was a retrospective observational cohort study. Data was collected from patient records on MND characteristics, neck weakness, respiratory function, and noninvasive ventilation (NIV) use. Multivariate modeling explored the effect of neck weakness on respiratory variables. RESULTS:MND-related neck weakness was evident in 41% of 324 participants. Fifty-four percent used NIV and 17% became dependent on NIV during disease progression. The presence of neck weakness in MND was predictive of time to respiratory function decline, for respiratory outcomes (forced vital capacity (FVC) <65%, FVC <50% and NIV use) as well as having an effect on time to death. Median time from neck weakness onset to death was 8 months (IQR 10 months; range 0 to 60 months) with bulbar onset the quickest, median of 7 months (IQR 7 months, range 0 to 43 months). CONCLUSIONS:The presence of neck weakness is associated with a more rapid respiratory function decline in MND. In addition, neck weakness can be considered a prognostic factor in MND survival.
INTRODUCTION:Symptomatic management of hereditary spastic paraplegia (HSP) often involves assistive devices, yet neither the timing nor the choice of device is standardized, and their immediate impact on mobility in HSP remains poorly characterized. We aimed to quantify the immediate effects of classical walking aids in HSP, and to identify individualized responses. METHODS:HSP patients and healthy controls performed a standardized 4 × 10 meters walking test under three conditions: unaided, with bilateral walking sticks, and with a four-wheel walker. Mobile gait parameters were recorded for each condition, and participants rated their perceived walking adaptations. RESULTS:In the patient cohort (n = 46), assistive devices significantly improved step length, while other gait parameters were unchanged or worsened. Subgroup analyses indicated that patients with less clinical impairment, but greater fear of falling, older age, and higher body weight derived particular benefit from the use of walking aids. Subjective ratings were generally positive, with most patients assessing the devices as more helpful than baseline. Perceived improvements largely aligned with objective gait changes. CONCLUSIONS:Classical assistive devices may yield measurable, immediate benefits in gait performance in HSP reflecting patient perceptions. Future studies should investigate longer familiarization periods to evaluate sustained functional adaptations and optimize device recommendations.
AIM:To provide evidence-based recommendations for the physiotherapy management of Amyotrophic Lateral Sclerosis (ALS). MATERIALS AND METHODS:Evidence-based recommendations were developed by a multidisciplinary team, including PhDs and master's-level researchers, physicians, and experienced physiotherapists specializing in neurological rehabilitation. RESULTS:After the selection process, 23 studies were included. Eighteen recommendations addressing motor aspects in ALS were formulated. CONCLUSIONS:Therapeutic exercise should be considered to improve or maintain ALSFRS-R scores in people with ALS. However, the effects of other interventions examined in this study remain uncertain with respect to motor aspects.
The microbiota-gut-brain axis (MGBA) is a bidirectional signaling pathway regulated by the gut microbiome and the central nervous system (CNS). Moreover, MGBA is crucial for normal growth, development, and physiology of the brain and gut of the host; dysfunction in MGBA has been closely linked with the development of neurological disorders. Gut dysbiosis and its metabolites modulate barrier permeability and cause gastrointestinal tract (GIT) inflammation, which is followed by an increase in pro-inflammatory cytokines, immune cell infiltration into the brain, and vagus nerve dysfunction, resulting in neuroinflammation and neuronal defects in the brain, as well as some other behavioral defects. In this review, we will discuss the molecular and neurobehavioral properties of Zebrafish as a research model to study MGBA, as well as current discoveries in humans, highlighting the vital role of MGBA in neuropathological conditions. Using Zebrafish as a genetic model in combination with in vivo imaging technology may suggest some novel mechanisms for the interaction between gut microbiota and CNS, particularly in the case of neurological disorders including Alzheimer's disease (AD), Parkinson's disease (PD) and autism spectrum disorder (ASD). A comprehensive literature search was conducted using electronic databases including PubMed, Scopus, Web of Science, and Google Scholar.
Frontotemporal dementia (FTD) is an umbrella term that encompasses a group of clinically heterogeneous neurodegenerative disorders. It is biologically referred to as Frontotemporal lobar degeneration (FTLD) and is characterized by progressive degeneration of frontal and/or temporal lobes. FTD poses substantial diagnostic and therapeutic challenges due to its heterogeneous clinical presentations, limited biomarker specificity, and overlap with other neurodegenerative and psychiatric diseases. This review synthesizes updated knowledge on the clinical phenotypes of FTD, their prognostic elements, and the underlying genetic and molecular mechanisms. Advances in diagnostic strategies are discussed, including structural and functional neuroimaging, fluid biomarkers, and genetic testing, together with emerging digital and AI-assisted tools that may enhance diagnostic precision. Evidence-based management approaches are examined, alongside the role of multidisciplinary care and caregiver support. Promising therapeutic strategies, including gene-targeted interventions, antisense oligonucleotides, progranulin restoration strategies, immunotherapies, and neuromodulation techniques, are discussed considering recent clinical and preclinical developments. Despite the absence of approved disease-modifying therapies, rapid progress in biomarker development, patient stratification, and personalized approaches offers encouraging prospects for more effective interventions across the FTD spectrum. PubMed/MEDLINE was searched for peer-reviewed articles on FTD diagnosis and management; reference lists of key articles were screened to identify additional sources.
INTRODUCTION:Gastrostomy decision-making for people living with motor neurone disease (MND) is complex. While international studies report healthcare professionals' (HCPs) beliefs and practices in this area, little is known about the Australian context. AIM:To examine Australian HCPs' beliefs, clinical practices, and support needs regarding gastrostomy decision-making in MND. METHODS:A national cross-sectional online survey of Australian HCPs involved in gastrostomy discussions (n = 123) was conducted, exploring five domains: 1) initiating discussions and timing; 2) patient education; 3) multidisciplinary coordination; 4) guideline use; 5) and professional development needs. Descriptive statistics were applied. RESULTS:Most HCPs initiated discussions about gastrostomy (74%), commonly prompted by swallowing difficulty, weight loss, or patient request. Although 72% believed discussions should occur before clinical indications, only 40% reported doing so. Earlier placement was favored in the context of respiratory decline compared with swallowing impairment, and 56% considered gastrostomy to be performed too late. Almost 40% used no formal guidelines, and 74% wanted further professional development. CONCLUSION:Australian HCPs valued person-centered practice, but belief-practice gaps highlight opportunities to improve consistency, timing, and quality of gastrostomy decision-making support. Enhanced national guidelines, improved multidisciplinary communication, and targeted professional development may help reduce delays and better align practice with evidence-based recommendations.
INTRODUCTION:As infectious agents may be associated with neurodegenerative diseases, this systematic review and meta-analysis investigated whether prior influenza infection is associated with an increased odds of subsequent Parkinson's disease (PD) diagnosis. METHODS:We searched PubMed, Web of Science, and Scopus for observational studies examining influenza infection and later PD diagnosis. Seven studies (comprising eight cohorts) were analyzed using frequentist and Bayesian random-effects meta-analyses. Meta-regression and subgroup analyses were conducted to explore the moderating effect of the time interval between influenza exposure and subsequent PD diagnosis (i.e. exposure window). RESULTS:A significant association was observed in both approaches: pooled OR = 1.87 (95% CI: 1.24-2.81) under the frequentist model, and posterior median OR = 1.88 (95% CrI: 1.07-3.36) under the Bayesian model. Meta-regression and subgroup analyses identified the influenza exposure window as a moderator (R2 = 36.6%, p < 0.05), with studies reporting influenza exposure within five years before PD diagnosis showing the strongest associations. CONCLUSION:Our findings support a probable and temporally sensitive association between influenza infection and subsequent PD diagnosis. However, these findings should be interpreted cautiously, given the retrospective and heterogeneous nature of the available data.
BACKGROUND:Multiple sclerosis (MS), often leading to a lower quality of life (QoL) for patients compared to those with other chronic diseases. Self-efficacy and self-management play crucial roles in influencing the QoL of MS patients. OBJECTIVES:This study aimed to investigate the association of self-efficacy and self-management with MS patients' QoL. METHODS:The research entailed a descriptive-analytical study involving 210 MS patients selected through simple random sampling. Data was collected with four questionnaires, demographic information, the MSSMs-R, MSSS, as well as MSQOL-54 scales. The gathered data were analyzed using multiple regression model. RESULTS:The study sample consisted of 150 females (71.4%), with 43.3% having university-level education and 82.58% scoring 1-4 on the EDSS scale. The results indicate that Self-efficacy (Beta = 0.283 and 0.389) is the most significant positive predictor of QoL. Along with Health Maintenance Behavior (Beta = 0.278), it accounts for 34.0% of the variance in mental health and, when combined with social/family support, explains 29.7% of the variance in physical health. CONCLUSIONS:The study found a strong association between self-management and self-efficacy and the QoL in patients with MS. Strengthening self-management and self-efficacy skills is recommended to improve the QoL. Furthermore, further research into other factors affecting QoL is suggested.
BACKGROUND:Non-motor symptoms, including depression and excessive daytime sleepiness (EDS), reduce quality of life in Parkinson's disease (PD). Pharmacological treatments may cause side-effects, highlighting the need for non-pharmacological approaches. We conducted an updated meta-analysis with linear and non-linear dose-response meta-regression to evaluate bright light therapy (BLT) on depression and EDS in PD. METHODS:PubMed, Scopus, and WOS were systematically searched through September 2025. Risk of bias was assessed using RoB-2 and NIH single-arm tools. Mean difference (MD) or standardized mean difference (SMD) with 95%confidence intervals (CI) were pooled using fixed-effects models. Linear and non-linear dose-response meta-regressions were performed. RESULTS:Eight studies were identified, six included in meta-analysis. For EDS, five studies (n = 159) showed no significant effect of BLT (MD =-1.14, 95%CI [-2.43, 0.15], p = 0.083, I2 = 0%), with no linear (p = 0.78) or non-linear (p = 0.97) dose-response relationship. For depression, five studies (n = 194) also showed no significant effect (SMD =-0.13, 95%CI [-0.41, 0.16], p = 0.38, I2 = 0%), without linear (p = 0.82) or non-linear (p = 0.85) associations. Sensitivity analyses were consistent. CONCLUSION:BLT was not associated with significant improvement in depression or EDS in PD, and no dose-response relationship was identified. Given methodological limitations, BLT cannot currently be recommended for clinical use. Future standardized dose-finding trials stratified by disease stage and retinal/ipRGC integrity are needed.
Mutations in superoxide dismutase 1 SOD1 are the second most common genetic cause of ALS, usually associated with prevalent lower motor neuron phenotypes. We describe a 66-year-old woman with slowly progressive spastic paraparesis, initially diagnosed as primary lateral sclerosis, who carried a heterozygous p.D91A mutation. Clinical and neurophysiological findings indicated predominant upper motor neuron involvement, an unusual presentation for this mutation. This case broadens the SOD1 phenotypic spectrum and highlights the importance of early genetic testing in atypical motor syndromes, given the availability of targeted therapies where diagnostic delay may limit benefit.
AIMS:Functional gastrointestinal disorders (FGIDs) are part of the non-motor spectrum of idiopathic Parkinson's disease (iPD). The prevalence and relevance of Rome IV-defined functional bowel disorders (FBDs) remain unclear. This study evaluated FBD prevalence and correlates in iPD using a gastroenterology-based control group. METHODS:This cross-sectional study included 64 iPD patients and 64 controls without neurological disease with Rome IV-defined FGIDs. FGIDs were assessed using the Rome IV Diagnostic Questionnaire. Non-motor symptoms, mood, and quality of life were evaluated using NMSS, Hamilton scales, PDQ-39, and GIQLI. Multivariable analyses were performed. RESULTS:FBD prevalence did not differ between iPD and the FGID-enriched control group (20.3% vs. 21.9%, p = 0.828; adjusted OR 0.83, 95% CI 0.23-2.95, p = 0.774). Within iPD, FBD positivity was associated with worse PDQ-39 scores and higher non-motor burden, particularly in attention/memory and sexual domains. Anxiety severity was negatively associated with GIQLI. CONCLUSION:In this FGID-enriched comparison, FBD prevalence was not higher in iPD. However, FBDs were associated with greater non-motor burden and poorer quality of life. These findings suggest FGIDs may be associated with variation in the non-motor phenotype rather than disease risk. Interpretation should be cautious due to control selection and demographic imbalance.
BACKGROUND:Visual hallucinations (VH) are clinically significant non-motor symptoms in Parkinson's disease (PD). Optical coherence tomography (OCT) provides objective retinal measurements, yet the relationship between optic disc structure and VH remains unclear. This study examined whether temporal optic disc alterations are associated with VH in PD. METHODS:In this exploratory cross-sectional study, 30 patients with PD underwent OCT imaging and clinical assessment. Retinal measurements included RNFL thickness and temporal optic disc thickness. VH were identified through structured interviews. Group comparisons and ANCOVA adjusting for non-motor symptom severity were performed. RESULTS:Patients with VH showed greater right temporal optic disc thickness than those without hallucinations (Cohen's d = 1.04, p = 0.009), and this association remained significant after adjustment for UPDRS-I. No differences in retinal measures were observed between tremor-dominant and akinetic-rigid PD subtypes. CONCLUSION:In this preliminary analysis, temporal optic disc thickening showed a nominal association with VH in PD independent of non-motor symptom severity. OCT may provide structural insights into neuropsychiatric heterogeneity in PD. Further studies are needed to clarify the biological basis of this finding and its potential clinical relevance.
BACKGROUND:Neurocognitive disorders involve progressive cognitive decline, reduced functional autonomy, and frequent emotional or neuropsychiatric symptoms. Their variable progression highlights the need to identify factors linked to faster deterioration. AIM:This study aims to longitudinally examine functional autonomy, cognitive performance, and neuropsychiatric symptoms in individuals with mild cognitive impairment (MCI) and dementia to support more targeted and personalized interventions. MATERIALS AND METHODS:This retrospective, single-center observational study includes patients who completed three neuropsychological evaluations approximately 12 months apart (T0, T1, T2). The dataset is expected to include at least 151participants . Data include demographic and diagnostic information, cognitive tests (MMSE, MoCA, MODA, FAB, CDT), functional measures (ADL, IADL), and emotional-behavioral scales (BDI, BAI, GDS, HDR-S, HRSA, NPI). Analyses involve descriptive statistics, group comparisons, longitudinal models, regression analyses, and propensity score methods. RESULTS:Dementia patients are expected to show greater functional decline than those with MCI, although some may maintain autonomy. Emotional-behavioral symptoms are anticipated to correlate with accelerated deterioration. CONCLUSIONS:This protocol offers a multidimensional framework for characterizing decline in neurocognitive disorders and identifying early predictors of progression, supporting more tailored monitoring and intervention strategies. CLINICAL TRIAL REGISTRATION:www.clinicaltrials.gov identifier is NCT07287410.
