The latest medical research on Neurodegenerative Disorders

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about neurodegenerative disorders gathered by our medical AI research bot.

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Structural Changes in the Arcuate Fasciculus and Recovery of Post-stroke Aphasia: A 6-Month Follow-up Study using Diffusion Tensor Imaging.

Neurorehabilitation and Neural Repair

Temporal changes in the structural connectivity of major language tracts after stroke and their contribution to aphasia recovery are unclear.

To investigate longitudinal arcuate fasciculus (AF) integrity changes and their relationship with post-stroke aphasia recovery using diffusion tensor imaging (DTI).

Thirty-five patients with aphasia due to first-ever left hemispheric stroke underwent the Korean version of the Western Aphasia Battery and DTI at 1- and 6-month post stroke onset. Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) of both AF tracts were analyzed to evaluate the temporal changes in tract integrity and determine the correlation between changes (Δ; follow-up - initial) in DTI parameters and language scores.

At 6 months post-stroke, the mean FA decreased, and mean MD and RD increased in both hemispheres; however, compared with mean AD observed after 1 month, the mean observed at 6 months increased only in the left hemisphere (P < .05). ΔFA of the left AF and proportional change in the aphasia quotient showed a significant positive correlation (r = 0.365, P = .031). No correlation was found between changes in the right AF parameters and language score. The group with increased FA in the left AF showed more significant language improvement than the group with decreased FA.

During the subacute stage, the integrity of AF decreased in both hemispheres in patients with aphasia, and the change in structural connectivity of the left AF was associated with language improvement.

Preoperative and postoperative memory in epilepsy patients with 'gliosis only' versus hippocampal sclerosis: a matched case-control study.

Neurology, Neurosurgery and Psychiatry

Gliosis only (GO) and hippocampal sclerosis (HS) are distinct histopathological entities in mesial temporal lobe epilepsy. This study explores whether this distinction also exists on a functional level when evaluating pre- and postoperative memory.

Using a retrospective matched case-control study design, we analysed verbal and visual memory performance in 49 patients with GO and 49 patients with HS before and one year after elective surgery.

Clinical differences were evident with a later age at seizure onset (18±12 vs 12±9 years) and fewer postoperative seizure-free patients in the GO group (63% vs 82%). Preoperatively, group and individual-level data demonstrated that memory impairments were less frequent, less severe and relatively non-specific in patients with GO compared with HS. Postoperatively, verbal memory declined in both groups, particularly after left-sided resections, with more significant losses in patients with GO. Factoring in floor effects, GO was also associated with more significant visual memory loss, particularly after left resections.

Compared with HS, GO is characterised by (1) a later onset of epilepsy, (2) less pronounced and more non-specific memory impairments before surgery, (3) a less successful surgical outcome and (4) a more significant memory decline after surgery. Overall, our results regarding cognition provide further evidence that GO and HS are distinct clinical entities. Functional integrity of the hippocampus appears higher in GO, as indicated by a better preoperative memory performance and worse memory outcome after surgery. The different risk-benefit ratios should be considered during presurgical patient counselling.

Somatic symptom disorder in patients with post-COVID-19 neurological symptoms: a preliminary report from the somatic study (Somatic Symptom Disorder Triggered by COVID-19).

Neurology, Neurosurgery and Psychiatry

To assess the diagnosis of somatic symptom disorder (SSD) in patients with unexplained neurological symptoms occurring after SARS-CoV-2 infection, also referred to as long COVID.

Patients were contacted for a standardised psychometric evaluation by phone, followed by a self-survey.

Although the patients did not meet the DSM-5 criteria for a functional neurological symptom disorder specifically, SSD diagnosis based on DSM-5 criteria was positive in 32 (64%) patients. In the remaining 18 patients, SSD was considered possible given the high score on diagnostic scales. Physical examination were normal for all. Brain MRI showed unspecific minor white matter hyperintensities in 8/46 patients. Neuropsychological assessment showed exclusively mild impairment of attention in 14 out of 15 tested patients, in discrepancy with their major subjective complaint. Forty-five (90%) patients met criteria for Chronic Fatigue Syndrome. Seventeen (32%) patients were screened positive for mood-anxiety disorders, 19 (38%) had a history of prior SSD and 27 (54%) reported past trauma. Additional self-survey highlighted post-traumatic stress disorder in 12/43 (28%), high levels of alexithymia traits and perfectionism. Long-lasting symptoms had a major impact with a high rate of insomnia (29/43, 67%), psychiatric follow-up (28/50, 56%) and work or pay loss (25/50, 50%).

A majority of patients with unexplained long-lasting neurological symptoms after mild COVID met diagnostic criteria for SSD and may require specific management.


Exploring the phenotype of Italian patients with ALS with intermediate ATXN2 polyQ repeats.

Neurology, Neurosurgery and Psychiatry

To detect the clinical characteristics of patients with amyotrophic lateral sclerosis (ALS) carrying an intermediate ATXN2 polyQ number of repeats in a large population-based series of Italian patients with ALS.

The study population includes 1330 patients with ALS identified through the Piemonte and Valle d'Aosta Register for ALS, diagnosed between 2007 and 2019 and not carrying C9orf72, SOD1, TARDBP and FUS mutations. Controls were 1274 age, sex and geographically matched Italian subjects, identified through patients' general practitioners.

We found 42 cases and 4 controls with≥31 polyQ repeats, corresponding to an estimated OR of 10.4 (95% CI 3.3 to 29.0). Patients with≥31 polyQ repeats (ATXN2+) compared with those without repeat expansion (ATXN2-) had more frequently a spinal onset (p=0.05), a shorter diagnostic delay (p=0.004), a faster rate of ALSFRS-R progression (p=0.004) and King's progression (p=0.004), and comorbid frontotemporal dementia (7 (28.0%) vs 121 (13.4%), p=0.037). ATXN2+ patients had a 1-year shorter survival (ATXN2+ patients 1.82 years, 95% CI 1.08 to 2.51; ATXN2- 2.84 years, 95% CI 1.67 to 5.58, p=0.0001). ATXN2 polyQ intermediate repeats was independently related to a worse outcome in Cox multivariable analysis (p=0.006).

In our population-based cohort, ATXN2+ patients with ALS have a distinctive phenotype, characterised by a more rapid disease course and a shorter survival. In addition, ATXN2+ patients have a more severe impairment of cognitive functions. These findings have relevant implications on clinical practice, including the possibility of refining the individual prognostic prediction and improving the design of ALS clinical trials, in particular as regards as those targeted explicitly to ATXN2.

Risk of stroke in multiple sclerosis and neuromyelitis optic spectrum disorder: a Nationwide cohort study in South Korea.

Neurology, Neurosurgery and Psychiatry

People with multiple sclerosis (MS) are more likely to develop stroke than those without. However, little is known about the association between neuromyelitis optica spectrum disorder (NMOSD) and the risk of stroke. We aimed to estimate the risk of stroke in patients with MS and NMOSD in South Korea.

Data from the Korean National Health Insurance between January 2010 and December 2017 were analysed. A total of 1541/1687 adult patients with MS/NMOSD, who were free of stroke were included. Matched controls were selected based on age, sex and the presence of hypertension, diabetes mellitus and dyslipidaemia.

The risk of developing stroke was 2.78 times higher (adjusted HR (aHR), 95% CI 1.91 to 4.05) in patients with MS compared with controls matched by age, sex, hypertension, diabetes mellitus and dyslipidaemia. The risk of stroke in NMOSD was also higher than that in matched controls (aHR=1.69, 95% CI 1.10 to 2.61) and not statistically different from that of MS (p=0.216). The patients with MS had a higher risk for either of ischaemic or haemorrhagic stroke (HR=2.63 and 2.93, respectively), whereas those with NMOSD had a higher risk for ischaemic stroke (HR=1.60) with marginal statistical significance.

The risk of stroke is increased in patients with MS and NMOSD and seemed comparable between the two conditions. This is the first study that estimates the risk of stroke in patients with MS and NMOSD within the same population.

Increasing the Amount and Intensity of Stepping Training During Inpatient Stroke Rehabilitation Improves Locomotor and Non-Locomotor Outcomes.

Neurorehabilitation and Neural Repair

The efficacy of traditional rehabilitation interventions to improve locomotion post-stroke, including providing multiple exercises targeting impairments and activity limitations, is uncertain. Emerging evidence rather suggests attempts to prioritize stepping practice at higher cardiovascular intensities may facilitate greater locomotor outcomes.

The present study was designed to evaluate the comparative effectiveness of high-intensity training (HIT) to usual care during inpatient rehabilitation post-stroke.

Changes in stepping activity and functional outcomes were compared over 9 months during usual-care (n = 131 patients < 2 months post-stroke), during an 18-month transition phase with attempts to implement HIT (n = 317), and over 12 months following HIT implementation (n = 208). The transition phase began with didactic and hands-on education, and continued with meetings, mentoring, and audit and feedback. Fidelity metrics included percentage of sessions prioritizing gait interventions and documenting intensity. Demographics, training measures, and outcomes were compared across phases using linear or logistic regression analysis, Kruskal-Wallis tests, or χ2 analysis.

Across all phases, admission scores were similar except for balance (usual-care>HIT; P < .02). Efforts to prioritize stepping and achieve targeted intensities during HIT vs transition or usual-care phases led to increased steps/day (P < .01). During HIT, gains in 10-m walk [HIT median = 0.13 m/s (interquartile range: 0-0.35) vs usual-care = 0.07 m/s (0-0.24), P = .01] and 6-min walk [50 (9.3-116) vs 2.1 (0-56) m, P < .01] were observed, with additional improvements in transfers and stair-climbing.

Greater efforts to prioritize walking and reach higher intensities during HIT led to increased steps/day, resulting in greater gains in locomotor and non-locomotor outcomes.

Effects of a Cognitively Challenging Agility Boot Camp Program on Balance and Gait in People With Parkinson's Disease: Does Freezing of Gait Status Matter?

Neurorehabilitation and Neural Repair

Individuals with Parkinson's disease (PD) with and without freezing of Gait (FoG) may respond differently to exercise interventions for several reasons, including disease duration. This study aimed to determine whether both people with and without FoG benefit from the Agility Boot Camp with Cognitive Challenges (ABC-C) program.

This secondary analysis of our ABC-C trial included 86 PD subjects: 44 without FoG (PD-FoG) and 42 with FoG (PD + FoG). We collected measures of standing sway balance, anticipatory postural adjustments, postural responses, and a 2-minute walk with and without a cognitive task. Two-way repeated analysis of variance, with disease duration as covariate, was used to investigate the effects of ABC-C program. Effect sizes were calculated using standardized response mean (SRM) for PD-FoG and PD + FoG, separately.

The ABC-C program was effective in improving gait performance in both PD-FoG and PD + FoG, even after controlling for disease duration. Specifically, dual-task gait speed (P < .0001), dual-cost stride length (P = .012), and these single-task measures: arm range of motion (P < .0001), toe-off angle (P = .005), gait cycle duration variability (P = .019), trunk coronal range of motion (P = .042), and stance time (P = .046) improved in both PD-FoG and PD + FoG. There was no interaction effect between time (before and after exercise) and group (PD-FoG/PD + FoG) in all 24 objective measures of balance and gait. Dual-task gait speed improved the most in PD + FoG (SRM = 1.01), whereas single-task arm range of motion improved the most in PD-FoG (SRM = 1.01).

The ABC-C program was similarly effective in improving gait (and not balance) performance in both PD-FoG and PD + FoG.

Balance Training Modulates Cortical Inhibition in Individuals with Parkinson's Disease: A Randomized Controlled Trial.

Neurorehabilitation and Neural Repair

Most individuals with Parkinson's disease (PD) develop balance dysfunction. Previous studies showed that individuals with PD have abnormal corticomotor changes related to severity of motor symptoms and disease progression. Cortical disinhibition was observed in PD and this alteration can be an early sign of PD. Balance training seems to be an effective intervention to improve balance in individuals with PD. However, it is not much known about the effect of balance training on cortical neuroplasticity in PD population.

To investigate the effects of balance training on corticomotor excitability in individuals with PD.

Twenty-eight PD participants were recruited and randomly assigned to either the balance training (BT) or the control (CON) group. Both groups underwent 16 training sessions over 8 weeks. Outcome measures for corticomotor inhibition included the cortical silent period (CSP) and short-interval intracortical inhibition (SICI) on transcranial magnetic stimulation. Balance performance was measured using the Mini-Balance Evaluation Systems Test (Mini-BEST) and the Timed Up and Go (TUG) test.

Participants in the BT group showed a significant increase in corticomotor inhibition (CSP: P = .028, SICI: P = .04) and a significant improvement in balance performance (Mini-BEST: P = .001, TUG: P = .04) after training. Compared to the CON group, the BT group showed a greater increase in corticomotor inhibition (CSP: P = .017, SICI: P = .046) and better improvement in balance (Mini-BEST: P = .046).

Balance training could modulate corticomotor inhibition in the primary motor cortex and improve balance performance in individuals with PD.

The Impact of Cognitive Impairment on Robot-Based Upper-Limb Motor Assessment in Chronic Stroke.

Neurorehabilitation and Neural Repair

Chronic upper extremity motor deficits are present in up to 65% of stroke survivors, and cognitive impairment is prevalent in 46-61% of stroke survivors even 10 years after their stroke. Robot-assisted therapy programs tend to focus on motor recovery and do not include stroke patients with cognitive impairment.

This study aims to investigate performance on the individual cognitive domains evaluated in the MoCA and their relation to upper-limb motor performance on a robotic system.

Participants were recruited from the stroke population with a wide range of cognitive and motor levels to complete a trajectory tracking task using the Haptic TheraDrive rehabilitation robot system. Motor performance was evaluated against standard clinical cognitive and motor assessments. Our hypothesis is that the cognitive domains involved in the visuomotor tracking task are significant predictors of performance on the robot-based task and that impairment in these domains results in worse motor performance on the task compared to subjects with no cognitive impairment.

Our results support the hypothesis that visuospatial and executive function have a significant impact on motor performance, with differences emerging between different functional groups on the various robot-based metrics. We also show that the kinematic metrics from this task differentiate cognitive-motor functional groups differently.

This study demonstrates that performance on a motor-based robotic assessment task also involves a significant visuospatial and executive function component and highlights the need to account for cognitive impairment in the assessment of motor performance.

The Reaching Phase of Feeding and Self-Care Actions Optimizes Action Observation Effects in Chronic Stroke Subjects.

Neurorehabilitation and Neural Repair

The Action Observation Therapy (AOT) is a well-established post-stroke rehabilitation treatment based on the theoretical framework of the Mirror Neuron System (MNS) activation. However, AOT protocols are still heterogeneous in terms of video contents of observed actions.

The aim of this study was to analyze electroencephalographic (EEG) recordings in stroke patients during the observation of different videos of task-specific upper limb movements, and to define which category of actions can elicit a stronger cortical activation in the observer's brain.

Signals were analyzed from 19 chronic stroke subjects observing customized videos that represented 3 different categories of upper limb actions: Finalized Actions, Non-Finalized Actions, and Control Videos. The Event-Related Desynchronization in the µ and β bands was chosen to identify the involvement of the cerebral cortex: the area of the normalized power spectral density was calculated for each category and, deepening, for the reaching and completion sub-phases of Finalized Actions. For descriptive purposes, the time course of averaged signal power was described. The Kruskal-Wallis test (P < .05) was applied.

The analysis showed a greater desynchronization when subjects observed Finalized Actions with respect to Non-Finalized in all recorded areas; Control videos provoked a synchronization in the same areas and frequency bands. The reaching phase of feeding and self-care actions evoked a greater suppression both in µ and β bands.

The observation of finalized arm movements seems to elicit the strongest activation of the MNS in chronic stroke patients. This finding may help the clinicians to design future AOT-based stroke rehabilitation protocols.

Clinical Trial Registration-URL: Unique identifier: NCT04047134.

Farnesyltransferase inhibitor LNK-754 attenuates axonal dystrophy and reduces amyloid pathology in mice.

Molecular Neurodegeneration

Amyloid plaque deposition and axonal degeneration are early events in AD pathogenesis. Aβ disrupts microtubules in presynaptic dystrophic neurites, resulting in the accumulation of impaired endolysosomal and autophagic organelles transporting β-site amyloid precursor protein cleaving enzyme (BACE1). Consequently, dystrophic neurites generate Aβ42 and significantly contribute to plaque deposition. Farnesyltransferase inhibitors (FTIs) have recently been investigated for repositioning toward the treatment of neurodegenerative disorders and block the action of farnesyltransferase (FTase) to catalyze farnesylation, a post-translational modification that regulates proteins involved in lysosome function and microtubule stability. In postmortem AD brains, FTase and its downstream signaling are upregulated. However, the impact of FTIs on amyloid pathology and dystrophic neurites is unknown.

We tested the effects of the FTIs LNK-754 and lonafarnib in the 5XFAD mouse model of amyloid pathology.

In 2-month-old 5XFAD mice treated chronically for 3 months, LNK-754 reduced amyloid plaque burden, tau hyperphosphorylation, and attenuated the accumulation of BACE1 and LAMP1 in dystrophic neurites. In 5-month-old 5XFAD mice treated acutely for 3 weeks, LNK-754 reduced dystrophic neurite size and LysoTracker-Green accumulation in the absence of effects on Aβ deposits. Acute treatment with LNK-754 improved memory and learning deficits in hAPP/PS1 amyloid mice. In contrast to LNK-754, lonafarnib treatment was less effective at reducing plaques, tau hyperphosphorylation and dystrophic neurites, which could have resulted from reduced potency against FTase compared to LNK-754. We investigated the effects of FTIs on axonal trafficking of endolysosomal organelles and found that lonafarnib and LNK-754 enhanced retrograde axonal transport in primary neurons, indicating FTIs could support the maturation of axonal late endosomes into lysosomes. Furthermore, FTI treatment increased levels of LAMP1 in mouse primary neurons and in the brains of 5XFAD mice, demonstrating that FTIs stimulated the biogenesis of endolysosomal organelles.

We show new data to suggest that LNK-754 promoted the axonal trafficking and function of endolysosomal compartments, which we hypothesize decreased axonal dystrophy, reduced BACE1 accumulation and inhibited amyloid deposition in 5XFAD mice. Our results agree with previous work identifying FTase as a therapeutic target for treating proteinopathies and could have important therapeutic implications in treating AD.

When the infectious environment meets the AD brain.

Molecular Neurodegeneration

The Amyloid theory of Alzheimer's disease (AD) suggests that the deposition of Amyloid β (Aβ) in the brain triggers a chain of events, involving the deposition of phosphorylated Tau and other misfolded proteins, leading to neurodegeneration via neuroinflammation, oxidative stress, and neurovascular factors. The infectious theory linked various infectious agents with the development of AD, raising the possibility that they serve as etiological causes of the disease. Are these theories mutually exclusive, or do they coincide?

In this review, we will discuss how the two theories converge. We present a model by which (1) the systemic infectious burden accelerates the development of AD brain pathology via bacterial Amyloids and other pathogen-associated molecular patterns (PAMPs), and (2) the developing AD brain pathology increases its susceptibility to the neurotoxicity of infectious agents -derived PAMPs, which drive neurodegeneration via activated microglia.

The reciprocal effects of amyloid deposition and systemic infectious burden may lead to a vicious cycle fueling Alzheimer's disease pathogenesis.