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Background: Examining the distribution of biochemical and haematological tests in different age groups of rural population is necessary to ensure that health care facilities are equipped to address the prevalent health conditions and manage age-related illness effectively. Hence, this study is aimed at seeing the distributions of blood biochemical and haematological parameters in rural population. Methods: This cross-sectional study investigated the distribution of 26 different haematological and biochemical parameters in longitudinal cohort study (Srinivaspura Aging, NeuoSenescence and COGnition - SANSCOG), from the villages of Srinivaspura, Kolar district, India. A total of 2592 participants (1240 males and 1352 females), aged ≥45 years who are cognitively healthy were included for the analysis. Mean, 2.5th, 5th, 25th, 50th, 75th, 95th and 97.5th percentiles were calculated for the entire sample. Additionally, median and percentiles were determined for both gender and age categories (45-54, 55-64, 65-74, and ≥75 years). Results: We observed the distinct distributions of various haematological and biochemical parameters, with elevated levels of glycaemic, lipid, liver, and thyroid parameters. Conclusion: Findings revealed the notable variations from the established reference ranges, indicating the potential undiagnosed cases and highlighting the gaps in health awareness and health seeking behaviour. [ABSTRACT FROM AUTHOR]

Background: Vascular Dementia (VaD) is the second most prevalent cause of dementia, arising from the blockage of blood vessels in the brain. One event responsible for the blockage or narrowing of small blood vessels is transient ischemic attack (TIA), and these changes resolve within 24 hours in humans. The molecular mechanism underlying these changes in recovery in small vessels still needs to be investigated. To address this gap, we have developed a mouse model by administering endothelin‐1 (ET‐1) into the lateral ventricles. This disrupts small vessel integrity, which leads to learning and memory deficits after 3 days of a single ET‐1 injection. Intriguingly, there is a subsequent recovery in these deficits after 30 days, mimicking the clinical scenario of TIAs. Bulk RNA sequencing from microvessels was performed to elucidate further the factors involved in recovery mechanisms. Method: ET‐1 injection was given to 4 groups of C57BL6/J mice, and mice were sacrificed at different time points of 3, 15, and 30 days along with saline counterparts. Microvessels were extracted from the pooled cortex and hippocampus, followed by RNA isolation. RNA samples were subjected to the cDNA library preparation, and RNA sequencing was conducted using the Illumina NovaSeq 6000® instrument. Transcriptomic analysis was carried out in the Linux environment. Differential gene expression was performed using R. Result: We observed biological processes such as vasculature development, angiogenesis, and wound healing start upregulating after 3 days of a single ET‐1 injection, whereas several processes involved in ion transport chains were downregulated. Further, biological processes for muscle development, mitochondrial electron transport chain, and neuronal development were upregulated after 15 days of a single ET‐1 injection. No biological processes were affected after 30 days of a single ET‐1 injection, suggesting a possible complete recovery from ET‐1‐mediated vascular insult by the 30th day. Conclusion: Our results highlight the temporal dynamics of biological processes in response to a single ET‐1 injection. It offers valuable insight for understanding the mechanism behind the recovery and factors involved in this process after vascular insult, paving the way for therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Vascular pathology is often seen in cases of mixed dementia affecting elderly population including Alzheimer's disease (AD). AD is generally characterized by the presence of amyloid‐β (Aβ) plaques and tau deposits. However, many factors influence the onset and progression of AD pathology. In the present study, we are looking for brain vascular pathology like blood brain barrier (BBB) breach by vascular insult and associated microglial activation in small vessels increase risk of developing pathology over age. It is often hypothesized that in presence of increased Aβ, vascular insults could synergistically trigger neuroinflammation leading to cognitive impairment accelerating neurodegeneration. Method: Learning and memory deficits were performed in slow progressing APPswe mice injected with 2µg/2μl of ET‐1(endothelin‐1) bilaterally into lateral ventricles after 30 days of ET‐1 injection. BBB structural changes were assessed by immunohistochemistry for markers of endothelial cells and pericytes. Aβ plaque load and vascular deposition of Aβ were tested to understand the effect of vascular insult on AD pathology in double transgenic J20 mice. Further, microglial activation was estimated using specific markers. Result: BBB breaching was increased after vasoconstriction following ET‐1 injection after 30 days with increasing age causing memory deficits in AD mice. The extent of structural changes in BBB increased with age indicating the susceptibility with mutation. Aβ plaque load and glial activation was increased in J20 mice after ET‐1 injection. Conclusion: APP mutation increases susceptibility to ET‐1 induced single vascular insult bringing about BBB leakage, memory deficits, increased Aβ aggregation and glial activation with increasing age given enough time of 30 days to rescue. However, there was rescue in case of wild type mice. [ABSTRACT FROM AUTHOR]

Background: Vascular insults, such as microinfarcts play a major role in mixed dementia including Alzheimer's disease (AD). Neuroimaging from longitudinal studies have shown involvement of white matter hyperintensities due to blood brain barrier (BBB) breakdown. In patients with AD the combined neurotoxic effects of amyloid‐β (Aβ) converge on brain vasculature synergistically leading to neuronal and synaptic dysfunction, which in turn leads to cognitive impairment. In the present study we examined the effect of vascular insult induced by enothelin‐1 (ET‐1, a vasoconstrictor peptide) on Aβ pathology in mouse models of AD. We further studied behavioral deficits during reduced cerebral blood flow changes and structural changes in BBB components. Method: We injected 2µg/2μl of ET‐1 bilaterally into lateral ventricles APPswe mice carrying point mutation for APP. Behavioral assays were performed to compare associative learning and spatial memory deficits, if any after 30 days of ET‐1 injection. Immunohistochemistry for markers of endothelial cells and pericytes were done to look at the structural changes in BBB. Aβ ELISA and plaque load were tested to understand the effect of vascular insult on AD pathology. Result: Vasoconstriction following ET‐1 injection after 30 days leads to memory deficits in AD mice while wildtype mice recovered. There were structural changes in BBB showing decreased expression of endothelial and pericyte marker, however these changes were not observed in wildtype mice. Aβ levels were increased in brain lysates of APPswe mice injected with ET‐1. Conclusion: Single vascular insult was adequate to bring about impairment in learning and memory in APPswe mice and structural changes in BBB, which were not seen in WT type mice indicating that ET‐1 induced cerebral hypoperfusion accelerated AD pathogenesis. [ABSTRACT FROM AUTHOR]