Imaging Synaptic Density in Aging and Alzheimer Disease with [F]SynVesT-1.

Synaptic density imaging with PET is a relatively new approach to monitoring synaptic injury in neurodegenerative diseases. However, there are remaining technical and clinical questions, including questions on reference region selection and on how specific phenotypic presentations and symptoms of Alzheimer disease (AD) are reflected in alterations in synaptic density. Using a synaptic vesicle glycoprotein 2A (SV2A) PET ligand radiolabeled with the F isotope ([F]SynVesT-1), we performed sensitivity analyses to determine the optimal reference tissue modeling approach to derive whole-brain ratio images.

Cognitive aging outcomes are related to both tau pathology and maintenance of cingulate cortex structure.

Introduction: Successful cognitive aging is related to both maintaining brain structure and avoiding Alzheimer's disease (AD) pathology, but how these factors interplay is unclear.

Methods: A total of 109 cognitively normal older adults (70+ years old) underwent amyloid beta (Aβ) and tau positron emission tomography (PET) imaging, structural magnetic resonance imaging (MRI), and cognitive testing. Cognitive aging was quantified using the cognitive age gap (CAG), subtracting chronological age from predicted cognitive age.

Robust and interpretable AI-guided marker for early dementia prediction in real-world clinical settings.

Background: Predicting dementia early has major implications for clinical management and patient outcomes. Yet, we still lack sensitive tools for stratifying patients early, resulting in patients being undiagnosed or wrongly diagnosed. Despite rapid expansion in machine learning models for dementia prediction, limited model interpretability and generalizability impede translation to the clinic.

Connectivity, Pathology, and ApoE4 Interactions Predict Longitudinal Tau Spatial Progression and Memory.

Tau pathology spread into neocortex indicates a transition from healthy aging to Alzheimer's disease (AD). Connectivity between tau epicenters and later accumulating regions of cortex has been proposed as a mechanism of tau spread, but how this relationship changes with greater AD pathology burden or genotype is not understood. We investigated tau accumulation in two key regions, precuneus and inferior temporal cortex, using resting state functional connectivity (rsFC) and longitudinal PET imaging from a multicohort sample of cognitively unimpaired older adults.

The interplay of age, gender and amyloid on brain and cognition in mid-life and older adults.

Deficits in memory are seen as a canonical sign of aging and a prodrome to dementia in older adults. However, our understanding of age-related cognition and brain morphology occurring throughout a broader spectrum of adulthood remains limited. We quantified the relationship between cognitive function and brain morphology (sulcal width, SW) using three cross-sectional observational datasets (PISA, AIBL, ADNI) from mid-life to older adulthood, assessing the influence of age, sex, amyloid (Aβ) and genetic risk for dementia.