Investigating BOLD signal variability and its physiological signal sources in Alzheimer's disease, behavioral variant frontotemporal dementia, and schizophrenia

Alzheimer's disease and frontotemporal dementia (bvFTD) are the two most common early-onset dementias. These diseases often have overlapping symptoms, making them difficult to identify, particularly in the early or pre-symptomatic stages. According to the literature, before a correct diagnosis is made, up to half of patients with bvFTD receive a wrong psychiatric diagnosis, such as schizophrenia. These challenges also slow down the development of effective treatments.

In this dissertation project, new methods were developed to detect changes in the brain's cleaning system known as glymphatic system. The study demonstrated that the pulsations of the blood vessels in the brain, as measured by functional magnetic resonance imaging (fMRI), differ from healthy controls in patients with both Alzheimer's disease and bvFTD.

Functional magnetic resonance imaging is traditionally based on measuring the BOLD signal, which depends on the oxygenation level of the blood. In this dissertation, brain BOLD signal variability in Alzheimer's disease and bvFTD, and their differential diagnostic challenge in schizophrenia, were investigated.

This study is the first to demonstrate significant changes in brain pulsations that could potentially aid in diagnostics. The study identified increased BOLD signal variability in Alzheimer's disease and bvFTD, which was not observed in schizophrenia data. Additionally, the study shows how brain signal fluctuations and gray matter atrophy affect the brain's resting state functional connections. In Alzheimer's disease, these changes were shown to be related to the arterial pulsation generated by the heartbeat and the pulsation in the brain associated with breathing. This finding suggests changes in the brain's glymphatic cleaning system.