Successful cognitive aging is associated with thicker anterior cingulate cortex and lower tau deposition compared to typical aging.

INTRODUCTION: There is no consensus on either the definition of successful cognitive aging (SA) or the underlying neural mechanisms. METHODS: We examined the agreement between new and existing definitions using: (1) a novel measure, the cognitive age gap (SA-CAG, cognitive-predicted age minus chronological age), (2) composite scores for episodic memory (SA-EM), (3) non-memory cognition (SA-NM), and (4) the California Verbal Learning Test (SA-CVLT). RESULTS: Fair to moderate strength of agreement was found between the four definitions. Most SA groups showed greater cortical thickness compared to typical aging (TA), especially in the anterior cingulate and midcingulate cortices and medial temporal lobes. Greater hippocampal volume was found in all SA groups except SA-NM. Lower entorhinal 18 F-Flortaucipir (FTP) uptake was found in all SA groups. DISCUSSION: These findings suggest that a feature of SA, regardless of its exact definition, is resistance to tau pathology and preserved cortical integrity, especially in the anterior cingulate and midcingulate cortices. HIGHLIGHTS: Different approaches have been used to define successful cognitive aging (SA). Regardless of definition, different SA groups have similar brain features. SA individuals have greater anterior cingulate thickness and hippocampal volume. Lower entorhinal tau deposition, but not amyloid beta is related to SA. A combination of cortical integrity and resistance to tau may be features of SA.

Tau accumulation and atrophy predict amyloid independent cognitive decline in aging.

INTRODUCTION: Amyloid beta (Aß) and tau pathology are cross-sectionally associated with atrophy and cognitive decline in aging and Alzheimer's disease (AD). METHODS: We investigated relationships between concurrent longitudinal measures of Aß (Pittsburgh compound B [PiB] positron emission tomography [PET]), tau (flortaucipir [FTP] PET), atrophy (structural magnetic resonance imaging), episodic memory (EM), and non-memory (NM) in 78 cognitively healthy older adults (OA). RESULTS: Entorhinal FTP change was correlated with EM decline regardless of Aß, but meta-temporal FTP and global PiB change were only associated with EM and NM decline in Aß+ OA. Voxel-wise analyses revealed significant associations between temporal lobe FTP change and EM decline in all groups. PiB and FTP change were not associated with structural change, suggesting a functional or microstructural mechanism linking these measures to cognitive decline. DISCUSSION: Our results show that longitudinal Aß is linked to cognitive decline only in the presence of elevated Aß, but longitudinal temporal lobe tau is associated with memory decline regardless of Aß status. HIGHLIGHTS: Entorhinal tau change was associated with memory decline in older adults (OA), regardless of amyloid beta (Aß). Greater meta-region of interest (ROI) tau change correlated with memory decline in Aß+ OA. Voxel-wise temporal tau change correlated with memory decline, regardless of Aß. Meta-ROI tau and global amyloid change correlated with non-memory change in Aß+ OA. Tau and amyloid accumulation were not associated with structural change in OA.

An empirical measure of resilience explains individual differences in the effect of tau pathology on memory change in aging.

Accurately measuring resilience to preclinical Alzheimer's disease (AD) pathology is essential to understanding an important source of variability in cognitive aging. In a cohort of cognitively normal older adults (n = 123, age 76.75 ± 6.15 yr), we built a multifactorial measure of resilience which moderated the effect of AD pathology on longitudinal cognitive change. Linear residuals-based measures of resilience, along with other proxy measures (education and vocabulary), were entered into a hierarchical partial least-squares path model defining a putative consolidated resilience latent factor (model goodness of fit = 0.77). In a set of validation analyses using linear mixed models predicting longitudinal cognitive change, there was a significant three-way interaction among consolidated resilience, tau and time on episodic memory change (P = 0.001) such that higher resilience blunted the effect of tau pathology on episodic memory decline. Interactions between consolidated resilience and amyloid pathology on non-memory cognition decline suggested that resilience moderates pathology-specific effects on different cognitive domains.