Background: According to the new 'AT(N)' system, those with a normal amyloid biomarker but with abnormal tauopathy or biomarkers of neurodegeneration or neuronal injury, have been labeled suspected non-Alzheimer's pathophysiology (SNAP). We aimed to estimate the long-term clinical and cognitive trajectories of SNAP individuals in non-demented elders and its comparison with individual in the Alzheimer's disease (AD) pathophysiology using 'AT(N)' system.
Methods: We included individuals with available baseline cerebrospinal fluid (CSF) Aβ (A), CSF phosphorylated tau examination (T) and 18F-uorodeoxyglucose PET or volumetric magnetic resonance imaging (N) from the Alzheimer's Disease Neuroimaging Initiative database. Longitudinal change in clinical outcomes are assessed using linear mixed effects models. Conversion risk from cognitively normal (CN) to cognitively impairment, and conversion from mild cognitive impairment (MCI) to dementia are assessed using multivariate Cox proportional hazard models.
Results: Totally, 366 SNAP individuals were included (114 A-T-N-, 154 A-T + N-, 54 A-T-N + and 44 A-T + N+) of whom 178 were CN and 188 were MCI. Compared with A-T-N-, CN elders with A-T + N-, A-T-N + and A-T + N + had a faster rate of ADNI-MEM score decline. Moreover, CN older individuals with A-T + N + also had a faster rate of decline in ADNI-MEM score than those with A-T + N- individuals. MCI patients with A-T + N + had a faster rate of ADNI-MEM and ADNI-EF decline and hippocampal volume loss compared with A-T-N- and A-T + N- profiles. CN older individuals with A-T + N + had an increased risk of conversion to cognitive impairment (CDR-GS ≥ 0.5) compared with A-T + N- and A-T-N-. In MCI patients, A-T + N + also had an increased risk of conversion to dementia compared with A-T + N- and A-T-N-. Compared with A-T + N-, CN elders and MCI patients with A + T + N- and A + T + N + had a faster rate of ADNI-MEM score, ADNI-EF score decline, and hippocampal volume loss. CN individuals with A + T + N + had a faster rate of ADNI-EF score decline compare with A-T + N + individuals. Moreover, MCI patients with A + T + N + also had a faster rate of decline in ADNI-MEM score, ADNI-EF score and hippocampal volume loss than those with A-T + N + individuals.
Conclusions: The findings from clinical, imaging and biomarker studies on SNAP, and its comparison with AD pathophysiology offered an important foundation for future studies.
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http://dx.doi.org/10.21203/rs.3.rs-2744271/v1 | DOI Listing |
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Service de chirurgie orthopédique, Hôpital Nord, Pôle Locomoteur, Assistance Publique-Hôpitaux de Marseille, Institut du Mouvement et de l'Appareil Locomoteur, Marseille, France.
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College of Nuclear Technology and Automation Engineering, Chengdu University of Technology, Chengdu, 610000, China; Applied Nuclear Technology in Geosciences Key Laboratory of Sichuan Province, Chengdu, 610000, China. Electronic address:
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Mpox, formerly known as monkeypox, has re-emerged as a significant global health concern, particularly during the widespread outbreak of 2022. As an orthopoxvirus related to the eradicated smallpox virus, mpox has been primarily managed with smallpox vaccines and treatments, including the antiviral agent Tecovirimat. This systematic review aims to evaluate the effectiveness and safety of Tecovirimat in treating mpox, focusing on its use during the 2022 outbreak, especially among high-risk populations, including men who have sex with men and people living with HIV.
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