A study of ultra-high field strength structural and spectroscopic MR imaging in dementia with Lewy bodies and Alzheimer’s disease
Despite its position as the second commonest form of neurodegenerative dementia, dementia with Lewy Bodies (DLB) is relatively poorly understood, with little research focusing on its pathophysiology or symptomatology in comparison with Alzheimer’s disease (AD) or Parkinson’s disease (PD), to which it is closely related. In contrast to AD, which typically presents with amnesic cognitive deficits, DLB more commonly presents with complex neuropsychiatric symptoms, including complex visual hallucinations, cognitive fluctuations, rapid eye movement (REM) sleep behaviour disorder (RBD), and parkinsonism. In this PhD thesis I present a detailed investigation of neuroimaging changes found in DLB compared to in AD, in comparison to cognitively healthy older adults, using ultra-high field, 7 tesla (7T), brain magnetic resonance imaging (MRI) and single voxel proton magnetic resonance spectroscopy (MRS). First, I conducted systematic reviews of the AD and DLB, MRI and MRS literature, demonstrating that DLB is under-represented in high (3T) and ultra-high (7T) field strength MR research. Next, I gathered neuropsychological and neuropsychiatric data, alongside 7T structural, susceptibility and spectroscopy imaging data, in a cohort of 65 participants with DLB, AD, and normal cognition. I collected this data as part of a study I conducted known as 7T-DLB. The aim of 7T-DLB is to utilise the benefits of 7T MR to gain a deeper understanding of the changes in brain structure, tissue susceptibility, and neurochemistry underlying DLB, and in association with its key symptoms. I analysed 7T-DLB structural data, concentrating on the measurement of subfield volumes in the hippocampus, amygdala, and thalamus, showing that, in mild to moderate DLB, pronounced amygdala subfield atrophy is present (compared to controls), is almost as marked as in AD, and is associated with measures of cognition and visual hallucinations. I also show that widespread hippocampal subfield atrophy is present in DLB (compared to controls), and though it is less pronounced than in AD, it is more extensive than has previously been described at lower MR field strengths. Finally, I analysed 7T-DLB spectroscopy data, from voxels placed in the left occipital lobe and left thalamic region showing that myoInositol (a putative marker of neuroinflammation) is higher in patients compared to controls. I also suggest that changes in concentrations of gamma-aminobutyric acid (GABA) and glutamate (the primary inhibitory and excitatory neurotransmitters in the brain) may be related to visual hallucinations and cognitive fluctuations, though these analyses were exploratory and findings tentative. In summary, 7T-DLB is a novel study as it uses a relatively new technology to investigate an under-researched disease and focuses on key non-cognitive symptoms. Together the findings presented in this thesis demonstrate the utility of ultra-high field imaging for the investigation of DLB.
Alzheimer's disease, dementia with Lewy bodies, magnetic resonance imaging, magnetic resonance spectroscopy, seven tesla MRI
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