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Parkinsonism & Related Disorders Oct 2023Physical activity benefits patients with Parkinson's disease (PD) and is assumed to possess disease-modifying potential. PD-related biomarkers, such as dopamine...
INTRODUCTION
Physical activity benefits patients with Parkinson's disease (PD) and is assumed to possess disease-modifying potential. PD-related biomarkers, such as dopamine transporter (DAT) imaging and cerebrospinal fluid (CSF) α-synuclein (α-syn) and amyloid β (Aβ), correlate with disease severity and, to some extent, reflect disease progression and pathology. However, the association between regular physical activity and PD biomarker changes remains unknown. This study aimed to investigate the association between physical activity and longitudinal trajectories of PD biomarkers.
METHODS
This retrospective study included 444 patients with a median follow-up time of 5 years from the Parkinson's Progression Markers Initiative cohort. Data collection included physical activity as scaled by the Physical Activity Scale for the Elderly questionnaire, dopamine transporter imaging, CSF assessment, and serum biomarkers. We analyzed the data using a linear mixed regression model.
RESULTS
Regular physical activity was associated with a slower decline of DAT uptake in the caudate (β = 0.063, p = 0.011) and the putamen (β = 0.062, p = 0.023). No association was detected between regular physical activity and CSF, as well as serum biomarkers.
CONCLUSION
Regular physical activity is associated with favorable PD biomarker progression, indicating a potential disease-modifying effect.
Topics: Humans; Aged; Parkinson Disease; Retrospective Studies; Amyloid beta-Peptides; alpha-Synuclein; Biomarkers; Patient Acuity
PubMed: 37648587
DOI: 10.1016/j.parkreldis.2023.105820 -
Human Brain Mapping Oct 2023Temporal lobe epilepsy (TLE) is associated with widespread brain alterations. Using quantitative susceptibility mapping (QSM) alongside transverse relaxation rate ( ),...
Temporal lobe epilepsy (TLE) is associated with widespread brain alterations. Using quantitative susceptibility mapping (QSM) alongside transverse relaxation rate ( ), we investigated regional brain susceptibility changes in 36 patients with left-sided (LTLE) or right-sided TLE (RTLE) secondary to hippocampal sclerosis, and 27 healthy controls (HC). We compared three susceptibility calculation methods to ensure image quality. Correlations of susceptibility and with age of epilepsy onset, frequency of focal-to-bilateral tonic-clonic seizures (FBTCS), and neuropsychological test scores were examined. Weak-harmonic QSM (WH-QSM) successfully reduced noise and removed residual background field artefacts. Significant susceptibility increases were identified in the left putamen in the RTLE group compared to the LTLE group, the right putamen and right thalamus in the RTLE group compared to HC, and a significant susceptibility decrease in the left hippocampus in LTLE versus HC. LTLE patients who underwent epilepsy surgery showed significantly lower left-versus-right hippocampal susceptibility. Significant changes were found between TLE and HC groups in the amygdala, putamen, thalamus, and in the hippocampus. Specifically, decreased R * was found in the left and right hippocampus in LTLE and RTLE, respectively, compared to HC. Susceptibility and were significantly correlated with cognitive test scores in the hippocampus, globus pallidus, and thalamus. FBTCS frequency correlated positively with ipsilateral thalamic and contralateral putamen susceptibility and with in bilateral globi pallidi. Age of onset was correlated with susceptibility in the hippocampus and putamen, and with in the caudate. Susceptibility and changes observed in TLE groups suggest selective loss of low-myelinated neurons alongside iron redistribution in the hippocampi, predominantly ipsilaterally, indicating QSM's sensitivity to local pathology. Increased susceptibility and in the thalamus and putamen suggest increased iron content and reflect disease severity.
Topics: Humans; Epilepsy, Temporal Lobe; Gray Matter; Brain Mapping; Functional Laterality; Hippocampus; Seizures; Magnetic Resonance Imaging
PubMed: 37493334
DOI: 10.1002/hbm.26432 -
Journal of Neurology Nov 2023We aimed to relate clinical measures of disability in chronic cerebellar degeneration to structural whole-brain changes using voxel-based and surface-based morphometry...
OBJECTIVE
We aimed to relate clinical measures of disability in chronic cerebellar degeneration to structural whole-brain changes using voxel-based and surface-based morphometry (vbm and sbm). We were particularly interested in remote effects of cerebellar degeneration in the cerebral cortex.
METHODS
We recruited 30 patients with cerebellar degeneration of different aetiologies (downbeat nystagmus syndrome, DBN n = 14, spinocerebellar ataxia, SCA n = 9, sporadic adult late-onset ataxia, SAOA n = 7). All patients were thoroughly characterised in the motor, cognitive, vestibular and ocular-motor domains. Vbm and sbm were used to evaluate structural differences between cerebellar degeneration patients and a group of healthy age- and gender-matched volunteers. Linear regression models were used to correlate functional measures of disease progression and postural stability with whole brain volumetry.
RESULTS
Patients with SCA and SAOA showed widespread volume loss in the cerebellar hemispheres and less prominently in the vermis. Patients with DBN showed a distinct pattern of grey matter volume (GMV) loss that was restricted to the vestibular and ocular-motor representations in lobules IX, X and V-VII. Falls were associated with brainstem white matter volume. VBM and SBM linear regression models revealed associations between severity of ataxic symptoms, cognitive performance and preferred gait velocity. This included extra-cerebellar (sub-)cortical hubs of the motor and locomotion network (putamen, caudate, thalamus, primary motor cortex, prefrontal cortex) and multisensory areas involved in spatial navigation and cognition.
CONCLUSION
Functional disability in multiple domains was associated with structural changes in the cerebral cortex.
Topics: Adult; Humans; Cerebellar Ataxia; Magnetic Resonance Imaging; Ataxia; Cerebellum; Cerebellar Diseases; Syndrome
PubMed: 37480400
DOI: 10.1007/s00415-023-11859-z -
NeuroImage Dec 2023Alterations in subcortical brain structure volumes have been found to be associated with several neurodegenerative and psychiatric disorders. At the same time,...
Alterations in subcortical brain structure volumes have been found to be associated with several neurodegenerative and psychiatric disorders. At the same time, genome-wide association studies (GWAS) have identified numerous common variants associated with brain structure. In this study, we integrate these findings, aiming to identify proteins, metabolites, or microbes that have a putative causal association with subcortical brain structure volumes via a two-sample Mendelian randomization approach. This method uses genetic variants as instrument variables to identify potentially causal associations between an exposure and an outcome. The exposure data that we analyzed comprised genetic associations for 2994 plasma proteins, 237 metabolites, and 103 microbial genera. The outcome data included GWAS data for seven subcortical brain structure volumes including accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus. Eleven proteins and six metabolites were found to have a significant association with subcortical structure volumes, with nine proteins and five metabolites replicated using independent exposure data. We found causal associations between accumbens volume and plasma protease c1 inhibitor as well as strong association between putamen volume and Agouti signaling protein. Among metabolites, urate had the strongest association with thalamic volume. No significant associations were detected between the microbial genera and subcortical brain structure volumes. We also observed significant enrichment for biological processes such as proteolysis, regulation of the endoplasmic reticulum apoptotic signaling pathway, and negative regulation of DNA binding. Our findings provide insights to the mechanisms through which brain volumes may be affected in the pathogenesis of neurodevelopmental and psychiatric disorders and point to potential treatment targets for disorders that are associated with subcortical brain structure volumes.
Topics: Humans; Mendelian Randomization Analysis; Genome-Wide Association Study; Multiomics; Brain; Biomarkers; Magnetic Resonance Imaging
PubMed: 37995919
DOI: 10.1016/j.neuroimage.2023.120466 -
Brain : a Journal of Neurology Apr 2024Degeneration of the noradrenergic system is now considered a pathological hallmark of Parkinson's disease, but little is known about its consequences in terms of...
Degeneration of the noradrenergic system is now considered a pathological hallmark of Parkinson's disease, but little is known about its consequences in terms of parkinsonian manifestations. Here, we evaluated two aspects of the noradrenergic system using multimodal in vivo imaging in patients with Parkinson's disease and healthy controls: the pigmented cell bodies of the locus coeruleus with neuromelanin sensitive MRI; and the density of α2-adrenergic receptors (ARs) with PET using 11C-yohimbine. Thirty patients with Parkinson's disease and 30 age- and sex-matched healthy control subjects were included. The characteristics of the patients' symptoms were assessed using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Patients showed reduced neuromelanin signal intensity in the locus coeruleus compared with controls and diminished 11C-yohimbine binding in widespread cortical regions, including the motor cortex, as well as in the insula, thalamus and putamen. Clinically, locus coeruleus neuronal loss was correlated with motor (bradykinesia, motor fluctuations, tremor) and non-motor (fatigue, apathy, constipation) symptoms. A reduction of α2-AR availability in the thalamus was associated with tremor, while a reduction in the putamen, the insula and the superior temporal gyrus was associated with anxiety. These results highlight a multifaceted alteration of the noradrenergic system in Parkinson's disease since locus coeruleus and α2-AR degeneration were found to be partly uncoupled. These findings raise important issues about noradrenergic dysfunction that may encourage the search for new drugs targeting this system, including α2-ARs, for the treatment of Parkinson's disease.
Topics: Humans; Parkinson Disease; Tremor; Carbon Radioisotopes; Positron-Emission Tomography; Norepinephrine; Locus Coeruleus; Magnetic Resonance Imaging; Melanins
PubMed: 37787503
DOI: 10.1093/brain/awad338 -
Journal of Neurochemistry Jul 2023The cholinergic neurons in the nucleus basalis of Meynert (NBM) are a key structure in cognition, the dysfunction of which is associated with various neurological...
The cholinergic neurons in the nucleus basalis of Meynert (NBM) are a key structure in cognition, the dysfunction of which is associated with various neurological disorders, especially dementias. However, the whole-brain neural connectivity to cholinergic neurons in the NBM remains to be further and comprehensively researched. Using virus-based, specific, retrograde, and anterograde tracing, we illustrated the monosynaptic inputs and axon projections of NBM cholinergic neurons in choline acetyltransferase (ChAT)-Cre transgenic mice. Our results showed that NBM cholinergic neurons received mainly inputs from the caudate putamen and the posterior limb of the anterior commissure in the subcortex. Moreover, the majority of cholinergic terminals from the NBM were observed in the cortex mantle, including the motor cortex, sensory cortex, and visual cortex. Interestingly, although NBM cholinergic neurons received input projections from the caudate putamen, interstitial nucleus of the posterior limb of the anterior commissure, and central amygdaloid nucleus, NBM cholinergic neurons sparsely sent axon projection to innervate these areas. Furthermore, primary motor cortex, secondary motor cortex, and primary somatosensory cortex received abundant inputs from the NBM but sent few outputs to the NBM. Taken together, our results reveal the detailed and specific connectivity of cholinergic neurons of the NBM and provide a neuroanatomic foundation for further studies to explore the important physiological functions of NBM cholinergic neurons.
Topics: Mice; Animals; Basal Nucleus of Meynert; Cholinergic Neurons; Cerebral Cortex; Axons; White Matter; Mice, Transgenic
PubMed: 37353897
DOI: 10.1111/jnc.15873 -
Brain Communications 2023Huntington's disease is caused by a CAG repeat expansion in the Huntingtin gene (), coding for polyglutamine in the Huntingtin protein, with longer CAG repeats causing...
Huntington's disease is caused by a CAG repeat expansion in the Huntingtin gene (), coding for polyglutamine in the Huntingtin protein, with longer CAG repeats causing earlier age of onset. The variable 'Age' × ('CAG'-L), where 'Age' is the current age of the individual, 'CAG' is the repeat length and L is a constant (reflecting an approximation of the threshold), termed the 'CAG Age Product' (CAP) enables the consideration of many individuals with different CAG repeat expansions at the same time for analysis of any variable and graphing using the CAG Age Product score as the X axis. Structural MRI studies have showed that progressive striatal atrophy begins many years prior to the onset of diagnosable motor Huntington's disease, confirmed by longitudinal multicentre studies on three continents, including PREDICT-HD, TRACK-HD and IMAGE-HD. However, previous studies have not clarified the relationship between striatal atrophy, atrophy of other basal ganglia structures, and atrophy of other brain regions. The present study has analysed all three longitudinal datasets together using a single image segmentation algorithm and combining data from a large number of subjects across a range of CAG Age Product score. In addition, we have used a strategy of normalizing regional atrophy to atrophy of the whole brain, in order to determine which regions may undergo preferential degeneration. This made possible the detailed characterization of regional brain atrophy in relation to CAG Age Product score. There is dramatic selective atrophy of regions involved in the basal ganglia circuit-caudate, putamen, nucleus accumbens, globus pallidus and substantia nigra. Most other regions of the brain appear to have slower but steady degeneration. These results support (but certainly do not prove) the hypothesis of circuit-based spread of pathology in Huntington's disease, possibly due to spread of mutant Htt protein, though other connection-based mechanisms are possible. Therapeutic targets related to prion-like spread of pathology or other mechanisms may be suggested. In addition, they have implications for current neurosurgical therapeutic approaches, since delivery of therapeutic agents solely to the caudate and putamen may miss other structures affected early, such as nucleus accumbens and output nuclei of the striatum, the substantia nigra and the globus pallidus.
PubMed: 37744022
DOI: 10.1093/braincomms/fcad214 -
Brain Communications 2023Apraxia of eyelid opening (or eye-opening apraxia) is characterized by the inability to voluntarily open the eyes because of impaired supranuclear control. Here, we...
Apraxia of eyelid opening (or eye-opening apraxia) is characterized by the inability to voluntarily open the eyes because of impaired supranuclear control. Here, we examined the neural substrates implicated in eye-opening apraxia through lesion network mapping. We analysed brain lesions from 27 eye-opening apraxia stroke patients and compared them with lesions from 20 aphasia and 45 hemiballismus patients serving as controls. Lesions were mapped onto a standard brain atlas using resting-state functional MRI data derived from 966 healthy adults in the Harvard Dataverse. Our analyses revealed that most eye-opening apraxia-associated lesions occurred in the right hemisphere, with subcortical or mixed cortical/subcortical involvement. Despite their anatomical heterogeneity, these lesions functionally converged on the bilateral dorsal anterior and posterior insula. The functional connectivity map for eye-opening apraxia was distinct from those for aphasia and hemiballismus. Hemiballismus lesions predominantly mapped onto the putamen, particularly the posterolateral region, while aphasia lesions were localized to language-processing regions, primarily within the frontal operculum. In summary, in patients with eye-opening apraxia, disruptions in the dorsal anterior and posterior insula may compromise their capacity to initiate the appropriate eyelid-opening response to relevant interoceptive and exteroceptive stimuli, implicating a complex interplay between salience detection and motor execution.
PubMed: 37953849
DOI: 10.1093/braincomms/fcad288 -
Journal of Psychiatric Research Jul 2023Non-suicidal self-injury (NSSI) behaviors are a major public health concern among adolescents with depression. Such behaviors may be associated with the reward system....
Non-suicidal self-injury (NSSI) behaviors are a major public health concern among adolescents with depression. Such behaviors may be associated with the reward system. However, the underlying mechanism in patients with depression and NSSI still remains unclear. A total of 56 drug-naïve adolescents with depression, including 23 patients with NSSI (the NSSI group) and 33 patients without NSSI (the nNSSI group), and 25 healthy controls (HCs) were recruited in this study. Seed-based functional connectivity (FC) was used to explore the NSSI-related FC alterations in the reward circuit. Correlation analysis was conducted between the altered FCs and clinical data. Compared with the nNSSI group, the NSSI group showed greater FC between left nucleus accumbens (NAcc) and right lingual gyrus and between right putamen accumbens and right angular gyrus (ANG). The NSSI group also had declined FC between right NAcc and left inferior cerebellum, between left cingulate gyrus (CG) and right ANG, between left CG and left middle temporal gyrus (MTG), and between right CG and bilateral MTG (voxel-wise p < 0.01, cluster-wise p < 0.05, Gaussian random field correction). The FC between right NAcc and left inferior cerebellum was found positively correlated with the score of addictive features of NSSI (r = 0.427, p = 0.042). Our findings indicated that the regions in the reward circuit with NSSI-related FC alterations included bilateral NAcc, right putamen and bilateral CG, which may provide new evidence on the neural mechanisms of NSSI behaviors in adolescents with depression.
Topics: Humans; Adolescent; Depression; Magnetic Resonance Imaging; Gyrus Cinguli; Self-Injurious Behavior; Reward
PubMed: 37244065
DOI: 10.1016/j.jpsychires.2023.05.068 -
Research progress in clinical trials of stem cell therapy for stroke and neurodegenerative diseases.Ibrain 2023The incidence of stroke and neurodegenerative diseases is gradually increasing in modern society, but there is still no treatment that is effective enough. Stem cells... (Review)
Review
The incidence of stroke and neurodegenerative diseases is gradually increasing in modern society, but there is still no treatment that is effective enough. Stem cells are cells that can reproduce (self-renew) and differentiate into the body, which have shown significance in basic research, while doctors have also taken them into clinical trials to determine their efficacy and safety. Existing clinical trials mainly include middle-aged and elderly patients with stroke or Parkinson's disease (mostly 40-80 years old), mainly involving injection of mesenchymal stem cells and bone marrow mesenchymal stem cells through the veins and the putamen, with a dosage of mostly 10-10 cells. The neural and motor functions of the patients were restored after stem cell therapy, and the safety was found to be good during the follow-up period of 3 months to 5 years. Here, we review all clinical trials and the latest advances in stroke, Alzheimer's disease, and Parkinson's disease, with the hope that stem cell therapy will be used in the clinic in the future to achieve effective treatment rates and benefit patients.
PubMed: 37786546
DOI: 10.1002/ibra.12095