Diagnostic accuracy of office blood pressure compared to home blood pressure in patients with mild cognitive impairment and dementia

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Effects of aging on cerebral oxygenation during working-memory performance: A functional near-infrared spectroscopy study

Contains fulltext : 102484.pdf (publisher's version ) (Open Access)Working memory is sensitive to aging-related decline. Evidence exists that aging is accompanied by a reorganization of the working-memory circuitry, but the underlying neurocognitive mechanisms are unclear. In this study, we examined aging-related changes in prefrontal activation during working-memory performance using functional Near-Infrared Spectroscopy (fNIRS), a noninvasive neuroimaging technique. Seventeen healthy young (21–32 years) and 17 healthy older adults (64–81 years) performed a verbal working-memory task (n-back). Oxygenated and deoxygenated hemoglobin concentration changes were registered by two fNIRS channels located over the left and right prefrontal cortex. Increased working-memory load resulted in worse performance compared to the control condition in older adults, but not in young participants. In both young and older adults, prefrontal activation increased with rising working-memory load. Young adults showed slight right-hemispheric dominance at low levels of working-memory load, while no hemispheric differences were apparent in older adults. Analysis of the time-activation curve during the high working-memory load condition revealed a continuous increase of the hemodynamic response in the young. In contrast to that, a quadratic pattern of activation was found in the older participants. Based on these results it could be hypothesized that young adults were better able to keep the prefrontal cortex recruited over a prolonged period of time. To conclude, already at low levels of working-memory load do older adults recruit both hemispheres, possibly in an attempt to compensate for the observed aging-related decline in performance. Also, our study shows that aging effects on the time course of the hemodynamic response must be taken into account in the interpretation of the results of neuroimaging studies that rely on blood oxygen levels, such as fMRI.11 p

Perioperative cerebral perfusion in aortic arch surgery: a potential link with neurological outcome

OBJECTIVES: The aim of this study was to examine whether perioperative changes in cerebral blood flow (CBF) relate to postoperative neurological deficits in patients undergoing aortic arch surgery involving antegrade selective cerebral perfusion (ASCP).METHODS: We retrospectively analysed data from patients who underwent aortic arch surgery involving ASCP and perioperative transcranial Doppler assessments. Linear mixed-model analyses were performed to examine perioperative changes in mean bilateral blood velocity in the middle cerebral arteries, reflecting changes in CBF, and their relation with neurological deficits, i.e. ischaemic stroke and/or delirium. Logistic regression analyses were performed to explore possible risk factors for postoperative neurological deficits.RESULTS: In our study population (N = 102), intraoperative blood velocities were lower compared to preoperative levels, and lowest during ASCP. Thirty-six (35%) patients with postoperative neurological deficits (ischaemic stroke, n = 9; delirium, n = 25; both, n = 2) had lower blood velocity during ASCP compared to patients without (25.4 vs 37.0 cm/s; P = 0.002). Logistic regression analyses revealed lower blood velocity during ASCP as an independent risk factor for postoperative neurological deficits (odds ratio = 0.959; 95% confidence interval: 0.923, 0.997; P = 0.037).CONCLUSIONS: Lower intraoperative CBF during ASCP seems independently related to postoperative neurological deficits in patients undergoing aortic arch surgery. Because CBF is a modifiable factor during ASCP, our observation has significant potential to improve clinical management and prevent neurological deficits.Neurological Motor Disorder

Applying systems thinking to unravel the mechanisms underlying orthostatic hypotension related fall risk

Orthostatic hypotension (OH) is an established and common cardiovascular risk factor for falls. An in-depth understanding of the various interacting pathophysiological pathways contributing to OH-related falls is essential to guide improvements in diagnostic and treatment opportunities. We applied systems thinking to multidisciplinary map out causal mechanisms and risk factors. For this, we used group model building (GMB) to develop a causal loop diagram (CLD). The GMB was based on the input of experts from multiple domains related to OH and falls and all proposed mechanisms were supported by scientific literature. Our CLD is a conceptual representation of factors involved in OH-related falls, and their interrelatedness. Network analysis and feedback loops were applied to analyze and interpret the CLD, and quantitatively summarize the function and relative importance of the variables. Our CLD contains 50 variables distributed over three intrinsic domains (cerebral, cardiovascular, and musculoskeletal), and an extrinsic domain (e.g., medications). Between the variables, 181 connections and 65 feedback loops were identified. Decreased cerebral blood flow, low blood pressure, impaired baroreflex activity, and physical inactivity were identified as key factors involved in OH-related falls, based on their high centralities. Our CLD reflects the multifactorial pathophysiology of OH-related falls. It enables us to identify key elements, suggesting their potential for new diagnostic and treatment approaches in fall prevention. The interactive online CLD renders it suitable for both research and educational purposes and this CLD is the first step in the development of a computational model for simulating the effects of risk factors on falls

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Cerebral hemodynamics in aging: the interplay between blood pressure, cerebral perfusion, and dementia.

Contains fulltext : 69883.pdf (publisher's version ) (Open Access)Advances in measurement techniques have made it possible to study dynamic changes in brain blood flow. Transcranial Doppler ultrasonography measures changes in cerebral blood flow-velocity in the larger cerebral arteries (e.g. the middle cerebral artery). Near infrared spectroscopy records changes in brain cortical tissue concentrations of hemoglobin. These techniques are non-invasive, and can be performed with the subject in supine, sitting or standing position. Together with photoplethysmography, which measures arterial blood pressure at the finger, these methods provide detailed information on beat-to-beat changes in cerebral hemodynamics. In this thesis, these techniques have been further explored, with specific attention for their potential use in elderly subjects. First, we have considered that measurements of cerebral perfusion, complimenting measurements of blood pressure, will provide valuable insight in disorders of blood pressure regulation. Second, we have proposed that measurements of blood pressure, cerebral blood flow, and their interaction, are important in dementia research.RU Radboud Universiteit Nijmegen, 25 november 2008Promotores : Olde Rikkert, M.G.M., Levine, B.D. Co-promotores : Zhang, R., Jansen, R.W.M.M.237 p

The gold standard: not a golden standard.

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New cardiovascular targets to prevent late onset Alzheimer disease

Item does not contain fulltextThe prevalence of dementia rises to between 20% and 40% with advancing age. The dominant cause of dementia in approximately 70% of these patients is Alzheimer disease. There is no effective disease-modifying pharmaceutical treatment for this neurodegenerative disease. A wide range of Alzheimer drugs that appeared effective in animal models have recently failed to show clinical benefit in patients. However, hopeful news has emerged from recent studies that suggest that therapeutic strategies aimed at reducing cardiovascular disease may also reduce the prevalence of dementia due to Alzheimer disease. This review summarizes the evidence for this link between cardiovascular disease and late onset Alzheimer dementia. Only evidence from human research is considered here. Longitudinal studies show an association between high blood pressure and pathological accumulation of the protein amyloid-beta42, and an even stronger association between vascular stiffness and amyloid accumulation, in elderly subjects. Amyloid-beta42 accumulation is considered to be an early marker of Alzheimer disease, and increases the risk of subsequent cognitive decline and development of dementia. These observations could provide an explanation for recent observations of reduced dementia prevalence associated with improved cardiovascular care

['Gold standard', not 'golden standard'],Liever 'goudstandaard' dan 'gouden standaard'.

Contains fulltext : 47381.pdf (publisher's version ) (Closed access)In medical literature, both 'gold standard' and 'golden standard' are employed to describe a reference test used for comparison with a novel method. The term 'gold standard' in its current sense in medical research was coined by Rudd in 1979, in reference to the monetary gold standard. In the same way that the monetary gold standard allowed for the comparison of different currencies, the medical gold standard allowed for the comparison of different diagnostic tests. Whereas the gold standard was never regarded as infallible, the incorrect term 'golden standard' implies a level of perfection that is unattainable in medical science. Consequently, the correct term should be 'gold standard'

Tellymedicine.

Contains fulltext : 47357.pdf (publisher's version ) (Closed access