Developing an anatomically valid segmentation protocol for anterior regions of the medial temporal lobe for neurodegenerative diseases.

Background: The anterior portion of the medial temporal lobe (MTL) is one of the first regions targeted by pathology in sporadic Alzheimer's disease (AD) and Limbic-predominant Age-related TDP-43 Encephalopathy (LATE) indicating a potential for metrics from this region to serve as imaging biomarkers. Leveraging a unique post-mortem dataset of histology and magnetic resonance imaging (MRI) scans we aimed to 1) develop an anatomically valid segmentation protocol for anterior entorhinal cortex (ERC), Brodmann Area (BA) 35, and BA36 for in vivo 3 tesla (T) MRI and 2) incorporate this protocol in an automated approach.

Methods: We included 20 cases (61-97 years old, 50% females) with and without neurodegenerative diseases (11 vs.

Dissociable spatial topography of cortical atrophy in early-onset and late-onset Alzheimer's disease: A head-to-head comparison of the LEADS and ADNI cohorts.

Introduction: Early-onset and late-onset Alzheimer's disease (EOAD and LOAD, respectively) have distinct clinical manifestations, with prior work based on small samples suggesting unique patterns of neurodegeneration. The current study performed a head-to-head comparison of cortical atrophy in EOAD and LOAD, using two large and well-characterized cohorts (LEADS and ADNI).

Methods: We analyzed brain structural magnetic resonance imaging (MRI) data acquired from 377 sporadic EOAD patients and 317 sporadicLOAD patients who were amyloid positive and had mild cognitive impairment (MCI) or mild dementia (i.

Characterizing and validating 12-month reliable cognitive change in Early-Onset Alzheimer's Disease for use in clinical trials.

Background: As literature suggests that Early-Onset Alzheimer's Disease (EOAD) and late-onset AD may differ in important ways, need exists for randomized clinical trials for treatments tailored to EOAD. Accurately measuring reliable cognitive change in individual patients with EOAD will have great value for these trials.

Objectives: The current study sought to characterize and validate 12-month reliable change from the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS) neuropsychological battery.

Mapping hippocampal glutamate in healthy aging with glutamate-weighted CEST (GluCEST) imaging.

Introduction: Hippocampal glutamate (Glu) dysfunction is a pertinent indicator of neurodegeneration, yet mapping typical age-related changes in Glu has been challenging. Here, we use a 7T MRI approach, Glutamate Chemical Exchange Saturation Transfer (GluCEST), to measure bilateral hippocampal Glu in healthy old (HOA) and young (HYA) adults.

Methods: Bilateral hippocampal GluCEST data was acquired from 27 HOA and 22 HYA using 7T MRI.

Heterogeneous clinical phenotypes of sporadic early-onset Alzheimer's disease: a neuropsychological data-driven approach.

Background: The clinical presentations of early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease are distinct, with EOAD having a more aggressive disease course with greater heterogeneity. Recent publications from the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS) described EOAD as predominantly amnestic, though this phenotypic description was based solely on clinical judgment. To better understand the phenotypic range of EOAD presentation, we applied a neuropsychological data-driven method to subtype the LEADS cohort.