Cognition falters at ~4 Hz in Parkinson's disease.

Cognitive impairments are common in Parkinson's disease (PD). We have linked this deficit to attenuated midfrontal 1-8-Hz activity that fails to engage cortical cognitive networks. We discuss the consequences of these impairments and how they might be leveraged for PD-specific neurophysiological markers and for novel brain stimulation paradigms.

Sex similarities and dopaminergic differences in interval timing.

Rodent behavioral studies have largely focused on male animals, which has limited the generalizability and conclusions of neuroscience research. Working with humans and rodents, we studied sex effects during interval timing that requires participants to estimate an interval of several seconds by making motor responses. Interval timing requires attention to the passage of time and working memory for temporal rules. We found no differences between human females and males in interval timing response times (timing accuracy) or the coefficient of variance of response times (timing precision). Consistent with prior work, we also found no differences between female and male rodents in timing accuracy or precision. In female rodents, there was no difference in interval timing between estrus and diestrus cycle stages. Because dopamine powerfully affects interval timing, we also examined sex differences with drugs targeting dopaminergic receptors. In both female and male rodents, interval timing was delayed after administration of sulpiride (D2-receptor antagonist), quinpirole (D2-receptor agonist), and SCH-23390 (D1-receptor antagonist). By contrast, after administration of SKF-81297 (D1-receptor agonist), interval timing shifted earlier only in male rodents. These data illuminate sex similarities and differences in interval timing. Our results have relevance for rodent models of both cognitive function and brain disease by increasing representation in behavioral neuroscience. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Enhanced Spine Stability and Survival Lead to Increases in Dendritic Spine Density as an Early Response to Local Alpha-Synuclein Overexpression in Mouse Prefrontal Cortex.

Lewy Body Dementias (LBD), including Parkinson's disease dementia and Dementia with Lewy Bodies, are characterized by widespread accumulation of intracellular alpha-Synuclein protein deposits in regions beyond the brainstem, including in the cortex. However, the impact of local pathology in the cortex is unknown. To investigate this, we employed viral overexpression of human alpha-Synuclein protein targeting the mouse prefrontal cortex (PFC). We then used in vivo 2-photon microscopy to image awake head-fixed mice via an implanted chronic cranial window to assess the early consequences of alpha-Synuclein overexpression in the weeks following overexpression. We imaged apical tufts of Layer V pyramidal neurons in the PFC of Thy1-YFP transgenic mice at 1-week intervals from 1 to 2 weeks before and 9 weeks following viral overexpression, allowing analysis of dynamic changes in dendritic spines. We found an increase in the relative dendritic spine density following local overexpression of alpha-Synuclein, beginning at 5 weeks post-injection, and persisting for the remainder of the study. We found that alpha-Synuclein overexpression led to an increased percentage and longevity of newly-persistent spines, without significant changes in the total density of newly formed or eliminated spines. A follow-up study utilizing confocal microscopy revealed that the increased spine density is found in cortical cells within the alpha-Synuclein injection site, but negative for alpha-Synuclein phosphorylation at Serine-129, highlighting the potential for effects of dose and local circuits on spine survival. These findings have important implications for the physiological role and early pathological stages of alpha-Synuclein in the cortex.

Characteristics, enablers, and barriers to the community health and wellbeing assessment component of the health promotion practice cycle: a scoping review protocol.

OBJECTIVE: The proposed review will describe the characteristics, enablers, and barriers to the community health and well-being assessment (CHWA) component of the health promotion practice cycle. INTRODUCTION: CHWA guides health promotion action in communities and populations. A "critical" approach to CHWA can be adopted, which addresses the social, political, cultural, economic, commercial, and environmental determinants of health and well-being to enhance health equity for priority communities and populations. Although tools exist to guide such a critical approach, little is known about the extent to which these tools are being used or the barriers and enablers to applying best practice CHWA. Such evidence is needed to inform future health promotion CHWA and research. INCLUSION CRITERIA: This review will consider literature that describes CHWA conducted in health promotion practice, focusing on an organizational, social, or geographical community or population. Literature that focuses on clinical practice or a specific health condition will be excluded. METHODS: Scopus, PubMed, Web of Science, and CINAHL (EBSCOhost) will be searched to identify peer-reviewed articles. Google Scholar and Google, as well as Public Health, Health & Medical, and Nursing and Allied Health (ProQuest) databases will be searched for gray literature. Articles will be screened and data extracted by 2 or more independent reviewers. The data extraction tool will be developed by the reviewers based on the JBI template and a critical health promotion approach to CHWA. Data will be analyzed and presented as frequency tables and narrative summaries of the characteristics, enablers, and barriers to CHWA. DETAILS OF THE PROTOCOL ARE AVAILABLE ON OPEN SCIENCE FRAMEWORK: osf.io/jq8th/.

Differences in Plasma Fatty Acid Composition Related to Chronic Pancreatitis: A Pilot Study.

OBJECTIVES: Chronic pancreatitis (CP) is an inflammatory disease affecting the absorption of fat-soluble nutrients. Signaling in pancreatic cells that lead to inflammation may be influenced by fatty acids (FAs) through diet and de novo lipogenesis. Here, we investigated the relationship between plasma FA composition in CP with heterogeneity of etiology and complications of CP. MATERIALS AND METHODS: Blood and clinical parameters were collected from subjects with CP (n = 47) and controls (n = 22). Plasma was analyzed for FA composition using gas chromatography and compared between controls and CP and within CP. RESULTS: Palmitic acid increased, and linoleic acid decreased in CP compared with controls. Correlations between age or body mass index and FAs are altered in CP compared with controls. Diabetes, pancreatic calcifications, and substance usage, but not exocrine pancreatic dysfunction, were associated with differences in oleic acid and linoleic acid relative abundance in CP. De novo lipogenesis index was increased in the plasma of subjects with CP compared with controls and in calcific CP compared with noncalcific CP. CONCLUSIONS: Fatty acids that are markers of de novo lipogenesis and linoleic acid are dysregulated in CP depending on the etiology or complication. These results enhance our understanding of CP and highlight potential pathways targeting FAs for treating CP.

Resting-state EEG measures cognitive impairment in Parkinson's disease.

Cognitive dysfunction is common in Parkinson's disease (PD). We developed and evaluated an EEG-based biomarker to index cognitive functions in PD from a few minutes of resting-state EEG. We hypothesized that synchronous changes in EEG across the power spectrum can measure cognition. We optimized a data-driven algorithm to efficiently capture these changes and index cognitive function in 100 PD and 49 control participants. We compared our EEG-based cognitive index with the Montreal cognitive assessment (MoCA) and cognitive tests across different domains from National Institutes of Health (NIH) Toolbox using cross-validations, regression models, and randomization tests. Finally, we externally validated our approach on 32 PD participants. We observed cognition-related changes in EEG over multiple spectral rhythms. Utilizing only 8 best-performing electrodes, our proposed index strongly correlated with cognition (MoCA: rho = 0.68, p value < 0.001; NIH-Toolbox cognitive tests: rho ≥ 0.56, p value < 0.001) outperforming traditional spectral markers (rho = -0.30-0.37). The index showed a strong fit in regression models (R2 = 0.46) with MoCA, yielded 80% accuracy in detecting cognitive impairment, and was effective in both PD and control participants. Notably, our approach was equally effective (rho = 0.68, p value < 0.001; MoCA) in out-of-sample testing. In summary, we introduced a computationally efficient data-driven approach for cross-domain cognition indexing using fewer than 10 EEG electrodes, potentially compatible with dynamic therapies like closed-loop neurostimulation. These results will inform next-generation neurophysiological biomarkers for monitoring cognition in PD and other neurological diseases.

Systemic Neutrophil Gelatinase-Associated Lipocalin Alterations in Chronic Pancreatitis: A Multicenter, Cross-Sectional Study.

INTRODUCTION: Chronic pancreatitis (CP) is a progressive fibroinflammatory disorder lacking therapies and biomarkers. Neutrophil gelatinase-associated lipocalin (NGAL) is a proinflammatory cytokine elevated during inflammation that binds fatty acids (FAs) such as linoleic acid. We hypothesized that systemic NGAL could serve as a biomarker for CP and, with FAs, provide insights into inflammatory and metabolic alterations. METHODS: NGAL was measured by immunoassay, and FA composition was measured by gas chromatography in plasma (n = 171) from a multicenter study, including controls (n = 50), acute and recurrent acute pancreatitis (AP/RAP) (n = 71), and CP (n = 50). Peripheral blood mononuclear cells (PBMCs) from controls (n = 16), AP/RAP (n = 17), and CP (n = 15) were measured by cytometry by time-of-flight. RESULTS: Plasma NGAL was elevated in subjects with CP compared with controls (area under the curve [AUC] = 0.777) or AP/RAP (AUC = 0.754) in univariate and multivariate analyses with sex, age, body mass index, and smoking (control AUC = 0.874; AP/RAP AUC = 0.819). NGAL was elevated in CP and diabetes compared with CP without diabetes ( P < 0.001). NGAL + PBMC populations distinguished CP from controls (AUC = 0.950) or AP/RAP (AUC = 0.941). Linoleic acid was lower, whereas dihomo-γ-linolenic and adrenic acids were elevated in CP ( P < 0.05). Linoleic acid was elevated in CP with diabetes compared with CP subjects without diabetes ( P = 0.0471). DISCUSSION: Elevated plasma NGAL and differences in NGAL + PBMCs indicate an immune response shift that may serve as biomarkers of CP. The potential interaction of FAs and NGAL levels provide insights into the metabolic pathophysiology and improve diagnostic classification of CP.

Bariatric surgery efficacy in patients with mood disorders.

BACKGROUND: Mood disorders are comorbid in patients with obesity and found in approximately 22.0% to 54.8% of patients who are eligible for bariatric surgery. Given the unclear effect of mood disorders on bariatric surgery outcomes, we aimed this study to assess the impact of mood disorders index bariatric surgery weight loss outcomes. METHODS: A retrospective study institutional database of index bariatric surgery patients at University Hospitals Cleveland Medical Center between 2016 and 2018. The primary outcome of body mass index was followed over a 4-year period. The secondary outcomes measured were mortality and suicide rates. Mood disorders defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, included depressive and bipolar disorders obtained from electronic medical records International Classification of Diseases, Tenth Revision, coding. RESULTS: A total of 790 patients underwent bariatric surgery between 2016 and 2018. Of these, 15 patients were excluded due to death in the postoperative period or insufficient weight loss data, and a total of 775 patients (620 women and 155 men) were included. Two hundred and ninety-five (38.1%) had an electronic medical record mood disorder diagnosis before surgery, while 480 (61.9%) did not. Both groups had a significant decrease in postoperative body mass index; however, there was no significant difference in the body mass index change between the mood disorder group (mean = 37.63, standard deviation = 9.88) and the control group (mean = 38.72, standard deviation = 9.54; t[294] = 1.40; P = .1634). CONCLUSION: Patients with mood disorders are as successful with weight loss after index bariatric surgery as those without mood disorders. There was no significant difference in mortality rates between the mood disorder group and the control group. Hence, mood disorders should not be prohibitive for weight loss surgery.

Consuming a Linoleate-Rich Diet Increases Concentrations of Tetralinoleoyl Cardiolipin in Mouse Liver and Alters Hepatic Mitochondrial Respiration.

BACKGROUND: Hepatic mitochondrial dysfunction is a major cause of fat accumulation in the liver. Individuals with fatty liver conditions have hepatic mitochondrial structural abnormalities and a switch in the side chain composition of the mitochondrial phospholipid, cardiolipin, from poly- to monounsaturated fatty acids. Linoleic acid (LA), an essential dietary fatty acid, is required to remodel nascent cardiolipin (CL) to its tetralinoleoyl cardiolipin (L4CL, CL with 4 LA side chains) form, which is integral for mitochondrial membrane structure and function to promote fatty acid oxidation. It is unknown, however, whether increasing LA in the diet can increase hepatic L4CL concentrations and improve mitochondrial respiration in the liver compared with a diet rich in monounsaturated and saturated fatty acids. OBJECTIVES: The main aim of this study was to test the ability of a diet fortified with LA-rich safflower oil (SO), compared with the one fortified with lard (LD), to increase concentrations of L4CL and improve mitochondrial respiration in the livers of mice. METHODS: Twenty-four (9-wk-old) C57 BL/J6 male mice were fed either the SO or LD diets for ∼100 d, whereas food intake and body weight, fasting glucose, and glucose tolerance tests were performed to determine any changes in glycemic control. RESULTS: Livers from mice fed SO diet had higher relative concentrations of hepatic L4CL species compared with LD diet-fed mice (P value = 0.004). Uncoupled mitochondria of mice fed the SO diet, compared with LD diet, had an increased baseline oxygen consumption rate (OCR) and succinate-driven respiration (P values = 0.03 and 0.01). SO diet-fed mice had increased LA content in all phospholipid classes compared with LD-fed mice (P < 0.05). CONCLUSIONS: Our findings reveal that maintaining or increasing hepatic L4CL may result in increased OCR in uncoupled hepatic mitochondria in healthy mice whereas higher oleate content of CL reduced mitochondrial function shown by lower OCR in uncoupled mitochondria.

Sedentary behaviour in Australian university students: The contribution of study-related sedentary behaviour to total sedentary behaviour.

ISSUE ADDRESSED: Seated activities are attributed to increased sedentary behaviour (SB) and adverse health effects, but little is currently known about university students' SB, particularly study-related SB. This study describes the sociodemographic variations of domain-specific SB in regional Australian university students and the contribution of study-related SB to total SB. METHODS: Self-reported daily SBs from a cross-sectional survey of 451 students were used. Domain-specific and total SB were described within sub-groups, and differences examined using independent t-tests. Multinomial regression was used to examine the association of tertiles of duration in study-related SB with total and other domain-specific SBs. RESULTS: Study participants were a median age of 21 (19-25 years), mostly female (76%) and represented different years of study. On average, students spent 882 ± 292 min/day in total SB, with most SB occurring in the study, screen time and 'other activity' domains. No sociodemographic variations were found in total SB, but significantly higher study-related SB were reported by students studying full time (p < .001) and who moved from their family home to study (p < .022). Study-related SB contributed 36% of total SB, with students most sedentary during study having the highest total SB. CONCLUSIONS: This study suggests university students have high levels of SB, primarily in the domains of study, screen time and other activities. SB reduction strategies in universities and targeting screen time, across various sociodemographic groups (e.g., gender, university enrolment status, and living arrangements), may be important in reducing SB in university students. SO WHAT?: University students are highly sedentary and should be included in SB programs especially students studying full time and those who moved from their family home in the study domain.

Enhanced spine stability and survival lead to increases in dendritic spine density as an early response to local alpha-synuclein overexpression in mouse prefrontal cortex.

Lewy Body Dementias (LBD), including Parkinson's disease dementia and Dementia with Lewy Bodies, are characterized by widespread accumulation of intracellular alpha-Synuclein protein deposits in regions beyond the brainstem, including in the cortex. Patients with LBDs develop cognitive changes, including abnormalities in executive function, attention, hallucinations, slowed processing, and cognitive fluctuations. The causes of these non-motor symptoms remain unclear; however, accumulation of alpha-Synuclein aggregates in the cortex and subsequent interference of synaptic and cellular function could contribute to psychiatric and cognitive symptoms. It is unknown how the cortex responds to local pathology in the absence of significant secondary effects of alpha-Synuclein pathology in the brainstem. To investigate this, we employed viral overexpression of human alpha-Synuclein protein targeting the mouse prefrontal cortex (PFC). We then used in vivo 2-photon microscopy to image awake head-fixed mice via an implanted chronic cranial window to assess the early consequences of alpha-Synuclein overexpression in the weeks following overexpression. We imaged apical tufts of Layer V pyramidal neurons in the PFC of Thy1-YFP transgenic mice at 1-week intervals from 1-2 weeks before and 9 weeks following viral overexpression, allowing analysis of dynamic changes in dendritic spines. We found an increase in the relative dendritic spine density following local overexpression of alpha-Synuclein, beginning at 5 weeks post-injection, and persisting for the remainder of the study. We found that alpha-Synuclein overexpression led to an increased percentage and longevity of newly-persistent spines, without significant changes in the total density of newly formed or eliminated spines. A follow up study utilizing confocal microscopy revealed that the increased spine density is found in cortical cells within the alpha-Synuclein injection site, but negative for alpha-Synuclein phosphorylation at Serine-129, highlighting the potential for effects of dose and local circuits on spine survival. These findings have important implications for the physiological role and early pathological stages of alpha-Synuclein in the cortex.

Characterization of critical health promotion: a scoping review protocol.

OBJECTIVE: This scoping review will explore how critical health promotion is characterized in the health promotion literature. INTRODUCTION: Critical health promotion has emerged as a social justice approach to health promotion to address the persistent global issue of health inequity. Whilst critical health promotion is not conceptually new and the term has been used in the literature, albeit sparingly, this approach has not been adopted as standard health promotion practice, compromising the advancement of health equity. Given that language shapes the understanding and practice of health promotion, it is imperative to explore how critical health promotion is characterized in the literature to increase uptake of the approach. INCLUSION CRITERIA: This review will consider sources that explore critical health promotion and are explicitly positioned as health promotion sources. METHODS: Scopus, CINAHL (EBSCOhost), PubMed, Global Health (CABI), and the Public Health Database (ProQuest) will be searched to identify relevant full-text papers, including original research, reviews, editorials, and opinion papers. Searches of Google Scholar, Google, and ProQuest Dissertations & Theses Global (ProQuest) will be undertaken to identify gray literature. No language or date restrictions will be applied. Two reviewers will screen sources and extract data using a tool that will be pilot tested, modified, and revised, as necessary. Analysis will involve basic frequency counts and descriptive qualitative content analysis through basic coding. The results will be presented in tables, charts, and word clouds, accompanied by a narrative summary.

Examining service utilisation and impact among consumers of a national mental health stepped care programme in Australia: a protocol using linked administrative data.

INTRODUCTION: Mental well-being is a global public health priority with increasing mental health conditions having substantial burden on individuals, health systems and society. 'Stepped care', where services are provided at an intensity to meet the changing needs of the consumer, is the chosen approach to mental health service delivery in primary healthcare in Australia for its efficiencies and patient outcomes; yet limited evidence exists on how the programme is being rolled out and its impact in practice. This protocol outlines a data linkage project to characterise and quantify healthcare service utilisation and impacts among a cohort of consumers of a national mental health stepped care programme in one region of Australia. METHODS AND ANALYSIS: Data linkage will be used to establish a retrospective cohort of consumers of mental health stepped care services between 1 July 2020 and 31 December 2021 in one primary healthcare region in Australia (n=approx. 12 710). These data will be linked with records from other healthcare service data sets (eg, hospitalisations, emergency department presentations, community-based state government-delivered mental healthcare, hospital costs). Four areas for analysis will include: (1) characterising the nature of mental health stepped care service use; (2) describing the cohort's sociodemographic and health characteristics; (3) quantifying broader service utilisation and associated economic costs; and (4) assessing the impact of mental health stepped care service utilisation on health and service outcomes. ETHICS AND DISSEMINATION: Approval from the Darling Downs Health Human Research Ethics Committee (HREA/2020/QTDD/65518) has been granted. All data will be non-identifiable, and research findings will be disseminated through peer-reviewed journals, conference presentations and industry meetings.

Evoked mid-frontal activity predicts cognitive dysfunction in Parkinson's disease.

BACKGROUND: Cognitive dysfunction is a major feature of Parkinson's disease (PD), but the pathophysiology remains unknown. One potential mechanism is abnormal low-frequency cortical rhythms which engage cognitive functions and are deficient in PD. We tested the hypothesis that mid-frontal delta/theta rhythms predict cognitive dysfunction in PD. METHOD: We recruited 100 patients with PD and 49 demographically similar control participants who completed a series of cognitive control tasks, including the Simon, oddball and interval-timing tasks. We focused on cue-evoked delta (1-4 Hz) and theta (4-7 Hz) rhythms from a single mid-frontal EEG electrode (cranial vertex (Cz)) in patients with PD who were either cognitively normal, with mild-cognitive impairments (Parkinson's disease with mild-cognitive impairment) or had dementia (Parkinson's disease dementia). RESULTS: We found that PD-related cognitive dysfunction was associated with increased response latencies and decreased mid-frontal delta power across all tasks. Within patients with PD, the first principal component of evoked electroencephalography features from a single electrode (Cz) strongly correlated with clinical metrics such as the Montreal Cognitive Assessment score (r=0.34) and with National Institutes of Health Toolbox Executive Function score (r=0.46). CONCLUSIONS: These data demonstrate that cue-evoked mid-frontal delta/theta rhythms directly relate to cognition in PD. Our results provide insight into the nature of low-frequency frontal rhythms and suggest that PD-related cognitive dysfunction results from decreased delta/theta activity. These findings could facilitate the development of new biomarkers and targeted therapies for cognitive symptoms of PD.

Area-level associations of travel behaviour metrics with waist circumference: findings from linkage of travel and health surveys.

Individual-level analyses have consistently shown associations of travel behaviours with obesity-related measures. However, transport planning policies often target areas rather than individuals. To better inform transport-related policies and initiatives for obesity prevention, area-level relationships need to be investigated. This study linked data from two travel surveys with data from the Australian National Health Survey at the level of Population Health Areas (PHAs) and examined to what extent area-level travel behaviours metrics (prevalence of active travel, mixed travel and sedentary travel, diversity of travel modes) were associated with the rate of high waist circumference. Data from 51,987 travel survey participants were aggregated into 327 PHAs. Bayesian conditional autoregressive models were used to account for spatial autocorrelation. It was found that statistically replacing participants who relied on cars for travel (without walking/cycling) with those engaging in 30+ min/d of walking/cycling (without car use) was associated with a lower rate of high waist circumference. Areas with greater diversity of travel modes (mix of walking/cycling, car use, public transport use) also had lower prevalence of high waist circumference. This data-linkage study suggests that area-level transport planning strategies addressing car dependency, shifting car use to walking/cycling over 30 min/d, may help to reduce obesity.

Effects of Very Low- and High-Frequency Subthalamic Stimulation on Motor Cortical Oscillations During Rhythmic Lower-Limb Movements in Parkinson's Disease Patients.

BACKGROUND: Standard high-frequency deep brain stimulation (HF-DBS) at the subthalamic nucleus (STN) is less effective for lower-limb motor dysfunctions in Parkinson's disease (PD) patients. However, the effects of very low frequency (VLF; 4 Hz)-DBS on lower-limb movement and motor cortical oscillations have not been compared. OBJECTIVE: To compare the effects of VLF-DBS and HF-DBS at the STN on a lower-limb pedaling motor task and motor cortical oscillations in patients with PD and with and without freezing of gait (FOG). METHODS: Thirteen PD patients with bilateral STN-DBS performed a cue-triggered lower-limb pedaling motor task with electroencephalography (EEG) in OFF-DBS, VLF-DBS (4 Hz), and HF-DBS (120-175 Hz) states. We performed spectral analysis on the preparatory signals and compared GO-cue-triggered theta and movement-related beta oscillations over motor cortical regions across DBS conditions in PD patients and subgroups (PDFOG-and PDFOG+). RESULTS: Both VLF-DBS and HF-DBS decreased the linear speed of the pedaling task in PD, and HF-DBS decreased speed in both PDFOG-and PDFOG+. Preparatory theta and beta activities were increased with both stimulation frequencies. Both DBS frequencies increased motor cortical theta activity during pedaling movement in PD patients, but this increase was only observed in the PDFOG + group. Beta activity was not significantly different from OFF-DBS at either frequency regardless of FOG status. CONCLUSION: Results suggest that VL and HF DBS may induce similar effects on lower-limb kinematics by impairing movement speed and modulating motor cortical oscillations in the lower frequency band.

Resting-state EEG measures cognitive impairment in Parkinson's disease.

Background: Cognitive dysfunction is common in Parkinson's disease (PD) and is diagnosed by complex, time-consuming psychometric tests which are affected by language and education, subject to learning effects, and not suitable for continuous monitoring of cognition. Objectives: We developed and evaluated an EEG-based biomarker to index cognitive functions in PD from a few minutes of resting-state EEG. Methods: We hypothesized that synchronous changes in EEG across the power spectrum can measure cognition. We optimized a data-driven algorithm to efficiently capture these changes and index cognitive function in 100 PD and 49 control participants. We compared our EEG-based cognitive index with the Montreal cognitive assessment (MoCA) and cognitive tests across different domains from the National Institutes of Health (NIH) Toolbox using cross-validation schemes, regression models, and randomization tests. Results: We observed cognition-related changes in EEG activities over multiple spectral rhythms. Utilizing only 8 best-performing EEG electrodes, our proposed index strongly correlated with cognition (rho = 0.68, p value < 0.001 with MoCA; rho ≥ 0.56, p value < 0.001 with cognitive tests from the NIH Toolbox) outperforming traditional spectral markers (rho = -0.30 - 0.37). The index showed a strong fit in regression models (R2 = 0.46) with MoCA, yielded 80% accuracy in detecting cognitive impairment, and was effective in both PD and control participants. Conclusions: Our approach is computationally efficient for real-time indexing of cognition across domains, implementable even in hardware with limited computing capabilities, making it potentially compatible with dynamic therapies such as closed-loop neurostimulation, and will inform next-generation neurophysiological biomarkers for monitoring cognition in PD and other neurological diseases.

A Pilot Study of Ex Vivo Human Prefrontal RNA Transcriptomics in Parkinson's Disease.

Parkinson's disease (PD) can dramatically change cortical neurophysiology. The molecular basis for PD-related cortical changes is unclear because gene expression data are usually derived from postmortem tissue collected at the end of a complex disease and they profoundly change in the minutes after death. Here, we studied cortical changes in tissue from the prefrontal cortex of living PD patients undergoing deep-brain stimulation implantation surgery. We examined 780 genes using the NanoString nCounter platform and found that 40 genes were differentially expressed between PD (n = 12) and essential tremor (ET; n = 9) patients. One of these 40 genes, STAT1, correlated with intraoperative 4-Hz rhythms and intraoperative performance of an oddball reaction-time task. Using a pre-designed custom panel of 780 targets, we compared these intraoperative data with those from a separate cohort of fresh-frozen tissue from the same frontal region in postmortem human PD donors (n = 6) and age-matched neurotypical controls (n = 6). This cohort revealed 279 differentially expressed genes. Fifteen of the 40 intraoperative PD-specific genes overlapped with postmortem PD-specific genes, including CALB2 and FOXP2. Transcriptomic analyses identified pathway changes in PD that had not been previously observed in postmortem cases. These molecular signatures of cortical function and dysfunction may help us better understand cognitive and neuropsychiatric aspects of PD.

Vitamin D status and risk of rheumatoid arthritis: systematic review and meta-analysis.

BACKGROUND: Vitamin D is important for immunomodulation and may play a role in autoimmune diseases. Studies have reported a high prevalence of vitamin D deficiency in rheumatoid arthritis (RA) patients, and vitamin D status, assessed by circulating 25-hydroxyvitamin D [25(OH)D] concentration, is inversely associated with RA disease activity. However, it is unclear whether vitamin D deficiency increases the risk of later developing RA. We conducted a systematic review and meta-analysis of pre-diagnostic 25(OH)D concentrations and risk of RA. METHODS: Medline and Embase databases were searched in December 2021 using various keywords for 'vitamin D', 'rheumatoid arthritis', and 'prospective study'. Publications identified from the search were screened for eligibility, studies were excluded if vitamin D status was measured at or after RA diagnosis, and data were extracted from relevant articles. Bayesian meta-analysis was used to estimate the summary relative risk (RR) and 95% credible interval (CrI) for risk of RA in relation to circulating 25(OH)D concentrations, as well as the between-study heterogeneity. RESULTS: The search strategy yielded 908 records, of which 4 publications reporting on 7 studies, involving a total of 15,604 participants and 1049 incident RA cases, were included in the meta-analysis. There was no suggestion of an association between 25(OH)D concentration and subsequent risk of RA. The pooled RR per 25 nmol/L increment in 25(OH)D was 0.96 (95% CrI 0.82-1.13; I2 = 52%). No associations were evident in men (RR = 1.02, 95% CrI 0.65-1.61; I2 = 77%, 2 studies) or women (RR = 0.94, 95% CrI 0.73-1.22; I2 = 71%, 4 studies). CONCLUSIONS: This systematic review and meta-analysis did not identify evidence of an association between 25(OH)D and RA risk, but there was notable between-study heterogeneity and a lack of precision. Investigations in large-scale prospective studies with long follow-up or suitably designed Mendelian randomisation studies with consideration of potential non-linear relationships are needed to determine whether vitamin D is involved in RA aetiology.