1. Neurodegenerative changes in early- and late-onset cognitive impairment with and without brain amyloidosis.
- Author
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Stage EC Jr, Svaldi D, Phillips M, Canela VH, Duran T, Goukasian N, Risacher SL, Saykin AJ, and Apostolova LG
- Subjects
- Aged, Amyloid beta-Peptides metabolism, Brain diagnostic imaging, Brain metabolism, Humans, Magnetic Resonance Imaging, Positron-Emission Tomography, tau Proteins metabolism, Alzheimer Disease, Amyloidosis complications, Amyloidosis diagnostic imaging, Cognitive Dysfunction diagnostic imaging
- Abstract
Background: A substantial number of patients clinically diagnosed with Alzheimer's disease do not harbor amyloid pathology. We analyzed the presence and extent of tau deposition and neurodegeneration in amyloid-positive (AD) and amyloid-negative (nonAD) ADNI subjects while also taking into account age of onset (< or > 65 years) as we expected that the emerging patterns could vary by age and presence or absence of brain amyloidosis., Methods: One hundred and ten early-onset AD (EOAD), 121 EOnonAD, 364 late-onset AD (LOAD), and 175 LOnonAD mild cognitive impairment (MCI) and dementia (DEM) subjects were compared to 291 ADNI amyloid-negative control subjects using voxel-wise regression in SPM12 with cluster-level family-wise error correction at p
FWE < 0.05). A subset of these subjects also received18 F-flortaucipir scans and allowed for analysis of global tau burden., Results: As expected, relative to LOAD, EOAD subjects showed more extensive neurodegeneration and tau deposition in AD-relevant regions. EOnonADMCI showed no significant neurodegeneration, while EOnonADDEM showed bilateral medial and lateral temporal, and temporoparietal hypometabolism. LOnonADMCI and LOnonADDEM showed diffuse brain atrophy and a fronto-temporo-parietal hypometabolic pattern. LOnonAD and EOnonAD subjects failed to show significant tau binding., Conclusions: LOnonAD subjects show a fronto-temporal neurodegenerative pattern in the absence of tau binding, which may represent underlying hippocampal sclerosis with TDP-43, also known as limbic-predominant age-related TDP-43 encephalopathy (LATE). The hypometabolic pattern observed in EOnonADDEM seems similar to the one observed in EOADMCI . Further investigation into the underlying etiology of EOnonAD is warranted.- Published
- 2020
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