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: Understanding the relationship between genetic variations and brain imaging phenotypes is an important issue in Alzheimer's disease (AD) research. As an alternative to GWAS univariate analyses, canonical correlation analysis (CCA) and its deep learning extension (DCCA) are widely used to identify associations between multiple genetic variants such as SNPs and multiple imaging traits such as brain ROIs from PET/MRI. However, with the recent availability of numerous genetic variants from genotyping and whole genome sequencing data for AD, these approaches often suffer from severe overfitting when dealing with 'fat' genetics data, e.

Biomarkers.

Background: Alzheimer's disease (AD) is a complex neurodegenerative disorder that has impacted millions of people worldwide. Identifying different risk groups converting to AD during the mild cognitive impairment (MCI) stage and determining their genetic basis would be immensely valuable for drug discovery and subsequent clinical treatment. Previous studies typically clustered subgroups by unsupervised learning techniques, neglecting the survival information.

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: The Alzheimer's Disease Center Fluid Biomarker (ADCFB) Initiative samples are analyzed centrally at NCRAD for AD plasma biomarkers. When combining NACC accessible data from across centers, biofluid biomarker data must be evaluated carefully. This will become more critical with the implementation of disease modifying therapies.

Public Health.

Background: Cardiovascular disease (CVD) increases the risk of cognitive impairment (CI), particularly in women. Physical activity and cognitive training can improve cognition, with potential interactive effects. The purpose of this study was to evaluate the efficacy of MindMoves, a 24-week multidomain physical activity and cognitive training intervention, on cognition in older women with CVD.

Public Health.

Background: Understanding the dynamics of markers throughout Alzheimer's disease (AD) progression in a representative population is critical for early detection of AD. Most existing studies used a single cohort to model the dynamics of AD-related markers, which may lead to biased and unreproducible results. The Alzheimer's Disease Sequencing Project Phenotype Harmonization Consortium (ADSP-PHC) harmonized rich endophenotype data across multiple cohort studies, providing valuable resources for ADRD research.

Public Health.

Background: Increasing underrepresented racial and ethnic minority group (URG) participation in early-stage Alzheimer's disease and related dementias (ADRD) research is critical to inclusive characterization of underlying pathology and testing of disease-modifying treatments. One promising recruitment strategy to accelerate URG participation is for healthcare professionals (HCPs) to facilitate referrals. The use of HCP-facilitated recruitment strategies across the Alzheimer's Disease Research Center (ADRC) network, a major referral source for ADRD multisite observational and clinical trials, has not been examined.

Public Health.

Background: Greater occupational complexity may be protective against dementia in later life, but it is unclear if it contributes to cognitive resilience and whether different aspects of occupational complexity are associated with resilience. We examined relationships between occupational complexity related to data, people, and things, and cognitive resilience to neurodegeneration.

Method: 1,699 participants from the Framingham Heart Study Offspring cohort who were aged ≥60 years, had a plasma total tau (t-tau) measure (a marker of neurodegeneration), and a neuropsychological (NP) exam visit within five years of the plasma t-tau measurement were included.

Public Health.

Background: To estimate the additive associations of cardiometabolic multimorbidity (CMM) and depression on long-term cognitive trajectory in multi-regional cohorts and validate the generalizability of the findings in varying clinical settings.

Method: Data harmonization was performed across 14 longitudinal cohort studies within the Cohort Studies of Memory in an International Consortium (COSMIC) group, spanning North America, South America, Europe, Africa, Asia, and Australia. Three external validation studies with distinct settings were employed to assess generalizability.

Public Health.

Background: Adverse social exposome (indexed by national Area Deprivation Index [ADI] 80-100 or 'high ADI') is linked to structural inequities and increased risk of Alzheimer's disease neuropathology. Twenty percent of the US population resides within high ADI areas, predominantly in inner cities, tribal reservations and rural areas. The percentage of brain donors from high ADI areas within the Alzheimer's Disease Research Center (ADRC) brain bank system is unknown.

Public Health.

Background: Asian Americans and Asian Canadians (ASACs) are the fastest growing minority group in the US and Canada. However, ASACs are under-sampled in Alzheimer's disease (AD) research. To address the need of culturally appropriate clinical protocols and community-based recruitment approaches for ASACs, the Asian Cohort for Alzheimer's Disease (ACAD), the first large dementia genetics cohort focusing on Chinese, Korean, and Vietnamese, launched in 2021 to examine genetic and non-genetic risk factors for AD among ASACs.

Public Health.

Background: Some evidence supports an association between traumatic brain injury (TBI) and greater risk of dementia, but the role of cognitive resilience in this association is poorly understood.

Method: 2,050 participants from the Framingham Heart Study Offspring cohort who were aged ≥60 year and had a plasma total tau (t-tau) measure at Exam 8 (2005-2008), and a neuropsychological (NP) exam visit within five years were included. Plasma t-tau was measured using the Simoa assay (Quanterix).

Public Health.

Background: Previous studies suggest limited knowledge about Alzheimer's Disease (AD) is a barrier to underrepresented group participation in AD research. Connections between knowledge of AD and factors like social determinants of health or confidence in biomarker research have not been carefully examined. We hypothesized perceived knowledge about AD would be associated with research hesitancy independent of sociodemographics and trust of researchers.

Public Health.

Background: The Mediterranean diet has been associated with decreased brain atrophy (Staubo et al. 2016,Alz&Dem), but the MIND (Mediterranean-Dietary Approaches to Stop Hypertension (DASH) Intervention for Neurodegenerative Delay) diet, designed for dementia prevention (Morris et al. 2015, Alz&Dem), remains underexplored for its impact on brain atrophy.

Public Health.

Background: Shared genetic risk between Alzheimer's disease (AD) and concussion may help explain the association between concussion and elevated risk for dementia. However, there has been little investigation into whether AD risk genes also associate with concussion severity/recovery, and the limited findings are mixed. We used AD polygenic risk scores (PRS) and APOE genotypes to investigate associations between AD genetic risk and concussion severity/recovery in the NCAA-DoD Grand Alliance CARE Consortium (CARE) dataset.

Biomarkers.

Background: Plasma amyloid-beta (Aβ) 42/40 ratio and phosphorylated tau 181 (pTau181) are promising blood biomarkers for AD. Compared to heterogenous clinical phenotypes, they are more objective and proximal to the pathological hallmarks of Aβ plaques and tau tangles. Biomarker-guided clustering using Aβ42/40 and pTau181 can potentially establish subpopulations that share similar mechanisms of AD and treatment responses.

Biomarkers.

Background: Alzheimer's disease (AD) patients have decline in cognitive domains including memory, language, visuospatial, and/or executive function and brain pathology including amyloid-β and tau deposition, neurodegeneration, and frequent vascular co-pathologies detectable by neuroimaging and/or cerebrospinal fluid biomarkers. However, molecular disease mechanisms are complex and heterogeneous. It is necessary to develop cost-effective blood-based biomarkers reflecting brain molecular perturbations in AD.

Biomarkers.

Background: Changes in brain network organization are influenced by aging. Accumulation of amyloid-beta (Aβ) and neurodegeneration in the neocortex are also expected to alter neuronal networks. Therefore, we examined the relationship between aging and brain functional connectivity (FC), as well as the effect of brain Aβ on this relationship.

Biomarkers.

Background: Glial fibrillary acidic protein (GFAP) is a marker of cerebral astrogliosis and occasionally elevated in patients with dementia. GFAP in cerebrospinal fluid (CSF), is routinely requested in referrals to neurochemistry laboratories; however, its ability to differentiate dementias and diagnostic capability is unclear. Our aim was to elucidate this, using two large datasets.

Biomarkers.

Background: The hippocampus, a region vital for memory and cognition, is prone to abnormal deposition of beta-amyloid (Aβ) during the early stages of the Alzheimer's disease. Aβ-associated pathophysiological mechanisms instigate dendritic deficit, neuronal loss, and neuroinflammation, leading to abnormal functional and behavioral changes. These factors directly impact tissue microstructures.

Biomarkers.

Background: The eye often reflects changes seen in the brain in neurodegenerative diseases. This study sought to examine the relationship of retinal vasculature measured using optical coherence tomography angiography (OCTA) with temporal lobe neurodegeneration, and cerebral amyloid and tau deposition, in older adults along the Alzheimer's disease (AD) continuum.

Method: Participants included 13 cognitively normal subjects, 5 with subjective cognitive decline (SCD), 7 with cognitive impairment (mild cognitive impairment [MCI] and AD) from the Indiana Memory and Aging Study at the Indiana ADRC.