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Investigating white matter alterations in Parkinson\u27s disease using multi-shell free-water DTI and NODDI: insights into neurodegeneration and levodopa effects
No full textINTRODUCTION: Parkinson\u27s disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms. Levodopa remains the primary treatment, temporarily restoring dopamine levels and improving motor symptoms. Advanced diffusion MRI techniques, such as free-water corrected diffusion tensor imaging (fw-DTI) and neurite orientation dispersion and density imaging (NODDI), provide insights into PD-related microstructural changes beyond conventional DTI. METHODS: This study investigates white matter alterations in PD using multi-shell fw-DTI and NODDI to compare voxel-wise differences between PD patients both OFF and ON levodopa, with comparison to healthy controls (HC). Effect sizes and receiver operating characteristic (ROC) analyses assessed the discriminative power of imaging metrics. RESULTS: PD (OFF) exhibited increased free-water, reduced neurite density (NDI), and altered orientation dispersion (ODI) in key motor pathways in comparison to HC, while fw-FA offered robust group discrimination (AUC=0.956). Levodopa (ON state) increased NDI and NODDI-FWF, suggesting acute microstructural plasticity, though this finding contrasted with minimal fw-DTI FW changes. Additionally, voxel-based correlation analyses linked free-water and neurite integrity metrics with disease severity. DISCUSSION: Our findings suggest that fw-DTI and NODDI provide complementary information on PD-related neurodegeneration and the transient effects of levodopa. These results underscore the potential of advanced diffusion MRI techniques as biomarkers for tracking PD progression and treatment response
Aneurysm formation and postcoiling recurrence in HIV-associated vasculopathy: illustrative case
No full textBACKGROUND: Human immunodeficiency virus (HIV) infection is linked with an uncommon vasculopathy syndrome, increasing the susceptibility of infected individuals to develop aneurysms across systemic vasculature, notably in the cerebral vasculature. Intracranial aneurysms have been detected in up to 14% of HIV-positive patients with neuroimaging, often manifesting in unusual locations or with atypical morphologies due to systemic pathophysiology. OBSERVATIONS: This case report describes a previously coiled middle cerebral artery sidewall aneurysm that subsequently recurred in an HIV-positive man in his late 20s, necessitating open treatment with microsurgical clip reconstruction, which was performed using a minipterional craniotomy and transsylvian approach. Intraoperative findings included diffuse cerebral dolichoectasia, a broad-necked recurrence of the M2 segment aneurysm, and a de novo A1 segment aneurysm. Both aneurysms were successfully treated with primary clipping reconstruction. The patient recovered well, with no new postoperative neurological deficits and radiographically confirmed obliteration of both aneurysms. LESSONS: Endovascular treatment of HIV-positive patients with cerebrovascular disease can be predisposed to failure, and such patients require close radiographic surveillance. The differential risk of recurrence by treatment modality is indeterminate; however, young HIV-positive patients with intracranial aneurysms can benefit from the preferential use of open clipping where equipoise exists. https://thejns.org/doi/10.3171/CASE24700
Time-restricted eating in Alzheimer\u27s disease: TREAD pilot trial design
No full textBACKGROUND AND OBJECTIVE: Time-restricted eating (TRE) may slow neurodegeneration and cognitive decline by stimulating metabolic processes that are neuroprotective. The primary aim of the TRE in Alzheimer\u27s Disease (TREAD) pilot trial is to evaluate the feasibility of implementing a TRE intervention among individuals with mild cognitive impairment (MCI) and to obtain preliminary data on cognitive domains and blood biomarkers that are responsive to TRE. METHODS: TREAD is an intervention trial for 30 adults aged 55-89 years with MCI. A pre/post design is used, with neuropsychological assessments, surveys, and blood biomarkers of cardiometabolic health and AD obtained before and after the intervention. The TRE intervention involves 16 h of continuous fasting and an 8 h eating window on 5 or more days per week for 12 weeks. Feasibility measures include participant enrollment, retention, adherence, acceptability of the intervention, and safety. Cognitive measures include executive function, working memory, processing speed, auditory attention, auditory verbal learning, visuospatial memory, category fluency, and phonemic fluency. SUMMARY: TREAD is exploring an innovative approach to address cognitive decline and will provide critical preliminary data to inform and power a larger, longer-term, randomized controlled trial of TRE on cognitive trajectory among adults with cognitive impairment
Characterizing Neurobehavioral Dysregulation Among Former American Football Players: Findings From the DIAGNOSE CTE Research Project
No full textOBJECTIVE: Neurobehavioral dysregulation (NBD), a core clinical feature of traumatic encephalopathy syndrome, encompasses neuropsychiatric symptoms reported among individuals with a history of repetitive head impact exposure, including contact sport athletes. The objective of this study was to examine the construct and subconstructs of NBD through a series of factor and cluster analyses. METHODS: Six clinician-scientists selected self-report questionnaire items relevant to NBD from seven available neuropsychiatric scales through a blinded voting process. These items were subjected to confirmatory factor analyses in a sample of 178 former college and professional American football players and 60 asymptomatic individuals without a history of repetitive head impact exposure. All participants were enrolled in the Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy Research Project. Factor scores were generated on the basis of the optimal expert-informed model for NBD. Construct validity was assessed with neuropsychiatric scales not included in generation of the factor scores. Cluster analyses with NBD factor scores were used to examine symptom profiles. RESULTS: Factor analyses confirmed that NBD was composed of four subconstructs: explosivity, emotional dyscontrol, impulsivity, and affective lability. Cluster analyses indicated four distinct symptom profiles of NBD in this group of former football players: asymptomatic (N=80, 45%), short fuse (N=33, 19%), high affective lability (N=34, 19%), and high NBD (N=31, 17%). CONCLUSIONS: These findings characterize NBD as a multifaceted clinical construct with a heterogeneous presentation, providing a foundation for empirical work on the diagnostic criteria for traumatic encephalopathy syndrome and research on the neurobiological underpinnings of NBD
Dispersion-based cognitive intra-individual variability in former American football players: Association with traumatic encephalopathy syndrome, repetitive head impacts, and biomarkers
No full textExposure to repetitive head impacts (RHI), such as those experienced in American football, is linked to cognitive dysfunction later in life. Traumatic encephalopathy syndrome (TES) is a proposed clinical syndrome thought to be linked to neuropath-ology of chronic traumatic encephalopathy (CTE), a condition associated with RHI from football. Cognitive intra-individual variability (d-CIIV) measures test-score dispersion, indicating cognitive dysfunction. This study examined d-CIIV in former football players and its associations with TES diagnosis, RHI exposure, and DTI and CSF biomarkers. Data included 237 males (45-74 years) from DIAGNOSE CTE Research Project, including former professional and college football players (COL) (n = 173) and asymptomatic men without RHI or TBI (n = 55). Participants completed neuropsychological tests. TES diagnosis was based on 2021 NINDS TES criteria. Years of football play and a cumulative head impact index (CHII) measured RHI exposure. Lumipulse technology was used for CSF assays. DTI fractional anisotropy assessed white matter integrity. Coefficient of variation (CoV) measured d-CIIV. ANCOVA compared d-CIIV among groups (football versus control; TES-status). Pearson correlations and linear regressions tested associations between d-CIIV, RHI exposure, and CSF and DTI biomarkers. Former professional players had higher d-CIIV than controls (F(7, 194) = 2.87, p = .007). d-CIIV was associated with TES diagnosis (F(8, 146) = 9.063, p \u3c .001), with highest d-CIIV in TES Possible/Probable-CTE. Higher d-CIIV correlated with higher CHII scores (r = 0.19), reduced CSF Aβ (β = -0.302), increased p-tau (β= 0.374), and reduced DTI FA (β = -0.202). d-CIIV is linked to RHI exposure and TES diagnosis in former football players, with associated changes in CSF biomarkers and white matter integrity
Linking Symptom Inventories Using Semantic Textual Similarity
No full textAn extensive library of symptom inventories has been developed over time to measure clinical symptoms of traumatic brain injury (TBI), but this variety has led to several long-standing issues. Most notably, results drawn from different settings and studies are not comparable. This creates a fundamental problem in TBI diagnostics and outcome prediction, namely that it is not possible to equate results drawn from distinct tools and symptom inventories. Here, we present an approach using semantic textual similarity (STS) to link symptoms and scores across previously incongruous symptom inventories by ranking item text similarities according to their conceptual likeness. We tested the ability of four pretrained deep learning models to screen thousands of symptom description pairs for related content-a challenging task typically requiring expert panels. Models were tasked to predict symptom severity across four different inventories for 6,607 participants drawn from 16 international data sources. The STS approach achieved 74.8% accuracy across five tasks, outperforming other models tested. Correlation and factor analysis found the properties of the scales were broadly preserved under conversion. This work suggests that incorporating contextual, semantic information can assist expert decision-making processes, yielding broad gains for the harmonization of TBI assessment
park+/+ and park-/- Drosophila have sexually dimorphic brain redox chemistry
No full textSexual dimorphism in Parkinson\u27s disease (PD) pathophysiology is poorly understood. Elucidating consequences of disease-causing mutations on brain redox chemistry may reveal therapeutic targets for all people with PD. We report that male Drosophila had increased hydrogen peroxide and glutathione (G-SH) redox disequilibrium in vulnerable dopaminergic neuron mitochondria. Levels of cysteine and oxidized cystine were decreased, with cysteine/cystine ratios (indicating less oxidative stress) and G-SH levels being elevated in parkin-null (park-/-) Drosophila brains, and more so in males. We report effects of parkin loss and sex on the levels of low-molecular-weight thiols involved in G-SH synthesis, providing clues as to mechanisms implicated in altered levels of brain G-SH, cysteine and cystine. Protein nitration was decreased in the brain of park-/- flies, especially in females, suggesting that decreased nitric oxide levels compensate for loss of parkin or lack of protective nitric oxide synthase activity. Our results imply that park-/- flies have elevated levels of G-SH that meet antioxidant demand in the absence of parkin in the whole brain, but not in vulnerable neurons. Identification of sexually dimorphic PD risk factors could inform symptom management and highlight sex-specific therapeutic strategies
Posterior cingulate cortex microRNA dysregulation differentiates cognitive resilience, mild cognitive impairment, and Alzheimer\u27s disease
No full textINTRODUCTION: MicroRNA (miRNA) activity is increasingly appreciated as a key regulator of pathophysiologic pathways in Alzheimer\u27s disease (AD). However, the role of miRNAs during the progression of AD, including resilience and prodromal syndromes such as mild cognitive impairment (MCI), remains underexplored. METHODS: We performed miRNA-sequencing on samples of posterior cingulate cortex (PCC) obtained post mortem from Rush Religious Orders Study participants diagnosed ante mortem with no cognitive impairment (NCI), MCI, or AD. NCI subjects were subdivided as low pathology (Braak stage I/II) or high pathology (Braak stage III/IV), suggestive of resilience. Bioinformatics approaches included differential expression, messenger RNA (mRNA) target prediction, interactome modeling, functional enrichment, and AD risk modeling. RESULTS: We identified specific miRNA groups, mRNA targets, and signaling pathways distinguishing AD, MCI, resilience, ante mortem neuropsychological test performance, post mortem neuropathological burden, and AD risk. DISCUSSION: These findings highlight the potential of harnessing miRNA activity to manipulate disease-modifying pathways in AD, with implications for precision medicine. HIGHLIGHTS: MicroRNA (MiRNA) dysregulation is a well-established feature of Alzheimer\u27s disease (AD). Novel miRNAs also distinguish subjects with mild cognitive impairment and putative resilience. MiRNAs correlate with cognitive performance and neuropathological burden. Select miRNAs are associated with AD risk with age as a significant covariate. MiRNA pathways include insulin, prolactin, kinases, and neurite plasticity
Artificial intelligence-based deep learning model for evaluating procedural consistency in microvascular anastomosis
No full textOBJECTIVE: Assessing the consistency and precision of microanastomosis performance is crucial in neurosurgical training. Traditional methods rely on expert observation, which can be subjective and time-consuming. The aim of this study was to develop and validate a deep learning model using long short-term memory (LSTM) architecture for objective evaluation of microanastomosis performance by predicting and comparing suturing executions. METHODS: An LSTM-based neural network was developed to model and predict hand movements during microvascular anastomosis simulation. Video data were collected from 2 expert neurosurgeons performing microanastomosis twice, 1 year apart (sessions 1 and 2). Surgeon 1 performed interrupted suturing, and surgeon 2 performed continuous suturing. Additionally, a trainee with minimal microsurgical experience performed the interrupted suturing procedure once. Model performance was quantitatively assessed by comparing predicted and actual suturing executions using Kullback-Leibler (KL) divergence. Economy and flow of motion were also analyzed. RESULTS: The LSTM-based model accurately predicted suturing movements. Surgeon 1 demonstrated KL divergence values of 0.00063 (session 1) and 0.00061 (session 2), and surgeon 2 had values of 0.00082 (session 1) and 0.00016 (session 2). The trainee exhibited higher KL divergence (0.00196), reflecting less consistent performance. The economy of motion was assessed, showing mean Euclidean distances of 7.41 mm (session 1) and 5.85 mm (session 2) for surgeon 1, 10.53 mm (session 1) and 14.46 mm (session 2) for surgeon 2, and 10.50 mm for the trainee. The flow of motion analysis indicated median time intervals between sutures of 31.96 seconds (session 1) and 29.57 seconds (session 2) for surgeon 1, 21.53 seconds (session 1) and 21.50 seconds (session 2) for surgeon 2, and 101.23 seconds for the trainee. CONCLUSIONS: The LSTM-based model objectively assessed microanastomosis performance, capturing consistency and efficiency. Economy and flow of motion metrics were further validated. Future studies will extend the model\u27s application to more surgeons and refine interpretation of the performance metrics