Reduced estimated glomerular filtration rate in Alzheimer's disease.

OBJECTIVES: Renal disease is increasingly regarded as an independent risk factor for vascular disease which in itself is believed to influence risk of AD. Alterations in amyloid homeostasis via reduced renal clearance of peripheral beta-amyloid (A|*beta*|) may represent another potential role for variation in renal function leading to increased risk of AD. We sought to examine estimates of glomerular filtration rate in AD and control groups. METHODS: AD patients were randomly recruited from the Memory Clinic of the Belfast City Hospital (n = 83). Genomic DNA was extracted from peripheral leucocytes and was genotyped for Apolipoprotein E using standard methods. Using creatinine values, age and gender, estimated Glomerular Filtration Rates (eGFR) were calculated using the isotope dilution mass spectrometry (IDMS)-traceable Modification of Diet in Renal Disease (MDRD) Study equation (using the United Kingdom National External Quality Assessment Scheme (UKNEQAS) correction factor). IDMS eGFR values were then compared between AD and control groups. RESULTS: Significant baseline differences in age, diastolic blood pressure, education level attained and APOE |*epsilon*|4 carriage were noted between cases and controls. The AD group had a significantly lower eGFR versus controls (69 vs 77 ml/min) which persisted after adjustment for possible confounders (p = 0.045). CONCLUSIONS: This case-control analysis suggests that using a relatively accurate estimate of renal function, patients with AD have greater renal impairment than cognitively normal controls. This may reflect impaired renal clearance of peripheral A|*beta*| or be a marker of shared vascular processes altering cerebral and renal functioning.

Country-Wide Analysis of Systemic Factors Associated With Acute Ischemic Stroke Door to Needle Time.

Objective: Pre-hospital, in-hospital, and patient factors are associated with variation in door to needle (DTN) time in acute ischemic stroke (AIS). Publications are usually from large single centers or multicenter registries with less reporting on national results. Materials and methods: All AIS patients treated with intravenous tissue plasminogen activator (iv-tPA) over 4 years (2013-2016) in Northern Ireland were recorded prospectively, including patient demographics, pre-hospital care, thrombolysis rate, and DTN time. Logistic regression was performed to identify factors associated with DTN time. Results: One thousand two hundred and one patients from 10,556 stroke admissions (11.4%) were treated with iv-tPA. Median NIHSS was 10 (IQR 6-17). Median DTN time was 54 min (IQR 36-77) with 61% treated < 60 min from arrival at hospital. National thrombolysis numbers increased over time with improving DTN time (P = 0.002). Arrival method at hospital (ambulance OR 2.3 CI1.4-3.8) pre-alert from ambulance (pre-alert OR = 5.3 CI3.5-8.1) and time of day (out of hours, n = 650, OR 0.20 CI 0.22-0.38) all P < 0.001, were the independent factors in determining DTN time. Variation in DTN time between centers occurred but was unrelated to volume of stroke admissions. Conclusion: Ambulance transport with pre-hospital notification and time of day are associated with shorter DTN time on a national level. Most thrombolysis was delivered outside of normal working hours but these patients are more likely to experience treatment delays. Re-organization of stroke services at a whole system level with emphasis on pre-hospital care and design of stroke teams are required to improve quality and equitable care in AIS nationally.

Moderately elevated plasma homocysteine, methylenetetrahydrofolate reductase genotype, and risk for stroke, vascular dementia, and Alzheimer disease in Northern Ireland.

BACKGROUND AND PURPOSE: Elevated plasma homocysteine level has been associated with increased risk for cardiovascular and cerebrovascular disease. Variation in the levels of this amino acid has been shown to be due to nutritional status and methylenetetrahydrofolate reductase (MTHFR) genotype. METHODS: Under a case-control design we compared fasting levels of homocysteine and MTHFR genotypes in groups of subjects consisting of stroke, vascular dementia (VaD), and Alzheimer disease patients and normal controls from Northern Ireland. RESULTS: A significant increase in plasma homocysteine was observed in all 3 disease groups compared with controls. This remained significant after allowance for confounding factors (age, sex, hypertension, cholesterol, smoking, creatinine, and nutritional measures). MTHFR genotype was not found to influence homocysteine levels, although the T allele was found to increase risk for VaD and perhaps dementia after stroke. CONCLUSIONS: We report that moderately high plasma levels of homocysteine are associated with stroke, VaD, and Alzheimer disease. This is not due to vascular risk factors, nutritional status, or MTHFR genotype.