Impact of alcohol use disorder on cognition in correlation with aging: a community-based retrospective cohort study.

Aims: Excessive alcohol use is associated with an increased risk of cognitive impairment. Since increased amyloid plaque burden exacerbates cognitive decline, we sought to assess the potential impact of alcohol use disorder (AUD) on cognition, memory, and amyloid burden corresponding with age.

Methods: We conducted the retrospective analysis with 6036 subjects, including 269 AUD+ subjects.

Mayo Normative Studies: Amyloid and Neurodegeneration Negative Normative Data for the Auditory Verbal Learning Test and Sex-Specific Sensitivity to Mild Cognitive Impairment/Dementia.

Background: Conventional normative samples include individuals with undetected Alzheimer's disease neuropathology, lowering test sensitivity for cognitive impairment.

Objective: We developed Mayo Normative Studies (MNS) norms limited to individuals without elevated amyloid or neurodegeneration (A-N-) for Rey's Auditory Verbal Learning Test (AVLT). We compared these MNS A-N- norms in female, male, and total samples to conventional MNS norms with varying levels of demographic adjustments.

Mayo normative studies: regression-based normative data for ages 30-91 years with a focus on the Boston Naming Test, Trail Making Test and Category Fluency.

Objective: Normative neuropsychological data are essential for interpretation of test performance in the context of demographic factors. The Mayo Normative Studies (MNS) aim to provide updated normative data for neuropsychological measures administered in the Mayo Clinic Study of Aging (MCSA), a population-based study of aging that randomly samples residents of Olmsted County, Minnesota, from age- and sex-stratified groups. We examined demographic effects on neuropsychological measures and validated the regression-based norms in comparison to existing normative data developed in a similar sample.

Modeling the temporal evolution of plasma p-tau in relation to amyloid beta and tau PET.

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.

Synthesizing images of tau pathology from cross-modal neuroimaging using deep learning.

Given the prevalence of dementia and the development of pathology-specific disease-modifying therapies, high-value biomarker strategies to inform medical decision-making are critical. In vivo tau-PET is an ideal target as a biomarker for Alzheimer's disease diagnosis and treatment outcome measure. However, tau-PET is not currently widely accessible to patients compared to other neuroimaging methods.

Evidence against a temporal association between cerebrovascular disease and Alzheimer's disease imaging biomarkers.

Whether a relationship exists between cerebrovascular disease and Alzheimer's disease has been a source of controversy. Evaluation of the temporal progression of imaging biomarkers of these disease processes may inform mechanistic associations. We investigate the relationship of disease trajectories of cerebrovascular disease (white matter hyperintensity, WMH, and fractional anisotropy, FA) and Alzheimer's disease (amyloid and tau PET) biomarkers in 2406 Mayo Clinic Study of Aging and Mayo Alzheimer's Disease Research Center participants using accelerated failure time models.

Deep learning-based brain age prediction in normal aging and dementia.

Brain aging is accompanied by patterns of functional and structural change. Alzheimer's disease (AD), a representative neurodegenerative disease, has been linked to accelerated brain aging. Here, we developed a deep learning-based brain age prediction model using a large collection of fluorodeoxyglucose positron emission tomography and structural magnetic resonance imaging and tested how the brain age gap relates to degenerative syndromes including mild cognitive impairment, AD, frontotemporal dementia and Lewy body dementia.

Mayo normative studies: A conditional normative model for longitudinal change on the Auditory Verbal Learning Test and preliminary validation in preclinical Alzheimer's disease.

Introduction: The aim of this study was to develop a conditional normative model for Rey's Auditory Verbal Learning Test (AVLT) that accounts for practice effects.

Methods: In our normative sample, robust conditional norms were derived from 1001 cognitively unimpaired (CU) adults ages 50 to 89 who completed the AVLT up to eight times. Linear mixed-effects models adjusted for baseline performance, prior test exposures, time, demographics, and interaction terms.

Long-term associations between amyloid positron emission tomography, sex, apolipoprotein E and incident dementia and mortality among individuals without dementia: hazard ratios and absolute risk.

Dementia and mortality rates rise inexorably with age and consequently interact. However, because of the major logistical difficulties in accounting for both outcomes in a defined population, very little work has examined how risk factors and biomarkers for incident dementia are influenced by competing mortality. The objective of this study was to examine long-term associations between amyloid PET, APOE ɛ4, sex, education and cardiovascular/metabolic conditions, and hazard and absolute risk of dementia and mortality in individuals without dementia at enrolment.

The Overlap Index as a Means of Evaluating Early Tau PET Signal Reliability.

In tau PET, a reliable method to detect early tau accumulation in the brain is crucial. Noise, artifacts, and off-target uptake impede detection of subtle true-positive ligand binding. We hypothesize that identifying voxels with stable activity over time can enhance detection of true-positive tau.

White matter changes in empirically derived incident MCI subtypes in the Mayo Clinic Study of Aging.

Introduction: The aim of this study was to examine white matter hyperintensities (WMH) and fractional anisotropy (FA) in empirically derived incident mild cognitive impairment (MCI) subtypes.

Methods: We evaluated 188 participants with incident MCI in the Mayo Clinic Study of Aging (MCSA) identified as having one of four cluster-derived subtypes: subtle cognitive impairment, amnestic, dysnomic, and dysexecutive. We used linear regression models to evaluate whole brain and regional WMH volumes.

A Comparison of Cross-Sectional and Longitudinal Methods of Defining Objective Subtle Cognitive Decline in Preclinical Alzheimer's Disease Based on Cogstate One Card Learning Accuracy Performance.

Background: Longitudinal, but not cross-sectional, cognitive testing is one option proposed to define transitional cognitive decline for individuals on the Alzheimer's disease continuum.

Objective: Compare diagnostic accuracy of cross-sectional subtle objective cognitive impairment (sOBJ) and longitudinal objective decline (ΔOBJ) over 30 months for identifying 1) cognitively unimpaired participants with preclinical Alzheimer's disease defined by elevated brain amyloid and tau (A+T+) and 2) incident mild cognitive impairment (MCI) based on Cogstate One Card Learning (OCL) accuracy performance.

Methods: Mayo Clinic Study of Aging cognitively unimpaired participants aged 50 + with amyloid and tau PET scans (n = 311) comprised the biomarker-defined sample.

Diagnostic accuracy of the Cogstate Brief Battery for prevalent MCI and prodromal AD (MCI A T ) in a population-based sample.

Introduction: This study evaluated the diagnostic accuracy of the Cogstate Brief Battery (CBB) for mild cognitive impairment (MCI) and prodromal Alzheimer's disease (AD) in a population-based sample.

Methods: Participants included adults ages 50+ classified as cognitively unimpaired (CU, n = 2866) or MCI (n = 226), and a subset with amyloid (A) and tau (T) positron emission tomography who were AD biomarker negative (A-T-) or had prodromal AD (A+T+).

Results: Diagnostic accuracy of the Learning/Working Memory Composite (Lrn/WM) for discriminating all CU and MCI was moderate (area under the curve [AUC] = 0.

Association of Initial β-Amyloid Levels With Subsequent Flortaucipir Positron Emission Tomography Changes in Persons Without Cognitive Impairment.

Importance: Tau accumulation in Alzheimer disease (AD) is closely associated with cognitive impairment. Quantitating tau accumulation by positron emission tomography (PET) will be a useful outcome measure for future clinical trials in the AD spectrum.

Objective: To investigate the association of β-amyloid (Aβ) on PET with subsequent tau accumulation on PET in persons who were cognitively unimpaired (CU) to gain insight into temporal associations between Aβ and tau accumulation and inform clinical trial design.

Mayo Normative Studies: Regression-Based Normative Data for the Auditory Verbal Learning Test for Ages 30-91 Years and the Importance of Adjusting for Sex.

Objective: Rey's Auditory Verbal Learning Test (AVLT) is a widely used word list memory test. We update normative data to include adjustment for verbal memory performance differences between men and women and illustrate the effect of this sex adjustment and the importance of excluding participants with mild cognitive impairment (MCI) from normative samples.

Method: This study advances the Mayo's Older Americans Normative Studies (MOANS) by using a new population-based sample through the Mayo Clinic Study of Aging, which randomly samples residents of Olmsted County, Minnesota, from age- and sex-stratified groups.

Diagnostic and Prognostic Accuracy of the Cogstate Brief Battery and Auditory Verbal Learning Test in Preclinical Alzheimer's Disease and Incident Mild Cognitive Impairment: Implications for Defining Subtle Objective Cognitive Impairment.

Background: There are detectable cognitive differences in cognitively unimpaired (CU) individuals with preclinical Alzheimer's disease (AD).

Objective: To determine whether cross-sectional performance on the Cogstate Brief Battery (CBB) and Auditory Verbal Learning Test (AVLT) could identify 1) CU participants with preclinical AD defined by neuroimaging biomarkers of amyloid and tau, and 2) incident mild cognitive impairment (MCI)/dementia.

Method: CU participants age 50+ were eligible if they had 1) amyloid (A) and tau (T) imaging within two years of their baseline CBB or 2) at least one follow-up visit.

Cortical atrophy patterns of incident MCI subtypes in the Mayo Clinic Study of Aging.

Introduction: We examined differences in cortical thickness in empirically derived mild cognitive impairment (MCI) subtypes in the Mayo Clinic Study of Aging.

Methods: We compared cortical thickness of four incident MCI subtypes (n = 192) to 1257 cognitive unimpaired individuals.

Results: The subtle cognitive impairment cluster had atrophy in the entorhinal and parahippocampal cortex.

Tau-positron emission tomography correlates with neuropathology findings.

Introduction: Comparison of tau (flortaucipir) positron emission tomography (FTP-PET) to autopsy is important to demonstrate the relationship of FTP-PET to neuropathologic findings.

Methods: Autopsies were performed on 26 participants who had antemortem FTP-PET. FTP-PET standardized uptake value ratios (SUVRs) were compared to autopsy diagnoses and Braak tangle stage.

Neuroimaging correlates with neuropathologic schemes in neurodegenerative disease.

Introduction: Neuroimaging biomarkers are important for early diagnosis of Alzheimer's disease, and comparing multimodality neuroimaging to autopsy data is essential.

Methods: We compared the pathologic findings from a prospective autopsy cohort (n = 100) to Pittsburgh compound B PET (PiB-PET), F-fluorodeoxyglucose PET (FDG-PET), and MRI. Correlations between neuroimaging biomarkers and neuropathologic schemes were assessed.

Neuropsychological subtypes of incident mild cognitive impairment in the Mayo Clinic Study of Aging.

Introduction: We evaluated whether incident mild cognitive impairment (MCI) subtypes could be empirically derived in the Mayo Clinic Study of Aging.

Methods: We performed cluster analysis on neuropsychological data from 506 participants with incident MCI.

Results: The 3-cluster solution resulted in (1) amnestic, (2) dysexecutive, (3) dysnomic subtypes.

Entorhinal cortex tau, amyloid-β, cortical thickness and memory performance in non-demented subjects.

As more biomarkers for Alzheimer's disease and age-related brain conditions become available, more sophisticated analytic approaches are needed to take full advantage of the information they convey. Most work has been done using categorical approaches but the joint relationships of tau PET, amyloid PET and cortical thickness in their continuous distributions to cognition have been under-explored. We evaluated non-demented subjects over age 50 years in the Mayo Clinic Study of Aging, 2037 of whom had undergone 3 T MRI scan, 985 amyloid PET scan with 11C-Pittsburgh compound B (PIB) and MRI, and 577 PIB-PET, 18F-AV1451 flortaucipir PET and MRI.

Predicting Progression to Mild Cognitive Impairment.

Despite much attention to the use of biomarkers for predicting Alzheimer disease, little information is available at the individual level. We used the population-based Mayo Clinic Study of Aging to estimate absolute risk of cognitive impairment by biomarker group. Risk increased with age and any biomarker abnormality.

Comparison of PC and iPad administrations of the Cogstate Brief Battery in the Mayo Clinic Study of Aging: Assessing cross-modality equivalence of computerized neuropsychological tests.

: Computerized neuropsychological assessments are increasingly used in clinical practice, population studies of cognitive aging and clinical trial enrichment. Subtle, but significant, performance differences have been demonstrated across different modes of test administration and require further investigation. : Participants included cognitively unimpaired adults aged 50 and older from the Mayo Clinic Study of Aging who completed the Cogstate Brief Battery and Cogstate's Groton Maze Learning Test (GMLT) on an iPad or a personal computer (PC) in the clinic.