Physiology (Bethesda)
November 2024
The mechanism underlying the possible causal association between long-term sleep disruption and Alzheimer's disease remains unclear Musiek et al. 2015. A hypothesised pathway through increased brain amyloid load was not confirmed in previous work in our cohort of maritime pilots with long-term work-related sleep disruption Thomas et al.
View Article and Find Full Text PDFThe major vascular cause of dementia is cerebral small vessel disease (SVD). Its diagnosis relies on imaging hallmarks, such as white matter hyperintensities (WMH). WMH present a heterogenous pathology, including myelin and axonal loss.
View Article and Find Full Text PDFSleep plays an essential role in physiology, allowing the brain and body to restore itself. Despite its critical role, our understanding of the underlying processes in the sleeping human brain is still limited. Sleep comprises several distinct stages with varying depths and temporal compositions.
View Article and Find Full Text PDFIntroduction: Systemic inflammation and endothelial dysfunction are potentially modifiable factors implicated in Alzheimer's disease (AD), which offer potential therapeutic targets to slow disease progression.
Methods: We investigated the relationship between baseline circulating levels of inflammatory (TNF-α, IL-1ß) and endothelial cell markers (VCAM-1, ICAM-1, E-selectin) and 18-month cognitive decline (ADAS-cog12) in 266 mild-to-moderate AD patients from the NILVAD study. We employed individual growth models to examine associations, potential mediation, and interaction effects while adjusting for confounders.
Orthostatic hypotension (OH) is prevalent in older adults and can cause falls and hospitalization. Diagnostic intermittent blood pressure (BP) measurements are only a proxy for cerebral perfusion and do not reflect daily-life BP fluctuations. Near-infrared spectroscopy (NIRS)-measured cerebral oxygenation potentially overcomes these drawbacks.
View Article and Find Full Text PDFBackground: Evidence on the effectiveness of multidomain lifestyle interventions to prevent cognitive decline in older people without dementia is mixed. Embedded in the World-Wide FINGERS initiative, FINGER-NL aims to investigate the effectiveness of a 2-year multidomain lifestyle intervention on cognitive functioning in older Dutch at risk individuals.
Methods: Multi-center, randomized, controlled, multidomain lifestyle intervention trial with a duration of 24 months.
Alzheimer's disease (AD) is characterized by an initial decline in declarative memory, while nondeclarative memory processing remains relatively intact. Error-based motor adaptation is traditionally seen as a form of nondeclarative memory, but recent findings suggest that it involves both fast, declarative, and slow, nondeclarative adaptive processes. If the declarative memory system shares resources with the fast process in motor adaptation, it can be hypothesized that the fast, but not the slow, process is disturbed in AD patients.
View Article and Find Full Text PDFBackground: Orthostatic hypotension (OH) is common in older adults with hypertension. Antihypertensive treatment (AHT) prevents cardio- and cerebrovascular events. However, physicians are concerned to cause OH, making them hesitant to initiate or augment AHT in older adults with hypertension.
View Article and Find Full Text PDFThis study aimed to examine the effects of intensive antihypertensive treatment (AHT), i.e., systolic blood pressure target ≤ 140 mmHg, on cerebral blood flow, cerebral autoregulation, and orthostatic hypotension, in a representative population of frail older adults.
View Article and Find Full Text PDFBackground: Patients with sporadic cerebral amyloid angiopathy (sCAA) frequently report cognitive or neuropsychiatric symptoms. The aim of this study is to investigate whether in patients with sCAA, cognitive impairment and neuropsychiatric symptoms are associated with a cerebrospinal fluid (CSF) biomarker profile associated with Alzheimer's disease (AD).
Methods: In this cross-sectional study, we included participants with sCAA and dementia- and stroke-free, age- and sex-matched controls, who underwent a lumbar puncture, brain MRI, cognitive assessments, and self-administered and informant-based-questionnaires on neuropsychiatric symptoms.
Objective: Recent evidence shows that during slow-wave sleep (SWS), the brain is cleared from potentially toxic metabolites, such as the amyloid-beta protein. Poor sleep or elevated cortisol levels can worsen amyloid-beta clearance, potentially leading to the formation of amyloid plaques, a neuropathological hallmark of Alzheimer disease. Here, we explored how nocturnal neural and endocrine activity affects amyloid-beta fluctuations in the peripheral blood.
View Article and Find Full Text PDFWhite matter hyperintensities (WMH) are the most prevalent markers of cerebral small vessel disease (SVD), which is the major vascular risk factor for dementia. Microvascular pathology and neuroinflammation are suggested to drive the transition from normal-appearing white matter (NAWM) to WMH, particularly in individuals with hypertension. However, current imaging techniques cannot capture ongoing NAWM changes.
View Article and Find Full Text PDFBackground: The role of small vessel disease in the development of dementia is not yet completely understood. Functional brain connectivity has been shown to differ between individuals with and without cerebral small vessel disease. However, a comprehensive measure of small vessel disease quantifying the overall damage on the brain is not consistently used and studies using such measure in mild cognitive impairment individuals are missing.
View Article and Find Full Text PDFA large interventional trial, the Systolic Blood Pressure Intervention Trial sub-study termed Memory and Cognition in Decreased Hypertension (SPRINT-MIND), found reduced risk of cognitive impairment in older adults with intensive, relative to standard, blood-pressure-lowering targets (systolic BP < 120 vs. <140 mm Hg). In this perspective, we discuss key questions and make recommendations for clinical practice and for clinical trials, following SPRINT-MIND.
View Article and Find Full Text PDFAlzheimer's disease is characterized by a decline in episodic memory and executive functioning, hampering learning ability. Insight into outcome-based learning capacity may be relevant for optimizing the learning potential of these patients. To date, mixed results have been found in studies in which cognitively impaired participants have to learn based on positive and negative outcomes.
View Article and Find Full Text PDFOrthostatic 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.
View Article and Find Full Text PDFObjective: Cerebral small vessel disease (SVD) is considered the most important vascular contributor to cognitive decline and dementia, although a causal relation between its MRI markers and dementia still needs to be established. The authors investigated the relation between baseline SVD severity as well as SVD progression on MRI markers and incident dementia, by subtype, in individuals with sporadic SVD over a follow-up period of 14 years.
Methods: The study included 503 participants with sporadic SVD, and without dementia, from the prospective Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort (RUN DMC) study, with screening for baseline inclusion conducted in 2006.
Research suggests an association between cerebrovascular health and cognitive decline, but previous work is limited by its cross-sectional nature or short (< 1-2 years) follow-up. Our aim was to examine, across 10 years of follow-up in healthy older adults, changes in cerebrovascular health and their relationship with subjective memory complaints as an early marker of cognitive decline. Between 2008 and 2010, twenty-eight healthy older adults (69 ± 4 years) underwent baseline blood pressure and transcranial Doppler measurements to assess middle cerebral artery blood velocity (MCAv), cerebrovascular resistance index (CVRi), and measures of cerebral autoregulation (CA).
View Article and Find Full Text PDFObjectives: 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.
Recent guidelines, including the ESC, have moved towards lower targets (<140 mmHg, 130 if tolerated systolic, < 80 mmHg diastolic) for antihypertensive treatment in older adults. The evidence for clinically relevant benefit against limited risk of side effects applies to relatively fit older adults, representing less than 30 % of older patients in clinical practice. We discuss that formal evidence of treatment benefit for frail older adults is absent, although there is limited evidence that this benefit is similar for frail and non-frail participants in clinical trials (e.
View Article and Find Full Text PDFThe major vascular cause of dementia is cerebral small vessel disease (SVD), including white matter hyperintensities (WMH) amongst others. While the underlying pathology of SVD remains unclear, chronic hypertension and neuroinflammation are recognized as important risk factors for SVD and for the conversion of normal-appearing white matter (NAWM) to WMH. Unfortunately, most studies investigating the role of neuroinflammation in WMH relied on peripheral blood markers, e.
View Article and Find Full Text PDFIntroduction: Cerebral hypoperfusion is thought to play an important role in the etiology of cerebral small vessel disease (SVD). Orthostatic hypotension (OH) is assumed to be a cause of cerebral hypoperfusion by causing recurrent hypoperfusion episodes, and might thus be related to progression of SVD. Here, we investigated whether presence of OH is associated with the progression of SVD MRI-markers and cognitive decline over a time period of 9 years in a cohort of sporadic SVD patients.
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