Background: Vascular disease and dysfunction are associated with the higher risk of Alzheimer's disease hypothetically due to cerebral hypoperfusion. Brain perfusion is protected by cerebral autoregulation, which, under normal conditions, maintains a constant cerebral blood flow and brain tissue oxygenation.
Objective: To determine whether dynamic regulation of cerebral blood flow and tissue oxygenation is impaired in patients with amnestic mild cognitive impairment (aMCI).
Methods: Twenty-seven patients with aMCI and 15 control subjects with normal cognitive function underwent the measurements of cerebral hemodynamics, brain MR imaging, and neurocognitive assessment. Dynamic regulation of cerebral blood flow and tissue oxygenation were assessed by transfer function analysis of changes in mean blood pressure (MBP), normalized cerebral blood flow velocity (CBFV%), and cerebral tissue oxygenation index (TOI) at baseline and during a sit-stand maneuver.
Results: Patients with aMCI demonstrated lower cognitive performance in memory and executive function, accompanied by smaller entorhinal cortex volumes. At baseline, cerebral TOI was lower in patients with aMCI than in control subjects. Lower cerebral TOI was also correlated with lower cognitive performance in memory and executive function in all subjects. Transfer function gain and phase between MBP and CBFV% and between CBFV% and cerebral TOI were not different between the groups. Within aMCI patients, greater oscillations of cerebral TOI and higher transfer function gain between cerebral TOI and CBFV% were associated with the lower scores on delayed recall.
Conclusion: Dynamic regulation of cerebral tissue oxygenation is associated with neurocognitive dysfunction in aMCI patients.
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http://dx.doi.org/10.3233/JAD-132018 | DOI Listing |
Bull Math Biol
January 2025
Université Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, 38000, Grenoble, France.
The extracellular matrix (ECM) is a complex structure involved in many biological processes with collagen being the most abundant protein. Density of collagen fibers in the matrix is a factor influencing cell motility and migration speed. In cancer, this affects the ability of cells to migrate and invade distant tissues which is relevant for designing new therapies.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Virginia, Charlottesville, VA, USA.
Background: The microvasculature of the central nervous system (CNS), which delivers oxygen and nutrients and forms a critical barrier protecting the CNS, is deleteriously affected by both Alzheimer's Disease (AD) and Type 2 Diabetes (T2D). Previous studies have shown pericyte dropout and vessel constriction in brain capillaries in AD, while other studies have shown pericyte bridging and dropout in retinal capillaries in T2D. T2D patients have increased risk of AD, suggesting potentially related microvascular pathological mechanisms.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Background: The proteasome plays key roles in synaptic plasticity and memory by regulating protein turnover, quality control, and elimination of oxidized/misfolded proteins. Here, we investigate proteasome function and localization at synapses in Alzheimer's disease (AD) post-mortem brain tissue and in experimental models.
Method: We used primary hippocampal cultures, amyloid-β oligomers (AβO)-injected or transgenic animal models, and human brain tissue to determine brain proteasome function and subcellular localization.
Alzheimers Dement
December 2024
Aligarh Muslim University, Aligarh, UttarPradesh, India.
Background: Following the genome-wide association studies (GWAS) discovery of microglia-specific genes, particularly Trem-2, SHIP-1, and CD33, significantly associated with higher Alzheimer's disease (AD) risk, the microglia TREM2 pathway has become central for regulating amyloid load, tissue damage, and limiting its spread. These discoveries have opened up the exciting possibility of therapeutic microglia TREM2 manipulation in AD. To date, however, several elements of TREM2 signaling remain unknown, ranging from the temporal activation pattern and receptor-ligand binding to modulation of the brain microenvironment.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
Background: Ischemic stroke (IS) is a risk factor for developing Alzheimer's disease (AD). In this context, microglial activation is a shared cellular response to these two conditions that can be either beneficial or detrimental. Previous research has established that mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) treatment leads to enhanced functional recovery and reduced brain infarct volume in animal IS models.
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