Abstract
The objectives of this study were to compare the topographical subcortical shape and to investigate the effects of tau or amyloid burden on atrophic patterns in early onset Alzheimer’s disease (EOAD) and late-onset Alzheimer’s disease (LOAD). One hundred and sixty-one participants (53 EOAD, 44 LOAD, 33 young controls, and 31 older controls) underwent [18F]THK5351 positron emission tomography (PET), [18F]flutemetamol (FLUTE) PET, and 3T MRI scans. We used surface-based analysis to evaluate subcortical structural shape, permutation-based statistics for group comparisons, and Spearman’s correlations to determine associations with THK, FLUTE, cortical thickness, and neuropsychological test results. When compared to their age-matched controls, EOAD patients exhibited shape reduction in the bilateral amygdala, hippocampus, caudate, and putamen, while in LOAD patients, the bilateral amygdala and hippocampus showed decreased shapes. In EOAD, widespread subcortical shrinkage, with less association of the hippocampus, correlated with THK retention and cortical thinning, while in LOAD patients, subcortical structures were limited which had significant correlation with THK or mean cortical thickness. Subcortical structural shape showed less correlation with FLUTE global retention in both EOAD and LOAD. Multiple cognitive domains, except memory function, correlated with the bilateral amygdala, caudate, and putamen in EOAD patients, while more restricted regions in the subcortical structures were correlated with neuropsychological test results in LOAD patients. Subcortical structures were associated with AD hallmarks in EOAD. However, the correlation was limited in LOAD. Moreover, relationship between subcortical structural atrophy and cognitive decline were quite different between EOAD and LOAD. These findings suggest that the effects of Alzheimer’s pathologies on subcortical structural changes in EOAD and LOAD and they may have different courses of pathomechanism.
Highlights
Alzheimer’s disease (AD) is a neurodegenerative disease associated with cognitive decline
We evaluated the degree of subcortical structural shape deformity in Early onset AD (EOAD) and late-onset Alzheimer’s disease (LOAD) patients, in terms of association with tau and amyloid global retention, cortical thickness, and neuropsychological test results
We found that the amygdala, hippocampus and thalamus were the major regions that differed in the direct group comparison with more shrinkage in LOAD patients than in EOAD patients
Summary
Alzheimer’s disease (AD) is a neurodegenerative disease associated with cognitive decline. Studies have found that EOAD patients have typical neuropsychological features with more progressive cognitive decline (Seltzer and Sherwin, 1983; Smits et al, 2012) as well as heterogenous neuroimaging findings (Frisoni et al, 2007; Migliaccio et al, 2015). Compared with LOAD patients, EOAD patients manifest with more widespread tau PET retention and heavier amyloid PET uptake in the brain cortices, and more severe gray matter loss suggesting different etiologies and predisposing factors for EOAD (Frisoni et al, 2007; Choo et al, 2011; Scholl et al, 2017; Wattmo and Wallin, 2017). More rapid volumetric declines in several subcortical structures including the caudate, putamen, and thalamus have been highlighted as distinct to LOAD patients (Cho et al, 2013; Pievani et al, 2013). It has been reported that characteristic symptoms of EOAD such as severe extrapyramidal signs (Chui et al, 1985) and non-memory cognitive dysfunction such as executive function, visuospatial functioning, and attention (Smits et al, 2012) are related to deterioration of the basal ganglia and the thalamus, both of which play major roles in movement symptoms, brain connectivity, and memory function (Hahn et al, 2016; Dipasquale and Cercignani, 2017)
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