Biomarkers.

Background: Studies suggest that approximately 60 to 70 percent of the variability observed in cognitive abilities during aging can be attributed to genetic factors. Therefore, investigating the longitudinal multiomics changes associated with alterations in cognitive measures, such as the Mini-Mental State Examination (MMSE) score, is of utmost importance.

Method: Longitudinal changes in gene and protein expression related to MMSE scores were examined in the Cameron County Hispanic Cohort (CCHC), an extensively phenotyped, randomly-recruited, cohort of Mexican Americans residing at the US-Mexico border.

Biomarkers.

Background: There is an urgent need to move the use of plasma biomarkers from research setting to clinical practice for the early detection of Alzheimer's disease (AD). The aims of the study were to explore the combined use of plasma p-tau181 and NfL in Subjective Cognitive Decline (SCD) and Mild Cognitive Impairment (MCI) patients, evaluating diagnostic accuracy and concordance to propose a flow chart for the clinical applicability.

Method: We included 43 SCD, 41 MCI and 21 AD-dementia (AD-d) patients, who underwent plasma p-tau181 and NfL analysis with SiMoA assay.

Biomarkers.

Background: Progressive supranuclear palsy (PSP) may show concomitant neuropathological findings such as Alzheimer's disease (AD)-related pathologies. Recent advances in CSF biomarkers enabled the estimation of neuropathological changes in brains in various neurodegenerative diseases. Clinical characteristic of subtypes of PSP defined by CSF biomarkers have not been well understood.

Biomarkers.

Background: Previous cross-sectional studies have extensively documented that higher educational attainment (EA) is associated with lower β-amyloid (Aβ) plaques and tau tangles in Alzheimer's disease (AD). However, studies investigating the relationship between EA and longitudinal tau accumulation are strikingly lacking.

Method: We analyzed Aβ-PET (A), tau-PET (T), and 3D T1-MRI images (N) from the ADNI cohort to identify 196 Aβ-PET positive participants (A+) and 114 cognitively unimpaired participants without evidence of AD pathology and neurodegeneration (A-/T-/N-/CU).

Biomarkers.

Background: Use of remote measurement of physiological parameters using digital biometrics (i.e., Electro Dermal Activities, heart rate, oxygen saturation, blood volume pulse, etc.

Oxygen Targets for Mechanically Ventilated Adults with Sepsis: Secondary Analysis of the PILOT Trial.

Background: Patients with sepsis frequently require invasive mechanical ventilation. How oxygenation during mechanical ventilation affects clinical outcomes for patients with sepsis remains uncertain.

Research Question: To evaluate the effects of different oxygen saturation targets on clinical outcomes for patients with sepsis receiving mechanical ventilation.

Biomarkers.

Background: The heterogeneity of Alzheimer's disease (AD) and lack of well-validated markers of co-pathologies present a substantial challenge for therapeutics. We previously found phenotypes defined by Tau (T) - Neurodegeneration (N) discordance linked to non-Alzheimer's pathologies (e.g.

Biomarkers.

Background: Adults with Down Syndrome (DS) have the highest risk of developing Alzheimer's disease (AD) worldwide. Triplication of the amyloid precursor protein gene on chromosome 21 results in early amyloid accumulation and Alzheimer's pathology. The cholinergic system is known to decline early in the development of AD and plays a fundamental role in observed cognitive deficits.

Biomarkers.

Background: Poor sleep has emerged as a potentially modifiable risk factor for Alzheimer's disease (AD) and related dementias (ADRD). Few previous studies have incorporated objectively-measured sleep and structural neuroimaging to understand if poor sleep relates to changes in brain structure. In a cohort of older adults, we investigated actigraphy-measured sleep health and associations with well-established magnetic resonance imaging (MRI) markers of AD-specific neurodegeneration.

Biomarkers.

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

Biomarkers.

Background: Alzheimer's disease (AD) is a pathologically heterogeneous disease making it a challenge to develop effective treatments. Emerging evidence suggests that there are pathological differences between women and men with AD. More biomarkers are needed to enhance sex-specific precision medicine in AD.

Biomarkers.

Background: New techniques have been developed to estimate the age when someone converted to amyloid positivity (EAOA) from PET, oftentimes offering information Aβout a participant decades before they joined a research study. EAOA is variable across populations but we do not know the causes for these differences. This study aims to validate APOE associations with EAOA and explore genetic and sex-based factors with EAOA.

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: Despite evidence that Alzheimer's disease (AD) is highly heritable, there remains substantial "missing" heritability, likely due in part to the effect of rare variants and to the past reliance on case-control analysis. Here, we leverage powerful endophenotypes of AD (cognitive performance across multiple cognitive domains) in a rare variant analysis to identify novel genetic drivers of cognition in aging and disease.

Method: We leveraged 8 cohorts of cognitive aging with whole genome sequencing data from the AD Sequencing Project to conduct rare variant analyses of multiple domains of cognition (N = 9,317; mean age = 73; 56% female; 52% cognitively unimpaired).

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.