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1.

Background and purpose

Vascular brain lesions, such as ischemic infarcts, are common among patients with atrial fibrillation (AF) and are associated with impaired cognitive function. The role of physical activity (PA) in the prevalence of brain lesions and cognition in AF has not been investigated.

Methods

Patients from the multicenter Swiss-AF cohort study were included in this cross-sectional analysis. We assessed regular exercise (RE; at least once weekly) and minutes of weekly PA using a validated questionnaire. We studied associations with ischemic infarcts, white matter hyperintensities, cerebral microbleeds, and brain volume on brain magnetic resonance imaging and with global cognition measured with a cognitive construct (CoCo) score.

Results

Among 1490 participants (mean age = 72 ± 9 years), 730 (49%) engaged in RE. In adjusted regression analyses, RE was associated with a lower prevalence of ischemic infarcts (odds ratio [OR] = 0.78, 95% confidence interval [CI] = 0.63–0.98, p = 0.03) and of moderate to severe white matter hyperintensities (OR = 0.78, 95% CI = 0.62–0.99, p = 0.04), higher brain volume (β-coefficient = 10.73, 95% CI = 2.37–19.09, p = 0.01), and higher CoCo score (β-coefficient = 0.08, 95% CI = 0.03–0.12, p < 0.001). Increasing weekly PA was associated with higher brain volume (β-coefficient = 1.40, 95% CI = 0.65–2.15, p < 0.001).

Conclusions

In AF patients, RE was associated with a lower prevalence of ischemic infarcts and of moderate to severe white matter disease, with larger brain volume, and with better cognitive performance. Prospective studies are needed to investigate whether these associations are causal. Until then, our findings suggest that patients with AF should be encouraged to remain physically active.  相似文献   

2.

Background and purpose

The study evaluated the utility of arterial spin labeling (ASL) perfusion imaging in Rasmussen's encephalitis (RE).

Material and methods

The hospital electronic database was searched using the search words “encephalitis,” “autoimmune encephalitis” and “Rasmussen's encephalitis” for the period of 1 Jan 2015 to 31 Jan 2017. Clinically diagnosed cases of RE for which epilepsy protocol magnetic resonance imaging (MRI) with perfusion imaging (ASL) performed on a 3T scanner were retrieved. The diagnosis of RE was based on Bien's criteria (Bien et al., 2005). We obtained patient's demographic details, clinical features, electrophysiological studies, and follow-up data from electronic hospital records.

Results

We included nine patients with RE of whom seven patients showed increased perfusion, and two patients decreased perfusion. Among these patients, MRI changes of gyral hyperintensity without volume loss corresponded to regional ASL hyperperfusion in six patients and ASL hypoperfusion in one patient. Two patients who showed ASL hypoperfusion had corresponding atrophy on MRI. Eight patients of RE had epilepsia partialis continua (EPC) or daily seizures, and one patient was seizure-free post-surgery. Five patients showed a concordance of ASL hyperperfusion with clinical ictal onset zone. Among the seven patients with ASL hyperperfusion, the finding was concordant (complete or partial) with the electroencephalogram (EEG) ictal onset zone in six patients and with interictal epileptiform discharges (IED) in seven patients.

Conclusion

Increased perfusion in ASL of the involved brain parenchyma in RE is a common MRI finding and may be due to either active inflammation of the brain involved or a seizure-related finding.  相似文献   

3.

Introduction:

The data in the scientific literature about the significance of seizure severity and frequency for the quality of life (QOL) of patients with refractory epilepsy (RE) are contradictory.

Objective:

Our objective was to assess the impact of the seizure severity and frequency on the QOL of Bulgarian patients with RE.

Materials and Methods:

A total of 70 patients with RE were studied by examining the medical documentation and seizure diaries. All study participants completed quality of life epilepsy inventory (QOLIE-89). Seizure severity of only 59 patients who had a seizure in the last month was assessed by the Liverpool seizure severity scale.

Results:

A limited negative impact of the seizure severity and frequency on some aspects of the physical health, epilepsy, all aspects of the social health and epilepsy and the overall QOL has been demonstrated. A weak to moderate reverse correlation between the specified factors and the respective QOLIE-89 subscales has been found.

Conclusion:

The clinical factors seizure severity and seizure frequency have a limited negative impact mostly on the social aspects of QOL. The study results support the multidisciplinary approach to persons with epilepsy.  相似文献   

4.

Objective

We aimed this study at identifying cortical areas involved in the generation of interictal spikes in Rasmussen’s Encephalitis (RE) patients using magnetoencephalography (MEG), at comparing spike localization with the degree of cortical atrophy detected by MRI, and at identifying short-term changes during the follow-up.

Methods

Five patients with RE underwent two MEG and magnetic resonance imaging (MRI) (six months interval). The sources of visually detected spikes were estimated using equivalent current dipoles technique; these were then superimposed on individual MRI and clustered; the locations of the clusters were related to the MRI stage of cortical atrophy.

Results

All patients showed spikes and clusters located in different cortical areas in both recordings; the locations had a limited correspondence with cortical atrophy. The second recordings showed changes in the localisation of spikes and clusters, and confirmed the dissimilarities with neuroradiological abnormalities.

Conclusions

The presence of clusters of spikes of variable localisation suggests that RE progresses in a multifocal and fluctuating manner. The cortical areas most involved in epileptogenesis did not completely coincide with the most atrophic areas.

Significance

MEG can contribute to evaluating multifocal hemispheric spikes in RE and to better understand the time course of epileptogenic process.  相似文献   

5.

Background and purpose

Rasmussen encephalitis (RE) is characterized by intractable epilepsy, progressive hemiparesis, and unilateral hemispheric atrophy. The progression of the symptoms to significant neurological impairment usually occurs within months to a few years. RE causes are unknown, although evidence of an autoimmune process has been extensively described in the literature. Antiepileptic drugs are usually not effective to control seizures or cerebral atrophy; despite data supporting a beneficial effect of early immunosuppressive and immunomodulatory interventions, for intractable seizures in RE patients with advanced disease, epilepsy surgery in the form of hemispheric disconnection has been considered the treatment of choice. This work describes the clinical and electrographic analyses, as well as the post-operative evolution of patients with RE.

Materials and methods

This work includes all the patients with RE evaluated from January 1995 to January 2008 by the Ribeirão Preto Epilepsy Surgery Program (CIREP), taking variables such as gender; age at epilepsy onset; seizure semiology; seizure frequency; interictal and ictal electroencephalographic (EEG) findings; age at surgery, when done; duration of epilepsy; surgery complications; follow-up duration; anatomo-pathological findings; post-surgery seizure; language and cognitive outcome; and anti-epileptic drug treatment after surgery into account.

Results

Twenty-five patients were evaluated; thirteen were female. Mean age of epilepsy onset was 4.4?±?2.0 years. There were no differences between patients with slow and fast evolution with respect to age of epilepsy onset (p?=?0.79), age at surgery (p?=?0.24), duration of epilepsy (0.06), and follow-up (p?=?0.40). There were no correlations between the presence of bilateral EEG abnormalities or the absence of spikes and post-operative seizure outcome (p?=?0.06). Immunomodulatory therapy was tried in 12 patients (48%). Twenty-three patients underwent surgery. The mean follow-up was 63.3 months. Eleven patients had total seizure control. Twelve individuals persisted with seizures consisting of mild facial jerks (six patients), occasional hemigeneralized tonic–clonic seizures (three patients), and frequent tonic–clonic seizures (three patients). Mental and language impairment was observed in 15 and 12 patients, after surgery, respectively. Eight patients presented post-operative cognitive decline, while only two patients had cognitive improvement. Comparing pre- and post-operative language deficits, 66.7% of the 12 patients with language disturbance did not improve after surgery.

Conclusions

This retrospective study reported the clinical and electrographic analysis, as well as the evolution of 23 patients with RE. Patients were divided into two groups: fast evolution and slow evolution to hemiparesis and epilepsia partialis continua. These groups may represent different RE substrates. Fourteen patients achieved satisfactory seizure control, three patients had partial response to surgery, and five patients had maintenance of the pre-operative condition. All patients with left-side involvement presented with some language disturbance, which did not improve after surgery in 66.6% of patients. Cognitive evaluation showed that the majority of the patients did not have any significant improvement, and 38.1% had cognitive deterioration after surgery.  相似文献   

6.
ObjectivesTo investigate the differences in clinical backgrounds, especially weekly variations of stroke occurrence, between hyper-acute ischemic stroke patients with and without regular employment (RE), as well as the impact of RE on outcome.Materials and methodsSymptomatic ischemic stroke patients with ≤4.5 h from onset to door were enrolled. First, we divided patients into the RE and non-RE group to analyze differences in clinical characteristics, especially relation between weekly variations of stroke occurrence and RE. Second, we divided the same patients into those with and without favorable outcomes (modified Rankin Scale score of 0 to 2 at 3 months from stroke onset) to analyze the impact of RE on outcomes.ResultsWe screened 1,249 consecutive symptomatic ischemic stroke patients and included 377 patients (284 [75%] males; median age, 67 years). Of these patients, 248 (66%) were included in RE group. First, RE was independently associated with occurrence of stroke on Monday in reference to Sunday or a public holiday (OR 2.562, 95% CI 1.004-6.535, p = 0.049). Second, RE (OR 2.888 95% CI 1.378-6.050, p = 0.005) was a factor independently associated with a favorable outcome.ConclusionsPatients with RE were more likely to have a hyper-acute ischemic stroke on Monday in reference to Sunday or a public holiday. However, RE before stroke onset appears to have a positive impact on outcome.  相似文献   

7.

Purpose

The aim of this study is to describe a series of pediatric hemispherectomies, reviewing pathologic substrate, epilepsy characteristics and seizure outcome as well as developmental profiles, before and after surgery, in different domains.

Methods

Seventeen patients with full pre-surgical work-up, minimum follow-up of 12 months, and at least one post-surgical neuropsychological evaluation were selected. Three had Rasmussen encephalitis (RE), five hemispheric malformations of cortical development (MCD), and nine hemispheric vascular lesions.

Results

At latest follow-up, all patients with RE and 66.7 % of those with vascular lesions are in Engel’s class I; in the latter group, pre-surgical independent contralateral EEG discharges statistically correlated with a worse seizure outcome. Patients with MCD showed the worst seizure outcome. Pre-surgical language transfer to the right hemisphere was confirmed in a boy with left RE, operated on at 6 years of age. Patients with MCD and vascular lesions already showed severe global developmental delay before surgery, which persists afterwards. A linear correlation was found between earlier age at surgery and better outcome in personal–social, gross motor, and adaptive domains, in the vascular lesions group. The case with highest cognitive improvement had continuous spike and wave during sleep on pre-surgical EEG.

Conclusions

Pathologic substrate was the main factor related with seizure outcome. In children with MCD and vascular lesions, although developmental progression is apparent, significant post-surgical improvements are restricted by the severity of pre-surgical neuropsychological disturbances and a slow maturation. Early surgery assessment is recommended to enhance the possibilities for a better quality of life in terms of seizure control, as well as better autonomy and socialization.  相似文献   

8.

Purpose

Rasmussen’s encephalitis (RE) is a hemispheric inflammatory disorder resulting in progressive epilepsy, hemiparesis, and cognitive decline. Controversy surrounds the most effective timing of surgery with respect to language dominance, functional status, and seizure outcome. We describe our experience with RE to inform treatment decisions.

Methods

A retrospective chart review was performed in children diagnosed with RE from 1983 to 2012.

Results

Thirteen consecutive cases were identified: six males and seven females with a mean age of 10.6 years (range 5–18). Nine patients received immunotherapy, with transient benefit in three, treatment-associated complications in two, and no difference in their mean time to treatment (5.38 vs 6.37 years p?=?0.74) or long-term outcome. Mean follow-up was 5.6 years (range 0.58–12.25). There was no difference in outcome based on pre-operative duration of seizures. At last follow-up, 63 % of surgically treated patients achieved seizure freedom, 100 % had improved seizure control, 90 % had improved cognitive function, 36 % stopped medication, and 63 % tapered medication. Language improved in 83 % of patients with dominant disease. These findings were not associated with age at treatment. All surgical patients were ambulatory at last follow-up.

Conclusions

Hemispherotomy achieves good seizure control with cognitive improvement and ambulatory status post-operatively. Time to surgery and dominant disease were not associated with outcome, suggesting that hemispherotomy can be offered early or late, with expectations of good seizure control and functional outcome, even with dominant disease.
  相似文献   

9.

Introduction

Deep brain stimulation (DBS) is a surgical technique used to manage aggression in patients who do not improve despite the use of appropriate drug treatment.

Objective

The objective of this study is to assess the impact of DBS on aggressive behavior refractory to the pharmacological and behavioral treatment of patients with Intellectual Disabilities (ID).

Methods

A follow-up was conducted on a cohort of 12 patients with severe ID, undergoing DBS in posteromedial hypothalamic nuclei; evaluated with the Overt Aggression Scale (OAS), before the intervention, at 6, 12, and 18 months of medical follow-up.

Results

After the surgical procedure, there was a significant reduction in the aggressiveness of patients in the follow-up medical evaluation at 6 months (t = 10.14; p < 0.01), 12 months (t = 14.06; p < 0.01), and 18 months (t = 15.34; p < 0.01), respect to the initial measurement; with a very large effect size (6 months: d = 2.71; 12 months: d = 3.75; 18 months: d = 4.10). From 12 months onward, emotional control stabilized and is sustained at 18 months (t = 1.24; p > 0.05).

Conclusion

DBS in posteromedial hypothalamic nuclei may be an effective treatment for the management of aggression in patients with ID refractory to pharmacological treatment.  相似文献   

10.

Background

Alterations in mitochondrial dysfunction have been implicated in the pathogenesis of Parkinson's disease (PD). Mitochondrial energy production is linked to glucose metabolism, and diabetes is associated with PD. However, studies investigating glucose metabolism in vivo in genetically stratified PD patients and controls have yet to be performed.

Objectives

The objectives of this study were to explore glucose production, gluconeogenesis, and the contribution of gluconeogenesis to glucose production in idiopathic and PRKN PD compared with healthy controls with state-of-the-art biochemical methods.

Methods

We applied a dried-blood sampling/gas chromatography/mass spectrometry approach to monitor fluxes in the Cori cycle in vivo.

Results

The contribution of gluconeogenesis to total glucose production is increased in idiopathic PD patients (n = 33), but not in biallelic PRKN mutation carriers (n = 5) compared with healthy controls (n = 13).

Conclusions

We provide first-time in vivo evidence for alterations in glucose metabolism in idiopathic PD, in keeping with the epidemiological evidence for an association between PD and diabetes. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.  相似文献   

11.
Microgliosis is prominent in Rasmussen's encephalitis (RE), a disease with severe seizure activity. However, it is unclear if microglial activation is similar with different histopathologic substrates. Iba1-immunolabelled microglial activation was assessed in neocortex from pediatric epilepsy surgery patients with RE (n = 8), cortical dysplasia (CD; n = 6) and tuberous sclerosis complex (TSC; n = 6). Microglial reactivity was increased, in severely affected RE areas (29% labeling) compared with minimally affected areas of RE cases (15%) and cases of TSC (14%) and CD (12%). There was no qualitative association of Iba1 immunolabelling with the presence of CD8+ cytotoxic T-cells and no statistical association with clinical epilepsy variables, such as seizure duration or frequency. Iba1 appears to be an excellent marker for detecting extensive microglial activation in patients with RE. In addition, this study supports the notion that Iba1-labeled microglial activation is increased in patients with active RE, compared with cases of CD and TSC.  相似文献   

12.

Objective

This study compares efficacy and safety of divalproate extended release (DVA‐ER) and amitriptyline (AMT) in migraine .

Materials and methods

Three hundred migraineurs having >4 attacks monthly were randomized into DVA‐ER or AMT. The primary end points were >50% reduction in frequency, ≥1 grade improvement in the severity, and >50% improvement in a visual analogue scale (VAS). Secondary end points were functional disability, rescue medication, and adverse events.

Results

The median age was 32 years, and 241 were women. 150 patients each received DVA‐ER and AMT. At 3 months, 74.7% in DVA‐ER and 62% patients in AMT group improved in headache frequency (= 0.02) and at 6 months, 65.3% and 54%, respectively (= 0.90). At 3 months, the VAS score improved by >50% in 80.7% in DVA‐ER and 64% in AMT (= 0.005). At 6 months, there was no significant difference between the two groups in VAS score (69.3% vs 56%; = 0.47) and other outcome parameters. The composite side effects were also not different between the two groups (68% vs 81%); however, hair fall, menstrual irregularity, polycystic ovary, and weight gain were commoner in DVA‐ER group.

Conclusion

Divalproate extended release is more effective at 3 months than AMT; however, at 6 months, both are equally effective in migraine prophylaxis.  相似文献   

13.

Background

The relationship between psychopathology and quality of life (QoL) and well‐being among young incarcerated offenders has hardly been explored.

Aims

Our aim was to test the hypothesis that higher self‐rated psychopathology would be associated with lower QoL among adolescents resident within youth correctional facilities in Lagos.

Methods

Psychopathology was assessed using the Strength and Difficulty Questionnaire (SDQ), while QoL was measured by using the Paediatric Quality of Life .

Results

One hundred and sixty‐five adolescents completed the study, mostly boys (n = 124; 75%) with a mean age of 14.3 ± 2.1 years. Nearly, a fifth (30, 18%) of respondents had abnormal total SDQ scores (≥17), suggestive of definite psychiatric disorder, while another 44 (27%) had highly probable psychopathology (total SDQ scores 15–16). There was strong negative correlation (r = ?0.51, p < 0.001) between total SDQ scores and overall self‐reported QoL among respondents.

Conclusions and implications for practice

Although we were unable to infer direction of relationship between psychopathology and QoL among these adolescents, it is plausible to suppose that treatment of mental health problems could have a positive impact on rehabilitation and reintegration. Given the rate of likely psychopathology, mental health screening within young offender institutions should be routine, and followed, as necessary with full assessment and resultant treatment. Copyright © 2017 John Wiley & Sons, Ltd.  相似文献   

14.

Aim

Individuals at clinical high risk (CHR) for psychosis often experience poor social functioning and impaired facial emotion recognition (FER); however, the impact of frequently comorbid symptoms upon these processes is underexplored. In particular, social anxiety is characteristic of this population and also related to poor social functioning and FER biases, such as misinterpreting neutral faces as negative or threatening; however, little is known about how social anxiety relates to these processes in CHR individuals. The present study examined the overlap of social anxiety, social functioning, and FER accuracy and bias.

Method

Participants (CHR N = 62, healthy controls N = 52) completed the self-report Social Interaction Anxiety Scale (SIAS), Penn Emotion Recognition-40 (ER-40) behavioural task, and interviewer-rated Global Functioning Scale-Social (GFS-S). The ER-40 was used to assess both FER accuracy (e.g., overall number of correct responses) and bias (e.g., mislabelling neutral faces as angry).

Results

Consistent with previous research, relative to controls, CHR participants had more social anxiety (d = −1.07), poorer social functioning (d = −1.62), and performed more poorly on the FER task (e.g., d = −.37). Within CHR participants, social anxiety was related to an anger detection bias (r = .28), above and beyond positive symptom severity, which in turn was related to FER accuracy (r = .26) and social functioning (r = −.28).

Conclusion

These findings suggest that ongoing work examining social processes within CHR individuals needs to account for social anxiety and that social anxiety may be a useful preventive intervention target.  相似文献   

15.

Objective

The purpose of this study was to examine the impact of falls on depressive symptoms among the oldest old in Germany longitudinally.

Methods

Data were used from 2 waves of the multicenter prospective cohort “Study on needs, health service use, costs and health‐related quality of life in a large sample of oldest‐old primary care patients (85+)” (AgeQualiDe). This study covers primary care patients ≥85 years (at baseline: n = 547, average age of 88.9 ± 3.0 years; ranging from 85 to 100 years). General practitioner‐diagnosed falls were used as explanatory variable. The Geriatric Depression Scale was used as outcome measure.

Results

Linear fixed effects regressions showed that the occurrence of falls is associated with an increase in depressive symptoms (β = .60, P = .02), whereas changes in marital status, ageing, social support, functional decline (instrumental activity of daily living), cognitive impairment, and an increase in chronic diseases did not affect depressive symptoms. In sensitivity analysis, an increase in depressive symptoms was associated with functional impairment (basic activities of daily living; Barthel index; β = ?.04, P = .005).

Conclusions

Based on a large, population‐based longitudinal study, this study underlined the impact of falls on depressive symptoms and consequently extended previous knowledge about an association between falls and depressive symptoms in the oldest old. Developing strategies to prevent falls might also help to prevent depressive symptoms.  相似文献   

16.

Aim

The aim of this study was to re-evaluate risk factors for post-ICH epilepsy (PICHE) and examine the impact of surgical hematoma evacuation on epilepsy development after ICH.

Background and purpose

Epilepsy is a common complication after intracerebral hemorrhage (ICH). Information on risk factors is still scarce and the role of ICH evacuation remains uncertain.

Methods

We retrospectively included patients with spontaneous ICH treated in our hospital in 2006–2019. Patients' medical records were analyzed. In addition, mailed questionnaires and telephone interviews were used to complete the dataset. Uni- and multivariable hazard ratios (HRs) were applied to investigate risk factors for PICHE and the impact of surgical ICH evacuation.

Results

Among 587 ICH patients available for analyses, 139 (23.7%) developed PICHE (mean follow-up 1795 ± 1378 days). The median time of epilepsy onset was 7 months after ICH (range 1–132 months). Risk factors associated with PICHE were cortical hemorrhage (multivariable HR 1.65 [95% CI 1.14–2.37]; p = 0.008), ICH volume > 10 ml (multivariable HR 1.91 [95% CI 1.33–2.73]; p < 0.001) and acute symptomatic seizures (multivariable HR 1.81 [95% CI 1.20–2.75]; p = 0.005). Patients with cortical ICH > 10 ml who underwent surgical hematoma evacuation were less likely to develop epilepsy than those with conservative treatment alone (multivariable HR 0.26 [95% CI 0.08–0.84]; p = 0.025).

Conclusions

Post-ICH epilepsy is frequent and predicted by large cortical ICH and acute symptomatic seizures. Hematoma evacuation reduced the risk of PICHE by more than 70% in patients with large cortical ICH. This finding could be considered in the clinical decision making on the acute treatment of ICH.  相似文献   

17.

Objectives

Recent data suggests that statins have positive effects on cognition in older adults. Studies in patients with mood disorders have found contradicting positive and negative effects of statins on mood and cognition, with limited data in bipolar disorder (BD). The objective of this study was to assess the association between statin use and cognition in older adults with BD.

Methods

In a cross‐sectional sample of 143 euthymic older adults with BD (age ≥ 50), statin users (n = 48) and nonusers (n = 95) were compared for cognitive outcomes: Global and cognitive domain z‐scores were calculated from detailed neuropsychological batteries using normative data from healthy comparators (n = 87).

Results

The sample had a mean age of 64.3 (±8.9) years, 65.0% were female, with an average of 15.1 (±2.79) years of education. Statin users did not differ from nonusers on global (?0.60 [±0.69] vs ?0.49 [±0.68], t[127] = 0.80, P = .42) or individual cognitive domains z‐score.

Conclusions

In older patients with BD, statin use is not independently associated with cognitive impairment. This suggests that in older BD patients, the cognitive dysfunction associated with BD trumps the potential cognitive benefit that is associated with statins in older adults without a psychiatric disorder. Further, statins do not seem to exacerbate this cognitive dysfunction. Future longitudinal studies are needed to confirm these findings.  相似文献   

18.

Aim

This study examined the relationship between recent substance use prior to intake and program graduation among young adults with early psychosis enrolled in coordinated specialty care.

Methods

Participants (N = 248) were from New Journeys, a network of coordinated specialty care programs in Washington State. Recent (i.e., past 30 days) alcohol, cannabis, and other substance use was collected at intake and process data (e.g., contact) was collected by clinicians across a 2-year period.

Results

At intake, 32% of participants reported alcohol use only, 26% cannabis use only, and 15% both alcohol and cannabis use. Participants who reported alcohol use only (p = .02), cannabis use only (p = .03), and any substance use (p = .02) had significantly lower chances of graduating from coordinated specialty care than individuals who do not use substances.

Conclusions

Unlike prior work, recent substance use influences clients' potential to graduate from New Journeys. Additional focus on the implementation of substance use treatment, with an emphasis on alcohol use, in coordinated specialty care programs is needed improve program completion rates.  相似文献   

19.

Background

The gut microbiome is altered in several neurologic disorders, including Parkinson's disease (PD).

Objectives

The aim is to profile the fecal gut metagenome in PD for alterations in microbial composition, taxon abundance, metabolic pathways, and microbial gene products, and their relationship with disease progression.

Methods

Shotgun metagenomic sequencing was conducted on 244 stool donors from two independent cohorts in the United States, including individuals with PD (n = 48, n = 47, respectively), environmental household controls (HC, n = 29, n = 30), and community population controls (PC, n = 41, n = 49). Microbial features consistently altered in PD compared to HC and PC subjects were identified. Data were cross-referenced to public metagenomic data sets from two previous studies in Germany and China to determine generalizable microbiome features.

Results

We find several significantly altered taxa between PD and controls within the two cohorts sequenced in this study. Analysis across global cohorts returns consistent changes only in Intestinimonas butyriciproducens. Pathway enrichment analysis reveals disruptions in microbial carbohydrate and lipid metabolism and increased amino acid and nucleotide metabolism in PD. Global gene-level signatures indicate an increased response to oxidative stress, decreased cellular growth and microbial motility, and disrupted intercommunity signaling.

Conclusions

A metagenomic meta-analysis of PD shows consistent and novel alterations in functional metabolic potential and microbial gene abundance across four independent studies from three continents. These data reveal that stereotypic changes in the functional potential of the gut microbiome are a consistent feature of PD, highlighting potential diagnostic and therapeutic avenues for future research. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.  相似文献   

20.

Background

Cholinergic nucleus 4 (Ch4) degeneration is associated with cognitive impairment in Parkinson's disease and dementia with Lewy bodies, but it is unknown if Ch4 degeneration is also present in isolated rapid eye movement sleep behavior disorder (iRBD).

Objective

The aim was to determine if there is evidence of Ch4 degeneration in patients with iRBD and if it is associated with cognitive impairment.

Methods

We analyzed the clinical and neuropsychological data of 35 iRBD patients and 35 age- and sex-matched healthy controls. Regional gray matter density (GMD) was calculated for Ch4 using probabilistic maps applied to brain magnetic resonance imaging (MRI).

Results

Ch4 GMD was significantly lower in the iRBD group compared to controls (0.417 vs. 0.441, P = 0.02). Ch4 GMD was also found to be a significant predictor of letter number sequencing (β-coefficient = 58.31, P = 0.026, 95% confidence interval [7.47, 109.15]), a measure of working memory.

Conclusions

iRBD is associated with Ch4 degeneration, and Ch4 degeneration in iRBD is associated with impairment in working memory. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.  相似文献   

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