Background

Amyloid-β (Aβ) likely plays a primary role in Alzheimer's disease pathogenesis, but longitudinal Aβ, tau, and neurodegeneration (A/T/N) measurements in the same individuals have rarely been examined to verify the temporal dynamics of these biomarkers.

Methods

In this study, we investigated the temporal ordering of Aβ, tau, and neurodegeneration using longitudinal biomarkers in nondemented elderly individuals. A total of 395 cognitively unimpaired individuals and 204 individuals with mild cognitive impairment (320 [53%] were female) were classified into 8 A±/T±/N± categories according to the abnormal (+)/normal (-) status of Aβ (¹⁸F-florbetapir or ¹⁸F-florbetaben) positron emission tomography (PET), ¹⁸F-flortaucipir PET, and adjusted hippocampal volume (aHCV). Follow-up Aβ PET, tau PET, and aHCV measurements at 0.6 to 4.1 years were available for 35% to 63% of the sample. Baseline Aβ, tau, and aHCV were compared between different A/T/N profiles. We investigated the associations of baseline and longitudinal Aβ, tau, and neurodegeneration in relation to one another continuously.

Results

Among T- participants, tau was higher for A+/T-/N- individuals compared with the A-/T-/N- group (p = .02). Among N- participants, neurodegeneration was worse among A+/T+/N- individuals compared with the A-/T-/N- group (p = .001). High baseline Aβ was associated (p < .001) with subsequent tau increase and high baseline tau was associated (p = .002) with subsequent aHCV decrease, whereas high tau and low aHCV at baseline were not associated with subsequent Aβ increase.

Conclusions

These findings define a sequence of pathological events in Alzheimer's disease that support a current model of Alzheimer's disease pathogenesis in which Aβ appears early, followed by deposition of abnormal tau aggregates and subsequent neurodegeneration.

Little is known about the association between personality and Alzheimer's disease (AD) biomarkers, and existing results are inconsistent. We aimed to determine whether personality was associated with β-amyloid (Aβ) accumulation in cognitively normal aging. One hundred twenty-nine participants were included in this cross-sectional study. Personality was measured with the Big Five Inventory (BFI) and brain Aβ deposition was assessed with [11C] Pittsburgh compound B (PiB)-positron emission tomography (PET) imaging. Conscientiousness scores had a negative association with global PiB distribution volume ratio (DVR) in all participants after adjusting for age, sex, education, and vascular risk factors (β[SE] = -0.19[0.09], 95% confidence interval [CI: -0.35, -0.02], p = .031), while agreeableness, extraversion, neuroticism, and openness had no association with global PiB DVR. Assuming the relative stability of personality traits, these findings suggest that conscientiousness may protect against Aβ accumulation in cognitively normal aging through mechanisms that are as yet unknown. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Introduction

Positron emission tomography targeting tau (tau-PET) is a promising diagnostic tool for the identification of Alzheimer's disease (AD). Currently available data rely on quantitative measures, and a visual interpretation method, critical for clinical translation, is needed.

Methods

We developed a visual interpretation method for ¹⁸F-flortaucipir tau-PET and tested it on 274 individuals (cognitively normal controls, patients with mild cognitive impairment [MCI], AD dementia, and non-AD diagnoses). Two readers interpreted ¹⁸F-flortaucipir PET using two complementary indices: a global visual score and a visual distribution pattern.

Results

Global visual scores were reliable, correlated with global cortical ¹⁸F-flortaucipir standardized uptake value ratio (SUVR) and were associated with clinical diagnosis and amyloid status. The AD-like ¹⁸F-flortaucipir pattern had good sensitivity and specificity to identify amyloid-positive patients with AD dementia or MCI.

Discussion

This ¹⁸F-flortaucipir visual rating scheme is associated with SUVR quantification, clinical diagnosis, and amyloid status, and constitutes a promising approach to tau measurement in clinical settings.