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1.
Arch Rehabil Res Clin Transl ; 6(2): 100339, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39006119

RESUMO

Objective: To describe the trajectories of linguistic, cognitive-communicative, and health-related quality of life (HRQOL) outcomes after stroke in persons with aphasia. Design: Longitudinal observational study from inpatient rehabilitation to 18 months after stroke. Setting: Four US mid-west inpatient rehabilitation facilities (IRFs). Participants: We plan to recruit 400 adult (older than 21 years) English speakers who meet the following inclusion criteria: (1) Diagnosis of aphasia after a left-hemisphere infarct confirmed by CT scan or magnetic resonance imaging (MRI); (2) first admission for inpatient rehabilitation due to a neurologic event; and (3) sufficient cognitive capacity to provide informed consent and participate in testing. Exclusion criteria include any neurologic condition other than stroke that could affect language, cognition or speech, such as Parkinson's disease, Alzheimer's disease, traumatic brain injury, or the presence of right-hemisphere lesions. Interventions: Not applicable. Main Outcome Measures: Subjects are administered a test battery of linguistic, cognitive-communicative, and HRQOL measures. Linguistic measures include the Western Aphasia Battery-Revised and the Apraxia of Speech Rating Scale. Cognitive-communicative measures include the Communication Participation Item Bank, Connor's Continuous Performance Test-3, the Communication Confidence Rating Scale for Aphasia, the Communication Effectiveness Index, the Neurological Quality of Life measurement system (Neuro-QoL) Communication short form, and the Neuro-QoL Cognitive Function short form. HRQOL measures include the 39-item Stroke & Aphasia Quality of Life Scale, Neuro-QoL Fatigue, Sleep Disturbance, Depression, Ability to Participate in Social Roles & Activities, and Satisfaction with Social Roles & Activities tests, and the Patient-Reported Outcome Measurement and Information System 10-item Global Health short form. The test battery is administered initially during inpatient rehabilitation, and at 3-, 6-, 12-, and 18-months post-IRF discharge. Biomarker samples are collected via saliva samples at admission and a subgroup of participants also undergo resting state fMRI scans. Results: Not applicable. Conclusions: This longitudinal observational study will develop trajectory models for recovery of clinically relevant linguistic, cognitive-communicative, and quality of life outcomes over 18 months after inpatient rehabilitation. Models will identify individual differences in the patterns of recovery based on variations in personal, genetic, imaging, and therapy characteristics. The resulting models will provide an unparalleled representation of recovery from aphasia resulting from stroke. This improved understanding of recovery will enable clinicians to better tailor and plan rehabilitation therapies to individual patient's needs.

3.
J Cardiothorac Surg ; 19(1): 330, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38867278

RESUMO

INTRODUCTION: To date, only a limited number of case reports have documented the co-occurrence of PNS and melanocytic nevus in the medical literature. This study aims to report an exceptionally rare case of posterior chest wall PNS in conjunction with a melanocytic nevus. CASE PRESENTATION: A 46-year-old female presented with a long-standing black lesion on her left upper posterior chest wall, that had become painful in the two months prior to presentation. There was a painful, dark blue, non-erythematous, and non-tender nodule on the left upper posterior chest wall. Based on the patient's desire for cosmetic purposes, the lesion was excised totally with primary closure under local anaesthesia. Histopathological examination revealed intradermal melanocytic nevus with inflamed pilonidal sinus. DISCUSSION: The rarity of posterior chest wall PNS associated with nevi poses unique diagnostic and therapeutic challenges for clinicians. The distinct anatomical location, different from the conventional region, and the rare association between the two conditions may delay accurate diagnosis and result in mismanagement or inappropriate interventions. CONCLUSION: The posterior chest wall PNS is another type of atypical PNS that is extremely rare. The association between PNS and blue nevus is a fascinating medical finding that deserves further investigation.


Assuntos
Nevo Pigmentado , Seio Pilonidal , Neoplasias Cutâneas , Parede Torácica , Humanos , Feminino , Pessoa de Meia-Idade , Parede Torácica/patologia , Parede Torácica/cirurgia , Seio Pilonidal/cirurgia , Seio Pilonidal/patologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Nevo Pigmentado/cirurgia , Nevo Pigmentado/patologia , Nevo Pigmentado/complicações
4.
Biomed Rep ; 21(2): 118, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38938739

RESUMO

The choice between nodulectomy and lobectomy for managing thyroid nodules is a subject of debate in the field of thyroid surgery. The present study aims to share the experience of a single center in managing solitary thyroid nodules through nodulectomy from January 2023 to October 2023. The inclusion criteria encompassed symptomatic or suspicious solitary nodules and medically necessitated cases. The extracted data included patient demographics, medical history, symptoms, diagnostic details, surgery indication, procedure outcome and histopathological findings. The follow-up included clinic visits and phone calls. The mean age of the patients was 36.64±11.63 years, with 85.0% females and 15.0% males. Predominantly, patients were housewives (58.5%). Neck swelling (62.3%) was the most common presentation. Ultrasound examination revealed mixed nodules in more than half of the cases (54.7%). Right nodulectomy was performed in 26 cases (49.1%) and left nodulectomy in 23 (43.4%), and four cases (7.5%) underwent isthmusectomy. The mean operation time was 36.04±9.37 min and no drainage tube was used in any of the cases. One case (1.9%) of seroma was the only observed complication during the observational period. Nodulectomy may be a suitable choice for managing benign, large, solitary thyroid nodules, small suspicious nodules or microcarcinomas.

5.
Alzheimers Res Ther ; 16(1): 105, 2024 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730496

RESUMO

BACKGROUND: Alzheimer disease (AD) is a major health problem of aging, with tremendous burden on healthcare systems, patients, and families globally. Lecanemab, an FDA-approved amyloid beta (Aß)-directed antibody indicated for the treatment of early AD, binds with high affinity to soluble Aß protofibrils, which have been shown to be more toxic to neurons than monomers or insoluble fibrils. Lecanemab has been shown to be well tolerated in multiple clinical trials, although risks include an increased rate of amyloid-related imaging abnormalities (ARIA) and infusion reactions relative to placebo. METHODS: Clarity AD was an 18-month treatment (Core study), multicenter, double-blind, placebo-controlled, parallel-group study with open-label extension (OLE) in participants with early AD. Eligible participants were randomized 1:1 across 2 treatment groups (placebo and lecanemab 10 mg/kg biweekly). Safety evaluations included monitoring of vital signs, physical examinations, adverse events, clinical laboratory parameters, and 12-lead electrocardiograms. ARIA occurrence was monitored throughout the study by magnetic resonance imaging, read both locally and centrally. RESULTS: Overall, 1795 participants from Core and 1612 participants with at least one dose of lecanemab (Core + OLE) were included. Lecanemab was generally well-tolerated in Clarity AD, with no deaths related to lecanemab in the Core study. There were 9 deaths during the OLE, with 4 deemed possibly related to study treatment. Of the 24 deaths in Core + OLE, 3 were due to intracerebral hemorrhage (ICH): 1 placebo in the Core due to ICH, and 2 lecanemab in OLE with concurrent ICH (1 on tissue plasminogen activator and 1 on anticoagulant therapy). In the Core + OLE, the most common adverse events in the lecanemab group (> 10%) were infusion-related reactions (24.5%), ARIA with hemosiderin deposits (ARIA-H) microhemorrhages (16.0%), COVID-19 (14.7%), ARIA with edema (ARIA-E; 13.6%), and headache (10.3%). ARIA-E and ARIA-H were largely radiographically mild-to-moderate. ARIA-E generally occurred within 3-6 months of treatment, was more common in ApoE e4 carriers (16.8%) and most common in ApoE ε4 homozygous participants (34.5%). CONCLUSIONS: Lecanemab was generally well-tolerated, with the most common adverse events being infusion-related reactions, ARIA-H, ARIA-E. Clinicians, participants, and caregivers should understand the incidence, monitoring, and management of these events for optimal patient care. TRIAL REGISTRATION: ClinicalTrials.gov numbers: Clarity AD NCT03887455).


Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/tratamento farmacológico , Masculino , Método Duplo-Cego , Feminino , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Pessoa de Meia-Idade , Peptídeos beta-Amiloides/metabolismo , Imageamento por Ressonância Magnética , Resultado do Tratamento
6.
Neurol Ther ; 13(4): 975-1013, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38743312

RESUMO

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder resulting from the deposition of misfolded and neurotoxic forms of tau protein in specific areas of the midbrain, basal ganglia, and cortex. It is one of the most representative forms of tauopathy. PSP presents in several different phenotypic variations and is often accompanied by the development of concurrent neurodegenerative disorders. PSP is universally fatal, and effective disease-modifying therapies for PSP have not yet been identified. Several tau-targeting treatment modalities, including vaccines, monoclonal antibodies, and microtubule-stabilizing agents, have been investigated and have had no efficacy. The need to treat PSP and other tauopathies is critical, and many clinical trials investigating tau-targeted treatments are underway. In this review, the PubMed database was queried to collect information about preclinical and clinical research on PSP treatment. Additionally, the US National Library of Medicine's ClinicalTrials.gov website was queried to identify past and ongoing clinical trials relevant to PSP treatment. This narrative review summarizes our findings regarding these reports, which include potential disease-modifying drug trials, modifiable risk factor management, and symptom treatments.

7.
Mov Disord ; 39(7): 1212-1217, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38597193

RESUMO

BACKGROUND: While preclinical studies have shown that alpha-synuclein can spread through cell-to-cell transmission whether it can be transmitted between humans is unknown. OBJECTIVES: The aim was to assess the presence of a synucleinopathy in autopsied conjugal couples. METHODS: Neuropathological findings in conjugal couples were categorized as Parkinson's disease (PD), dementia with Lewy bodies (DLB), Alzheimer's disease with Lewy bodies (ADLB), incidental Lewy body disease (ILBD), or no Lewy bodies. RESULTS: Ninety conjugal couples were included; the mean age of death was 88.3 years; 32 couples had no Lewy bodies; 42 couples had 1 spouse with a synucleinopathy: 10 PD, 3 DLB, 13 ADLB, and 16 ILBD; 16 couples had both spouses with a synucleinopathy: in 4 couples both spouses had PD, 1 couple had PD and DLB, 4 couples had PD and ADLB, 2 couples had PD and ILBD, 1 couple had DLB and ADLB, in 3 couples both had ADLB, and 1 couple had ADLB and ILBD. No couples had both spouses with ILBD. CONCLUSIONS: This large series of 90 autopsied conjugal couples found 16 conjugal couples with synucleinopathies, suggesting transmission of synucleinopathy between spouses is unlikely. © 2024 International Parkinson and Movement Disorder Society.


Assuntos
Doença por Corpos de Lewy , Doença de Parkinson , Sinucleinopatias , Humanos , Feminino , Masculino , Idoso de 80 Anos ou mais , Doença de Parkinson/patologia , Doença de Parkinson/metabolismo , Doença por Corpos de Lewy/patologia , Doença por Corpos de Lewy/metabolismo , Idoso , Sinucleinopatias/patologia , Autopsia , alfa-Sinucleína/metabolismo , Cônjuges , Doença de Alzheimer/patologia , Doença de Alzheimer/metabolismo , Corpos de Lewy/patologia
8.
Front Aging Neurosci ; 16: 1362613, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38562990

RESUMO

Introduction: Cognitive impairment (CI) due to Alzheimer's disease (AD) encompasses a decline in cognitive abilities and can significantly impact an individual's quality of life. Early detection and intervention are crucial in managing CI, both in the preclinical and prodromal stages of AD prior to dementia. Methods: In this preliminary study, we investigated differences in resting-state functional connectivity and dynamic network properties between 23 individual with CI due to AD based on clinical assessment and 15 healthy controls (HC) using Independent Component Analysis (ICA) and Dominant-Coactivation Pattern (d-CAP) analysis. The cognitive status of the two groups was also compared, and correlations between cognitive scores and d-CAP switching probability were examined. Results: Results showed comparable numbers of d-CAPs in the Default Mode Network (DMN), Executive Control Network (ECN), and Frontoparietal Network (FPN) between HC and CI groups. However, the Visual Network (VN) exhibited fewer d-CAPs in the CI group, suggesting altered dynamic properties of this network for the CI group. Additionally, ICA revealed significant connectivity differences for all networks. Spatial maps and effect size analyses indicated increased coactivation and more synchronized activity within the DMN in HC compared to CI. Furthermore, reduced switching probabilities were observed for the CI group in DMN, VN, and FPN networks, indicating less dynamic and flexible functional interactions. Discussion: The findings highlight altered connectivity patterns within the DMN, VN, ECN, and FPN, suggesting the involvement of multiple functional networks in CI. Understanding these brain processes may contribute to developing targeted diagnostic and therapeutic strategies for CI due to AD.

9.
Sci Rep ; 14(1): 7649, 2024 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561418

RESUMO

Pain is a global health problem that leads to sedentary behavior and tends to cause negative emotion. In contrast, exercise is widely recommended for a health promotion, while pain often worsens with physical activity. Although exercise therapy is often prescribed to people with pain, the mechanisms of exercise effect on pain remains unclear. In this study, we tried to identify a universal association factor between regular exercise and pain intensity utilizing a cross-sectional web-based survey involving 52,353 adult participants from a large national study conducted in Japan. Using principal component analysis, we uncovered a mediation model of exercise effect on pain through psychological components. Analyses were performed in half of the population with pain (n = 20,330) and validated in the other half (n = 20,330), and showed that high-frequency exercise had a significant association with reduction in pain intensity. We also found Negative Affect and Vigor, two psychological components, are fully associating the exercise effect on pain (indirect effect = - 0.032, p < 0.001; association proportion = 0.99) with a dose-dependent response corresponding to the frequency of exercise. These findings were successfully validated (indirect effect of high-frequency exercise = - 0.028, p < 0.001; association proportion = 0.85). Moreover, these findings were also identified in subpopulation analyses of people with low back, neck, knee pain, and the tendency of the exercise effect on pain was increased with older people. In conclusion, the effect of exercise on pain is associated with psychological components and these association effects increased in parallel with the frequency of exercise habit regardless pain location.


Assuntos
Exercício Físico , Dor , Adulto , Humanos , Idoso , Estudos Transversais , Japão/epidemiologia , Terapia por Exercício
10.
Biomed Rep ; 20(4): 62, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38476604

RESUMO

Granulomatous mastitis (GM) in accessory breast tissue is rare. The present study aimed to report a rare case of GM in accessory breast tissue. A 39-year-old female patient presented with right axillary discomfort and swelling for ~5 days. On clinical examination, a tender, firm lump was detected in the right axillary region. The ultrasound showed diffuse parenchymal heterogeneity and surrounding edema in the right accessory breast associated with reactive axillary lymph nodes. Following unresponsiveness to conservative treatment, a surgical procedure was performed in the form of an excisional biopsy and the lesion was diagnosed as GM. During the six-month follow-up, there were no recurrences. The exact cause of GM remains uncertain and the etiology within accessory breast tissue is even less understood. Proposed mechanisms suggest that it may result from an exaggerated immune response triggered by various factors, such as infection, autoimmunity or hormonal fluctuations. GM in accessory breast tissue is a rare and challenging clinical condition to be diagnosed. Due to the rarity of this condition, it highlights the importance of including GM in the differential diagnosis of axillary masses.

11.
J Alzheimers Dis Rep ; 8(1): 241-255, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38405349

RESUMO

 Huge investments continue to be made in treatment for Alzheimer's disease (AD), with more than one hundred drugs currently in development. Pharmacological approaches and drug development, particularly those targeting amyloid-ß, have dominated the therapeutic landscape. At the same time, there is also a growing interest in devices for treating AD. This review aimed to identify and describe devices under development for AD treatment. In this review, we queried the devices that are in development for the treatment of AD. PubMed was searched through the end of 2021 using the terms "device," "therapeutics," and "Alzheimer's" for articles that report on devices to treat AD. Ten devices with 31 references were identified as actively being developed for the treatment of AD. Many of these devices are far along in development. Device-based therapies are often overlooked when evaluating treatment approaches to AD. However, many devices for treating AD are in development and some show promising results.

12.
medRxiv ; 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38370783

RESUMO

Chronic pain is commonly treated with long-term opioids, but the neuropsychological outcomes associated with stable long-duration opioid use remain unclear. Here, we contrasted the psychological profiles, brain activity, and brain structure of 70 chronic back pain patients on opioids (CBP+O, average opioid exposure 6.2 years) with 70 patients managing their pain without opioids. CBP+O exhibited moderately worse psychological profiles and small differences in brain morphology. However, CBP+O had starkly different spontaneous brain activity, dominated by increased mesocorticolimbic and decreased dorsolateral-prefrontal activity, even after controlling for pain intensity and duration. These differences strongly reflected cortical opioid and serotonin receptor densities and mapped to two antagonistic resting-state circuits. The circuits' dynamics were explained by mesocorticolimbic activity and reflected negative affect. We reassessed a sub-group of CBP+O after they briefly abstained from taking opioids. Network dynamics, but not spontaneous activity, reflected exacerbated signs of withdrawal. Our results have implications for the management and tapering of opioids in chronic pain.

13.
Alzheimer Dis Assoc Disord ; 38(1): 8-13, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38277642

RESUMO

OBJECTIVE: To assess the value of rescreening patients with Alzheimer's disease who do not meet the inclusion criteria for the Repeatable Battery for the Assessment of Neuropsychological Status Delayed Memory Index (RBANS DMI) at the initial assessment. PATIENTS AND METHODS: Participants (aged 50-85 years, without dementia, Mini-Mental State Examination score ≥22, valid Clinical Dementia Rating [CDR] global score, and amyloid status at baseline) were identified in the European Prevention of Alzheimer's Dementia database. Changes from baseline in RBANS DMI were estimated using a mixed model for repeated measurements. Logistic regressions were used to estimate the probability of participants with baseline RBANS DMI 86-95 having RBANS DMI ≤85, CDR global score ≥0.5, and amyloid positivity at 6 and 12 months. RESULTS: There was significant variability in the change in RBANS DMI scores over time (median change at 6 months: 2.0). An estimated 15% of participants with RBANS DMI 86-95 at baseline progressed to ≤85 at 6 months; 8% also achieved CDR global score ≥0.5 and 5% were also amyloid positive. CONCLUSIONS: The results from our analysis indicate that there is limited value in rescreening patients based on their initial RBANS DMI score.


Assuntos
Doença de Alzheimer , Humanos , Testes Neuropsicológicos , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/psicologia , Proteínas Amiloidogênicas , Repressão Psicológica
14.
Biomedicines ; 12(1)2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38255204

RESUMO

Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) are chronic, progressive disorders affecting the elderly, which fosters global healthcare concern with the growing aging population. Both T2DM and AD have been linked with increasing age, advanced glycosylation end products, obesity, and insulin resistance. Insulin resistance in the periphery is significant in the development of T2DM and it has been posited that insulin resistance in the brain plays a key role in AD pathogenesis, earning AD the name "type 3 diabetes". These clinical and epidemiological links between AD and T2DM have become increasingly pronounced throughout the years, and serve as a means to investigate the effects of antidiabetic therapies in AD, such as metformin, intranasal insulin, incretins, DPP4 inhibitors, PPAR-γ agonists, SGLT2 inhibitors. The majority of these drugs have shown benefit in preclinical trials, and have shown some promising results in clinical trials, with the improvement of cognitive faculties in participants with mild cognitive impairment and AD. In this review, we have summarize the benefits, risks, and conflicting data that currently exist for diabetic drugs being repurposed for the treatment of AD.

15.
Mol Biol Rep ; 51(1): 79, 2024 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-38183501

RESUMO

BACKGROUND AND AIM: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019 caused a pandemic of acute respiratory disease, named coronavirus disease 2019 (COVID-19). COVID-19 became one of the most challenging health emergencies, hence the necessity to find different prognostic factors for disease progression, and severity. Membrane bound O-acyltransferase domain containing 7 (MBOAT7) demonstrates anti-inflammatory effects through acting as a fine-tune regulator of the amount of cellular free arachidonic acid. We aimed in this study to evaluate MBOAT7 expression in COVID-19 patients and to correlate it with disease severity and outcomes. METHODS: This case-control study included 56 patients with confirmed SARS-CoV-2 diagnosis and 28 control subjects. Patients were further classified into moderate (n = 28) and severe (n = 28) cases. MBOAT7, tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) mRNA levels were evaluated in peripheral blood mononuclear cells (PBMC) samples isolated from patients and control subjects by real time quantitative polymerase chain reaction (RT-qPCR). In addition, circulating MBOAT7 protein levels were assayed by enzyme-linked immunosorbent assay (ELISA). RESULTS: Significant lower levels of circulating MBOAT7 mRNA and protein were observed in COVID-19 patients compared to control subjects with severe COVID-19 cases showing significant lower levels compared to moderate cases. Moreover, severe cases showed a significant upregulation of TNF-α and IL-1ß mRNA. MBOAT7 mRNA and protein levels were significantly correlated with inflammatory markers (TNF-α, IL-1ß, C-reactive protein (CRP), and ferritin), liver enzymes, severity, and oxygen saturation levels. CONCLUSION: COVID-19 is associated with downregulation of MBAOT7, which correlates with disease severity.


Assuntos
COVID-19 , Humanos , COVID-19/genética , SARS-CoV-2 , Leucócitos Mononucleares , Teste para COVID-19 , Estudos de Casos e Controles , Fator de Necrose Tumoral alfa , Progressão da Doença , RNA Mensageiro , Aciltransferases , Proteínas de Membrana
16.
Artigo em Inglês | MEDLINE | ID: mdl-38281998

RESUMO

Diverse psychological consequences of the COVID-19 pandemic have been reported for 6 months after infection. We conducted a prospective study to evaluate the psychological impact of COVID-19 infection in newly diagnosed cases that were followed up at 1, 6, and 9 months after infection. 137 people were recruited and divided into four groups based on the COVID-19 Treatment Guidelines. They were evaluated using the Pittsburgh Sleep Quality Index (PSQI), Post-traumatic stress disorder Checklist for DSM-5 (PCL-5), and Symptom Checklist 90 (SCL-90). We found that 9 months after infection, patients continued to report poor sleep (74.5%), PTSD (78.3%), somatization (17%), anxiety (17%), aggression (5.7%), phobic anxiety (4.7%), psychoticism (1.9%), paranoid (3.8%), and obsessive-compulsive (9.4%) symptoms, as well as depression and interpersonal sensitivity. The most significant risk factors for psychiatric complications were older age, level of education, smoking, hospitalization duration, hypertension, and critical severity. The negative mental health effects of COVID-19 persist after hospital discharge, and many patients continue to experience moderate-to-severe issues that may endure for 9 months. Notably, there was a progressive improvement in these symptoms over that time.

17.
Alzheimers Dement ; 20(1): 549-562, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37740924

RESUMO

INTRODUCTION: The National Institute on Aging - Alzheimer's Association (NIA-AA) ATN research framework proposes to use biomarkers for amyloid (A), tau (T), and neurodegeneration (N) to stage individuals with AD pathological features and track changes longitudinally. The overall aim was to utilize this framework to characterize pre-mortem ATN status longitudinally in a clinically diagnosed cohort of dementia with Lewy bodies (DLB) and to correlate it with the post mortem diagnosis. METHODS: The cohort was subtyped by cerebrospinal fluid (CSF) ATN category. A subcohort had longitudinal data, and a subgroup was neuropathologically evaluated. RESULTS: We observed a significant difference in Aß42/40 after 12 months in the A+T- group. Post mortem neuropathologic analyses indicated that most of the p-Tau 181 positive (T+) cases also had a high Braak stage. DISCUSSION: This suggests that DLB patients who are A+ but T- may need to be monitored to determine whether they remain A+ or ever progress to T positivity. HIGHLIGHTS: Some A+T- DLB subjects transition from A+ to negative after 12-months. Clinically diagnosed DLB with LBP-AD (A+T+) maintain their positivity. Clinically diagnosed DLB with LBP-AD (A+T+) maintain their positivity. Monitoring of the A+T- sub-type of DLB may be necessary.


Assuntos
Doença de Alzheimer , Doença por Corpos de Lewy , Humanos , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/líquido cefalorraquidiano , Doença por Corpos de Lewy/diagnóstico , Doença por Corpos de Lewy/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Fragmentos de Peptídeos/líquido cefalorraquidiano
18.
Med Image Anal ; 91: 103041, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38007978

RESUMO

Spatial normalization-the process of mapping subject brain images to an average template brain-has evolved over the last 20+ years into a reliable method that facilitates the comparison of brain imaging results across patients, centers & modalities. While overall successful, sometimes, this automatic process yields suboptimal results, especially when dealing with brains with extensive neurodegeneration and atrophy patterns, or when high accuracy in specific regions is needed. Here we introduce WarpDrive, a novel tool for manual refinements of image alignment after automated registration. We show that the tool applied in a cohort of patients with Alzheimer's disease who underwent deep brain stimulation surgery helps create more accurate representations of the data as well as meaningful models to explain patient outcomes. The tool is built to handle any type of 3D imaging data, also allowing refinements in high-resolution imaging, including histology and multiple modalities to precisely aggregate multiple data sources together.


Assuntos
Doença de Alzheimer , Processamento de Imagem Assistida por Computador , Humanos , Processamento de Imagem Assistida por Computador/métodos , Encéfalo/diagnóstico por imagem , Imageamento Tridimensional , Mapeamento Encefálico/métodos , Doença de Alzheimer/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos
19.
Expert Opin Emerg Drugs ; 28(4): 311-332, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38100555

RESUMO

INTRODUCTION: Despite the recent full FDA approval of lecanemab, there is currently no disease modifying therapy (DMT) that can efficiently slow down the progression of Alzheimer's disease (AD) in the general population. This statement emphasizes the need to identify novel DMTs in the shortest time possible to prevent a global epidemic of AD cases as the world population experiences an increase in lifespan. AREAS COVERED: Here, we review several classes of anti-cancer drugs that have been or are being investigated in Phase II/III clinical trials for AD, including immunomodulatory drugs, RXR agonists, sex hormone therapies, tyrosine kinase inhibitors, and monoclonal antibodies. EXPERT OPINION: Given the overall course of brain pathologies during the progression of AD, we express a great enthusiasm for the repositioning of anti-cancer drugs as possible AD DMTs. We anticipate an increasing number of combinatorial therapy strategies to tackle AD symptoms and their underlying pathologies. However, we strongly encourage improvements in clinical trial study designs to better assess target engagement and possible efficacy over sufficient periods of drug exposure.


Assuntos
Doença de Alzheimer , Antineoplásicos , Reposicionamento de Medicamentos , Humanos , Doença de Alzheimer/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico
20.
Chaos ; 33(10)2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37782829

RESUMO

In a new memristive generalized FitzHugh-Nagumo bursting model, adaptive resonance (AR), in which the neuron system's response to a varied stimulus can be improved by the ideal intensity of adaptation currents, is examined. We discovered that, in the absence of electromagnetic induction, there is signal detection at the greatest resonance peak of AR using the harmonic balance approach. For electromagnetic induction's minor impacts, this peak of the AR is optimized, whereas for its larger effects, it disappears. We demonstrate dependency on adaption strength as a bifurcation parameter, the presence of period-doubling, and chaotic motion regulated and even annihilated by the increase in electromagnetic induction using bifurcation diagrams and Lyapunov exponents at specific resonance frequencies. The suggested system shows the propagation of localized excitations as chaotic or periodic modulated wave packets that resemble breathing structures. By using a quantitative recurrence-based analysis, it is possible to examine these plausible dynamics in the structures of the recurrence plot beyond the time series and phase portraits. Analytical and numerical analyses are qualitatively consistent.

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