Ageing, Blood Pressure, and Neurodegeneration: A Lifelong Concern that Dietary Magnesium may Help Address

Abstract

The growing global burden of neurodegenerative diseases, cognitive decline, and dementia highlights the urgent need to identify modifiable risk factors that promote healthy brain ageing and slow the progression of dementia. This thesis investigates the impact of high blood pressure (BP) – a prevalent risk factor – on brain ageing. It also investigates the role dietary magnesium (Mg) can play in addressing this risk factor and promoting brain health. Five studies were conducted to address the objectives of this thesis. The initial study involved a comprehensive literature review to generate insights into the relationship between BP, magnesium, neurodegeneration, and cognitive decline within the context of ageing. This process involved summarizing the mechanisms and effects to enhance understanding of how these factors potentially interact in the ageing brain. This review generated essential background knowledge that the subsequent studies sought to build upon. In the second study, a systematic review and meta-analysis were performed to quantify the existing literature on the relationship between continuous BP and total/regional brain volumes and white matter lesions (WMLs). The systematic review revealed a significant association between higher BP, lower brain volumes, and larger WMLs across the entire range, extending beyond individuals with hypertension or pre-hypertension. This finding suggests that high BP is associated with poorer brain health in non-hypertensive individuals within a broader population. The third study built upon the findings of the second study, examining the impact of age, gender, and other risk factors on the association between BP and brain health. This investigation quantified the relationships between continuous BP levels, brain volumes, and WMLs while also considering various risk factors such as age, sex, BMI, and use of antihypertensive medication. The findings reveal a consistent association between BP, lower brain volumes, and larger WMLs across the entire BP range, even within the upper normal BP range. This association affects individuals of all ages, particularly younger adults, and exhibits stronger effects in women. Notably, lower BMI and the use of antihypertensive medication appear to exert a protective effect against the detrimental impact of BP on brain health. These findings have substantial implications for population health, suggesting that even minor increases in BP over a lifespan can significantly contribute to the overall disease burden. This underscores the importance of implementing early preventative measures to maintain optimal BP levels. The fourth and fifth studies explored the associations between Mg intake, brain volumes, and WMLs. Additionally, these studies investigated whether BP and inflammation mediate the neuroprotective effect of Mg. The findings from both the fourth and fifth studies demonstrate that high dietary Mg intake is associated with larger brain volumes and lower WMLs. These results imply that a diet rich in Mg could contribute to enhanced brain health and potentially decrease the risk of dementia in the general population. Surprisingly, the neuroprotective impact of Mg is found not to be mediated by BP levels. Instead, the neuroprotective effect of dietary Mg is partially mediated through inflammation. This supports the potential of Mg intake as an effective, scalable, and affordable intervention in reducing inflammation and protecting against premature brain ageing in the general population. In conclusion, this thesis highlights the significant impact of high BP on brain health and finds that dietary Mg intake yields a neuroprotective effect, which can be attributed to its anti- inflammatory properties. Overall, the findings paint an optimistic picture for general population health, emphasizing the potential benefits of early interventions targeting modifiable risk factors. Thus, sufficient support at the health policy, clinical, and community levels can help reduce or prevent certain known risks to brain health.