Abstract
Background: Mild cognitive impairment (MCI) is a condition with diverse causes and clinical outcomes that can be categorized into subtypes. [18F]THK5351 has been known to detect reactive astrogliosis as well as tau which is accompanied by neurodegenerative changes. Here, we identified heterogeneous groups of MCI patients using THK retention patterns and a graph theory approach, allowing for the comparison of risk of progression to dementia in these MCI subgroups.Methods: Ninety-seven participants including 60 MCI patients and individuals with normal cognition (NC, n = 37) were included and undertook 3T MRI, [18F]THK5351 PET, and detailed neuropsychological tests. [18F]Flutemetamol PET was also performed in 62 participants. We calculated similarities between MCI patients using their regional standardized uptake value ratio of THK retention in 75 ROIs, and clustered subjects with similar retention patterns using the Louvain method based on the modularity of the graph. The clusters of patients identified were compared with an age-matched control group using a general linear model. Dementia conversion was evaluated after a median follow-up duration of 34.6 months.Results: MCI patients were categorized into four groups according to their THK retention patterns: (1) limbic type; (2) diffuse type; (3) sparse type; and (4) AD type (retention pattern as in AD). Subjects of the limbic type were characterized by older age, small hippocampal volumes, and reduced verbal memory and frontal/executive functions. Patients of the diffuse type had relatively large vascular burden, reduced memory capacity and some frontal/executive functions. Co-morbidity and mortality were more frequent in this subgroup. Subjects of the sparse type were younger and declined only in terms of visual memory and attention. No individuals in this subgroup converted to dementia. Patients in the AD type group exhibited the poorest cognitive function. They also had the smallest hippocampal volumes and the highest risk of progression to dementia (90.9%).Conclusion: Using cluster analyses with [18F]THK5351 retention patterns, it is possible to identify clinically-distinct subgroups of MCI patients and those at greater risk of progression to dementia.
Highlights
Mild cognitive impairment (MCI) is a pathologically and clinically heterogeneous disease characterized by lower cognitive performance, and is considered to be a transitional state between normal cognition and dementia (Petersen et al, 1999; Brooks and Loewenstein, 2010)
Our major finding is that significant differences in topographical patterns of [18F]THK5351 retention which detects reactive astrogliosis and tau, can be used to distinguish MCI subtypes
Cluster analysis based on [18F]THK5351 retention patterns showed that MCI patients can be categorized distinctly according to anatomical differences
Summary
Mild cognitive impairment (MCI) is a pathologically and clinically heterogeneous disease characterized by lower cognitive performance, and is considered to be a transitional state between normal cognition and dementia (Petersen et al, 1999; Brooks and Loewenstein, 2010). NFT pathology can be visualized in vivo thanks to the development of radiotracers for tau imaging (Xia et al, 2013; Villemagne et al, 2014; Okamura et al, 2016). Ongoing PET studies using tau-targeted tracers are expected to provide greater insight into the pathology associated with MCI. Recent studies showed [18F]THK5351 may be a suitable imaging marker to detect neurodegenerative changes caused. We identified heterogeneous groups of MCI patients using THK retention patterns and a graph theory approach, allowing for the comparison of risk of progression to dementia in these MCI subgroups
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