Biomarkers.

Background: Diagnosing sporadic early-onset AD (EOAD, age-at-onset<65) is challenging: in the multi-center Longitudinal Early-onset Alzheimer's Disease Study, ∼25% of patients with clinically diagnosed EOAD are amyloid-PET-negative. Here we used FDG-PET to characterize the heterogeneity of hypometabolic profiles in these patients and better identify underlying etiologies.

Method: Seventy-four amyloid-PET-negative patients with clinical diagnosis of sporadic EOAD (MCI or mild dementia stage) underwent FDG-PET.

Biomarkers.

Background: Tau-PET imaging allows in-vivo detection of neurofibrillary tangles. One tau-PET tracer (i.e.

Biomarkers.

Background: The variability in the regional distribution of Aβ-PET signal and its relation to clinical features is debated. We used data-driven approaches to uncover heterogeneity in cortical Aβ-PET signal from a large representative sample collected through the IDEAS study.

Methods: We analysed cross-sectional Aβ-PET collected from 10,361 patients with MCI or mild dementia scanned in 295 PET facilities using one of the 3 FDA-approved tracers.

Biomarkers.

Background: APOE-ɛ4 is a major risk factor for Alzheimer's disease (AD); its effects have been examined in late-onset AD (LOAD) but less so in early-onset AD (EOAD). In LOAD, APOE genotype has strong effects on episodic memory and medial temporal lobe (MTL) atrophy (Wolk & Dickerson, 2010). However, EOAD often presents with more cognitive impairments in executive function, language, and visuospatial abilities than memory.

Biomarkers.

Background: There is a significant need for biomarkers of neurodegenerative burden in Early-onset Alzheimer's disease (EOAD). Evidence suggests that levels of specific CSF biomarkers (e.g.

Biomarkers.

Background: Prior work has advanced our understanding of cortical atrophy in early-onset Alzheimer's disease (EOAD), but longitudinal data are sparse. Current longitudinal MRI studies point to progressive atrophy in cerebral cortex exhibiting a posterior-to-anterior gradient, but these studies include small samples with mostly amnestic EOAD. Here, we analyzed a large sample of sporadic EOAD patients from the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS) to test the central hypothesis that areas in our recently described EOAD signature (Touroutoglou et al.

Biomarkers.

Background: The timing of tau-PET accumulation and cognitive decline in sporadic early-onset Alzheimer's disease (eoAD, age-at-onset<65) has not been established and is needed to optimize tau-PET as an outcome measure in clinical trials. Here we leverage large-sample, longitudinal data from the Longitudinal Early-onset Alzheimer's Disease Study (LEADS) to model tau-PET accumulation in three regions relative to cognitive decline.

Method: Longitudinal [F]Flortaucipir-PET (FTP) and CDR-SB scores were acquired in 195 amyloid-PET-positive, sporadic eoAD patients with MCI or mild dementia due to AD at baseline (Table 1).

Biomarkers.

Background: The Centiloid framework was developed to harmonize amyloid-PET quantification across radiotracers and processing pipelines to facilitate data sharing and merging; it is now widely used across research and clinical trials. As we just completed the quantification of 10,361 amyloid-PET scans from the largest "real-world" study of amyloid-PET (IDEAS) and are about to release the data, we aimed to compare the distribution of IDEAS Centiloid values with other available datasets.

Method: In IDEAS, amyloid scans were acquired across 343 facilities and centrally processed at UCSF using a PET-only pipeline.

Biomarkers.

Background: Previous studies on sex differences in amyloid burden have shown inconsistent findings. We examined the effect of sex on amyloid-PET outcomes in a large, real-world, cohort of individuals with cognitive impairment.

Method: The IDEAS study evaluated the clinical utility of amyloid-PET in 18,295 Medicare beneficiaries age ≥65 years with MCI or dementia.

Biomarkers.

Background: Residence in a disadvantaged neighborhood (e.g., high poverty rate, poor housing, etc.

Biomarkers.

Background: Understanding how early-onset Alzheimer's disease (EOAD) differs from typical late-onset AD (LOAD) is an important goal of AD research that may help increase the sensitivity of unique biomarkers for each phenotype. Building upon prior work based on small samples, here we leveraged two large, well-characterized natural history study cohorts of AD patients (LEADS and ADNI3) to test the hypothesis that EOAD patients would show more prominent lateral and medial parietal and lateral temporal cortical atrophy sparing the medial temporal lobe (MTL), whereas LOAD patients would show prominent MTL atrophy.

Method: We investigated differences in the spatial topography of cortical atrophy between EOAD and LOAD patients by analyzing structural MRI data collected from 211 patients with sporadic EOAD and 88 cognitively unimpaired (CU) participants from the LEADS cohort as well as 144 patients with LOAD and 365 CU participants from the ADNI3 cohort.

Biomarkers.

Background: Large-scale studies comparing sporadic early-onset AD (EOAD, age<65) and late-onset AD (LOAD, age≥65) are lacking. We compared amyloid-PET outcomes (positivity rate and amyloid burden) between patients clinically diagnosed with sporadic EOAD vs LOAD, leveraging data from the Longitudinal Early-Onset AD Study (LEADS) and the Alzheimer's Disease Neuroimaging Initiative 3 (ADNI3).

Method: 731 patients meeting the 2011 NIA-AA criteria for AD dementia or MCI were included (505 early-onset from LEADS, 226 late-onset from ADNI3, Table 1).

Biomarkers.

Background: Neurodegeneration in sporadic early-onset Alzheimer disease (EOAD) is topographically heterogeneous, as suggested by variability in syndromic presentation. We performed an unsupervised clustering analysis of structural MRI data to identify anatomical subtypes of EOAD. We hypothesized that distinct clusters will be present but will: (1) share areas of overlap focused around posterior regions of our newly developed EOAD signature of cortical atrophy (Touroutoglou et al.

Biomarkers.

Background: The Imaging Dementia-Evidence for Amyloid Scanning (IDEAS) study demonstrated that amyloid PET changes patient management in >60% of Medicare beneficiaries with MCI/atypical dementia. IDEAS had limited racial/ethnic diversity and excluded patients with "typical" amnestic clinical presentations. Here we present preliminary results from the New IDEAS study, which evaluates the clinical impact of amyloid PET in a more racially, ethnically and clinically diverse cohort.

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: Early-onset Alzheimer's disease (EOAD) occurs before age 65 and has more diverse disease presentations than late-onset AD. To improve our understanding of phenotypic heterogeneity among EOAD individuals, we analyzed cognitive scores using data-driven statistical analysis.

Method: Baseline cognitive data from 286 sporadic EOAD individuals from the Longitudinal EOAD study (LEADS) were transformed to z-scores using data from 95 cognitively normal (CN) individuals.

Alzheimer's Imaging Consortium.

Background: Tau-PET imaging allows in-vivo detection of neurofibrillary tangles. One tau-PET tracer (i.e.

Alzheimer's Imaging Consortium.

Background: The variability in the regional distribution of Aß-PET signal and its relation to clinical features is debated. We used data-driven approaches to uncover heterogeneity in cortical Aß-PET signal from a large representative sample collected through the IDEAS study.

Methods: We analysed cross-sectional Aß-PET collected from 10,361 patients with MCI or mild dementia scanned in 295 PET facilities using one of the 3 FDA-approved tracers.

Alzheimer's Imaging Consortium.

Background: The timing of tau-PET accumulation and cognitive decline in sporadic early-onset Alzheimer's disease (eoAD, age-at-onset<65) has not been established and is needed to optimize tau-PET as an outcome measure in clinical trials. Here we leverage large-sample, longitudinal data from the Longitudinal Early-onset Alzheimer's Disease Study (LEADS) to model tau-PET accumulation in three regions relative to cognitive decline.

Method: Longitudinal [18F]Flortaucipir-PET (FTP) and CDR-SB scores were acquired in 195 amyloid-PET-positive, sporadic eoAD patients with MCI or mild dementia due to AD at baseline (Table 1).

Alzheimer's Imaging Consortium.

Background: Large-scale studies comparing sporadic early-onset AD (EOAD, age<65) and late-onset AD (LOAD, age = 65) are lacking. We compared amyloid-PET outcomes (positivity rate and amyloid burden) between patients clinically diagnosed with sporadic EOAD vs LOAD, leveraging data from the Longitudinal Early-Onset AD Study (LEADS) and the Alzheimer's Disease Neuroimaging Initiative 3 (ADNI3).

Method: 731 patients meeting the 2011 NIA-AA criteria for AD dementia or MCI were included (505 early-onset from LEADS, 226 late-onset from ADNI3, Table 1).

Alzheimer's Imaging Consortium.

Background: Diagnosing sporadic early-onset AD (EOAD, age-at-onset<65) is challenging: in the multi-center Longitudinal Early-onset Alzheimer's Disease Study, ∼25% of patients with clinically diagnosed EOAD are amyloid-PET-negative. Here we used FDG-PET to characterize the heterogeneity of hypometabolic profiles in these patients and better identify underlying etiologies.

Method: Seventy-four amyloid-PET-negative patients with clinical diagnosis of sporadic EOAD (MCI or mild dementia stage) underwent FDG-PET.

Alzheimer's Imaging Consortium.

Background: Residence in a disadvantaged neighborhood (e.g., high poverty rate, poor housing, etc.

Alzheimer's Imaging Consortium.

Background: Understanding how early-onset Alzheimer's disease (EOAD) differs from typical late-onset AD (LOAD) is an important goal of AD research that may help increase the sensitivity of unique biomarkers for each phenotype. Building upon prior work based on small samples, here we leveraged two large, well-characterized natural history study cohorts of AD patients (LEADS and ADNI3) to test the hypothesis that EOAD patients would show more prominent lateral and medial parietal and lateral temporal cortical atrophy sparing the medial temporal lobe (MTL), whereas LOAD patients would show prominent MTL atrophy.

Method: We investigated differences in the spatial topography of cortical atrophy between EOAD and LOAD patients by analyzing structural MRI data collected from 211 patients with sporadic EOAD and 88 cognitively unimpaired (CU) participants from the LEADS cohort as well as 144 patients with LOAD and 365 CU participants from the ADNI3 cohort.

Drug Development.

Background: The LatAm-FINGERS trial marks a pioneering initiative as the first non-pharmacological clinical trial encompassing participants from 12 Latin American countries, including Argentina, Brazil, Bolivia, Chile, Colombia, Costa Rica, Ecuador, Dominican Republic, Mexico, Peru, Puerto Rico, and Uruguay. This initiative represents a significant advancement in promoting inclusivity and diversity in clinical trial recruitment, particularly in underserved populations.

Method: The LatAm-FINGERS trial is a multicenter randomized clinical trial evaluating a lifestyle intervention tailored for the Latin American population.

Drug Development.

Real-World data platforms for Alzheimer's Disease (AD) offer a unique opportunity to improve health equity through better understanding of health disparities and inclusivity in research, which is critical to translatability of research findings. AD research in the US and globally remains largely inaccessible to many individuals due to individual-level, study-level, investigator-level and larger systemic barriers. ALZ-NET, a US-based registry to evaluate longitudinal outcomes of patients being evaluated for or treated with novel FDA-approved AD therapy, and New IDEAS, an observational US-based longitudinal study of amyloid PET clinical utility, both offer opportunities for examining care, inclusivity, and disparities.