Evaluation of WMH severity. Furthermore, we had data on a number

Evaluation of WMH severity. Furthermore, we had data on a number of potential causal or risk factors for WMH, enabling us to include these in the analyses. Limitations include the cross-sectional design, the relatively small order PHA-739358 sample size, and orthostatic BP measurements in a number of cases obtained 1326631 from the sitting, instead of the supine position. It has previously been demonstrated that sit-stand MedChemExpress TKI-258 lactate testing for OH has a very low diagnostic accuracy [50]. However, sit-stand measurement only has been used in recent, similar studies [51,52]. In addition, no standing BP measurements were made after 3 minutes. According to a previous study [53], at least 20?0 of dementia patients have a delayed orthostatic response. Thus, our methodology would tend to underestimate the prevalence of OH, thereby possibly masking the potential association between OHand WMH. Furthermore, the consensus definition of OH, which was employed in the present study, does not in itself require the orthostatic BP to be measured on more than one occasion. This is a potential limitation, as this approach cannot distinguish those having only transient OH from those having more persistent or frequently recurring OH. The latter groups may have a higher risk of being afflicted with the potential adverse consequences of BP drops, such as syncope and cerebral hypoperfusion, and possibly also the development of WMH. Ideally, in order to identify individuals with more than transient OH, orthostatic blood pressures should have been measured repeatedly over a period of e.g. a few weeks. Moreover, if OH does play a role in the development of WMH in mild dementia, it probably exerts its effects over an extended period of time, also prior to the diagnosis of dementia. Exploring this clearly would require a longitudinal study. One final point is that due to missing data for some variables, a relatively low number of subjects could be included in the multiple logistic regression analyses, thus limiting the number of predictors that could be entered into these analyses, as well as their power. Our results suggest that OH or low standing BP may not be associated with WMH in older people with mild dementia, at least not cross-sectionally. Instead, these changes may primarily be associated with neurodegenerative disease [14], ageing [54], hypertension and smoking [2,11], genetics [55], or combinations of these factors. However, recent longitudinal studies indicate that an unfavourable vascular risk factor status from midlife and onwards may be of importance for the development of WMH in later life [10,56,57]. Thus, the best opportunities for potential prevention of these changes may lie in controlling established vascular risk factors, starting no later than in midlife.ConclusionIn a sample of older people with mild dementia, we found no cross-sectional association between OH and WMH load. Future studies should include larger samples, use a longitudinal design, and use more rigorous BP measurement protocols.Author ContributionsConceived and designed the experiments: HS DWN DA. Performed the experiments: HS KO OJG MKB. Analyzed the data: HS DA. Wrote the paper: HS DA.
Subsequent to vasculogenesis, endothelial cells specialize into arterial and venous cell types through a complex mechanism that 12926553 starts with a number of key signaling molecules. The Notch receptor system is one of the pathways that have been implicated to play a critical role in the determination of arterial cell fate [1?]. Pertur.Evaluation of WMH severity. Furthermore, we had data on a number of potential causal or risk factors for WMH, enabling us to include these in the analyses. Limitations include the cross-sectional design, the relatively small sample size, and orthostatic BP measurements in a number of cases obtained 1326631 from the sitting, instead of the supine position. It has previously been demonstrated that sit-stand testing for OH has a very low diagnostic accuracy [50]. However, sit-stand measurement only has been used in recent, similar studies [51,52]. In addition, no standing BP measurements were made after 3 minutes. According to a previous study [53], at least 20?0 of dementia patients have a delayed orthostatic response. Thus, our methodology would tend to underestimate the prevalence of OH, thereby possibly masking the potential association between OHand WMH. Furthermore, the consensus definition of OH, which was employed in the present study, does not in itself require the orthostatic BP to be measured on more than one occasion. This is a potential limitation, as this approach cannot distinguish those having only transient OH from those having more persistent or frequently recurring OH. The latter groups may have a higher risk of being afflicted with the potential adverse consequences of BP drops, such as syncope and cerebral hypoperfusion, and possibly also the development of WMH. Ideally, in order to identify individuals with more than transient OH, orthostatic blood pressures should have been measured repeatedly over a period of e.g. a few weeks. Moreover, if OH does play a role in the development of WMH in mild dementia, it probably exerts its effects over an extended period of time, also prior to the diagnosis of dementia. Exploring this clearly would require a longitudinal study. One final point is that due to missing data for some variables, a relatively low number of subjects could be included in the multiple logistic regression analyses, thus limiting the number of predictors that could be entered into these analyses, as well as their power. Our results suggest that OH or low standing BP may not be associated with WMH in older people with mild dementia, at least not cross-sectionally. Instead, these changes may primarily be associated with neurodegenerative disease [14], ageing [54], hypertension and smoking [2,11], genetics [55], or combinations of these factors. However, recent longitudinal studies indicate that an unfavourable vascular risk factor status from midlife and onwards may be of importance for the development of WMH in later life [10,56,57]. Thus, the best opportunities for potential prevention of these changes may lie in controlling established vascular risk factors, starting no later than in midlife.ConclusionIn a sample of older people with mild dementia, we found no cross-sectional association between OH and WMH load. Future studies should include larger samples, use a longitudinal design, and use more rigorous BP measurement protocols.Author ContributionsConceived and designed the experiments: HS DWN DA. Performed the experiments: HS KO OJG MKB. Analyzed the data: HS DA. Wrote the paper: HS DA.
Subsequent to vasculogenesis, endothelial cells specialize into arterial and venous cell types through a complex mechanism that 12926553 starts with a number of key signaling molecules. The Notch receptor system is one of the pathways that have been implicated to play a critical role in the determination of arterial cell fate [1?]. Pertur.

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