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Alzheimer's & Dementia : the Journal of... Jun 2024The National Institute on Aging and the Alzheimer's Association convened three separate work groups in 2011 and single work groups in 2012 and 2018 to create...
The National Institute on Aging and the Alzheimer's Association convened three separate work groups in 2011 and single work groups in 2012 and 2018 to create recommendations for the diagnosis and characterization of Alzheimer's disease (AD). The present document updates the 2018 research framework in response to several recent developments. Defining diseases biologically, rather than based on syndromic presentation, has long been standard in many areas of medicine (e.g., oncology), and is becoming a unifying concept common to all neurodegenerative diseases, not just AD. The present document is consistent with this principle. Our intent is to present objective criteria for diagnosis and staging AD, incorporating recent advances in biomarkers, to serve as a bridge between research and clinical care. These criteria are not intended to provide step-by-step clinical practice guidelines for clinical workflow or specific treatment protocols, but rather serve as general principles to inform diagnosis and staging of AD that reflect current science. HIGHLIGHTS: We define Alzheimer's disease (AD) to be a biological process that begins with the appearance of AD neuropathologic change (ADNPC) while people are asymptomatic. Progression of the neuropathologic burden leads to the later appearance and progression of clinical symptoms. Early-changing Core 1 biomarkers (amyloid positron emission tomography [PET], approved cerebrospinal fluid biomarkers, and accurate plasma biomarkers [especially phosphorylated tau 217]) map onto either the amyloid beta or AD tauopathy pathway; however, these reflect the presence of ADNPC more generally (i.e., both neuritic plaques and tangles). An abnormal Core 1 biomarker result is sufficient to establish a diagnosis of AD and to inform clinical decision making throughout the disease continuum. Later-changing Core 2 biomarkers (biofluid and tau PET) can provide prognostic information, and when abnormal, will increase confidence that AD is contributing to symptoms. An integrated biological and clinical staging scheme is described that accommodates the fact that common copathologies, cognitive reserve, and resistance may modify relationships between clinical and biological AD stages.
PubMed: 38934362
DOI: 10.1002/alz.13859 -
Movement Disorders : Official Journal... Jun 2024Neuroimaging studies in rapid eye movement sleep behavior disorder (RBD) can inform fundamental questions about the pathogenesis of Parkinson's disease (PD). Across... (Review)
Review
Neuroimaging studies in rapid eye movement sleep behavior disorder (RBD) can inform fundamental questions about the pathogenesis of Parkinson's disease (PD). Across modalities, functional magnetic resonance imaging (fMRI) may be better suited to identify changes between neural networks in the earliest stages of Lewy body diseases when structural changes may be subtle or absent. This review synthesizes the findings from all fMRI studies of RBD to gain further insight into the pathophysiology and progression of Lewy body diseases. A total of 32 studies were identified using a systematic review conducted according to PRISMA guidelines between January 2000 to February 2024 for original fMRI studies in patients with either isolated RBD (iRBD) or RBD secondary to PD. Common functional alterations were detectable in iRBD patients compared with healthy controls across brainstem nuclei, basal ganglia, frontal and occipital lobes, and whole brain network measures. Patients with established PD and RBD demonstrated decreased functional connectivity across the whole brain and brainstem nuclei, but increased functional connectivity in the cerebellum and frontal lobe compared with those PD patients without RBD. Finally, longitudinal changes in resting state functional connectivity were found to track with disease progression. Currently, fMRI studies in RBD have demonstrated early signatures of neurodegeneration across both motor and non-motor pathways. Although more work is needed, such findings have the potential to inform our understanding of disease, help to distinguish between prodromal PD and prodromal dementia with Lewy bodies, and support the development of fMRI-based outcome measures of phenoconversion and progression in future disease modifying trials. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
PubMed: 38934216
DOI: 10.1002/mds.29898 -
Stereotactic and Functional Neurosurgery Jun 2024We present our surgical complications resulting in neurological deficit or additional surgery during 25 years of DBS of the subthalamic nucleus (STN) for Parkinson's...
INTRODUCTION
We present our surgical complications resulting in neurological deficit or additional surgery during 25 years of DBS of the subthalamic nucleus (STN) for Parkinson's disease (PD).
METHODS
We conducted a retrospective chart review of all PD patients that received STN DBS in our DBS center between 1998 and 2023. Outcomes were complications resulting in neurological deficit or additional surgery. Potential risk factors (number of microelectrode recording tracks, age, anesthesia method, hypertension, and sex) for symptomatic intracerebral hemorrhage (ICH) were analyzed. Furthermore, lead fixation techniques were compared.
RESULTS
Eight hundred PD patients (507 men, 293 women) received unilateral (n = 11) or bilateral (n = 789) implantation of STN electrodes. Neurological deficit due to ICH, edema, delirium, or infarction was seen in 8.4% of the patients (7.4% transient, 1.0% permanent). Twenty-two patients (2.8%) had a symptomatic ICH following STN DBS, for which we did not find any risk factors, and five had permanent sequelae due to ICH (0.6%). Of all patients, 18.4% required additional surgery; the proportion was reduced from 27% in the first 300 cases to 13% in the last 500 cases (p < 0.001). The infection rate was 3.5%, which decreased from 5.3% in the first 300 cases to 2.2% in the last 500 cases. The use of a lead anchoring device led to significantly less lead migrations than miniplate fixation.
CONCLUSION
STN DBS leads to permanent neurological deficit in a small number of patients (1.0%), but a substantial proportion needs some additional surgical procedure after the first DBS system implantation. The risk of revision surgery was reduced over time but remained significant. These findings need to be discussed with the patient in the preoperative informed consent process in addition to the expected health benefit.
PubMed: 38934196
DOI: 10.1159/000539483 -
Stereotactic and Functional Neurosurgery Jun 2024The aim of this study was to present a novel technique for subthalamic nucleus (STN) deep brain stimulation (DBS) implantation under general anesthesia by using...
Mapping of Capsular Side Effects by using Intraoperative Motor-Evoked Potentials during Asleep Deep Brain Stimulation Surgery of the Subthalamic Nucleus for Parkinson's Disease.
INTRODUCTION
The aim of this study was to present a novel technique for subthalamic nucleus (STN) deep brain stimulation (DBS) implantation under general anesthesia by using intraoperative motor-evoked potentials (MEPs) through direct lead stimulation and determining their correlation to the thresholds of postoperative stimulation-induced side effects.
METHODS
This study included 22 consecutive patients with advanced Parkinson's disease who underwent surgery in our institution between January 2021 and September 2023. All patients underwent bilateral implantation in the STN (44 leads) under general anesthesia without microelectrode recordings (MERs) by using MEPs with electrostimulation directly through the DBS lead. No cortical stimulation was performed during this process. Intraoperative fluoroscopic guidance and immediate postoperative computed tomography were used to verify the electrode's position. The lowest MEP thresholds were recorded and were correlated to the postoperative stimulation-induced side-effect threshold. The predictive values of the MEPs were analyzed. Five DBS leads were repositioned intraoperatively due to the MEP results.
RESULTS
A moderately strong positive correlation was found between the MEP threshold and the capsular side-effect threshold (RS = 0.425, 95% CI, 0.17-0.67, p = 0.004). The highest sensitivity and specificity for predicting a side-effect threshold of 5 mA were found to be at 2.4 mA MEP threshold (sensitivity 97%, specificity 87.5%, positive predictive value 97%, and negative predictive value 87.5%). We also found high sensitivity and specificity (100%) at 1.15 mA MEP threshold and 3 mA side-effect threshold. Out of the total 44 leads, 5 (11.3%) leads were repositioned intraoperatively due to MEP thresholds lower than 1 mA (4 leads) or higher than 5 mA (1 lead). The mean accuracy on postoperative CT was 1.05 mm, and there were no postoperative side-effects under 2.8 mA.
CONCLUSION
Intraoperative MEPs with electrostimulation directly through the contacts of the DBS lead correlate with the stimulation-induced capsular side effects. The lead reposition based on intraoperative MEP may enlarge the therapeutic window of DBS stimulation.
PubMed: 38934180
DOI: 10.1159/000539433 -
Frontiers in Neuroscience 2024Parkinson's disease (PD) is a common neurodegenerative disease with a rapid increase in incidence in recent years. Existing treatments cannot slow or stop the...
BACKGROUND
Parkinson's disease (PD) is a common neurodegenerative disease with a rapid increase in incidence in recent years. Existing treatments cannot slow or stop the progression of PD. It was proposed that neuroinflammation leads to neuronal death, making targeting neuroinflammation a promising therapeutic strategy. Our previous studies have demonstrated that rhein protects neurons by inhibiting neuroinflammation, and it has been found to exhibit neuroprotective effects in Alzheimer's disease and epilepsy, but its neuroprotective mechanisms and effects on PD are still unclear.
METHODS
PD animal model was induced by 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP). ELISA, RT-qPCR, western blot and Immunofluorescence were used to detect the levels of inflammatory cytokines and M1 polarization markers. The protein expression levels of signaling pathways were measured by western blot. Hematoxylin-eosin (HE) staining showed that rhein did not damage the liver and kidney. Two behavioral tests, pole test and rotarod test, were used to evaluate the improvement effect of rhein on movement disorders. The number of neurons in the substantia nigra was evaluated by Nissl staining. Immunohistochemistry and western blot were used to detect tyrosine hydroxylase (TH) and α-synuclein.
RESULTS
Rhein inhibited the activation of MAPK/IκB signaling pathway and reduced the levels of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and M1 polarization markers of microglia . In a mouse model of PD, rhein ameliorated movement disorders, reduced dopaminergic neuron damage and α-synuclein deposition.
CONCLUSION
Rhein inhibits neuroinflammation through MAPK/IκB signaling pathway, thereby reducing neurodegeneration, α-synuclein deposition, and improving movement disorders in Parkinson's disease.
PubMed: 38933815
DOI: 10.3389/fnins.2024.1396345 -
Frontiers in Pharmacology 2024Recent studies have demonstrated dysregulation of the autophagy pathway in patients with Parkinson's disease (PD) and in animal models of PD, highlighting its emerging... (Review)
Review
Recent studies have demonstrated dysregulation of the autophagy pathway in patients with Parkinson's disease (PD) and in animal models of PD, highlighting its emerging role in disease. In particular, several studies indicate that autophagy, which is an essential degradative process for the damaged protein homeostasis and the management of cell balance, can manifest significant variations according to gender. While some evidence suggests increased autophagic activation in men with PD, women may have distinct regulatory patterns. In this review, we examined the existing literature on gender differences in PD-associated autophagic processes, focusing on the autophagy related proteins (ATGs) and leucine rich repeat kinase 2 (LRRK2) genes. Also, this review would suggest that an in-depth understanding of these gender differences in autophagic processes could open new perspectives for personalized therapeutic strategies, promoting more effective and targeted management of PD.
PubMed: 38933683
DOI: 10.3389/fphar.2024.1408152 -
Frontiers in Computational Neuroscience 2024Parkinson's disease (PD) is a globally significant health challenge, necessitating accurate and timely diagnostic methods to facilitate effective treatment and...
Parkinson's disease (PD) is a globally significant health challenge, necessitating accurate and timely diagnostic methods to facilitate effective treatment and intervention. In recent years, self-supervised deep representation pattern learning (SS-DRPL) has emerged as a promising approach for extracting valuable representations from data, offering the potential to enhance the efficiency of voice-based PD detection. This research study focuses on investigating the utilization of SS-DRPL in conjunction with deep learning algorithms for voice-based PD classification. This study encompasses a comprehensive evaluation aimed at assessing the accuracy of various predictive models, particularly deep learning methods when combined with SS-DRPL. Two deep learning architectures, namely hybrid Long Short-Term Memory and Recurrent Neural Networks (LSTM-RNN) and Deep Neural Networks (DNN), are employed and compared in terms of their ability to detect voice-based PD cases accurately. Additionally, several traditional machine learning models are also included to establish a baseline for comparison. The findings of the study reveal that the incorporation of SS-DRPL leads to improved model performance across all experimental setups. Notably, the LSTM-RNN architecture augmented with SS-DRPL achieves the highest F1-score of 0.94, indicating its superior ability to detect PD cases using voice-based data effectively. This outcome underscores the efficacy of SS-DRPL in enabling deep learning models to learn intricate patterns and correlations within the data, thereby facilitating more accurate PD classification.
PubMed: 38933392
DOI: 10.3389/fncom.2024.1414462 -
Frontiers in Neurology 2024
PubMed: 38933325
DOI: 10.3389/fneur.2024.1434924 -
Dementia & Neuropsychologia 2024Corticobasal syndrome (CBS) is a rare cause of dementia and comprises varied combinations of subcortical signs (akinetic-rigid parkinsonism, dystonia, or myoclonus) with...
Corticobasal syndrome (CBS) is a rare cause of dementia and comprises varied combinations of subcortical signs (akinetic-rigid parkinsonism, dystonia, or myoclonus) with cortical signs (apraxia, alien hand or cortical sensory deficit), usually asymmetric. We aimed to report and compare the clinical and neuroimaging presentation of two patients diagnosed with CBS. While case 1 had severe non-fluent aphasia associated with mild apraxia and limb rigidity, case 2 had a more posterior cognitive impairment, with a different language pattern associated with marked visuospatial errors and hemineglect. FDG PET played a significant role in diagnosis, suggesting, in the first case, corticobasal degeneration and, in the second, Alzheimer's disease pattern. CBS has been widely studied with the advent of new methods such as brain FDG PET. Studies that deepen the phenotypic and biomarker heterogeneity of CBS will be of great importance for better classification, prognosis, and treatment of the condition.
PubMed: 38933079
DOI: 10.1590/1980-5764-DN-2023-0085 -
Nuclear Medicine and Molecular Imaging Jun 2024N-3-[F]fluoropropyl-2β-carbomethoxy-3β-4-iodophenyl nortropane ([F]FP-CIT) is a radiopharmaceutical for dopamine transporter (DAT) imaging using positron emission... (Review)
Review
N-3-[F]fluoropropyl-2β-carbomethoxy-3β-4-iodophenyl nortropane ([F]FP-CIT) is a radiopharmaceutical for dopamine transporter (DAT) imaging using positron emission tomography (PET) to detect dopaminergic neuronal degeneration in patients with parkinsonian syndrome. [F]FP-CIT was granted approval by the Ministry of Food and Drug Safety in 2008 as the inaugural radiopharmaceutical for PET imaging, and it has found extensive utilization across numerous institutions in Korea. This review article presents an imaging procedure for [F]FP-CIT PET to aid nuclear medicine physicians in clinical practice and systematically reviews the clinical studies associated with [F]FP-CIT PET.
PubMed: 38932763
DOI: 10.1007/s13139-024-00840-x