Neuroimaging correlates of progressive cognitive decline and clinical symptoms in prodromal Lewy body disease. A multimodal imaging study

Abstract

Introduction There has been an interest in earlier diagnosis of cognitive impairment at the prodromal stage. Mild cognitive impairment (MCI) is a prodromal cognitive phenotype of dementia. Differentiating MCI with Lewy bodies (MCI-LB) and MCI due to AD (MCI-AD) using clinical features alone is challenging and biomarkers are likely to aid diagnosis. This thesis investigated whether cross-sectional structural magnetic resonance imaging (MRI) or repeat 123I-FP-CIT single photon emission tomography (SPECT) could be utilised to differentiate between MCI-LB and MCI-AD. Methods Prospective repeat 133I-FP-CIT SPECT study: 85 subjects were included in this analysis, consisting of; healthy controls (HC) (n=29), MCI-AD (n=19), possible MCI-LB (n=10), probable MCI-LB (n=27). All subjects underwent comprehensive clinical and neuropsychological assessment as well as repeat 123I-FP-CIT SPECT and baseline cardiac 123I-MIBG scintigraphy. Cross- sectional MRI study: 97 subjects were included in this analysis, consisting of; HC (n=31), MCIAD (n=32), probable MCI-LB (n=34). All subjects underwent comprehensive clinical and neuropsychological assessment as well as baseline 123I-FP-CIT SPECT, cardiac 123I-MIBG scintigraphy and structural magnetic resonance imaging. Results Progressive dopaminergic loss was detected in MCI-LB in excess of HC, with mean annual striatal decline of 6% in the MCI-LB cohorts. MCI-AD had no difference in longitudinal striatal uptake when compared to HC. Structural MRI data found: (1) grey matter volume loss in the frontal and temporal lobes in MCI-LB compared to HC, (2) bilateral cerebellar volume reduction in MCI-LB compared to iii MCI-AD, (3) no relative preservation of the medical temporal lobe in MCI-LB compared to MCI-AD, (4) no cortical thickness difference between MCI-LB and MCI-AD (5) thalamic volume loss and relative preservation of the amygdala in MCI-LB compared to MCI-AD. Conclusion Sequential 123I-FP-CIT SPECT imaging is a promising biomarker for identifying MCI-LB. Structural MRI showed no difference in cortical indexes but some differences in subcortical and cerebellar measures between MCI-LB and MCI-AD.