Developing Topics.

Background: Agitation, manifesting as aggressive and non-aggressive behaviors, is one of the most common neuropsychiatric symptoms in Alzheimer's dementia, presenting in approximately half of all patients. Despite the high prevalence, recognition of agitation in Alzheimer's dementia (AAD) remains a challenge that impacts timely diagnosis and treatment. The International Psychogeriatric Association (IPA) established a new standard definition of agitation in cognitive disorders, which provides guidance for advancing recognition and improving patient care.

Developing Topics.

Background: Purinergic signaling is vital in various cellular processes like neuroinflammation, synaptic transmission, Aβ clearance, and tau phosphorylation regulation. This study aims to examine if SNPs in purinergic signaling genes are associated to A/T(N) status biomarkers in Alzheimer's Disease through Genome Wide Association Studies.

Method: The SNPRelate package was used to analyze SNPs in genes related to purinergic signaling and A/T(N) markers.

Developing Topics.

Background: Amyloid deposition occurs during the preclinical stages of Alzheimer's disease (AD) a decade or more before clinical symptoms emerge. We leveraged blood transcriptomics and positron emission tomography (PET) measures of amyloidosis to identify cell types and gene networks in the blood that relate to amyloid burden in the brain.

Method: Whole blood RNA sequencing and amyloid PET data were leveraged from 1771 participants (62% females, mean age 71, 32% amyloid+) in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) Study.

Developing Topics.

Background: Alzheimer's disease (AD) is a devastating form of dementia, and its prevalence is rising as human lifespan increases. Our lab created the AD-BXD mouse model, which expresses AD mutations across a genetically diverse reference panel (BXD), to identify factors that confer resilience to cognitive decline in AD. This model mimics key characteristics of human AD including variation in age of onset and severity of cognitive decline.

Developing Topics.

Background: Understanding the relationship between cardiovascular burden, amyloid, and cognition in Alzheimer's disease (AD) is essential for targeted interventions, especially in ethnically diverse populations where research remains limited. This study aimed to investigate these relationships in a cohort of Korean older adults along the AD spectrum.

Method: 526 participants from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) cohort were included in this study.

Developing Topics.

Background: The residual approach has found wide application in researching cognitive resilience, a phenomenon conceptually understood as cognitive performance being better-than-typical for an individual, despite apparent AD pathology. The standard residual approach extracts information about an individual's resilience from the residuals of a linear model predicting cognition. This approach is subject to several limiting assumptions.

Developing Topics.

Background: Adults with Down syndrome (DS) are at a high risk of developing Alzheimer's disease (AD) due to the triplication of the amyloid precursor protein on chromosome 21. Despite the high incidence of AD within the DS population, there is less understanding of how AD progresses, although it may be reflected in an accelerated aging phenotype. Compared to typically developing populations, there is less understanding of the decline of cholinergic integrity with aging in adults with DS.

Developing Topics.

Background: Sleep dysfunctions are highly comorbid with Alzheimer's disease (AD), though often associated with later stages of AD, sleep disruptions have been noted to appear decades before the onset of cognitive symptoms. Here, we provide the first evidence that genetic factors interact with AD mutations to influence sleep behavior even before the onset of cognitive symptoms.

Method: To identify novel genetic factors underlying disordered sleep that precede cognitive decline in our AD-BXD mouse genetic reference panel (n = 179 mice across 25 strains, 7-months-old), we first used sleep phenotypes measured in the PiezoSleep chambers and performed quantitative trait loci (QTL) mapping and discovered Kirrel3 as the novel gene candidate associated with disordered sleep.

Developing Topics.

Background: Cognitive impairment with age remains undetected until it interferes daily life activity or presents dementia symptoms. In the US, 61% of dementia population is not diagnosed, which is in part due to limited sensitivity of clinical neuroimaging modalities in assessing early gray matter (GM) changes. Here we look at microstructural changes in GM using mean apparent propagator (MAP-MRI) in cognitively underperforming (CU) and healthy aging (HA) cohorts, grouped according to their cognitive performance based on the NIH Toolbox.

Developing Topics.

Background: MR-visible perivascular space (PVS) burden is associated with clinical and MRI features of cerebrovascular disease. Its utility as an in vivo biomarker of post-mortem pathology is uncertain.

Method: Eighteen older adults (age at death 98.

Developing Topics.

Background: Socioeconomic neighborhood disadvantage has been linked to accelerated biological aging, cognitive decline, and core Alzheimer's disease neuropathology independent of individual-level factors. Our recent work indicates neighborhood disadvantage is also implicated in cerebrovascular changes known to exacerbate the development of AD, including neurovascular and hemodynamic dysfunction. Here, we investigated how neighborhood disadvantage relates to microstructural changes in white matter, a sensitive biomarker for emerging cerebrovascular disease and related neurodegeneration.

Developing Topics.

Background: Females tend to exhibit more Alzheimer's disease (AD) pathology and have more clinical symptoms compared to males with similar levels of pathology. Post-mortem studies in patients with AD have revealed that neuropathology is related to cognitive decline trajectories before death. However, what remains unclear is the intersection between sex differences in post-mortem pathology and cognitive decline.

Developing Topics.

Background: Extensive research on the cerebral cortex and the hippocampus has improved our understanding of mild cognitive impairment (MCI) and Alzheimer's disease (AD). Historically, however, the cerebellum's role in these stages of cognitive decline has been traditionally neglected due to its associations with motor function. Recent research has demonstrated cerebellar structural and connectivity differences in MCI and AD.

Developing Topics.

Background: Alzheimer's disease (AD) is characterized by the accumulation of pathological amyloid protein deposits in the brain. Analyzing the proteomic composition amyloid plaques is essential for advancing biomedical research on Alzheimer's disease. Laser capture microdissection (LCM) is a technique that enables precise isolation and collection of specific cells or structures from tissue samples.

Developing Topics.

Background: Previous models of resilience to Alzheimer's Disease (AD) have relied on cross-sectional designs and inclusion of measures of neuropathology. Here, we present a novel modeling approach incorporating longitudinal data and the use of APOE and higher order interaction terms to approximate neuropathological resilience, vastly increasing participant diversity and statistical power. We validate this approach and report novel genetic associations with neuropathological resilience.

Alzheimer's Imaging Consortium.

Background: This study investigated microstructural features of the locus coeruleus to entorhinal cortex pathway (LC-EC) in relation to amyloid (A), tau (T), neurodegeneration (N) markers and cognitive impairment in memory clinic patients.

Method: 124 participants were recruited from the Geneva Memory Clinic (n=30 cognitively unimpaired - CU; n=80 MCI and n=14 dementia - CI) and underwent clinical assessment, 3T MRI scan including diffusion weighted imaging, amyloid PET, and tau PET. Diffusivity indices (fractional anisotropy - FA, mean, axial and radial diffusivities - MD, AxD, RD) were assessed in the LC-EC pathway using a probabilistic atlas.

Alzheimer's Imaging Consortium.

Background: Older females, particularly susceptible to Alzheimer's disease (AD), may be affected by hormonal fluctuation during life. We aim to investigate the relationship between changes in brain volume and sex steroid hormones over time. We hypothesize that levels of sex hormones (17ß-estradiol, progesterone, and testosterone) relate to changes in brain volume, especially in the hippocampus (HPC) and cerebellum (CB).

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: Recent research emphasizes the significance of white matter tracts and the free-water (FW) component in understanding cognitive decline. The goal of this study is to conduct a large-scale assessment on the role of white matter microstructure on longitudinal cognitive decline.

Method: This study used a cohort collated from seven longitudinal cohorts of aging (ADNI, BIOCARD, BLSA, NACC, ROS/MAP/MARS, VMAP, and WRAP).

Alzheimer's Imaging Consortium.

Background: Medial temporal lobe (MTL) atrophy is an early feature of multiple neurodegenerative diseases. In genetic frontotemporal lobar degeneration (FTLD, i.e.

Alzheimer's Imaging Consortium.

Background: APOE is in linkage disequilibrium with the length of poly-T repeats at the rs10524523 ('523) locus of the TOMM40 gene. APOE-e3 is associated with short (S) and (VL) variants of '523 in white and Black individuals. In white individuals, APOE-e4 is associated with the long (L) '523 variant, but is associated with '523-S, '523-L, and '523-VL variants in Black individuals.

Alzheimer's Imaging Consortium.

Background: Aging is linked to significant white matter abnormalities, which are often studied using traditional diffusion tensor imaging (DTI) metrics; however, these traditional metrics have limited sensitivity/specificity to neurobiological characteristics. Here, we use fixel-based analysis (FBA) - an approach with more precision in areas of crossing fibers - to study age-related white matter microstructural decline.

Method: This study uses cross-sectional data from the Vanderbilt Memory & Aging Project cohort [n=325, age at baseline: 72.

Alzheimer's Imaging Consortium.

Background: Financial exploitation vulnerability (FEV) denotes the risk for falling victim to financial fraud and older adults reportedly lose an estimated $36 billion annually to scams. Socioemotional and cognitive impairments are potential risk factors for FEV in older adults with dementia. The present study examines whether the socioemotional measures of sensitivity to unfairness and self-unawareness of socioemotional dysfunction and brain atrophy are associated with increased risk for FEV in Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD).

Alzheimer's Imaging Consortium.

Background: Underrepresented racial and ethnic groups have higher rates of clinical dementia symptoms and are given clinical diagnoses of Alzheimer's disease without confirmatory AD biomarkers.

Method: We compared amyloid PET positivity in cohort of all rural and suburban Southeastern participants from a single clinical practice who met appropriate-use criteria for amyloid PET imaging between January 2020-December 2024. We used a paired nominal date test McNemar test to compare amyloid PET positivity proportions between matched racial and ethnic groups and multivariable logistic regression to assess the odds of having a positive amyloid PET scan.

Alzheimer's Imaging Consortium.

Background: Although ß-amyloid and tau PET positivity (A+T+) has been related to neurodegeneration and cognitive decline in Alzheimer's disease (AD), the driving force of neurodegeneration in discordant AT cases remains controversial. We investigated the impact of AT status on longitudinal rates of cortical atrophy and cognitive decline.

Method: A subset of 349 individuals (cognitively unimpaired [CU; n = 230], cognitively impaired [CI; n = 119]) with ß-amyloid and tau PET (a priori baseline), longitudinal MRI (interval; Mean = 4.