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Background: We compared the ability of several plasma biomarkers versus amyloid positron emission tomography (PET) to predict rates of memory decline among cognitively unimpaired individuals., Methods: We studied 645 Mayo Clinic Study of Aging participants. Predictor variables were age, sex, education, apolipoprotein E (APOE) ε4 genotype, amyloid PET, and plasma amyloid beta (Aβ)42/40, phosphorylated tau (p-tau)181, neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and p-tau217. The outcome was a change in a memory composite measure., Results: All plasma biomarkers, except NfL, were associated with mean memory decline in models with individual biomarkers. However, amyloid PET and plasma p-tau217, along with age, were key variables independently associated with mean memory decline in models combining all predictors. Confidence intervals were narrow for estimates of population mean prediction, but person-level prediction intervals were wide., Discussion: Plasma p-tau217 and amyloid PET provide useful information about predicting rates of future cognitive decline in cognitively unimpaired individuals at the population mean level, but not at the individual person level., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: The timing of plasma biomarker changes is not well understood. The goal of this study was to evaluate the temporal co-evolution of plasma and positron emission tomography (PET) Alzheimer's disease (AD) biomarkers., Methods: We included 1408 Mayo Clinic Study of Aging and Alzheimer's Disease Research Center participants. An accelerated failure time (AFT) model was fit with amyloid beta (Aβ) PET, tau PET, plasma p-tau217, p-tau181, and glial fibrillary acidic protein (GFAP) as endpoints., Results: Individual timing of plasma p-tau progression was strongly associated with Aβ PET and GFAP progression. In the population, GFAP became abnormal first, then Aβ PET, plasma p-tau, and tau PET temporal meta-regions of interest when applying cut points based on young, cognitively unimpaired participants., Discussion: Plasma p-tau is a stronger indicator of a temporally linked response to elevated brain Aβ than of tau pathology. While Aβ deposition and a rise in GFAP are upstream events associated with tau phosphorylation, the temporal link between p-tau and Aβ PET was the strongest., Highlights: Plasma p-tau progression was more strongly associated with Aβ than tau PET. Progression on plasma p-tau was associated with Aβ PET and GFAP progression. P-tau181 and p-tau217 become abnormal after Aβ PET and before tau PET. GFAP became abnormal first, before plasma p-tau and Aβ PET., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: We aimed to provide cut points for the automated Elecsys Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers., Methods: Cut points for Elecsys amyloid beta 42 (Aβ42), total tau (t-tau), hyperphosphorylated tau (p-tau), and t-tau/Aβ42 and p-tau/Aβ42 ratios were evaluated in Mayo Clinic Study of Aging (n = 804) and Mayo Clinic Alzheimer's Disease Research Center (n = 70) participants., Results: The t-tau/Aβ42 and p-tau/Aβ42 ratios had a higher percent agreement with normal/abnormal amyloid positron emission tomography (PET) than the individual CSF markers. Reciever Operating Characteristic (ROC)-based cut points were 0.26 (0.24-0.27) for t-tau/Aβ42 and 0.023 (0.020-0.025) for p-tau/Aβ42. Ratio cut points derived from other cohorts performed as well in our cohort as our own did. Individual biomarkers had worse diagnostic properties and more variable results in terms of positive and negative percent agreement (PPA and NPA)., Conclusion: CSF t-tau/Aβ42 and p-tau/Aβ42 ratios are very robust indicators of AD. For individual biomarkers, the intended use should determine which cut point is chosen., (© 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: Our goal was to develop cut points for amyloid positron emission tomography (PET), tau PET, flouro-deoxyglucose (FDG) PET, and MRI cortical thickness., Methods: We examined five methods for determining cut points., Results: The reliable worsening method produced a cut point only for amyloid PET. The specificity, sensitivity, and accuracy of cognitively impaired versus young clinically normal (CN) methods labeled the most people abnormal and all gave similar cut points for tau PET, FDG PET, and cortical thickness. Cut points defined using the accuracy of cognitively impaired versus age-matched CN method labeled fewer people abnormal., Discussion: In the future, we will use a single cut point for amyloid PET (standardized uptake value ratio, 1.42; centiloid, 19) based on the reliable worsening cut point method. We will base lenient cut points for tau PET, FDG PET, and cortical thickness on the accuracy of cognitively impaired versus young CN method and base conservative cut points on the accuracy of cognitively impaired versus age-matched CN method., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Inexpensive, non-invasive tools for assessing Alzheimer-type pathophysiologies are needed. Computerized cognitive assessments are prime candidates., Methods: Cognitively normal participants, aged 51-71, with magnetic resonance imaging, fluorodeoxyglucose-positron emission tomography (FDG-PET), amyloid PET, CogState computerized cognitive assessment, and standard neuropsychological tests were included. We first examined the association between the CogState battery and neuroimaging measures. We then compared that association to the one between standard neuropsychological z-scores and neuroimaging., Results: Slower reaction times for CogState Identification and One Back, and lower memory and attention z-scores, were associated (P < .05) with FDG-PET hypometabolism. Slower time on the Groton Maze Learning Task and worse One Card Learning accuracy were associated (P < .05) with smaller hippocampal volumes. There were no associations with amyloid PET. Associations of CogState and neuropsychological Z-scores with neuroimaging were small and of a similar magnitude., Conclusions: CogState subtests were cross-sectionally comparable to standard neuropsychological tests in their relatively weak associations with neurodegeneration imaging markers., (Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Background: Positron-emission tomography (PET) imaging of amyloid with Pittsburgh Compound B (PIB) and Aβ42 levels in the cerebrospinal fluid (CSF Aβ42) demonstrate a highly significant inverse correlation. Both these techniques are presumed to measure brain Aβ amyloid load. The objectives of this study were to develop a method to transform CSF Aβ42 measures into calculated PIB measures (PIBcalc) of Aβ amyloid load, and to partially validate the method in an independent sample of subjects., Methods: In all, 41 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) underwent PIB PET imaging and lumbar puncture (LP) at the same time. This sample, referred to as the "training" sample (nine cognitively normal subjects, 22 subjects with mild cognitive impairment, and 10 subjects with Alzheimer's disease), was used to develop a regression model by which CSF Aβ42 (with apolipoprotein E ɛ4 carrier status as a covariate) was transformed into units of PIB PET (PIBcalc). An independent "supporting" sample of 362 ADNI subjects (105 cognitively normal subjects, 164 subjects with mild cognitive impairment, and 93 subjects with Alzheimer's disease) who underwent LP but not PIB PET imaging had their CSF Aβ42 values converted to PIBcalc. These values were compared with the overall PIB PET distribution found in the ADNI subjects (n=102)., Results: A linear regression model demonstrates good prediction of actual PIB PET from CSF Aβ42 measures obtained in the training sample (R(2)=0.77, P<.001). PIBcalc data (derived from CSF Aβ42) in the supporting sample of 362 ADNI subjects who underwent LP but not PIB PET imaging demonstrate group-wise distributions that are highly consistent with the larger ADNI PIB PET distribution and with published PIB PET imaging studies., Conclusion: Although the precise parameters of this model are specific for the ADNI sample, we conclude that CSF Aβ42 can be transformed into PIBcalc measures of Aβ amyloid load. Brain Aβ amyloid load can be ascertained at baseline in therapeutic or observational studies by either CSF or amyloid PET imaging and the data can be pooled using well-established multiple imputation techniques that account for the uncertainty in a CSF-based PIBcalc value., (Copyright © 2011 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)