LRP1 in vascular mural cells modulates cerebrovascular integrity and function in the presence of APOE4.

Cerebrovasculature is critical in maintaining brain homeostasis; its dysregulation often leads to vascular cognitive impairment and dementia (VCID) during aging. VCID is the second most prevalent cause of dementia in the elderly, after Alzheimer's disease (AD), with frequent cooccurrence of VCID and AD. While multiple factors are involved in the pathogenesis of AD and VCID, APOE4 increases the risk for both diseases. A major apolipoprotein E (apoE) receptor, the low-density lipoprotein receptor-related protein 1 (LRP1), is abundantly expressed in vascular mural cells (pericytes and smooth muscle cells). Here, we investigated how deficiency of vascular mural cell LRP1 affects the cerebrovascular system and cognitive performance using vascular mural cell-specific Lrp1-KO mice (smLrp1-/-) in a human APOE3 or APOE4 background. We found that spatial memory was impaired in the 13- to 16-month-old APOE4 smLrp1-/- mice but not in the APOE3 smLrp1-/- mice, compared with their respective littermate control mice. These disruptions in the APOE4 smLrp1-/- mice were accompanied with excess paravascular glial activation and reduced cerebrovascular collagen IV. In addition, blood-brain barrier (BBB) integrity was disrupted in the APOE4 smLrp1-/- mice. Together, our results suggest that vascular mural cell LRP1 modulates cerebrovasculature integrity and function in an APOE genotype-dependent manner.

Frailty prevalence and its associations in a subacute geriatric ward in Singapore

INTRODUCTION@#Our aim was to study the prevalence of frailty and its associated factors in a subacute geriatric ward.@*METHODS@#This was a cross-sectional study of 167 participants between June 2018 and June 2019. Baseline demographics and participants' Mini Nutritional Assessment, Geriatric Depression Scale, Mini Mental State Examination, Charlson's Comorbidity Index and LACE index scores were obtained. Functional measurements such as modified Barthel's Index scores and hand grip strength (HGS) were taken. Frailty was assessed using the Clinical Frailty Scale (CFS) and the FRAIL scale. Data on history of healthcare utilisation, medications, length of stay, selected blood investigations and presence of geriatric syndromes were also collected.@*RESULTS@#The prevalence of pre-frailty (CFS 4) and frailty (CFS ≥ 5) was 16.2% and 63.4%, respectively. There were significant associations between CFS and age (pre-frail vs. non-frail: odds ratio [OR] 1.14, 95% confidence interval [CI] 1.04-1.25, P = 0.006; frail vs. non-frail: OR 1.08, 95% CI 1.01-1.15, P = 0.021), HGS at discharge (frail vs. non-frail: OR 0.90, 95% CI 0.82-0.99, P = 0.025), serum albumin (frail vs. non-frail: OR 0.90, 95% CI 0.82-0.99, P = 0.035) and the presence of urinary incontinence (frail vs. non-frail: OR 3.03, 95% CI 1.19-7.77, P = 0.021).@*CONCLUSION@#Frailty is highly prevalent in the subacute geriatric setting and has many associated factors. In this study, independent factors associated with frailty were age, HGS at discharge, serum albumin and urinary incontinence. This has implications for future resource allocation for frail older inpatients and may help direct further research to study the effectiveness of frailty-targeted interventions.

Approach to frailty in the elderly in primary care and the community

Frailty is a distinct clinical syndrome wherein the individual has low reserves and is highly vulnerable to internal and external stressors. Although it is associated with disability and multiple comorbidities, it can also be present in individuals who seem healthy. Frailty is multidimensional and its pathophysiology is complex. Early identification and intervention can potentially decrease or reverse frailty, especially in the early stages. Primary care physicians, community nurses and community social networks have important roles in the identification of pre-frail and frail elderly through the use of simple frailty screening tools and rapid geriatric assessments. Appropriate interventions that can be initiated in a primary care setting include a targeted medical review for reversible medical causes of frailty, medication appropriateness, nutritional advice and exercise prescription. With ongoing training and education, the multidisciplinary engagement and coordination of care of the elderly in the community can help to build resilience and combat frailty in our rapidly ageing society.

Expression of glucose transporter-3 mRNA in rats' focal cerebral ischemic penumbra / 临床神经病学杂志

Objective To investigate the expression of glucose transporter 3(GLUT 3) transcription level at different ischemic time in rats' focal cerebral ischemic penumbra and core of cortices.Methods Focal ischemic models of middle cerebral artery occlusion (MCAO) in rats were made by inserting nylon surgical thread. Brain samples were harvested from ischemic penumbra and core of cortices. The change of GLUT 3 mRNA was assessed by RT PCR.Results GLUT 3 mRNA in the penumbra regions slightly increased at 3 h after ischemia, and reached a peak at 24 h, in 96h following ischemia it came back to the normal level. As for ischemic core regions, GLUT 3 mRNA had a short time increase at 3 h after ischemia, and then rapidly decrease to the low level. Conclusion GLUT 3 mRNA expression was notably up regulated in the penumbra regions after focal cerebral ischemia,it may be a protective reaction against ischemic injury.