A systematic review of the association between dementia risk factors and cerebrovascular reactivity.

Cumulative evidence suggests that impaired cerebrovascular reactivity (CVR), a regulatory response critical for maintaining neuronal health, is amongst the earliest pathological changes in dementia. However, we know little about how CVR is affected by dementia risk, prior to disease onset. Understanding this relationship would improve our knowledge of disease pathways and help inform preventative interventions. This systematic review investigates 59 studies examining how CVR (measured by magnetic resonance imaging) is affected by modifiable, non-modifiable, and clinical risk factors for dementia. We report that non-modifiable risk (older age and apolipoprotein ε4), some modifiable factors (diabetes, traumatic brain injury, hypertension) and some clinical factors (stroke, carotid artery occlusion, stenosis) were consistently associated with reduced CVR. We also note a lack of conclusive evidence on how other behavioural factors such as physical inactivity, obesity, or depression, affect CVR. This review explores the biological mechanisms underpinning these brain-behaviour associations, highlights evident gaps in the literature, and identifies the risk factors that could be managed to preserve CVR in an effort to prevent dementia.

Vascular smooth muscle cell dysfunction in neurodegeneration.

Vascular smooth muscle cells (VSMCs) are the key moderators of cerebrovascular dynamics in response to the brain's oxygen and nutrient demands. Crucially, VSMCs may provide a sensitive biomarker for neurodegenerative pathologies where vasculature is compromised. An increasing body of research suggests that VSMCs have remarkable plasticity and their pathophysiology may play a key role in the complex process of neurodegeneration. Furthermore, extrinsic risk factors, including environmental conditions and traumatic events can impact vascular function through changes in VSMC morphology. VSMC dysfunction can be characterised at the molecular level both preclinically, and clinically ex vivo. However the identification of VSMC dysfunction in living individuals is important to understand changes in vascular function at the onset and progression of neurological disorders such as dementia, Alzheimer's disease, and Parkinson's disease. A promising technique to identify changes in the state of cerebral smooth muscle is cerebrovascular reactivity (CVR) which reflects the intrinsic dynamic response of blood vessels in the brain to vasoactive stimuli in order to modulate regional cerebral blood flow (CBF). In this work, we review the role of VSMCs in the most common neurodegenerative disorders and identify physiological systems that may contribute to VSMC dysfunction. The evidence collected here identifies VSMC dysfunction as a strong candidate for novel therapeutics to combat the development and progression of neurodegeneration, and highlights the need for more research on the role of VSMCs and cerebrovascular dynamics in healthy and diseased states.

'Kindness by Post': A Mixed-Methods Evaluation of a Participatory Public Mental Health Project.

BACKGROUND: Random acts of kindness can improve wellbeing. However, less is known about the impacts of giving and receiving acts of kindness with strangers on wellbeing and loneliness. Therefore, this study's objectives were to evaluate a participatory public mental health project involving sending and receiving a card with goodwill messages, to understand how such acts of kindness influence wellbeing and loneliness, and to investigate the potential mechanisms underlying the project's impacts. MATERIALS AND METHODS: This study was an analysis of anonymized service evaluation data collected in the 'Kindness by Post' (KBP) project in 2020. It used a mixed-methods single-group design and data from 289 participants. Changes in wellbeing, loneliness, sense of belonging and hope from baseline (12th-14th February) to follow-up (26th February-2nd March) were analyzed using linear or multinomial logistic regression. Regression models also examined the associations between changes in wellbeing and baseline loneliness or participation level. Free text responses about experiences and suggestions for the project were analyzed using thematic analysis. RESULTS: Participants had a small, but statistically significant improvement, in wellbeing equating to 0.21 standard deviations (95% CI: 0.12-0.30) after taking part in the project, as well as improvements in loneliness, sense of belonging and hope. How lonely a participant was at baseline and whether participants both sent and received a kindness card were not associated with improvements in wellbeing. In the qualitative analysis, a desire to help others emerged as the main motivator to take part in the card exchange. Participants reported enhanced personal fulfillment, leading to improvements in wellbeing. Receiving a card could make people feel special and cherished, which was reported to establish a sense of connection with others, with potential benefits for reducing loneliness. CONCLUSION: This study provided preliminary evidence that the KBP project might improve wellbeing, loneliness, sense of belonging and hope. Sending a kindness card in this project played a predominant role in wellbeing enhancement, and receiving a kindness card could reduce loneliness. This study suggests that the KBP project can be replicated in more contexts in the future, and might improve wellbeing and loneliness in large communities.