Risultati per: Identificata la causa della progressione dell’Alzheimer nel cervello

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.

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