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1.
Int J Neurosci ; : 1-4, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38178642

RESUMO

AIM OF THE STUDY: Expand the differential diagnosis of secondary headache to include rare intracranial tumours, detected incidentally on brain imaging. Intracranial lipomas are rare congenital malformations, and are usually pericallosal asymptomatic midline lesions. However, some cases present with headache and seizures. Symptomatic intracranial lipomas are very rare and often detected incidentally on brain imaging. METHODS: We present a 52-year-old woman referred to our tertiary centre with a history of hypothyroidism presented with headache for 2 years. She had generalised body pains for six months. Her headache was persistent despite being on medications. Physical and neurological examination was unremarkable. Her visual acuity and fundus examination were normal. RESULTS: Her brain imaging revealed a lesion over the corpus callosum and in the interhemispheric fissure with signal attenuation on the fat suppression sequence, features suggestive of curvilinear pericallosal lipoma. Symptomatic treatment with analgesics and anti-inflammatory agents were slightly effective. It is debatable whether tumour removal is required, as the risks of surgical intervention far outweigh the potential benefits. CONCLUSION: Corpus callosal lipoma is a rare and unrecognised cause of secondary headache. It should be suspected in patients with an atypical headache without papilledema and who are unresponsive to analgesics. This may be the only presenting feature of intracranial lipomas rendering it even more difficult to suspect and diagnose, thus emphasising the importance of evaluating secondary headaches. Diagnosis is important because long-term follow-up may be required if patients develop new focal deficits, which may necessitate surgical intervention.

2.
Alzheimers Dement ; 20(4): 2620-2631, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38376105

RESUMO

INTRODUCTION: Lifelong bilingualism is associated with a delayed age at onset of dementia, but evidence from community-based studies is limited. We investigated the relationship between bilingualism and the prevalence of cognitive impairment in a linguistically diverse community. METHODS: A door-to-door community study was conducted from January to December 2021 in urban Bengaluru, India. 1234 individuals aged ≥60 years participated in the study. Participants were diagnosed with no cognitive impairment (NCI), mild cognitive impairment (MCI), or dementia using established diagnostic criteria. RESULTS: Dementia prevalence was higher in monolinguals (4.9%) than bilinguals (0.4%) (P = .001). The prevalence of MCI was also higher in monolinguals (8.5%) than bilinguals (5.3%) (P = .001). The study also revealed better cognitive function in bilinguals than monolinguals with NCI, after controlling for confounding variables. DISCUSSION: The current study provides significant support for the protective effect of bilingualism on cognitive impairment in an urban community with extensive bilingual interactional contexts in everyday life. HIGHLIGHTS: Bilingualism has been demonstrated to protect against dementia and mild cognitive impairment in a linguistically diverse community with extensive code-switching contexts. Bilingual older individuals had superior baseline cognitive performance compared to monolingual older individuals. Bilingualism was found to have an independent effect on general cognition after adjusting for major social determinants of health in the group without cognitive impairment.


Assuntos
Disfunção Cognitiva , Demência , Multilinguismo , Humanos , Envelhecimento/psicologia , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/psicologia , Cognição , Demência/epidemiologia , Demência/prevenção & controle , Demência/psicologia
3.
Alzheimers Dement ; 20(6): 4290-4314, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38696263

RESUMO

Two of every three persons living with dementia reside in low- and middle-income countries (LMICs). The projected increase in global dementia rates is expected to affect LMICs disproportionately. However, the majority of global dementia care costs occur in high-income countries (HICs), with dementia research predominantly focusing on HICs. This imbalance necessitates LMIC-focused research to ensure that characterization of dementia accurately reflects the involvement and specificities of diverse populations. Development of effective preventive, diagnostic, and therapeutic approaches for dementia in LMICs requires targeted, personalized, and harmonized efforts. Our article represents timely discussions at the 2022 Symposium on Dementia and Brain Aging in LMICs that identified the foremost opportunities to advance dementia research, differential diagnosis, use of neuropsychometric tools, awareness, and treatment options. We highlight key topics discussed at the meeting and provide future recommendations to foster a more equitable landscape for dementia prevention, diagnosis, care, policy, and management in LMICs. HIGHLIGHTS: Two-thirds of persons with dementia live in LMICs, yet research and costs are skewed toward HICs. LMICs expect dementia prevalence to more than double, accompanied by socioeconomic disparities. The 2022 Symposium on Dementia in LMICs addressed advances in research, diagnosis, prevention, and policy. The Nairobi Declaration urges global action to enhance dementia outcomes in LMICs.


Assuntos
Envelhecimento , Demência , Países em Desenvolvimento , Humanos , Demência/diagnóstico , Demência/terapia , Demência/epidemiologia , Encéfalo , Congressos como Assunto , Pesquisa Biomédica
4.
Dement Geriatr Cogn Disord ; 51(1): 90-100, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35184061

RESUMO

OBJECTIVES: Little is known regarding the cognitive and behavioral status of patients with dementia and their caregivers in lower middle-income countries during the COVID-19 pandemic. This study aimed to understand the impact of the pandemic on persons with dementia and their caregivers in India. METHODS: This was an observational study. A cohort of 66 persons with dementia and their caregivers were evaluated during the COVID-19 pandemic in 2 specialist hospitals in South India. Caregivers were interviewed at 2 distinct time points of the pandemic: during the national lockdown and 5 months after during later periods of the "cluster of cases" transmission phase. Participants were assessed via telephone utilizing validated instruments (Neuropsychiatric Inventory [NPI], Clinical Dementia Rating [CDR] Scale, and Depression, Anxiety and Stress Scale [DASS-21]) and a semi-structured questionnaire. The questionnaire documented sociodemographic information, clinical history, infection measures adopted, changes in caregiving routines, involvement in functional rehabilitation activities, and access to medical and long-term care support services. RESULTS: The 2-phase follow-up study found a significant worsening of behavior in dementia patients, demonstrated by a difference in the NPI sub-domain scores for anxiety (mean difference [standard deviation, SD] = -0.552 [1.993], t58 = -2.109, p = 0.039) and eating disturbances (mean difference [SD] = -1.121 [2.493], t59 = -3.424, p = 0.001). A relatively high proportion of patients developed anxiety (cumulative incidence = 24.53%) and eating disturbances (cumulative incidence = 26.92%), without having these symptoms at baseline. There was a trend toward an increase in proportion of persons with severe dementia (19.7% vs. 39.4%) on follow-up. Caregiver distress reported was significantly associated with neuropsychiatric symptoms (r = 0.712, p < 0.001) and dementia severity (ρ = 0.365, p = 0.004). In addition, difficulties in accessing medical care persisted between the 2 assessments, and there were statistically significant differences between functional rehabilitation activities such as indoor activities (p < 0.001), outdoor activities (p = 0.013), and physical exercises (p = 0.003) between baseline and follow-up. CONCLUSION: Findings suggest interruption of functional rehabilitation activities and disruption in medical care services are likely to have had an adverse impact on patients with dementia and contributed toward caregiver distress.


Assuntos
COVID-19 , Demência , Cuidadores/psicologia , Cognição , Controle de Doenças Transmissíveis , Demência/psicologia , Seguimentos , Humanos , Pandemias
5.
Acta Neurol Scand ; 145(4): 399-406, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34841512

RESUMO

BACKGROUND: Recently, TANK binding kinase 1 (TBK1) mutation has been reported as a causative gene for overlap frontotemporal dementia (FTD)-amyotrophic lateral sclerosis (ALS) syndrome. However, there are no reports from families of South Asian ethnicity. OBJECTIVE: To report a case study of a family with the proband having overlap FTD-ALS syndrome caused by a novel TBK1 variant. MATERIALS AND METHODS: Clinical, brain imaging, genetic analysis and laboratory data of the patient with FTD-ALS were performed. In addition, family-based segregation analysis of identified novel variants was also done. RESULTS: This study pertains to genetic analysis in 11 members in a family with only one member affected with overlap FTD-ALS syndrome. The whole-exome sequencing analysis in the symptomatic member showed a novel loss-of-function (LoF) variant c.1810G>T(p.E604X) in the TBK1 gene. Neuroimaging showed a pattern of asymmetric frontotemporal atrophy and hypometabolism. Segregation analysis of the variation demonstrated its presence in several family members, although none of the other members was symptomatic. Further, we observed another missense variation in the NEFH gene (p.Pro683Leu) which was seen in the symptomatic and two asymptomatic family members, the pathogenicity of which is unclear. CONCLUSION: This is the first study of a rare novel TBK1 variant associated with FTD-ALS from India. Asymptomatic family members with the variant have important clinical implications and necessitate the genetic evaluation and long-term follow-up of family members of patients detected with TBK1 mutations. Therefore, although infrequent, genetic screening for the TBK1 gene should be considered when encountering overlap FTD syndromes.


Assuntos
Esclerose Lateral Amiotrófica , Demência Frontotemporal , Proteínas Serina-Treonina Quinases , Esclerose Lateral Amiotrófica/diagnóstico , Demência Frontotemporal/diagnóstico por imagem , Demência Frontotemporal/genética , Testes Genéticos , Humanos , Mutação , Proteínas Serina-Treonina Quinases/genética
6.
Int J Geriatr Psychiatry ; 37(10)2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36069187

RESUMO

INTRODUCTION AND OBJECTIVES: Early dementia diagnosis in low and middle-income countries (LMIC) is challenging due to limited availability of brief, culturally appropriate, and psychometrically validated tests. Montreal Cognitive Assessment (MoCA) is one of the most widely used cognitive screening tests in primary and secondary care globally. In the current study, we adapted and validated MoCA in five Indian languages (Hindi, Bengali, Telugu, Kannada, and Malayalam) and determined the optimal cut-off points that correspond to screening for clinical diagnosis of dementia and MCI. METHODS: A systematic process of adaptation and modifications of MoCA was fulfilled. A total of 446 participants: 214 controls, 102 dementia, and 130 MCI were recruited across six centers. RESULTS: Across five languages, the area under the curve for diagnosis of dementia varied from 0.89 to 0.98 and MCI varied from 0.73 to 0.96. The sensitivity, specificity and optimum cut-off scores were established separately for five Indian languages. CONCLUSIONS: The Indian adapted MoCA is standardized and validated in five Indian languages for early diagnosis of dementia and MCI in a linguistically and culturally diverse population.

7.
Neurol Sci ; 43(1): 265-273, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33966130

RESUMO

BACKGROUND: Semantic memory deficits are frequently encountered in dementia and distinct patterns of semantic impairment characterize the subtypes of dementia. Life course and cultural experiences significantly influence semantic memory. Hence, there is a need to assess semantic memory using culturally appropriate tests, to aid accurate diagnosis of dementia and facilitate cross-cultural collaborative research. AIMS: In this prospective study, we adapted and validated the Cambridge Semantic Memory (CSM) test battery to the Indian cultural context and studied the patterns of semantic memory impairment across dementia subtypes. METHODS: The CSM battery was modified using standard methods and by incorporating culturally appropriate changes and new semantic categories relevant to India. The adapted Indian Semantic Memory (ISM) test battery was administered to a cohort of 121 subjects, consisting of controls and dementia: Alzheimer's disease (AD), progressive non-fluent aphasia (PNFA), semantic dementia (SD), and behavioral variant fronto-temporal dementia (BvFTD). Profile of semantic memory performance across groups was examined. RESULTS: The ISM battery was found to be a valid measure of semantic memory. The novel semantic categories of gods/religious icons, vegetables, and food items added value to the diagnostic process. Distinct semantic memory profiles in SD, PNFA, AD, and BvFTD were demonstrated. CONCLUSIONS: The cultural adaptation of a semantic memory battery for the Indian context provided sensitive evidence of semantic memory impairment in dementia and its subtypes. The clinical and research application of the ISM battery will enhance diagnostic evaluation that can aid in early and accurate identification of deficits and devising intervention strategies and enable research across cultures.


Assuntos
Doença de Alzheimer , Demência Frontotemporal , Comparação Transcultural , Humanos , Transtornos da Memória/diagnóstico , Transtornos da Memória/etiologia , Testes Neuropsicológicos , Estudos Prospectivos , Semântica
8.
Dement Geriatr Cogn Disord ; 50(2): 153-160, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34237731

RESUMO

OBJECTIVE: In the background of an emerging role for immune dysregulation in neurodegenerative dementias, this study aimed to investigate the relationship between systemic autoimmunity and dementia. The objective was to study the frequency and profile of disease-specific autoantibodies in Alzheimer's dementia (AD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB). METHODS: Immunological testing was performed in a large cohort of neurodegenerative dementia diagnosed based on standard clinical and imaging criteria. Patients were evaluated for the presence of autoantibodies specific for systemic autoimmune diseases that included anti-extractable nuclear antibody profile, rheumatoid factor antibody (RA), perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA), and cytoplasmic anti-neutrophil cytoplasmic antibody (c-ANCA) in serum. RESULTS: Of 174 patients with degenerative dementia (FTD = 114, AD = 53, and DLB = 7) evaluated with immunological testing, 18.9% (n = 33) were seropositive for autoantibodies. The common antibodies detected were anti-Scl-70 (25%), anti-Ro-52 (18.7%), anti-nRNP-Sm (12.5%), and anti-CENP-B (9.3%). There were no significant systemic complaints in the majority of patients. A wider range of antibodies were positive in FTD compared to AD and DLB. While no difference was observed in the mean age, sex, or duration of illness between seropositive and negative patients, family history of dementia was more frequent among seronegative patients. CONCLUSION: Our findings indicate an emerging role for immune dysregulation in patients with classical neurodegenerative dementias, especially those with FTD. These autoantibodies could play a role in immune degradation of protein aggregates that characterize neurodegeneration. Study findings emphasize the need to explore the complex relationship between systemic autoimmunity and neurodegenerative dementia.


Assuntos
Doença de Alzheimer , Demência Frontotemporal , Doença por Corpos de Lewy , Doença de Pick , Doença de Alzheimer/diagnóstico , Autoanticorpos , Demência Frontotemporal/diagnóstico , Humanos
9.
Neurocase ; 27(6): 484-489, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34983323

RESUMO

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare white matter degenerative disease manifesting as progressive cognitive decline, pyramidal, and extrapyramidal features resulting from mutations in the colony-stimulating factor-1 receptor (CSF1R) gene. We describe a sporadic case of a young man who developed five months history of progressive cognitive decline with predominant neuropsychiatric symptoms, suggestive of frontotemporal dementia. Brain magnetic resonance imaging (MRI) showed bilateral frontotemporal atrophy, high signal intensities in frontal and high parietal deep white matter with persistent diffusion restriction on follow-up imaging. Genetics showed a novel heterozygous mutation in CSF1R gene confirming the diagnosis of ALSP. Being a rare disease, and given its particular adult-onset presentation especially presenile cognitive impairment, it can pose a unique diagnostic challenge. The study highlights the importance of recognizing the disease early and broadens the clinical, genetic, and imaging spectrum of CSF1R gene mutation.


Assuntos
Demência Frontotemporal , Leucoencefalopatias , Substância Branca , Adulto , Seguimentos , Demência Frontotemporal/diagnóstico , Demência Frontotemporal/genética , Demência Frontotemporal/patologia , Humanos , Leucoencefalopatias/diagnóstico por imagem , Leucoencefalopatias/genética , Imageamento por Ressonância Magnética , Masculino , Mutação , Substância Branca/patologia
13.
Dement Geriatr Cogn Dis Extra ; 14(1): 14-28, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38910897

RESUMO

Introduction: Microglia exert a crucial role in homeostasis of white matter integrity, and several studies highlight the role of microglial dysfunctions in neurodegeneration. Primary microgliopathy is a disorder where the pathogenic abnormality of the microglia causes white matter disorder and leads to a neuropsychiatric disease. Triggering receptor expressed on myeloid cells (TREM2), TYRO protein tyrosine kinase binding protein (TYROBP) and colony-stimulating factor 1 receptor (CSF1R) are genes implicated in primary microgliopathy. The clinical manifestations of primary microgliopathy are myriad ranging from neuropsychiatric syndrome, motor disability, gait dysfunction, ataxia, pure dementia, frontotemporal dementia (FTD), Alzheimer's dementia (AD), and so on. It becomes imperative to establish the diagnosis of microgliopathy masquerading as degenerative dementia, especially with promising therapies on horizon for the same. We aimed to describe a case series of subjects with dementia harbouring novel genes of primary microgliopathy, along with their clinical, neuropsychological, cognitive profile and radiological patterns. Methods: The prospective study was conducted in a university referral hospital in South India, as a part of an ongoing clinico-genetic research on dementia subjects, and was approved by the Institutional Ethics Committee. All patients underwent detailed assessment including sociodemographic profile, clinical and cognitive assessment, pedigree analysis and comprehensive neurological examination. Subjects consenting for blood sampling underwent genetic testing by whole-exome sequencing (WES). Results: A total of 100 patients with dementia underwent genetic analysis using WES and three pathogenic variants, one each of TREM2, TYROBP, and CSF1R and two variants of uncertain significance in CSF1R were identified as cause of primary microgliopathy. TREM2 and TYROBP presented as frontotemporal syndrome whereas CSF1R presented as frontotemporal syndrome and as AD. Conclusion: WES has widened the spectrum of underlying neuropathology of degenerative dementias, and diagnosing primary microglial dysfunction with emerging therapeutic options is of paramount importance. The cases of primary microgliopathy due to novel mutations in TREM2, TYROBP, and CSF1R with the phenotype of degenerative dementia are being first time reported from Indian cohort. Our study enriches the spectrum of genetic variants implicated in degenerative dementia and provides the basis for exploring complex molecular mechanisms like microglial dysfunction, as underlying cause for neurodegeneration.

14.
Artigo em Inglês | MEDLINE | ID: mdl-38273465

RESUMO

BACKGROUND: Literacy is an important factor that predicts cognitive performance. Existing cognitive screening tools are validated only in educated populations and are not appropriate for older adults with little or no education leading to poor performance on these tests and eventually leading to misdiagnosis. This challenge for clinicians necessitates a screening tool suitable for illiterate or low-literate older individuals. OBJECTIVES: The objective was to adapt and validate Addenbrooke's Cognitive Examination-III (ACE-III) for screening general cognitive functions in illiterate and low-literate older populations in the Indian context in three languages. METHOD: The Indian illiterate ACE-III was systematically adapted by modifying the original items of the Indian literate ACE-III to assess the cognitive functions of illiterates and low-literates with the consensus of an expert panel of professionals working in the area of dementia and related disorders. A total of 180 illiterate or low-literate participants (84 healthy-controls, 50 with dementia, and 46 with mild cognitive impairment [MCI]) were recruited from three different centers speaking Bengali, Hindi, and Kannada to validate the adapted version. RESULTS: The optimal cut-off score for illiterate ACE-III to distinguish controls from dementia in all 3 languages was 75. The optimal cut-off scores in distinguishing between controls and MCI ranged from 79 to 82, with a sensitivity ranging from 93% to 99% and a specificity ranging from 72% to 99%. CONCLUSION: The test is found to have good psychometric properties and is a reliable cognitive screening tool for identifying dementia and MCI in older adults with low educational backgrounds in the Indian context.

15.
Artigo em Inglês | MEDLINE | ID: mdl-38929036

RESUMO

The WHO Dementia Global Action Plan states that rehabilitation services for dementia are required to promote health, reduce disability, and maintain quality of life for those living with dementia. Current services, however, are scarce, particularly for people with young-onset dementia (YOD). This article, written by an international group of multidisciplinary dementia specialists, offers a three-part overview to promote the development of rehabilitation services for YOD. Firstly, we provide a synthesis of knowledge on current evidence-based rehabilitative therapies for early-onset Alzheimer's disease (EOAD), behavioural variant frontotemporal dementia (bvFTD), primary progressive aphasia (PPA), and posterior cortical atrophy (PCA). Secondly, we discuss the characteristics of rehabilitation services for YOD, providing examples across three continents for how these services can be embedded in existing settings and the different roles of the rehabilitation multidisciplinary team. Lastly, we conclude by highlighting the potential of telehealth in making rehabilitation services more accessible for people with YOD. Overall, with this paper, we aim to encourage clinical leads to begin introducing at least some rehabilitation into their services, leveraging existing resources and finding support in the collective expertise of the broader multidisciplinary dementia professional community.


Assuntos
Demência , Humanos , Demência/reabilitação , Demência/terapia , Idade de Início , Países em Desenvolvimento , Países Desenvolvidos , Telemedicina
16.
Front Neurol ; 14: 1198882, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37614974

RESUMO

Respect is a feeling of admiration for someone. It forms one of the core values of the Global Brain Health Institute (GBHI), which strives to protect the world's aging populations from threats to brain health. These values guide us as we advocate for reducing the global impact of dementia. By taking a values-based approach to brain health, we can drive global changes for millions of people. Respect fortifies gratitude and embraces diversity. Philosophical discussions of the ideas support the assertion that respect is crucial in everyday conversations and actions as well as in personal, social, political, and moral spheres. No one can become a leader unless they genuinely respect and care about the success of each team member. Diversity, equity, and inclusivity form the fundamental cornerstones of respect. Understanding this core value of respect will ensure altruistic behavior among the leaders that may help mitigate racism, cultural insults, gender discrimination, stigmatization, religious hatred, and, worst of all, poor leadership abilities that have been the disconcerting examples of disrespect in recent years. We present the underlying neurobiology of respect and its impact on equity and leadership.

17.
Front Public Health ; 11: 1284692, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38145063

RESUMO

Millions of dollars have been lost in dementia research over the last 30 years owing to unsuccessful clinical trials aimed at finding an effective treatment for the condition. Although two promising drugs have been identified, the research effort is insufficient. The dehumanization of patients and the pressure to publish have led to a decline in the quality and usefulness of scientific research. One way to tackle these problems is establishing close contact with those who put their faith in researchers. Fine-tuning the participation of patients with dementia and caregivers in research design and improving their connection and communication with researchers could positively contribute to enhancing the perspectives and designing strategies for scientists in order to generate a new and enriching vision. The Walking the Talk for Dementia event showed that people can still live with dementia despite their condition. Approximately 300 people participated in the all-week "Santiago's Camino" symposium. People living with dementia, caregivers, healthcare professionals, activists, clinicians, and researchers participated in this event. The "Walking the Talk for Dementia" (WTD) event vividly demonstrated a strong commitment to upholding Global Brain Health Institute's (GBHI) core values of Authenticity, Fairness, Openness, Respect, Courage, and Empathy (A FORCE) to advance equity in brain health. These values provide clear guidance for their advocacy initiatives aimed at mitigating the global impact of dementia. Research and development are essential across scientific fields, especially in clinical contexts where involving patients and caregivers is critical. The WTD initiative exemplifies this aspect by bringing together researchers, caregivers, and dementia patients on the Camino de Santiago in Spain.


Assuntos
Demência , Humanos , Demência/terapia , Cuidadores , Pessoal de Saúde , Empatia , Comunicação
18.
J Alzheimers Dis ; 94(s1): S387-S397, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36336935

RESUMO

BACKGROUND: Alzheimer's disease (AD) and frontotemporal dementia (FTD) are pathologically distinct neurodegenerative disorders with certain overlap in cognitive and behavioral symptoms. Both AD and FTD are characterized by synaptic loss and accumulation of misfolded proteins, albeit, in different regions of the brain. OBJECTIVE: To investigate the synaptic and organellar markers in AD and FTD through assessment of the levels of synaptic protein, neurogranin (Ng) and organellar proteins, mitofusin-2 (MFN-2), lysosomal associated membrane protein-2 (LAMP-2), and golgin A4 from neuronal exosomes. METHODS: Exosomes isolated from the plasma of healthy controls (HC), AD and FTD subjects were characterized using transmission electron microscopy. Neurodegenerative status was assessed by measurement of neurofilament light chain (NfL) using Simoa. The pooled exosomal extracts from each group were analyzed for Ng, MFN-2, LAMP-2, and golgin A4 by western blot analysis using enhanced chemiluminescence method of detection. RESULTS: The densitometric analysis of immunoreactive bands demonstrated a 65% reduction of Ng in AD and 53% in FTD. Mitochondrial protein MFN-2 showed a significant reduction by 32% in AD and 46% in FTD. Lysosomal LAMP-2 and Golgi complex associated golgin A4 were considerably increased in both AD and FTD. CONCLUSION: Changes in Ng may reflect the ongoing synaptic degeneration that are linked to cognitive disturbances in AD and FTD. Importantly, the rate of synaptic degeneration was more pronounced in AD. Changes to a similar extent in both the dementia groups in organellar proteins indicates shared mechanisms of protein accumulation/degradation common to both AD and FTD.


Assuntos
Doença de Alzheimer , Exossomos , Demência Frontotemporal , Humanos , Doença de Alzheimer/metabolismo , Demência Frontotemporal/diagnóstico , Exossomos/metabolismo , Proteínas da Matriz do Complexo de Golgi/metabolismo , Neurônios/metabolismo , Neurogranina
19.
Brain Connect ; 13(10): 610-620, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37930734

RESUMO

Introduction: Unraveling the network pathobiology in neurodegenerative disorders is a popular and promising field in research. We use a relatively newer network measure of assortativity in metabolic connectivity to understand network differences in patients with Alzheimer's Disease (AD), compared with those with mild cognitive impairment (MCI). Methods: Eighty-three demographically matched patients with dementia (56 AD and 27 MCI) who underwent positron emission tomography-magnetic resonance imaging (PET-MRI) study were recruited for this exploratory study. Global and nodal network measures obtained using the BRain Analysis using graPH theory toolbox were used to derive group-level differences (corrected p < 0.05). The methods were validated in age, and gender-matched 23 cognitively normal, 25 MCI, and 53 AD patients from the publicly available Alzheimer's Disease Neuroimaging Initiative (ADNI) data. Regions that revealed significant differences were correlated with the Addenbrooke's Cognitive Examination-III (ACE-III) scores. Results: Patients with AD revealed significantly increased global assortativity compared with the MCI group. In addition, they also revealed increased modularity and decreased participation coefficient. These findings were validated in the ADNI data. We also found that the regional standard uptake values of the right superior parietal and left superior temporal lobes were proportional to the ACE-III memory subdomain scores. Conclusion: Global errors associated with network assortativity are found in patients with AD, making the networks more regular and less resilient. Since the regional measures of these network errors were proportional to memory deficits, these measures could be useful in understanding the network pathobiology in AD.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Doença de Alzheimer/metabolismo , Encéfalo/patologia , Imageamento por Ressonância Magnética/métodos , Disfunção Cognitiva/patologia , Neuroimagem , Tomografia por Emissão de Pósitrons/métodos
20.
J Clin Neurosci ; 108: 37-75, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36586226

RESUMO

BACKGROUND: Recent studies have shown various neurological adverse events associated with COVID-19 vaccine. OBJECTIVE: We aimed to retrospectively review and report the neurological diseases temporally associated with COVID-19 vaccine. METHODS: We performed a retrospective chart review of admitted patients from 1st February 2021 to 30th June 2022. A total of 4672 medical records were reviewed of which 51 cases were identified to have neurological illness temporally associated with COVID-19 vaccination. RESULTS: Out of 51 cases, 48 had probable association with COVID-19 vaccination while three had possible association. Neurological spectrum included CNS demyelination (n = 39, 76.5 %), Guillain-Barré-syndrome (n = 3, 5.9 %), stroke (n = 6, 11.8 %), encephalitis (n = 2, 3.9 %) and myositis (n = 1, 2.0 %). Female gender had a greater predisposition (F:M, 1.13:1). Neurological events were more commonly encountered after the first-dose (n = 37, 72.5%). The mean latency to onset of symptoms was 13.2 ± 10.7 days after the last dose of vaccination. COVIShield (ChAdOx1) was the most commonly administered vaccine (n = 43, 84.3 %). Majority of the cases with demyelination were seronegative (n = 23, 59.0 %) which was followed by anti-Myelin oligodendrocyte-glycoprotein associated demyelination (MOGAD) (n = 11, 28.2 %) and Neuromyelitis optica (NMOSD) (n = 5, 12.8 %). Out of 6 Stroke cases, 2 cases (33.3 %) had thrombocytopenia and coagulopathy. At discharge, 25/51 (49.0 %) of the cases had favourable outcome (mRS 0 to 1). Among six patients of stroke, only one of them had favourable outcome. CONCLUSION: In this series, we describe the wide variety of neurological syndromes temporally associated with COVID-19 vaccination. Further studies with larger sample size and longer duration of follow-up are needed to prove or disprove causality association of these syndromes with COVID-19 vaccination.


Assuntos
COVID-19 , Doenças do Sistema Nervoso , Neuromielite Óptica , Acidente Vascular Cerebral , Humanos , ChAdOx1 nCoV-19 , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Doenças do Sistema Nervoso/etiologia , Estudos Retrospectivos
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