Risultati per: Studio chiarisce come l’Alzheimer si diffonde nel cervello

Stroke, Volume 56, Issue Suppl_1, Page ATP205-ATP205, February 1, 2025. Introduction:Alzheimer’s Disease (AD), characterized by extracellular deposition of amyloid beta (Aβ) plaques in brain tissue, is often comorbid with cerebral amyloid angiopathy, which carries an elevated risk of intracranial hemorrhage. Furthermore, severe hemorrhagic complications have been observed following the use of new Aβ-targeted immunotherapies for AD. However, there are limited population-based data regarding the risk of intracranial hemorrhage associated with AD.Methods:We performed a retrospective cohort study using inpatient and outpatient claims between 2008-2018 from a nationally representative 5% sample of Medicare beneficiaries ≥65 years of age. The exposure variable was AD, defined byICD-9-CMcode 331.0 andICD-10-CMcode G30.x. The primary outcome was non-traumatic intracranial hemorrhage, defined as a composite of intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), and subdural hemorrhage (SDH) using validatedICD-9-CMandICD-10-CMdiagnosis codes. Secondary outcomes were ICH, SAH, and SDH assessed separately. Cox proportional hazards models were used to determine the associations between AD and outcomes after adjustment for demographics, vascular risk factors, and Charlson comorbidities.Results:Of 2,107,151 patients included, 87,751 (4.1%) had a diagnosis of AD. A total of 14,400 (0.7%) patients were diagnosed with ICH, 6,003 with SAH (0.3%), and 6,650 (0.3%) with SDH. In multivariable Cox proportional hazards analysis, AD was associated with an increased risk of intracranial hemorrhage (adjusted hazard ratio [aHR], 1.54, 95% confidence interval [CI], 1.44-1.65). In adjusted analyses of secondary outcomes, AD was associated with an increased risk of ICH (aHR, 1.35; 95% CI, 1.23-1.48), SAH (aHR, 2.59; 95% CI, 2.26-2.97), and SDH (aHR, 2.05; 95% CI, 1.83-2.30).Conclusions:In a nationally representative cohort of Medicare beneficiaries, AD was associated with an increased risk of spontaneous intracranial hemorrhage. This increased risk was also present for ICH, SAH, and SDH when examined separately.

Stroke, Volume 56, Issue Suppl_1, Page A101-A101, February 1, 2025. Introduction:Previous studies have shown an association between vascular disease and Alzheimer’s disease, but there are few studies have considered a relationship between brain arterial remodeling and biomarkers of Alzheimer’s disease. Our study aims to find the association between specific arterial characteristics in brain arterial remodeling and Alzheimer’s pathology.Method:We analyzed 132 brain autopsy cases from the Brain Arterial Remodeling Study (BARS), a collection of brains from multiple brain banks in the United States and abroad. Brain sections were obtained systematically by each brain bank, and the anatomical location was harmonized across the banks. The brain slides were stained with LH&E to measure the lumen and wall thickness of the pial, CSF-floating small arteries, parenchymal arteries, and arterioles. Then lumen area, wall thickness, lumen-to-wall ratio (LWR), and wall proportion (which serves as a measure of vessel stenosis) were calculated. We used immunohistochemistry to stain for beta-amyloid, phospho-tau, and Iba1, a measure of microglia. Each stained slide was processed automatically using Visiopharm (version 2021.12) by color thresholding and pattern detection to quantify the number of amyloid plaques and microglial (Iba1+ cells) per 100 µm2and the percentage of tissue area stained positive by phospho-tau, and the number of microglial cells per 100 µm2.Results:Overall, a thicker arterial wall was associated with a greater area of tau staining and a lower lumen-to-wall ratio (suggestive of inward remodeling) was associated with a higher number of microglial cells (table 1). There was a statistical interaction between measures of arterial remodeling by anatomical location (pial vs. parenchymal, P

Stroke, Volume 56, Issue Suppl_1, Page ATP252-ATP252, February 1, 2025. Alzheimer’s Disease (AD) is the most common form of dementia and is characterized by progressive neurodegeneration and cognitive decline. Cardiovascular risk factors in AD lead to decreased cerebral blood flow (CBF), particularly in capillaries, which play a crucial role in the exchange of oxygen and nutrients in response to neuronal activity. Deficits in capillary-level cerebral blood flow are likely to induce vascular inflammation and disrupt the shear forces associated with blood flow, both of which are hallmarks of Alzheimer’s disease and aging. The Piezo1 channel has been shown to be a crucial mechanosensor in brain capillaries that mediates mechanically induced endothelial cell Ca2+transients, suggesting a possible role for Piezo1 in CBF regulation. Here, we investigated the contribution of mechanosensitive Piezo1 ion channels to capillary stalling and CBF reductions in the 5xFAD mouse model of AD. We performed cranial window implantation on twelve 4-month-old 5xFAD mice and twelve age-matched wild-type controls. Usingin vivomultiphoton imaging, we measured cerebral blood flow and capillary stalling in 5xFAD mice following injection with Yoda1, a Piezo1 agonist, before, 24 hrs and one week after Piezo1 activation. Our findings demonstrated that modulating Piezo1 activity reduced capillary stalling and improved CBF in response to Piezo1 activation. Further, Yoda1 injection for one week improved functional hyperemia, measured using laser speckle contrast imaging, in 7-month-old 5xFAD mice. These results suggest the crucial implication of Piezo1 in vascular dysfunction during AD. Importantly, this work highlights the potential therapeutic targeting of Piezo1 to mitigate the effects of impaired cerebral perfusion in AD.

Stroke, Volume 56, Issue Suppl_1, Page ATP26-ATP26, February 1, 2025. Early deficits in cerebral blood flow (CBF) precede age-related neurodegeneration in Alzheimer’s disease (AD). We previously showed CBF deficits in 12-month 5xFAD mice, a familiar model of AD(Mughal et al., Function 2021). However, these mice already have neurodegeneration at 12-months age. We hypothesized that impaired neurovascular coupling begins at an early age (

Stroke, Volume 56, Issue Suppl_1, Page AWP400-AWP400, February 1, 2025. SARS-COV-2 causes neurological and cognitive impairments and aggravates Alzheimer’s Disease-Related Dementia (ADRD). Yet, the molecular mechanism is not fully understood. We have previously shown that SARS-CoV-2 spike protein disturbs the brain’s renin-angiotensin system (RAS) and increases cerebrovascular inflammation. We hypothesize that SARS-CoV-2 spike protein will accelerate hypoxia-induced ADRD via augmenting cerebrovascular inflammation and impairing blood-brain-barrier (BBB) functions. We propose that the pharmacological restoration of the RAS balance using Losartan, an AT1receptor blocker, will improve SARS-CoV-2 spike protein-induced ADRD.Methods:Hypoxia-induced ADRD was produced in humanized ACE2 mice, a COVID-19 mouse model, using a permanent unilateral common carotid artery ligation (UCCL). Cerebral hypoxia was confirmed by laser speckle imaging. hACE-2 mice received either vehicle, SARS-CoV-2 spike protein via jugular vein, or spike protein with Losartan (10 mg/kg) in drinking water after UCCL. ADRD was assessed via Novel Object Recognition at baseline, seven days, and fourteen days after surgery. Cerebrovascular inflammatory markers and tight junction proteins (TNF-α, Il-6, VEGF, MMP-9, and occludin) were measured in brain homogenate using RT-PCR and Western Blots.Results:Blood flow analysis confirmed cerebrovascular hypoxia in all groups. Spike protein further decreased cerebral blood flow, which was prevented with Losartan (P

L’inizio tardivo della fase Rem è associato a un maggior rischio di ammalarsi

Objective
The aim of the present study was to explore the experiences and viewpoints of professional family caregivers in the management of behavioural and psychological symptoms of dementia (BPSDs) to identify the ecopsychosocial strategies applied by them.

Design
Qualitative study.

Setting
Kerman, Iran.

Participants
Stories were collected from 40 professional family caregivers of dementia patients.

Measurement
The guidelines of the National Consensus Project (NCP) of the USA served as the conceptual framework for the deductive thematic analysis of our qualitative data. A schematic of the entire process was performed in five steps.

Results
30 stories relevant to the aim of this study were included in the analysis from April to June 2021. A majority of the stories were written by female caregivers. We identified 19 ecopsychosocial interventions, which covered the NCP dimensions except ‘Care of the patient nearing the end of life’. More than half of these interventions were classified into psychological/psychiatric and physical aspects of care (57.8%). In addition to the care/support provided by special care units or home care, some caregivers believe that support from the government, various care organisations, social media and even other family members/friends is necessary to better manage BPSDs.

Conclusion
Despite limitations, such as having a small sample size and analysing only one story from each caregiver, our results indicate that dementia caregivers need more educational and cultural support in their ecopsychosocial strategies. Government involvement would yield more positive outcomes in managing BPSDs.

Studio pubblicato nella rivista Nature Communications

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Rischio più alto per donne; attesi 1 milione di nuovi casi annui

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Ricerca a Trieste, dopo il 2003 diminuiscono i casi

Ricerca coordinata dal Cro Aviano pubblicata su Modern Pathology

Ricerca coordinata dal Cro Aviano pubblicata su Modern Pathology