Browsing by Subject "Hippocampal sclerosis"

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    Differential diagnosis of amnestic dementia patients based on an FDG-PET signature of autopsy-confirmed LATE-NC
    (Wiley, 2023) Grothe, Michel J.; Moscoso, Alexis; Silva-Rodríguez, Jesús; Lange, Catharina; Nho, Kwangsik; Saykin, Andrew J.; Nelson, Peter T.; Schöll, Michael; Buchert, Ralph; Teipel, Stefan; Alzheimer’s Disease Neuroimaging Initiative; Radiology and Imaging Sciences, School of Medicine
    Introduction: Limbic age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is common in advanced age and can underlie a clinical presentation mimicking Alzheimer's disease (AD). We studied whether an autopsy-derived fluorodeoxyglucose positron emission tomography (FDG-PET) signature of LATE-NC provides clinical utility for differential diagnosis of amnestic dementia patients. Methods: Ante mortem FDG-PET patterns from autopsy-confirmed LATE-NC (N = 7) and AD (N = 23) patients were used to stratify an independent cohort of clinically diagnosed AD dementia patients (N = 242) based on individual FDG-PET profiles. Results: Autopsy-confirmed LATE-NC and AD groups showed markedly distinct temporo-limbic and temporo-parietal FDG-PET patterns, respectively. Clinically diagnosed AD dementia patients showing a LATE-NC-like FDG-PET pattern (N = 25, 10%) were significantly older, showed less abnormal AD biomarker levels, lower APOE ε4, and higher TMEM106B risk allele load. Clinically, they exhibited a more memory-predominant profile and a generally slower disease course. Discussion: An autopsy-derived temporo-limbic FDG-PET signature identifies older amnestic patients whose clinical, genetic, and molecular biomarker features are consistent with underlying LATE-NC.
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    Neurodegenerative changes in early- and late-onset cognitive impairment with and without brain amyloidosis
    (BMC, 2020-08-05) Stage, Eddie C.; Svaldi, Diana; Phillips, Meredith; Canela, Victor Hugo; Duran, Tugce; Goukasian, Naira; Risacher, Shannon L.; Saykin, Andrew J.; Apostolova, Liana G.; Neurology, School of Medicine
    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 pFWE < 0.05). A subset of these subjects also received 18F-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.