Substantia nigra and locus coeruleus microstructural abnormalities in isolated rapid eye movement sleep behaviour disorder and Parkinson’s disease

\ua9 The Author(s) 2025. Published by Oxford University Press on behalf of the Guarantors of Brain.Substantia nigra (SN) and locus coeruleus (LC) are two catecholaminergic, neuromelanin-rich nuclei that are affected in Parkinson’s disease (PD) and may show neuroimaging abnormalities before the onset of motor manifestations. The simultaneous, multimodal investigation of their microstructural abnormalities may provide useful insights on the spatial diffusion and tissue characteristics of neurodegeneration, and this may in turn help develop markers for disease-modifying clinical trials. Therefore, through neuromelanin-sensitive and diffusion MRI, we aimed to investigate microstructural abnormalities in those nuclei in isolated REM sleep behaviour disorder (iRBD) and PD. Fourteen participants with polysomnography-confirmed iRBD, 18 with PD and 18 healthy controls were scanned with structural, neuromelanin-sensitive and neurite orientation dispersion and density imaging (NODDI) MRI. iRBD participants also underwent dopamine transporter imaging. SN neuromelanin and NODDI diffusion parameters and LC neuromelanin signals were extracted. Motor and global cognitive assessments were also collected. iRBD and PD participants showed significantly reduced neuromelanin contrast in the LC middle section compared with healthy controls. PD also showed significantly reduced caudal LC and posterior SN neuromelanin signal. No differences in SN NODDI parameters were detected between iRBD and healthy controls. Five iRBD participants showed reduced striatal dopamine transporter. In the combined disease groups (iRBD and PD), significant associations were shown between SN neuromelanin signal and neurite density index (r = −0.610, corr-p = 0.001) and between SN neurite density index and free water fraction (r = 0.417, corr-p = 0.042). In the same group, motor scores were negatively associated with nigral neuromelanin signal (r = −0.404, corr-p = 0.044) and free water fraction (r = 0.486, corr-p = 0.018). In conclusion, iRBD participants showed significant neuromelanin loss in the LC, with a minority showing initial nigrostriatal dopaminergic abnormalities. Across the entire iRBD–PD spectrum, the association between SN neuromelanin signal loss, diffusion parameters and motor scores has the potential to capture different yet related aspects of SN degeneration

Idiopathic intracranial hypertension: the association between weight loss and the requirement for systemic treatment

<p>Abstract</p> <p>Background</p> <p>To determine whether weight loss is significantly associated with a discontinuation of treatment for idiopathic intracranial hypertension</p> <p>Methods</p> <p>The notes of 36 patients with idiopathic intracranial hypertension under regular review for at least 12 months by a single neuro-ophthalmologist were retrospectively reviewed. Weight was recorded at each assessment and weight loss recommended. Treatment was adjusted according to symptoms, visual function including visual fields and optic disc appearance only. Patients were divided according to duration of continuous follow-up, and then sub-divided as to whether they were on or not on treatment at most recent review and whether weight loss had been achieved compared to presentation. Survival analysis was performed to assess the probability of remaining on treatment having lost weight.</p> <p>Results</p> <p>Considering the patients as 3 groups, those with at least 12 months follow-up (n = 36), those with at least 18 months follow-up (n = 24) and those with 24 months or more follow-up (n = 19), only the group with 24 months or more follow-up demonstrated a significant association between weight loss and stopping systemic treatment (Fisher's exact test, p = 0.04). Survival analysis demonstrated that the probability of being on treatment at 5 years having gained weight was 0.63 and having lost weight was 0.38 (log rank test, p = 0.04). The results suggest that final absolute body mass index is more important than the change in body mass index for patients who stop treatment (Mann Whitney U, p = 0.05).</p> <p>Conclusion</p> <p>This is the first study to demonstrate that weight loss is associated with discontinuation of treatment. Unlike previous studies, our results suggest that final absolute body mass index is more important for stopping treatment than a proportional reduction in weight.</p

Hippocampal and Insula volume in mild cognitive impairment with Lewy bodies

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordIntroduction: Diagnostic criteria for prodromal dementia with Lewy bodies have recently been published. These include the use of imaging biomarkers to distinguish mild cognitive impairment with Lewy bodies (MCI-LB) from MCI due to other causes. Two potential biomarkers listed, though not formally included in the diagnostic criteria, due to insufficient evidence, are relatively preserved hippocampi, and atrophy of the insula cortex on structural brain imaging. Methods: In this report, we sought to investigate these imaging biomarkers in 105 research subjects, including well characterised groups of patients with MCI-LB (n=38), MCI with no core features of Lewy body disease (MCI-AD; n=36) and healthy controls (N=31). Hippocampal and insula volumes were determined from T1 weighted structural MRI scans, using grey matter segmentation performed with SPM software. Results: Adjusting for age, sex and intracranial volume, there were no differences in hippocampal or insula volume between MCI-AD and MCI-LB, although in both conditions volumes were significantly reduced relative to controls. Conclusion: Our results do not support the use of either hippocampal or insula volume to identify prodromal dementia with Lewy bodies.Alzheimer’s Research UKNational Institute for Health Research (NIHR

Changes in DTI-ALPS index and its associations with neuronal damage in Lewy body disease

Introduction: Dysfunction of the glymphatic system is thought to lead to build up of toxic proteins including β-amyloid and α-synuclein, and thus may be involved in dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD). The Diffusion Tensor Image Analysis Along the Perivascular Space (DTI-ALPS) index has been proposed as a marker of glymphatic function. Aims: To investigate DTI-ALPS in mild cognitive impairment (MCI) and dementia, and determine its relationship with cognitive decline, and biomarkers of neurodegeneration. Methods: DTI-ALPS was calculated on participants with DLB [N=32], AD [N=14], MCI with Lewy bodies (MCI-LB) [N=31], MCI-AD [N=31] and healthy comparators (HC) [N=48]. Plasma biomarkers were available for amyloid-β, glial fibrillary acidic protein (GFAP) , neurofilament light (NfL), and phosphorylated tau. Amyloid PET imaging with 18F florbetapir was performed on a subset of participants. Results: DTI-ALPS values were significantly lower compared to HC in both DLB (Estimate=-0.084 [-0.14 to -0.03], p=0.004) and MCI-LB (Estimate=-0.058 [-0.11 to -0.002], p=0.047) DTI-ALPS was also significantly associated with both baseline (t[147]=2.22, p=0.028) and longitudinal decline (t[127]=2.41,p=0.017) in cognitive score. There were significant associations of DTI-ALPS with plasma NfL (t[141]=-2.72, p=0.007), and GFAP (t[141]=-2.83, p=0.005), but not amyloid levels, nor with amyloid PET uptake. Conclusions: DTI-ALPS is reduced in DLB compared to healthy comparators. Our findings suggest that dysfunction of the glymphatic system may contribute to neuronal damage in Lewy body disease. However further research is needed to clarify the role of the glymphatic system, and also the specificity of DTI-ALPS as a marker of glymphatic function

Effects of Alcohol on the Acquisition and Expression of Fear Potentiated Startle in Mouse Lines Selectively Bred for High and Low Alcohol Preference

Rationale: Anxiety disorders and alcohol-use disorders frequently co-occur in humans perhaps because alcohol relieves anxiety. Studies in humans and rats indicate that alcohol may have greater anxiolytic effects in organisms with increased genetic propensity for high alcohol consumption. Objectives and Methods: The purpose of this study was to investigate the effects of moderate doses of alcohol (0.5, 1.0, 1.5 g/kg) on the acquisition and expression of anxiety-related behavior using a fear-potentiated startle (FPS) procedure. Experiments were conducted in two replicate pairs of mouse lines selectively bred for high- (HAP1 and HAP2) and low- (LAP1 and LAP2) alcohol preference; these lines have previously shown a genetic correlation between alcohol preference and FPS (HAP\u3eLAP; Barrenha and Chester 2007). In a control experiment, the effect of diazepam (4.0 mg/kg) on the expression of FPS was tested in HAP2 and LAP2 mice. Results: The 1.5 g/kg alcohol dose moderately decreased the expression of FPS in both HAP lines but not LAP lines. Alcohol had no effect on the acquisition of FPS in any line. Diazepam reduced FPS to a similar extent in both HAP2 and LAP2 mice. Conclusions: HAP mice may be more sensitive to the anxiolytic effects of alcohol than LAP mice when alcohol is given prior to the expression of FPS. These data collected in two pairs of HAP/LAP mouse lines suggest that the anxiolytic response to alcohol in HAP mice may be genetically correlated with their propensity toward high alcohol preference and robust FPS

High-throughput mass spectrometry maps the sepsis plasma proteome and differences in patient response

Sepsis, the dysregulated host response to infection causing life-threatening organ dysfunction, is a global health challenge requiring better understanding of pathophysiology and new therapeutic approaches. Here, we applied high-throughput tandem mass spectrometry to delineate the plasma proteome for sepsis and comparator groups (noninfected critical illness, postoperative inflammation, and healthy volunteers) involving 2612 samples (from 1611 patients) and 4553 liquid chromatography–mass spectrometry analyses acquired through a single batch of continuous measurements, with a throughput of 100 samples per day. We show how this scale of data can delineate proteins, pathways, and coexpression modules in sepsis and be integrated with paired leukocyte transcriptomic data (837 samples from n = 649 patients). We mapped the plasma proteomic landscape of the host response in sepsis, including changes over time, and identified features relating to etiology, clinical phenotypes (including organ failures), and severity. This work reveals subphenotypes informative for sepsis response state, disease processes, and outcome; identifies potential biomarkers; and advances opportunities for a precision medicine approach to sepsis