Decoding visual evoked potential latency: revealing neurological connections in Parkinson's disease.

Parkinson's disease (PD) is a complex neurodegenerative disorder characterized by diverse motor and non-motor symptoms. Visual evoked potentials (VEPs) provide valuable insights into the neurological changes in PD. This study examines VEP latency to explore potential connections between visual processing and PD progression, focusing on whether inter-eye latency differences are influenced by disease severity and symptomatology. A cross-sectional observational study was conducted with 59 PD patients at the Neurology I Clinic, Cluj-Napoca County Emergency Clinical Hospital, from October 2019 to October 2021. Patients underwent neurological and psychological evaluations, including VEP testing with a reversal pattern technique. P100 wave latency was assessed for both eyes, and associations with clinical indicators like Hoehn and Yahr stages, UPDRS scores, and non-motor symptoms were analyzed. VEP latencies for the right and left eyes were 108.7 ± 10.6 ms and 108.4 ± 9.7 ms, respectively, with no significant inter-eye differences (P = 0.8). UPDRS item 4 scores correlated significantly with both latencies (P = 0.003 for the left eye and P <0.001 for the right). Latency differences between eyes were shorter in patients with symmetrical parkinsonism compared to those with unilateral predominance. Age correlated weakly with P100 latency, and a weak correlation was found between anhedonia scores and right-eye latency. VEP latency is sensitive to PD motor severity, with shorter inter-eye latency differences in symmetrical parkinsonism, suggesting balanced dopaminergic dysfunction. VEP latency differences offer insights into neurophysiological changes in PD, reflecting dopaminergic dysfunction and its impact on visual processing. These findings support the potential of VEPs as diagnostic and prognostic tools in PD assessment.

Non-motor symptoms of Parkinson`s disease-insights from genetics.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by both motor and non-motor symptoms (NMS). NMS including sleep disturbances, depression, anxiety, and constipation are diverse, can precede motor symptoms, and significantly impact patients` quality of life. The severity and type of NMS vary based on age, disease severity, and motor symptoms, and while some respond to dopaminergic treatments, others may be induced or exacerbated by such treatments. NMS also play a role in differentiating PD from drug-induced parkinsonism and are related to gait dysfunction in both early and advanced stages. Genetic factors play a significant role in the development of NMS in PD, with mutations in genes such as SNCA, LRRK2, PRKN, and GBA being associated with severe and early NMS. Familial studies and identification of susceptibility factors have provided insights into the genetic underpinnings of NMS in PD. Neurobehavioral changes, including cognitive decline, are common NMS in PD, and their genetic basis involves a spectrum of mutations shared with other neurodegenerative disorders. Further research is needed to elucidate the functional implications of these genetic factors and their contributions to the pathogenesis of NMS in PD.

Clinical Characteristics of Patients with De Novo Parkinson's Disease and a Positive Family History.

Background/Objectives: A family history of Parkinson's disease (PD) is an important risk factor for developing PD. Because only a few studies have investigated the clinical characteristics of PD patients based on family history, this study compared the clinical characteristics of PD patients with and without a family history of PD. Methods: The study involved 356 patients with de novo PD. The data on the patients' PD family histories were obtained from the patients and their caregivers. Motor and non-motor PD symptoms were assessed using the appropriate scales. Results: Out of the 356 PD patients, 26 (7.3%) had a family history of PD. Compared with patients without a family history of PD, those with a family history of PD tended to be younger at diagnosis (67.9 years vs. 62.2 years, respectively; p = 0.009) and exhibited significantly more severe rigidity (p = 0.036). Motor subtype was not different between the PD patients with and without a family history. PD patients with a family history experienced significantly fewer falls/cardiovascular symptoms within the Non-Motor Symptoms Scale domains (p = 0.001) compared to their counterparts, although this was not statistically significant upon adjusting for age (p = 0.119). Conclusions: In de novo PD patients, having a family history of PD is associated with a younger age at diagnosis and more severe rigidity.

Relationship of Glymphatic Function with Cognitive Impairment, Sleep Disorders, Anxiety and Depression in Patients with Parkinson's Disease.

Introduction: Previous studies have predominantly explored the relationship of the glymphatic system with motor symptoms in Parkinson's disease (PD); however, research on non-motor symptoms remains limited. Therefore, this study investigated the association between glymphatic function and non-motor symptoms, including cognitive impairment and sleep disorders, in PD patients. Methods: This study recruited 49 PD patients and 38 healthy controls (HC). Glymphatic function was evaluated using enlarged perivascular spaces (EPVS) in the basal ganglia (BG) region and diffusion tensor image analysis along the perivascular space (DTI-ALPS) index. Cognition, sleep, anxiety, and depression scales were assessed in all participants. According to the scale scores, PD patients were further divided into several groups to identify the presence of non-motor symptoms. Differences in EPVS numbers and ALPS index between PD subgroups and HC group were compared. Spearman correlation analysis was performed to investigate the association between the PD non-motor symptoms and ALPS index. Additionally, receiver operating characteristic (ROC) curves analysis was conducted for ALPS index to predict cognitive impairment and insomnia in PD patients. Results: PD patients with and without non-motor symptoms all showed more EPVS numbers than the controls, and the EPVS numbers in PD patients with cognitive impairment were also greater than those without. Notably, except for the depression subgroup, PD patients with non-motor symptoms showed significantly lower ALPS index than the controls. The Montreal Cognitive Assessment (MoCA) scores were positively correlated, whereas the Parkinson's Disease Sleep Scale (PDSS)-2 and REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) scores were negatively correlated with the ALPS index in PD patients (r=0.3618, P=0.0053; r=-0.4146, P=0.0015; r=-0.2655, P=0.0326, respectively). The ALPS index proved to be predictive of cognitive impairment and insomnia in PD patients (AUC=0.7733, P=0.001; AUC=0.7993, P=0.0004, respectively). Conclusion: Glymphatic function is closely associated with cognition and sleep of PD patients.

Functional hearing impairment common in Parkinson's disease: Insights from a pilot study.

INTRODUCTION: Hearing impairments in Parkinson's Disease (PD) have received limited attention in the past, possibly because PD patients often report no perceived hearing disability, yet negative consequences of hearing impairment might aggravate communication difficulties and social withdrawal. OBJECTIVE: Our aim was to investigate functional hearing (speech in noise recognition) in PD and evaluate its relationship to neuropsychiatric symptoms, cognition and quality of life. METHODS: Participants with PD were recruited in a tertiary movement disorder clinic. Demographic, audiological, neuropsychiatric and quality of life data were collected. Participants underwent pure tone audiometry (PTA) and Hearing in Noise test (HINT) as a part of their audiological evaluation. RESULTS: A total of 29 participants (mean age: 65.8±8.3 years, M:F= 1.6:1, mean disease duration 5.2 ± 4.0 years) completed the study. All assessments were done in the ON state. 19/29 (65.5 %) participants had normal tone audiometry for age; functional hearing loss, however, was present in 17/29 (58.6 %) according to the HINT. 65 % (11/17) of the affected participants had a disease duration of <4 years. The majority (72.4 %) with poor functional hearing did not perceive any hearing impairment. Hearing deficits did not correlate with non-motor symptoms (NMS), including cognition or other quality of life measures. CONCLUSIONS: Functional hearing loss is common in PD, often presents early in the disease and the majority of PD patients are unaware of their functional hearing loss. Its potential impact on cognition, communication and quality of life requires further investigation and tailored treatment.

Investigating the impact of socioeconomic status on amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the gradual death of motor neurons in the brain and spinal cord, leading to fatal paralysis. Socioeconomic status (SES) is a measure of an individual's shared economic and social status, which has been shown to have an association with health outcomes. Understanding the impact of SES on health conditions is crucial, as it can influence and be influenced by health-related variables. The role of socioeconomic status in influencing the risk and progression of ALS has not been established, and understanding the various factors that impact ALS is important in developing strategies for treatment and prevention. To investigate this relationship, we recruited 413 participants with definite, probable, or possible ALS according to the El Escorial criteria, from three tertiary centers in London, Sheffield, and Birmingham. Logistic regression was used to examine the association between case-control status, socioeconomic criteria, and ALS risk. Linear regression was used to examine the association between age of onset and socioeconomic variables. Two sensitivity analyses were performed, one using an alternative occupational classifier, and the other using Mendelian Randomization analysis to examine association. There was no significant relationship between any variables and ALS risk. We found an inverse relationship between mean lifetime salary and age of ALS onset (Beta = -0.157, p = 0.011), but no effect of education or occupation on the age of onset. The finding was confirmed in both sensitivity analyses and in Mendelian Randomization. We find that a higher salary is associated with a younger age of ALS onset taking into account sex, occupation, years of education, and clinical presentation.

Diffusion tensor metrics, motor and non-motor symptoms in de novo Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic neurons' degeneration of the substantia nigra, presenting with motor and non-motor symptoms. We hypothesized that altered diffusion metrics are associated with clinical symptoms in de novo PD patients. METHODS: Fractional Anisotropy (FA) and Mean (MD), Axial (AD), and Radial Diffusivity (RD) were assessed in 55 de novo PD patients (58.62 ± 9.85 years, 37 men) and 55 age-matched healthy controls (59.92 ± 11.25 years, 34 men). Diffusion-weighted images and clinical variables were collected from the Parkinson's Progression Markers Initiative study. Tract-based spatial statistics were used to identify white matter (WM) changes, and fiber tracts were localized using the JHU-WM tractography atlas. Motor and non-motor symptoms were evaluated in patients. RESULTS: We observed higher FA values and lower RD values in patients than controls in various fiber tracts (p-TFCE < 0.05). No significant MD or AD difference was observed between groups. Diffusion metrics of several regions significantly correlated with non-motor (state and trait anxiety and daytime sleepiness) and axial motor symptoms in the de novo PD group. No correlations were observed between diffusion metrics and other clinical symptoms evaluated. CONCLUSION: Our findings suggest microstructural changes in de novo PD fiber tracts; however, limited associations with clinical symptoms reveal the complexity of PD pathology. They may contribute to understanding the neurobiological changes underlying PD and have implications for developing targeted interventions. However, further longitudinal research with larger cohorts and consideration of confounding factors are necessary to elucidate the underlying mechanisms of these diffusion alterations in de novo PD.

Relationships between physical activities performed under free-living conditions and non-motor symptoms in people with Parkinson's: A systematic review and meta-analysis.

BACKGROUND: Physical activities performed under free-living conditions that are unsupervised in the home or community have the potential to modulate non-motor symptoms in people with Parkinson's disease. OBJECTIVE: This systematic review investigates the relationships between physical activities performed in free-living conditions and non-motor symptoms in people with Parkinson's disease: cognition, anxiety, apathy, depression, sleep disturbances, fatigue, and pain. DATA SOURCES: A database search was performed on Scopus, Web of Science, Ovid (PsycINFO), CINAHL, PubMed, and ProQuest (Health and Medicine). REVIEW METHODS: Observational studies published from 2000 to 2024 that examined the relationships between physical activity and non-motor symptoms were included. The methodological quality of reports was evaluated using critical appraisal checklists appropriate to the study design. Where appropriate, a meta-analysis was conducted to combine data from the included articles. RESULTS: A total of 14 articles met the criteria and used various tools to evaluate non-motor symptoms and physical activity. Meta-analyses showed that people with Parkinson's who are more physically active have better global cognition [ß ranged from 0.12 to 0.28; p = 0.00-0.02] and less affective disorders [ß -0.20, p = 0.00]. Increased physical activity levels were also associated with better sleep quality (n = 1) and less chronic pain (n = 1). The overall methodological quality of the included articles was considered high. CONCLUSION: Engagement in increased levels of physical activities performed under free-living conditions is associated with better cognition and less anxiety, apathy, and depression in people with Parkinson's disease.

Cortical morphological alterations in cognitively normal Parkinson's disease with severe hyposmia.

Olfactory dysfunction is a common non-motor symptom of Parkinson's disease(PD) and may hold valuable insights into the disease's underlying pathophysiology. This study aimed to investigate cortical morphometry alterations in PD patients with severe hyposmia(PD-SH) and mild hyposmia(PD-MH) using surface-based morphometry(SBM) methods. Participants included 36 PD-SH patients, 38 PD-MH patients, and 40 healthy controls(HCs). SBM analysis revealed distinct patterns of cortical alterations in PD-SH and PD-MH patients. PD-MH patients exhibited reduced cortical thickness in the right supramarginal gyrus, while PD-SH patients showed widespread cortical thinning in regions including the bilateral pericalcarine cortex, bilateral lingual gyrus, left inferior parietal cortex, left lateral occipital cortex, right pars triangularis, right cuneus, and right superior parietal cortex. Moreover, PD-SH patients displayed reduced cortical thickness in the right precuneus compared to PD-MH patients. Fractal dimension analysis indicated increased cortical complexity in PD-MH patients' right superior temporal cortex and right supramarginal gyrus, as well as decreased complexity in the bilateral postcentral cortex, left superior parietal cortex, and right precentral cortex. Similarly, cortical gyrification index and cortical sulcal depth exhibited heterogeneous patterns of changes in PD-SH and PD-MH patients compared to HCs. These findings underscore the multifaceted nature of olfactory impairment in PD, with distinct patterns of cortical morphometry alterations associated with different degrees of hyposmia. The observed discrepancies in brain regions showing alterations reflect the complexity of PD's pathophysiology. These insights contribute to a deeper understanding of olfactory dysfunction in PD and provide potential avenues for early diagnosis and targeted interventions.

Prevalence and clinical correlates of nonmotor symptoms in Parkinson's disease in a tertiary health-care center in Turkey.

OBJECTIVE: The objective was to determine the prevalence and clinical correlates of nonmotor symptoms in Parkinson's disease patients in movement disorders outpatient clinics. METHODS: We enrolled all consecutive PD patients who visited our movement disorders outpatient clinics between January and December 2023; and agreed to participate in the study. In addition to the evaluation of demographic and clinical features, clinical scales, including the MDS-UPDRS, NMSS, and FOOGQ, were performed. RESULTS: Overall, we enrolled 163 PD subjects with a mean age of 63.9 ± 10.4 (F/M = 27/136). The disease duration was 3.5 (20) y [median (range)]. The median score of the NMSS was 41 points. The NMSs burden levels were severe in 25.2%, and very severe in 25.2% of the subjects. The subitems with the highest scores were sleep/fatigue, mood/cognition, urinary, and miscellaneous. The analyses within the patient group with newly diagnosed PD also revealed high NMSS scores. Comparisons of the NMSS between distinct PD stages revealed greater NMSS scores in the severe stage than in the mild stage (p = 0.001). Correlation analyses between the clinical scores and the NMSS scores revealed positive correlations between the NMSS scores and the scores on all the clinical scales including the MDS-UPDRS 1-4, and FOGQ. CONCLUSION: We reported the first data regarding the NMS burden in PD patients from Turkey. We found a high prevalence and severity of various domains of NMSs, most of which were sleep/fatigue, mood/cognition, urinary, and miscellaneous. More than half of the patients had severe to very severe NMS burden. Although NMSs were more common severe-stage disease, they were also prevalent in the subgroup with newly diagnosed patients.

Therapeutic Application of Modulators of Endogenous Cannabinoid System in Parkinson's Disease.

The endogenous cannabinoid system (ECS) of the brain plays an important role in the molecular pathogenesis of Parkinson's disease (PD). It is involved in the formation of numerous clinical manifestations of the disease by regulating the level of endogenous cannabinoids and changing the activation of cannabinoid receptors (CBRs). Therefore, ECS modulation with new drugs specifically designed for this purpose may be a promising strategy in the treatment of PD. However, fine regulation of the ECS is quite a complex task due to the functional diversity of CBRs in the basal ganglia and other parts of the central nervous system. In this review, the effects of ECS modulators in various experimental models of PD in vivo and in vitro, as well as in patients with PD, are analyzed. Prospects for the development of new cannabinoid drugs for the treatment of motor and non-motor symptoms in PD are presented.

Burden of non-motor symptoms of Parkinson's disease: cost-of-illness and quality-of-life estimates through a scoping review.

INTRODUCTION: Parkinson's Disease (PD) is a progressive, chronic neurodegenerative disease, representing significant economic and social burdens. It is typically defined by motor symptoms (MSs), however, this does not reflect the full patient burden. Non-motor symptoms (NMSs) are increasingly recognized as central characteristics of PD. However, they still lack recognition in research. Therefore, this study aims to identify relevant NMSs, their prevalence, and the effect they have on Quality-of-Life (QoL) and Cost-of-Illness (COI). Secondly, it aims to identify gaps in the current body of knowledge and propose possible ways future research could bridge those gaps. METHODS: The study employed a scoping review, identifying 60 records for inclusion, using PubMed and Web of Science. It included studies from Spain or Italy, including data on People with Parkinson's Disease. A comparative analysis was performed using Microsoft Excel. RESULTS: It showed that the body of evidence relevant to NMSs, their prevalence, QoL, and COI is limited, or that estimates vary to an extent where interpretation is difficult. CONCLUSION: Most studies suffer from generalization, representation, and standardization issues, stemming from their designs and methodological decisions. Although the findings of this study should be interpreted with caution, several recommendations are made for future research.

In-Patient Multimodal Intensive Neurorehabilitation and Care Improve Motor and Non-Motor Functions in the Moderately Advanced Stages of Parkinson's Disease: A Retrospective Study in a U.S. Facility.

(1) Background: Previous studies, mostly performed in European centers, have shown that in-patient multimodal intensive rehabilitation treatments lasting for two to four weeks can improve both motor and non-motor symptoms of Parkinson's disease (PD) with long-lasting effects. Here, we ascertain the effects of a similar in-patient program in a U.S. center with a retrospective study in a cohort of 153 patients in the moderately advanced stage of PD. (2) Methods: We compared indices of motor and non-motor functions before and immediately after such treatment and investigated the possible differences between men and women. We used the available records of the Beck Depression Inventory, PDQ39, PD Sleep Scale, Timed Up and Go, Vocal Volume, Voice Handicap, and total UPDRS scores. (3) Results: We found that at the end of treatment, which lasted an average of 14 days, all outcome measures significantly improved independently of sex. (4) Conclusions: These results confirm the previous findings with a similar in-patient approach in European centers. They further suggest that this in-patient treatment is a care model that is feasible in U.S. centers and can provide a more immediate benefit to the motor function and quality of life of patients with moderately advanced PD.

Central Role of Hypothalamic Circuits for Acupuncture's Anti-Parkinsonian Effects.

Despite clinical data stretching over millennia, the neurobiological basis of the effectiveness of acupuncture in treating diseases of the central nervous system has remained elusive. Here, using an established model of acupuncture treatment in Parkinson's disease (PD) model mice, we show that peripheral acupuncture stimulation activates hypothalamic melanin-concentrating hormone (MCH) neurons via nerve conduction. We further identify two separate neural pathways originating from anatomically and electrophysiologically distinct MCH neuronal subpopulations, projecting to the substantia nigra and hippocampus, respectively. Through chemogenetic manipulation specifically targeting these MCH projections, their respective roles in mediating the acupuncture-induced motor recovery and memory improvements following PD onset are demonstrated, as well as the underlying mechanisms mediating recovery from dopaminergic neurodegeneration, reactive gliosis, and impaired hippocampal synaptic plasticity. Collectively, these MCH neurons constitute not only a circuit-based explanation for the therapeutic effectiveness of traditional acupuncture, but also a potential cellular target for treating both motor and non-motor PD symptoms.

Non-Motor Effects of Low-Frequency Deep Brain Stimulation of the Subthalamic Nucleus in Parkinson's Disease: A Systematic Review.

INTRODUCTION: Deep brain stimulation of the subthalamic nucleus is an effective therapy for the motor symptoms of Parkinson's disease (PD). Typically, stimulation is applied at a high frequency (≥100 Hz) to alleviate motor symptoms. However, the effects on non-motor symptoms can be variable. Low-frequency oscillations are increasingly recognized as playing an important role in the non-motor functions of the subthalamic nucleus. Therefore, it has been hypothesized that low-frequency stimulation of the subthalamic nucleus (<100 Hz) may have a direct effect on these non-motor functions, thereby preferentially impacting non-motor symptoms of PD. Despite important therapeutic implications, the literature on this topic has not been summarized. METHOD: To understand the current state of the field, we performed a comprehensive systematic review of the literature assessing the non-motor effects of low-frequency stimulation of the subthalamic nucleus in PD. We performed a supplementary meta-analysis to assess the effects of low- versus high-frequency stimulation on verbal fluency outcomes. RESULTS: Our search returned 7,009 results, of which we screened 4,199 results. A total of 145 studies were further assessed for eligibility, and a total of 21 studies met our inclusion criteria, representing 297 patients. These studies were a mix of case reports and control trials. The four clinical outcomes measured were sleep, sensory perception, cognition, and mood. A supplementary meta-analysis of six studies investigating the impact of low-frequency stimulation on verbal fluency did not find any significant results when pooling across subgroups. CONCLUSION: LFS of the STN may have benefits on a range of cognitive and affective symptoms in PD. However, current studies in this space are heterogeneous, and the effect sizes are small. Factors that impact outcomes can be divided into stimulation and patient factors. Future work should consider the interactions between stimulation location and stimulation frequency as well as how these interact depending on the specific non-motor phenotype.

Pain in Multiple System Atrophy: A Community-Based Survey.

BACKGROUND: Pain is a frequent yet poorly characterized symptom of multiple system atrophy (MSA). Understanding the factors influencing pain and its burden is crucial for improving the symptomatic treatment and quality of life of MSA individuals. OBJECTIVE: This study aimed at assessing the prevalence, characteristics, and current treatment strategies for pain in MSA. METHODS: A community-based, online survey was conducted from February to May 2023. Invitations were extended to MSA individuals and informal MSA caregivers through patient advocacies and social media. RESULTS: We included 190 persons with MSA and 114 caregivers. Eighty-seven percent of MSA individuals reported pain, which was more prevalent among women (odds ratio [OR]: 6.38 [95% confidence interval, CI: 1.27-32.08], P = 0.025) and low-income groups (OR: 5.02 [95% CI: 1.32-19.08], P = 0.018). Neck and shoulders (58%), back (45%), and legs (45%) were mostly affected. In the neck and shoulders, pain was associated with MSA core features, like orthostatic intolerance (OR: 4.80 [95% CI: 1.92-12.02], P = 0.001) and antecollis (OR: 3.24 [95% CI: 1.54-6.82], P = 0.002). Seventy-six percent of individuals experiencing pain received treatment, mostly nonsteroidal anti-inflammatory drugs (47%), acetaminophen (39%), and opioids (28%). Only 53% of respondents reported at least partial satisfaction with their current pain management. Pain mostly impacted work, household activities, and hobbies of MSA individuals, and caregivers' social activities. CONCLUSIONS: Pain is more prevalent than previously reported in MSA and particularly affects women and low-income groups. Despite its frequency, pain management remains suboptimal, highlighting an urgent therapeutic need, likely entailing an optimized management of MSA core motor and non-motor features. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Alpha Synuclein Toxicity and Non-Motor Parkinson's.

Parkinson's disease (PD) is a common multisystem neurodegenerative disorder affecting 1% of the population over the age of 60 years. The main neuropathological features of PD are the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the presence of alpha synuclein (αSyn)-rich Lewy bodies both manifesting with classical motor signs. αSyn has emerged as a key protein in PD pathology as it can spread through synaptic networks to reach several anatomical regions of the body contributing to the appearance of non-motor symptoms (NMS) considered prevalent among individuals prior to PD diagnosis and persisting throughout the patient's life. NMS mainly includes loss of taste and smell, constipation, psychiatric disorders, dementia, impaired rapid eye movement (REM) sleep, urogenital dysfunction, and cardiovascular impairment. This review summarizes the more recent findings on the impact of αSyn deposits on several prodromal NMS and emphasizes the importance of early detection of αSyn toxic species in biofluids and peripheral biopsies as prospective biomarkers in PD.

[The association of single-nucleotide polymorphism rs6265 of the brain-derived neurotrophic factor gene with clinical features in Parkinson's disease]. / Assotsiatsiya odnonukleotidnogo polimorfizma rs6265 gena neirotroficheskogo faktora golovnogo mozga s osobennostyami klinicheskoi kartiny bolezni Parkinsona.

OBJECTIVE: To evaluate the frequency and severity of various clinical symptoms of Parkinson's disease (PD) depending on the BDNF rs6265 polymorphism. MATERIAL AND METHODS: The study included 533 patients with PD. The stage of PD was assessed using the Hoehn and Yahr scale (1967), motor symptoms were evaluated with MDS-UPDRS. Assessment of non-motor symptoms (NMS) in PD was conducted using the Beck Depression Inventory II (BDI-II); the Hospital Anxiety and Depression Scale (HADS); the Apathy Scale; the Montreal Cognitive Assessment (MoCA test); the Questionnaire for Impulsive-Compulsive Disorders in PD -Rating Scale (QUIP-RS). Genotyping of the BDNF variant (rs6265) was performed using real-time PCR with TaqMan probes. RESULTS: Most PD patients have a combination of NMS increasing as the disease progresses and is determined by molecular-genetic individual characteristics. There are significant differences in the severity of motor symptoms and NMS: individuals with the AA genotype showed significantly pronounced motor symptoms (p<0.0001); emotional-affective symptoms (p<0.0001); cognitive and impulsive behavioral disorders (p<0.0001). CONCLUSION: The rs6265 BDNF allele A is associated with a wide range of NMS, increasing the risk of their development in patients with PD, thus playing the important role in the etiopathogenesis of this pathology.

Non-Motor Symptoms in Primary Familial Brain Calcification.

Background/Objectives: Primary Familial Brain Calcification is a rare neurodegenerative disorder of adulthood characterized by calcium deposition in the basal ganglia and other brain areas; the main clinical manifestations include movement disorders, mainly parkinsonism. Non-motor symptoms are not well defined in PFBC. This work aims at defining the burden of non-motor symptoms in PFBC. Methods: A clinical, genetic and neuropsychological evaluation of a cohort of PFBC patients, COMPASS-31 scale administration. Results: A total of 50 PFBC patients were recruited; in 25, the genetic test was negative; 10 carried mutations in SLC20A2 gene, 8 in MYORG, 3 in PDGFB, 1 in PDGFRB, 2 in JAM2 (single mutations), and one test is still ongoing. The main motor manifestation was parkinsonism. Headache was reported in 26% of subjects (especially in PDGFB mutation carriers), anxiety or depression in 62%, psychosis or hallucinations in 10-12%, sleep disturbances in 34%; 14% of patients reported hyposmia, 32% constipation, and 34% urinary disturbances. A neuropsychological assessment revealed cognitive involvement in 56% (sparing memory functions, to some extent). The COMPASS-31 mean score was 20.6, with higher sub-scores in orthostatic intolerance and gastrointestinal problems. MYORG patients and subjects with cognitive decline tended to have higher scores and bladder involvement compared to other groups. Conclusions: The presence of non-motor symptoms is frequent in PFBC and should be systematically assessed to better meet patients' needs.