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  • Wu, Y. T., et al. (författare)
  • Dementia in western Europe: epidemiological evidence and implications for policy making
  • 2016
  • Ingår i: Lancet Neurology. - : Elsevier BV. - 1474-4422. ; 15:1, s. 116-124
  • Forskningsöversikt (refereegranskat)abstract
    • Dementia is receiving increasing attention from governments and politicians. Epidemiological research based on western European populations done 20 years ago provided key initial evidence for dementia policy making, but these estimates are now out of date because of changes in life expectancy, living conditions, and health profiles. To assess whether dementia occurrence has changed during the past 20-30 years, investigators of five different studies done in western Europe (Sweden [Stockholm and Gothenburg], the Netherlands [Rotterdam], the UK [England], and Spain [Zaragoza]) have compared dementia occurrence using consistent research methods between two timepoints in well-defined geographical areas. Findings from four of the five studies showed non-significant changes in overall dementia occurrence. The only significant reduction in overall prevalence was found in the study done in the UK, powered and designed explicitly from its outset to detect change across generations (decrease in prevalence of 22%; p=0.003). Findings from the study done in Zaragoza (Spain) showed a significant reduction in dementia prevalence in men (43%; p=0.0002). The studies estimating incidence done in Stockholm and Rotterdam reported non-significant reductions. Such reductions could be the outcomes from earlier population-level investments such as improved education and living conditions, and better prevention and treatment of vascular and chronic conditions. This evidence suggests that attention to optimum health early in life might benefit cognitive health late in life. Policy planning and future research should be balanced across primary (policies reducing risk and increasing cognitive reserve), secondary (early detection and screening), and tertiary (once dementia is present) prevention. Each has their place, but upstream primary prevention has the largest effect on reduction of later dementia occurrence and disability.
  • Koch, Philipp, et al. (författare)
  • Emerging concepts in neural stem cell research: autologous repair and cell-based disease modelling
  • 2009
  • Ingår i: Lancet Neurology. - 1474-4465. ; 8:9, s. 819-829
  • Forskningsöversikt (refereegranskat)abstract
    • The increasing availability of human pluripotent stem cells provides new prospects for neural-replacement strategies and disease-related basic research. With almost unlimited potential for self-renewal, the use of human embryonic stem cells (ESCs) bypasses the restricted supply and expandability of primary cells that has been a major bottleneck in previous neural transplantation approaches. Translation of developmental patterning and cell-type specification techniques to human ESC cultures enables in vitro generation of various neuronal and glial cell types. The derivation of stably proliferating neural stem cells from human ESCs further facilitates standardisation and circumvents the problem of batch-to-batch variations commonly encountered in "run-through" protocols, which promote terminal differentiation of pluripotent stem cells into somatic cell types without defined intermediate precursor stages. The advent of cell reprogramming offers an opportunity to translate these advances to induced pluripotent stem cells, thereby enabling the generation of neurons and glia from individual patients. Eventually, reprogramming could provide a supply of autologous neural cells for transplantation, and could lead to the establishment of cellular model systems of neurological diseases.
  • Rothwell, P. M., et al. (författare)
  • Effects of beta blockers and calcium-channel blockers on within-individual variability in blood pressure and risk of stroke
  • 2010
  • Ingår i: The Lancet Neurology. - 1474-4422. ; 9:5, s. 469-480
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Analyses of some randomised trials show that calcium-channel blockers reduce the risk of stroke more than expected on the basis of mean blood pressure alone and that beta blockers are less effective than expected. We aimed to investigate whether the effects of these drugs on variability in blood pressure might explain these disparities in effect on stroke risk. METHODS: The Anglo-Scandinavian Cardiac Outcomes Trial Blood Pressure Lowering Arm (ASCOT-BPLA) compared amlodipine-based regimens with atenolol-based regimens in 19 257 patients with hypertension and other vascular risk factors and the Medical Research Council (MRC) trial compared atenolol-based and diuretic-based regimens versus placebo in 4396 hypertensive patients aged 65-74 years. We expressed visit-to-visit variability of blood pressure during follow-up in the two trials as standard deviation (SD) and as transformations uncorrelated with mean blood pressure. For ASCOT-BPLA, we also studied within-visit variability and variability on 24 h ambulatory blood-pressure monitoring (ABPM). RESULTS: In ASCOT-BPLA, group systolic blood pressure (SBP) SD was lower in the amlodipine group than in the atenolol group at all follow-up visits (p<0.0001), mainly because of lower within-individual visit-to-visit variability. Within-visit and ABPM variability in SBP were also lower in the amlodipine group than in the atenolol group (all p<0.0001). Analysis of changes from baseline showed that variability decreased over time in the amlodipine group and increased in the atenolol group. The lower risk of stroke in the amlodipine group (hazard ratio 0.78, 95% CI 0.67-0.90) was partly attenuated by adjusting for mean SBP during follow-up (0.84, 0.72-0.98), but was abolished by also adjusting for within-individual SD of clinic SBP (0.99, 0.85-1.16). Findings were similar for coronary events. In the ABPM substudy, reduced variability in daytime SBP in the amlodipine group (p<0.0001) partly accounted for the reduced risk of vascular events, but reduced visit-to-visit variability in clinic SBP had a greater effect. In the MRC trial, group SD SBP and all measures of within-individual visit-to-visit variability in SBP were increased in the atenolol group compared with both the placebo group and the diuretic group during initial follow-up (all p<0.0001). Subsequent temporal trends in variability in blood pressure during follow-up in the atenolol group correlated with trends in stroke risk. INTERPRETATION: The opposite effects of calcium-channel blockers and beta blockers on variability of blood pressure account for the disparity in observed effects on risk of stroke and expected effects based on mean blood pressure. To prevent stroke most effectively, blood-pressure-lowering drugs should reduce mean blood pressure without increasing variability; ideally they should reduce both. FUNDING: None.
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