Abstract
Early- and late-onset Alzheimer’s disease (AD) patients often exhibit distinct features. We sought to compare overall white matter connectivity and evaluate the pathological factors (amyloid, tau, and vascular pathologies) that affect the disruption of connectivity in these two groups. A total of 50 early- and 38 late-onset AD patients, as well as age-matched cognitively normal participants, were enrolled and underwent diffusion-weighted magnetic resonance imaging to construct fractional anisotropy-weighted white matter connectivity maps. [18F]-THK5351 PET, [18F]-Flutemetamol PET, and magnetic resonance imaging were used for the evaluation of tau and related astrogliosis, amyloid, and small vessel disease markers (lacunes and white matter hyperintensities). Cluster-based statistics was performed for connectivity comparisons and correlation analysis between connectivity disruption and the pathological markers. Both patient groups exhibited significantly disrupted connectivity compared to their control counterparts with distinct patterns. Only THK retention was related to connectivity disruption in early-onset AD patients, and this disruption showed correlations with most cognitive scores, while late-onset AD patients had disrupted connectivity correlated with amyloid deposition, white matter hyperintensities, and lacunes in which only a few cognitive scores showed associations. These findings suggest that the pathogenesis of connectivity disruption and its effects on cognition are distinct between EOAD and LOAD.
Highlights
Alzheimer’s disease (AD) is the most common type of neurodegenerative disease, marked by amyloid plaques and neurofibrillary tangles present in gray matter (Blennow et al, 2006; Bastin and Salmon, 2014)
late-onset AD (LOAD) patients had higher values for the number of lacunes and white matter hyperintensities (WMH) volume compared to early-onset AD (EOAD) patients, whereas EOAD patients had greater values for global FLUTE retention than LOAD patients
We observed that AD patients had significantly weaker white matter (WM) structural connectivity compared to their age-matched control counterparts, and the patterns of disrupted connectivity were distinct between EOAD and LOAD
Summary
Alzheimer’s disease (AD) is the most common type of neurodegenerative disease, marked by amyloid plaques and neurofibrillary tangles present in gray matter (Blennow et al, 2006; Bastin and Salmon, 2014). Regarding AD pathology, EOAD patients have shown a greater extent of neuritic plaque and neurofibrillary tangle burden in the frontal and parietal lobes than LOAD patients in postmortem studies (Marshall et al, 2007). In amyloid PET studies, EOAD patients have exhibited higher amyloid burden in the parietal cortex (Ossenkoppele et al, 2012), basal ganglia, and thalamus (Cho et al, 2013b). Recent tau PET studies with [18F]flortaucipir showed that EOAD had greater tau burden in the neocortex compared to LOAD patients (Cho et al, 2017; Schöll et al, 2017). [18F]-THK5351 PET showed greater retention in the association cortex including prefrontal, parietal, precuneus, and posterior cingulate cortex in EOAD patients compared to LOAD (Noh et al, 2017). Vascular pathology is known to be part of the multifactorial mechanisms present in LOAD (Ortner et al, 2015; Iturria-Medina et al, 2016)
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