Risultati per: Nuovi possibili trattamenti per il morbo di Alzheimer

New England Journal of Medicine, Volume 388, Issue 1, Page 80-81, January 2023.

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New England Journal of Medicine, Ahead of Print.

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Previene la perdita dei neuroni responsabile dei sintomi motori

Introduction
According to the World Alzheimer’s Report 2019, around 50 million people suffer from dementia, worldwide. Observational analysis revealed the existence of particular factors associated with the onset and progression of Alzheimer’s disease (AD). There are no international homogeneous principles for the early detection and evaluation of memory impairment and possible AD. This work aimed at (1) determining the prevalence of possible AD in the elderly residing in urban and rural regions in Cuba and (2) identifying the main factors that could significantly influence on its occurrence.

Methods and analysis
The study includes four neuropsychological tests (Clock Drawing Test, Mini-Mental Status Examination, Short Portable Mental Status Questionnaire, Cognitive and Non-Cognitive Alzheimer’s Disease Assessment Scale) and two scales (Clinical Dementia Rating and Global Deterioration Scale). Moreover, the protocol includes a survey with demographic and socioeconomic information, educational level, occupation, health, neuropsychological status of subjects, familial pathological history, comorbidities and lifestyles. The study will comprise a total of 1092 subjects aged ≥60, of both genders, and from every ethnic group settled in rural and urban areas. Primary outcomes: prevalence of possible AD. Secondary outcomes: correlation among risk and protective factors and AD, and comparison of the performance of neuropsychological tests and scales.

Ethics and dissemination
This research met the ethical codes of the Declaration of Helsinki. The Scientific Research Council of the Promoting Research Institute and the Ethics Committee of the Health Authorities approved the protocol. The proper written informed consent is also incorporated. The results of the survey will be published in scientific papers and shared with the Health Authorities of each municipality.

Circulation, Volume 146, Issue Suppl_1, Page A12707-A12707, November 8, 2022. Introduction:Contemporary HFrEF patients are older and have a higher prevalence of cognitive impairment compared to those studied in the original beta-blocker (BB) trials. While BB decrease mortality and morbidity in HFrEF, their use has been linked to higher fall risk and possibly acceleration of cognitive decline among older adults with Alzheimer’s Disease and Related Dementias (ADRD). The risk/benefit trade-off of beta blocker (BB) use in patients with HFrEF and dementia has not been examined.Methods:Using a 100% sample of patients enrolled in Medicare A, B and a 40% sample of D with ≥1 hospitalization for HFrEF between 2008 and 2018, we created a cohort of beneficiaries with HFrEF but no prior diagnosis of ADRD. We then subset to the population to those that developed ADRD in the year after their HFrEF hospitalization and compared BB use pre/post ADRD diagnosis and is association with outcomes using a time varying exposure.Results:The highest 1-year survival after ADRD diagnosis was observed among those continued on BB after ADRD diagnosis, regardless of whether they were on BB before (HR 0.427, 95% CI 0.406, 0.465, p

Circulation, Volume 146, Issue Suppl_1, Page A11528-A11528, November 8, 2022. Alzheimer’s disease (AD) is a complex and incurable neurodegenerative disorder characterized by cerebral amyloid β (Aβ) deposition and tau pathology, accompanied by a gradual loss of the two main neuromodulators, NGF and BDNF. The progressive degeneration of the cerebral neuro-signaling pathways triggers a gradual decline in neurotrophic factors with significant derangement of the peripheral nervous system. This may culminate in detrimental effects on other organs, including the heart. However, whether and how AD modulates neurotrophins, innervation, and amyloidosis in the cardiac tissue is still undefined. Here, we investigated, for the first time, cardiovascular remodeling and neuro signaling pathway dysregulation in a mouse model of Alzheimer’s disease. Hence, 12 months old Tg2576 transgenic mice, a model of cerebral amyloidosis, were compared to age-matched WT littermates. Echocardiographic analysis showed significant deterioration in LV function, evidenced by a severe decline both in ejection fraction and fraction shortening percentage in the Tg2576 group compared to WT mice. Tg2576 mice exhibited a relevant increase in interstitial fibrosis, with progressive accumulation of amyloid aggregates, resulting in severe cardiac nervous system dysfunction. The transgenic line showed a remarkable decrease in cardiac nerve fiber density, both adrenergic (stained with tyrosine hydroxylase- TH) and regenerating nerve endings (labeled with GAP-43) compared to the WT mice. This myocardial denervation was associated with a robust reduction in NGF and BDNF protein expression both at the neuronal and cardiac level, accompanied by a significant decline in GAP-43 activity in the heart and cerebral cortex lysates of Tg2576 mice. Additionally, human neuroblastoma cells (SH-SY5Y) challenged with human Aβ-40 or Aβ-42 oligomers showed a severe downregulation of both BDNF and GAP-43 protein levels. Overall, our evidence highlights a possible detrimental effect of cerebral amyloidosis on the peripheral nervous system and cardiac tissue, providing potential therapeutic targets, such as the neuro-signaling pathway, to prevent or delay some of the effects caused by AD on the cardiovascular system.

Circulation, Volume 146, Issue Suppl_1, Page A11829-A11829, November 8, 2022. Introduction:Little is known about the outcomes of patients with Alzheimer’s disease (AD) following acute myocardial infarction (AMI).Methods:We used the 2017 National Inpatient Sample, including patients ages ≥60 with a primary diagnosis of STEMI and NSTEMI and those with any diagnostic code for AD. Any differences between AD and non-AD patients were calculated via Chi-square tests. The mortality rates of each group and their odds ratio (aOR) adjusted via multivariable logistic regression were also found.Results:A total of 104,860 cases of STEMI and 352,120 patients of NSTEMI were identified, amongst which 1,130 and 5,810 also had a diagnosis of Alzheimer’s disease. The incidence of Atrial flutter (160 cases, 1416 cases per 10,000 AD patients with STEMI), atrial fibrillation (320 cases, 2832 cases per 10,000 AD patients with STEMI), and long QT syndrome (15 cases, 133 cases per 10,000 AD patients with STEMI) for STEMI patients were higher among the AD patients (p

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Con più di un bicchiere al giorno -7% probabilità di gravidanza

Con più di un bicchiere al giorno -7% probabilità di gravidanza

Stroke, Ahead of Print. BACKGROUND:Species-specific differences in astrocytes and their Alzheimer disease-associated pathology may influence cellular responses to other insults. Herein, human glial chimeric mice were generated to evaluate how Alzheimer disease predisposing genetic background in human astrocytes contributes to behavioral outcome and brain pathology after cortical photothrombotic ischemia.METHODS:Neonatal (P0) immunodeficient mice of both sexes were transplanted with induced pluripotent stem cell–derived astrocyte progenitors from Alzheimer disease patients carryingPSEN1exon 9 deletion (PSEN1ΔE9), with isogenic controls, with cells from a healthy donor, or with mouse astrocytes or vehicle. After 14 months, a photothrombotic lesion was produced with Rose Bengal in the motor cortex. Behavior was assessed before ischemia and 1 and 4 weeks after the induction of stroke, followed by tissue perfusion for histology.RESULTS:Open field, cylinder, and grid-walking tests showed a persistent locomotor and sensorimotor impairment after ischemia and female mice had larger infarct sizes; yet, these were not affected by astrocytes withPSEN1ΔE9 background. Staining for human nuclear antigen confirmed that human cells successfully engrafted throughout the mouse brain. However, only a small number of human cells were positive for astrocytic marker GFAP (glial fibrillary acidic protein), mostly located in the corpus callosum and retaining complex human-specific morphology with longer processes compared with host counterparts. While host astrocytes formed the glial scar, human astrocytes were scattered in small numbers close to the lesion boundary. Aβ (beta-amyloid) deposits were not present inPSEN1ΔE9 astrocyte-transplanted mice.CONCLUSIONS:Transplanted human cells survived and distributed widely in the host brain but had no impact on severity of ischemic damage after cortical photothrombosis in chimeric mice. Only a small number of transplanted human astrocytes acquired GFAP-positive glial phenotype or migrated toward the ischemic lesion forming glial scar.PSEN1ΔE9 astrocytes did not impair behavioral recovery after experimental stroke.

This JAMA Internal Medicine Patient Page describes use of aducanumab for treatment of Alzheimer disease, including potential benefits, harms, and concerns about use.