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The distinct contributions of cardiovascular risk factors to cognitive ageing


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Authors

King, Deborah 

Abstract

This thesis aims to understand how individuals within an ageing global population can maintain cognitive health and independence throughout life. It is generally accepted that what is good for the heart is also good for the brain. However, it is not clear whether different aspects of cardiovascular health – such as blood pressure or heart rate – affect the brain through shared or independent pathways, partly because they are often condensed into a single composite score or examined in isolation. The research reported in the following chapters asks: do distinct elements of cardiovascular health have independent effects on cognition? And, if so, do they act by impairing brain structure and or brain function? The research builds a framework mapping unique pathways from multiple vascular factors to cognition. Understanding these pathways could inform the selection of specific vascular factors as targets for developing interventions to preserve cognition into old age.

Chapter 1 is the General Introduction and describes the importance of cardiovascular health for cognitive performance. It also reviews the evidence for individual vascular risk factors, such as blood pressure, and how these might affect the brain’s structure and function.

Chapter 2 is the General Methods and briefly summarises approaches shared across the three subsequent empirical chapters. These chapters use interdisciplinary and multivariate statistical analyses, applied to a large cohort of healthy adults (n=708, 18-88 years).

Chapter 3 investigates whether multiple discrete vascular factors make distinct contributions to cognition. It shows unique and additive contributions from multiple vascular factors, including that high pulse pressure (systolic – diastolic) predicts a marker of cognitive decline. Pulse pressure typically increases with age and indicates increasing stiffness and decreasing elasticity of the major arteries, which then shunt the pulsatile wave of blood flow towards the brain, where it causes damage. In my analysis, the effects of pulse pressure on cognition are stronger for older adults. Importantly, the effects of pulse pressure are independent to other vascular risk factors, education and medications.

Chapter 4 hypothesizes that pulse pressure impairs cognition by disrupting white matter microstructure. It shows a significant and substantial effect where high pulse pressure disrupts white matter, which then slows processing speed. It also indicates that pulse pressure driven declines in processing speed impair higher cognitive abilities such as problem solving, which is termed fluid intelligence. Overall, this chapter highlights the broad importance of pulse pressure in cognitive ageing.

Chapter 5 investigates whether distinct vascular factors have unique associations with patterns of connectivity in large-scale structural and functional brain networks. It shows significant effects for heart rate variability, which represents the variation in the time interval between heart beats, where high variability is healthy. Lower variability associated with changes in the connectivity of functional brain networks, and lower fluid intelligence. This chapter also builds on the previous findings, to show that functional connectivity links with the now established effects of pulse pressure on white matter and processing speed. Altogether, this provides further evidence for the multivariate nature of vascular ageing. The results are discussed in the context of distinct aspects of cardiovascular health contributing to cumulative differences between individuals in the maintenance of brain tissues, and in the development of reserves in cognitive function, which both become important in old age.

Chapter 6 brings together the findings of the three previous empirical chapters to draw a hypothetical framework of the multivariate contributions of cardiovascular health to cognitive ageing. The framework is hypothetical at this stage because it is informed by findings in cross-sectional data. I outline ideas to validate the framework in longitudinal datasets. Overall, I propose that managing pulse pressure may help to preserve cognition, particularly in older adults.

Description

Date

2023-11-29

Advisors

Tsvetanov, Kamen A
Henson, Richard

Keywords

age, ageing, blood pressure, cardiovascular, cognition, dementia, health, neuroscience, pulse pressure

Qualification

Doctor of Philosophy (PhD)

Awarding Institution

University of Cambridge
Sponsorship
Biotechnology and Biological Sciences Research Council (2274385)