A multimodal investigation of brain health: cerebral blood flow, cognitive performance and quality of life

Understanding brain health is crucial in diagnosing, preventing and treating neurocognitive conditions (e.g., dementia). However, the literature reveals discrepancies around the interpretation of brain health and differences between populations. This thesis investigates brain health measures from different disciplines, including: resting cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) (using transcranial Doppler (TCD) ultrasound and magnetic resonance imaging (MRI)); cognition (including attention and memory); and quality of life (QoL) questionnaires. Differences between age (younger versus older) and cardiorespiratory fitness (fit versus unfit) groups were also investigated. Importantly, these multimodal brain health measures were completed in the same cohort. Declines were observed between younger and older groups in resting CBF measures (derived using TCD and MRI), and cognitive performance measures (attention-switching, learning and memory). In the older group, higher fitness offset declines in resting CBF and improved markers of cognition. In both groups, fitness significantly positively correlated with better QoL. However, no differences between age or fitness groups were observed in CVR measures. Further, CVR differed significantly depending on the imaging and analysis approach used. Future research is required to elucidate the cause of discrepancies and determine differences between groups (i.e., age/fitness/disease). Further, robust approaches to assess brain vascular health are needed

GPs at the Deep End Report 33: Increasing undergraduate education in primary care in areas of socio-economic deprivation (the Deep End)

No abstract available

GPs at the Deep End Report 33: Increasing undergraduate education in primary care in areas of socio-economic deprivation (the Deep End)

No abstract available

Higher physical fitness levels are associated with less language decline in healthy ageing

publishedVersio

Physical restraint in older people: A statement from the early career network of the international psychogeriatric association

The International Psychogeriatric Association (IPA) has expressed significant concerns over the use of physical restraints in older people across diverse aged care settings. Following an extensive analysis of the available literature, the IPA\u27s Early Career Network (ECN) has formulated a collection of evidence-based recommendations aimed at guiding the use of physical restraints within various care contexts and demographic groups. Physical restraints not only infringe upon human rights but also raise significant safety concerns that adversely impact the physical, psychological, social, and functional well-being of older adults. Furthermore, their effectiveness in geriatric settings remains inadequate. Given these considerations, the IPA and its ECN firmly assert that the use of physical restraints should only be considered as a final recourse in the care of older people

The CO2 stimulus duration and steady-state time point used for data extraction alters the cerebrovascular reactivity outcome measure

Cerebrovascular reactivity to carbon dioxide (CVR) is a common functional test to assess brain vascular health, though conflicting age and fitness effects have been reported. Studies have used different CO 2 stimulus durations to induce CVR and extracted data from different time points for analysis. Therefore, this study examined whether these differences alter CVR and explain conflicting findings. Eighteen healthy volunteers (24 5 years) inhaled CO ± 2 for four stimulus durations (1, 2, 4 and 5 min) of 5% CO 2 (in air) via the open-circuit Douglas bag method, in a randomized order. CVR data were derived from transcranial Doppler (TCD) measures of middle cerebral artery blood velocity (MCAv), with concurrent ventilatory sensitivity to the CO 2 stimulus (̇ V E,CO 2). Repeated measures ANOVAs compared CVR and ̇ V E,CO 2 measures between stimulus durations and steady-state time points. An effect of stimulus duration was observed (P = 0.002, í µí¼ 2 = = 0.140), with 1 min (P 0.010) and 2 min (P < 0.001) differing from 4 min, and 2 min differing from 5 min (P = 0.019) durations. ̇ V E CO , 2 sensitivity increased ∼3-fold from 1 min to 4 and 5 min durations (P < 0.001, í µí¼ 2 = 0.485). CVRs calculated from different steady-state time points within each stimulus duration were different (P < 0.001, í µí¼ 2 = = 0.454), specifically for 4 min (P 0.001) and 5 min (P P < 0.001), but not 2 min stimulus durations (= 0.273). These findings demonstrate that methodological differences alter the CVR measure

Progressive Motor Neuron Pathology and the Role of Astrocytes in a Human Stem Cell Model of VCP-Related ALS.

Motor neurons (MNs) and astrocytes (ACs) are implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS), but their interaction and the sequence of molecular events leading to MN death remain unresolved. Here, we optimized directed differentiation of induced pluripotent stem cells (iPSCs) into highly enriched (> 85%) functional populations of spinal cord MNs and ACs. We identify significantly increased cytoplasmic TDP-43 and ER stress as primary pathogenic events in patient-specific valosin-containing protein (VCP)-mutant MNs, with secondary mitochondrial dysfunction and oxidative stress. Cumulatively, these cellular stresses result in synaptic pathology and cell death in VCP-mutant MNs. We additionally identify a cell-autonomous VCP-mutant AC survival phenotype, which is not attributable to the same molecular pathology occurring in VCP-mutant MNs. Finally, through iterative co-culture experiments, we uncover non-cell-autonomous effects of VCP-mutant ACs on both control and mutant MNs. This work elucidates molecular events and cellular interplay that could guide future therapeutic strategies in ALS