Biomarkers.

Background: The relationship between tau pathology and cognition as a function of age and whether these relationships are consistent across samples is unknown. A growing number of studies now perform positron emission tomography with tau ligands (tau-PET), making it possible for an improved understanding of the dynamics of tau and cognition in relation to other biomarkers.

Method: We used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort (ages 55-90) and The 90+ Study (Table 1) to cover a broad age range.

Biomarkers.

Background: The cerebellum is frequently used as the reference region for amyloid PET analysis. However, this reference region has been shown to demonstrate longitudinal variability, particularly with [F]florbetapir (FBP) PET (Landau, JNM 2015). For investigations in individuals with Down syndrome (DS), cerebellar atrophy and rapid disease progression may increase these longitudinal variabilities.

Biomarkers.

Background: There is an increased risk of epilepsy in Down syndrome (DS), especially after the age of 40. The onset of this co-occurring disease is closely associated with Alzheimer's disease (AD) related cognitive deterioration. Therefore, understanding the impact of late-onset epilepsy on AD biomarkers in people with DS is crucial.

Girls and Boys Typically Have Similar Math Value Beliefs: Replication Evidence Across Historical Time, High School, and Racial/Ethnic Groups.

Introduction: Individuals' math value beliefs are theorized to influence who persists in STEM. However, the existing findings on gender differences in adolescents' math value beliefs are inconsistent. The goal of this study was to use three existing datasets to help clarify when gender differences emerge for high school adolescents and for whom (i.

Developing Topics.

Background: Adverse social exposome (indexed by high national Area Deprivation Index [ADI]) is linked to structural inequities and increased risk of clinical dementia diagnosis, yet linkage to ADRD neuropathology remains largely unknown. Early work from single site brain banks suggests a relationship, but assessment in large national cohorts is needed to increase generalizability and depth, particularly for rarer neuropathology findings.

Objective: Determine the association between adverse social exposome by ADI and ADRD neuropathology for brain donors from 21 Alzheimer's Disease Research Center (ADRC) brain banks as part of the on-going Neighborhoods Study.

Developing Topics.

Background: Most hospice-eligible patients with dementia report agitation with antipsychotics and antidepressants with major side effects predominantly used in this population to control symptoms. Little is known about current evidence on randomized controlled trials (RCTs) on reducing agitation in this population.

Objectives: We aimed to summarize and evaluate the existing literature on RCTs aimed at reducing agitation among hospice-eligible patients with dementia.

Developing Topics.

Background: The medial temporal lobe (MTL) has distinct cortical subregions that are differentially vulnerable to pathology and neurodegeneration in diseases such as Alzheimer's disease. However, previous protocols for segmentation of MTL cortical subregions on magnetic resonance imaging (MRI) vary substantially across research groups, and have been informed by different cytoarchitectonic definitions, precluding consistent interpretations. The Hippocampal Subfields Group aims to create a harmonized, histology-based protocol for segmentation of MTL cortical subregions that can reliably be applied to T2-weighted MRI with high in-plane resolution.

Developing Topics.

Background: Peptide antigens that mimic disease-related conformations of Aβ and tau were designed and created, and antibodies against these peptide antigens were generated and characterized.

Method: The peptide antigens were designed to mimic β-strands formed by Aβ and tau in the cryo-EM structures of the Alzheimer's disease brain-derived fibrils. Peptide antigens were also designed to mimic β-hairpins of Aβ and oligomers formed by the β-hairpins.

Developing Topics.

Background: Free water (FW) and white matter hyperintensities (WMH) are key biomarkers of white matter integrity yet are understudied in racially/ethnically diverse populations and those over age 80. We describe FW and WMH across age, sex, and education in a diverse cohort.

Method: Data were harmonized from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE; mean age = 78±6 years) Study, Study of Healthy Aging in African Americans (STAR; mean age = 69±9 years), and LifeAfter90 (LA90; mean age = 93±2 years) Study, which are ongoing cohorts of racially/ethnically diverse participants who are long-term members of Kaiser Permanente Northern California.

Developing Topics.

Background: The Institute on Methods and Protocols for Advancement of Clinical Trials in Alzheimer's Disease and Alzheimer's Disease Related Dementias (AD/ADRD) (IMPACT-AD) is a novel multi-disciplinary training program funded by the National Institute on Aging (NIA) and the Alzheimer's Association for individuals seeking expertise in designing and conducting AD/ADRD trials. IMPACT-AD offers a Professionals Track for investigators in a variety of trial roles and a Fellowship Track for future AD/ADRD clinical trial principal investigators.

Method: To evaluate long-term training outcomes, alumni-scholars from the 2020-2022 courses (n = 109) were surveyed via REDCap in January 2024.

Developing Topics.

Background: Prior studies suggest that obstructive sleep apnea (OSA) may be associated with Alzheimer's disease (AD) pathology, including Aβ42/Aβ40 and p-Tau181. However, less is known about relationships between OSA and non-AD pathology, including neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), S100, chitinase 3-like 1 (YKL40), and soluble triggering receptor expressed on myeloid cells 2 (sTREM2), as well as the effect of potential moderating factors. The present study investigated the relationship between the apnea-hypopnea index (AHI) and cerebrospinal fluid (CSF) biomarkers of AD and related pathology.

Developing Topics.

Background: Perivascular spaces (PVS), the small spaces surrounding vasculature in the brain which are critical for glymphatic clearance, are an emerging marker of cerebrovascular dysfunction. Abnormal expansion of PVS has been associated with Alzheimer's disease (AD), and, therefore, may provide a measure of disease risk. Here, we investigate the relationship between PVS burden, memory performance, neurodegeneration, and biomarkers of AD pathology in community-dwelling older adults without cognitive impairment.

Developing Topics.

Background: Recent advances in optical clearing and light sheet imaging have opened an exciting new avenue for brain-wide, cellular resolution immunostaining at the forefront of a dimensional shift from 2D to 3D histology. When looking for read-outs of genetic or pharmacological manipulations that affect the entire brain, traditional 2D immunohistochemistry approaches limit observations to brain regions of interest. Providing access to the intricate anatomy of the whole intact brain, tissue clearing offers neuroscientists unbiased and complete views of brain anatomy and function.

Developing Topics.

Background: To look deep inside tissues, traditional histological methods cut specimens into thin slices. Providing access to the intricate anatomy of intact organs, tissue clearing offers neuroscientists unbiased and complete views of brain anatomy and function. One area where these methods have particular utility is in the development of CNS therapeutics where they can be used to examine the regional distribution of the therapeutics in the brain as well as brain-wide target engagement and phenotypic efficacy.

Alzheimer's Imaging Consortium.

Background: Virtually all adults with Down Syndrome(DS) show Alzheimer's disease(AD)-related pathologic change by the age of 40 years. While sex differences in Aß-dependent tauopathy are apparent during early sporadic AD, sex differences in the DS population remain under-investigated. Moreover, menopause onset occurs earlier in the DS population(45 years), and it remains unknown whether menopause status and hormone therapy(HT) exposure influences Aß-dependent tauopathy in women with DS.

Alzheimer's Imaging Consortium.

Background: The posterior-medial network is crucial for episodic memory. However, the medial temporal lobe (MTL) and posteromedial cortex (PMC) regions are vulnerable to aging and early Alzheimer's disease (AD). Both processes might elicit distinct early functional connectivity (FC) changes which could be detrimental or protective/ compensatory regarding cognition.

Alzheimer's Imaging Consortium.

Background: The Motoric Cognitive Risk Syndrome (MCR) is a predementia stage characterized by slow gait speed and subjective cognitive complaints. Defining the heterogeneity of brain volumetrics in individuals with MCR will improve current dementia risk assessments.

Method: We used data from 6 cohorts from the MCR consortium (N=2,007).

Alzheimer's Imaging Consortium.

Background: Alzheimer's disease exhibits heterogeneity through varied phenotypic and pathological manifestations. Here, we aimed to investigate the potential of semi-supervised pattern classification applied to volumetric MRI data in identifying relatively homogeneous subgroups of individuals exhibiting cognitive decline (CD) throughout the study period.

Method: We used data from the placebo arm of trial of Solanezumab for mild dementia due to AD (EXPEDITION-3 trial).

Alzheimer's Imaging Consortium.

Background: Aging is associated with disruptions in non-rapid eye movement (NREM) sleep and memory decline. Cerebral small vessel disease (CSVD) increases with age and is associated with clinical sleep disturbance, but little is known about its relationship with local expression of NREM sleep. Here, we explore associations between CSVD burden, memory, and local electroencephalography (EEG) measures during NREM sleep in older adults.

Alzheimer's Imaging Consortium.

Background: The relationship between tau pathology and cognition as a function of age and whether these relationships are consistent across samples is unknown. A growing number of studies now perform positron emission tomography with tau ligands (tau-PET), making it possible for an improved understanding of the dynamics of tau and cognition in relation to other biomarkers.

Method: We used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort (ages 55-90) and The 90+ Study (Table 1) to cover a broad age range.

Alzheimer's Imaging Consortium.

Background: The cerebellum is frequently used as the reference region for amyloid PET analysis. However, this reference region has been shown to demonstrate longitudinal variability, particularly with [18F]florbetapir (FBP) PET (Landau, JNM 2015). For investigations in individuals with Down syndrome (DS), cerebellar atrophy and rapid disease progression may increase these longitudinal variabilities.

Alzheimer's Imaging Consortium.

Background: There is an increased risk of epilepsy in Down syndrome (DS), especially after the age of 40. The onset of this co-occurring disease is closely associated with Alzheimer's disease (AD) related cognitive deterioration. Therefore, understanding the impact of late-onset epilepsy on AD biomarkers in people with DS is crucial.

Alzheimer's Imaging Consortium.

Background: Trisomy 21 in Down syndrome (DS) is associated with an earlier accumulation of beta-amyloid (Aß) plaques and a higher rate of Alzheimer's Disease due to the triplication of the amyloid precursor protein gene. In this study we compare accumulation rates of Aß measured with [C-11]PiB PET between large longitudinal cohorts of DS and neurotypical (NT) participants at a single site.

Methods: Participants imaged at the University of Wisconsin with =2 PiB scans and =2 years between scans were included in this study.

Alzheimer's Imaging Consortium.

Background: Recent studies have suggested a transient glucose hypermetabolism in early phases of Alzheimer's Disease (AD), which is followed by a characteristic glucose hypometabolism in dementia stages. This phenomenon desveres further investigation and it is suggested to be associated to glial/inflammatory or compensatory neuronal responses. Here, we aimed to longitudinally investigate brain glucose metabolism in an AD animal model and explore associated cellular and inflammatory changes.

Alzheimer's Imaging Consortium.

Background: Diffusion tensor imaging has traditionally been used to assess white matter (WM) integrity in Alzheimer's disease (AD). However, the tensor model is limited in modeling complex WM structure. Neurite Orientation Dispersion and Density Imaging (NODDI), a cutting-edge technique applied to multishell diffusion MRI, can offer more precise insights into microstructural features of WM integrity.