Quantitative assessment of neurovascular dynamics in ageing, Alzheimer’s disease and Huntington’s disease

Bjerkan, Juliane and Stefanovska, Aneta and Crawford, Trevor (2025) Quantitative assessment of neurovascular dynamics in ageing, Alzheimer’s disease and Huntington’s disease. PhD thesis, Lancaster University.

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Abstract

As individuals age, the risk of neurodegenerative disorders such as Alzheimer’s disease increases, largely due to changes in the brain and vasculature. The brain, which consumes about 20% of the body’s energy, relies on the cardiovascular system for nutrient transport. This dependence is represented by the neurovascular unit (NVU). Understanding how the functioning of the NVU changes with healthy ageing and neurodegenerative diseases remains insufficiently explored, particularly through in vivo measurements in humans. With an ageing population, the prevalence of dementia is expected to rise, highlighting the urgent need for accessible, non-invasive, and cost-effective diagnostic and monitoring tools. Here, data were collected from younger and older participants, as well as from patients with Alzheimer’s and Huntington’s diseases, using non-invasive monitoring techniques. Brain oxygenation was measured via functional nearinfrared spectroscopy, brain electrical activity via the lectroencephalogram, and cardiorespiratory function via the electrocardiogram and a respiration belt. We treat the brain and cardiovascular system as interacting oscillators operating far-fromequilibrium. To analyse their functioning, we apply methods suited to multiscale, time-varying and non-stationary dynamics. The wavelet transform was used to calculate the power of oscillations with logarithmic frequency resolution, and wavelet phase coherence was used to calculate the coordination of oscillations. The efficiency of the NVU was quantified as the wavelet phase coherence between brain electrical activity and oxygenation. Our findings indicate that NVU efficiency declines with age and is further reduced in patients with Alzheimer’s and Huntington’s diseases compared to age-matched controls. Specific changes in power and coherence associated with ageing and these neurodegenerative diseases were identified. Previous research on cardiovascular and brain oscillations allows us to link these findings to physiological changes. Thus, the methods presented offer a novel approach for quantitative evaluation of the neurovascular efficiency in ageing and dementia.