In Vivo Investigation of Glucose Metabolism in Idiopathic and PRKN-Related Parkinson's Disease

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.     

Deep brain stimulation may be a viable option for resistant to treatment aggression in children with intellectual disability

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.     

Amitriptyline vs divalproate in migraine prophylaxis: a randomized controlled trial

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 (P = 0.02) and at 6 months, 65.3% and 54%, respectively (P = 0.90). At 3 months, the VAS score improved by >50% in 80.7% in DVA‐ER and 64% in AMT (P = 0.005). At 6 months, there was no significant difference between the two groups in VAS score (69.3% vs 56%; P = 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.     

Clozapine as a first‐ or second‐line treatment in schizophrenia: a systematic review and meta‐analysis

Objective

No consensus exists on whether clozapine should be prescribed in early stages of psychosis. This systematic review and meta‐analysis therefore focus on the use of clozapine as first‐line or second‐line treatment in non‐treatment‐resistant patients.

Methods

Articles were eligible if they investigated clozapine compared to another antipsychotic as a first‐ or second‐line treatment in non‐treatment‐resistant schizophrenia spectrum disorders (SCZ) patients and provided data on treatment response. We performed random‐effects meta‐analyses.

Results

Fifteen articles were eligible for the systematic review (N = 314 subjects on clozapine and N = 800 on other antipsychotics). Our meta‐analysis comparing clozapine to a miscellaneous group of antipsychotics revealed a significant benefit of clozapine (Hedges’ g = 0.220, P = 0.026, 95% CI = 0.026–0.414), with no evidence of heterogeneity. In addition, a sensitivity analysis revealed a significant benefit of clozapine over risperidone (Hedges’ g = 0.274, P = 0.030, 95% CI = 0.027–0.521).

Conclusion

The few eligible trials on this topic suggest that clozapine may be more effective than other antipsychotics when used as first‐ or second‐line treatment. Only large clinical trials may comprehensively probe disease stage‐dependent superiority of clozapine and investigate overall tolerability.     

Correlations between psychopathology and self‐reported quality of life among adolescents in youth correctional facilities in Lagos,Nigeria: A short report

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.     

Impact of falls on depressive symptoms among the oldest old: Results from the AgeQualiDe study

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.     

Subarachnoid Hemorrhage: The First 24 hours. A Surgeon’s Perspective

Background  

The first 24 h in the management of aneurysmal subarachnoid hemorrhage (SAH) represent a critical time period for medical intervention.     

Integrated Multi-Cohort Analysis of the Parkinson's Disease Gut Metagenome

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.     

Methodological Issues in Research on Web-Based Behavioral Interventions

Background  

Web-based behavioral intervention research is rapidly growing.     

Microdialysis in the management of hepatic encephalopathy

Introduction  

Fulminant hepatic encephalopathy has a high mortality.     

Olfactory training with older people

Background/objectives

Loss of olfactory function is largely found with aging. Such a reduction in olfactory function affects quality of life and enhances likelihood of depressive symptoms. Furthermore, it has been shown that reduction in olfactory function is associated with cognitive impairment and several diseases such as major depression. Because several studies suggest that discontinuous exposure to odors may improve general olfactory function, the primary aim of this study was to investigate whether such “olfactory training” has positive effects on subjective well‐being and cognitive function.

Design

We performed a controlled, unblinded, longitudinal study

Setting

The study took place at an outpatients' clinic of a Department of Otorhinolaryngology at a Medical University.

Participants

A total of 91 participants (age 50 to 84 years) completed testing. They were randomly assigned to an olfactory training (OT) group (N = 60) and a control group (N = 31). The study included two appointments at the Smell and Taste Clinic.

Measurements

Olfactory and cognitive function as well as subjective well‐being was tested using standardized tests.

Intervention

During the 5‐month interval between sessions, the OT group completed daily olfactory exposure. During the same time, the control group completed daily Sudoku problems.

Results

Analyses show a significant improvement of olfactory function for participants in the OT group and improved verbal function and subjective well‐being. In addition, results indicated a decrease of depressive symptoms.

Conclusion

Based on the present results, OT may constitute an inexpensive, simple way to improve quality of life in older people. Copyright © 2017 John Wiley & Sons, Ltd.     

Recent substance use among clients with early psychosis and the potential to graduate from New Journeys

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.     

Cancer Distress Reduction with a Couple-Based Skills Training: A Randomized Controlled Trial

Background  

There are few interventions for couples facing cancer.     

Postoperative confusion and basilar artery stroke

Introduction  

Non-focal postoperative mental status changes can be challenging.     

Speech and gait abnormalities in motor subtypes of de-novo Parkinson's disease

Aim

To investigate the presence and relationship of temporal speech and gait parameters in patients with postural instability/gait disorder (PIGD) and tremor-dominant (TD) motor subtypes of Parkinson's disease (PD).

Methods

Speech samples and instrumented walkway system assessments were acquired from a total of 60 de-novo PD patients (40 in TD and 20 in PIGD subtype) and 40 matched healthy controls. Objective acoustic vocal assessment of seven distinct speech timing dimensions was related to instrumental gait measures including velocity, cadence, and stride length.

Results

Compared to controls, PIGD subtype showed greater consonant timing abnormalities by prolonged voice onset time (VOT) while also shorter stride length during both normal walking and dual task, while decreased velocity and cadence only during dual task. Speaking rate was faster in PIGD than TD subtype. In PIGD subtype, prolonged VOT correlated with slower gait velocity (r = −0.56, p = 0.01) and shorter stride length (r = −0.59, p = 0.008) during normal walking, whereas relationships were also found between decreased cadence in dual task and irregular alternating motion rates (r = −0.48, p = 0.04) and prolonged pauses (r = −0.50, p = 0.03). No correlation between speech and gait was detected in TD subtype.

Conclusion

Our findings suggest that speech and gait rhythm disorder share similar underlying pathomechanisms specific for PIGD subtype.     

Retinal ganglion cell loss is associated with future disability worsening in early relapsing–remitting multiple sclerosis

Background and purpose

Thinning of the retinal combined ganglion cell and inner plexiform layer (GCIP) as measured by optical coherence tomography (OCT) is a common finding in patients with multiple sclerosis. This study aimed to investigate whether a single retinal OCT analysis allows prediction of future disease activity after a first demyelinating event.

Methods

This observational cohort study included 201 patients with recently diagnosed clinically isolated syndrome or relapsing–remitting multiple sclerosis from two German tertiary referral centers. Individuals underwent neurological examination, magnetic resonance imaging, and OCT at baseline and at yearly follow-up visits.

Results

Patients were included at a median disease duration of 2.0 months. During a median follow-up of 59 (interquartile range = 43–71) months, 82% of patients had ongoing disease activity as demonstrated by failing the no evidence of disease activity 3 (NEDA-3) criteria, and 19% presented with confirmed disability worsening. A GCIP threshold of ≤77 μm at baseline identified patients with a high risk for NEDA-3 failure (hazard ratio [HR] = 1.7, 95% confidence interval [CI] = 1.1–2.8, p = 0.04), and GCIP measures of ≤69 μm predicted disability worsening (HR = 2.2, 95% CI = 1.2–4.3, p = 0.01). Higher rates of annualized GCIP loss increased the risk for disability worsening (HR = 2.5 per 1 μm/year increase of GCIP loss, p = 0.03).

Conclusions

Ganglion cell thickness as measured by OCT after the initial manifestation of multiple sclerosis may allow early risk stratification as to future disease activity and progression.     

Analysis of positron emission tomography hypometabolic patterns and neuropsychiatric symptoms in patients with dementia syndromes

Aims

To estimate the proportions of specific hypometabolic patterns and their association with neuropsychiatric symptoms (NPS) in patients with cognitive impairment (CI).

Methods

This multicenter study with 1037 consecutive patients was conducted from December 2012 to December 2019. ¹⁸F-FDG PET and clinical/demographic information, NPS assessments were recorded and analyzed to explore the associations between hypometabolic patterns and clinical features by correlation analysis and multivariable logistic regression models.

Results

Patients with clinical Alzheimer's disease (AD, 81.6%, 605/741) and dementia with Lewy bodies (67.9%, 19/28) mostly had AD-pattern hypometabolism, and 76/137 (55.5%) of patients with frontotemporal lobar degeneration showed frontal and anterior temporal pattern (FT-P) hypometabolism. Besides corticobasal degeneration, patients with behavioral variant frontotemporal dementia (36/58), semantic dementia (7/10), progressive non-fluent aphasia (6/9), frontotemporal lobar degeneration and amyotrophic lateral sclerosis (3/5), and progressive supranuclear palsy (21/37) also mostly showed FT-P hypometabolism. The proportion of FT-P hypometabolism was associated with the presence of hallucinations (R = 0.171, p = 0.04), anxiety (R = 0.182, p = 0.03), and appetite and eating abnormalities (R = 0.200, p = 0.01) in AD.

Conclusion

Specific hypometabolic patterns in FDG-PET are associated with NPS and beneficial for the early identification and management of NPS in patients with CI.     

Evaluation of the implementation of the Meeting Centres Support Program in Italy,Poland, and the UK; exploration of the effects on people with dementia

Objectives

MEETINGDEM investigated whether the Dutch Meeting Centres Support Programme (MCSP) could be implemented in Italy, Poland, and the UK with comparable benefits. This paper reports on the impact on people living with dementia attending pilot Meeting Centres in the 3 countries.

Methods

Nine pilot Meeting Centres (MCs) participated (Italy—5, Poland—2, UK—2). Effectiveness of MCSP was compared with Usual Care (UC) on outcomes measuring behavioural and psychological symptoms (NPI), depression (CSDD), and quality of life (DQoL, QOL‐AD), analysed by ANCOVAs in a 6‐month pre‐test/post‐test controlled trial.

Results

Pre/post data were collected for 85 people with dementia and 93 carers (MCSP) and 74 people with dementia /carer dyads' receiving UC. MCSP showed significant positive effects for DQoL [Self‐esteem (F = 4.8, P = 0.03); Positive Affect (F = 14.93, P < 0.00); Feelings of Belonging (F = 7.77, P = 0.01)] with medium and large effect sizes. Higher attendance levels correlated with greater neuropsychiatric symptom reduction (rho = 0.24, P = 0.03) and a greater increase in feelings of support (rho = 0.36, P = 0.001).

Conclusions

MCSPs showed significant wellbeing and health benefits compared with UC, building on the evidence of effectiveness from the Netherlands. In addition to the previously reported successful implementation of MCSP in Italy, Poland, and the UK, these findings suggest that further international dissemination of MCSP is recommended.     

Pleasure in decision-making situations

Background  

This study explores the role of pleasure in decision making.     

Statins and cognition in late‐life bipolar disorder

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.