Alzheimer's & dementia : the journal of the Alzheimer's Association
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The overall goal of the Alzheimer's Disease Neuroimaging Initiative (ADNI) is to validate biomarkers for Alzheimer's disease (AD) clinical trials. ADNI is a multisite, longitudinal, observational study that has collected many biomarkers since 2004. Recent publications highlight the multifactorial nature of late-onset AD. We discuss selected topics that provide insights into AD progression and outline how this knowledge may improve clinical trials. ⋯ ADNI publications from 2016 and 2017 supported the idea of AD as a multifactorial disease and provided insights into the complexities of AD disease progression. These findings guided the development of novel biomarkers and suggested that subject selection on the basis of multiple factors may lower AD clinical trial costs and duration. The use of multiple concurrent therapies in these trials may prove more effective in reversing AD disease progression.
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The interplay between midlife vascular risk factors and midlife cognitive function with later life mild cognitive impairment (MCI) and dementia (DEM) is not well understood. ⋯ Later life MCI and DEM were independently associated with midlife vascular risk factors and midlife cognition.
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We studied whether fully automated Elecsys cerebrospinal fluid (CSF) immunoassay results were concordant with positron emission tomography (PET) and predicted clinical progression, even with cutoffs established in an independent cohort. ⋯ Elecsys CSF biomarker assays may provide reliable alternatives to PET in Alzheimer's disease diagnosis.
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Neurofilament light (NFL) levels in the cerebrospinal fluid are increased in several neurodegenerative dementias. However, their diagnostic accuracy in the differential diagnostic context is unknown. ⋯ Increased NFL levels are a common feature in neurodegenerative dementias.
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Cross-sectional findings using the tau tracer [18F]THK5317 (THK5317) have shown that [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) data can be approximated using perfusion measures (early-frame standardized uptake value ratio; ratio of tracer delivery in target to reference regions). In this way, a single PET study can provide both functional and molecular information. ⋯ Our findings suggest a spatiotemporal offset between functional changes and tau pathology and a partial uncoupling between perfusion and metabolism, possibly as a function of Alzheimer's disease severity.