Informing etiological heterogeneity of mild cognitive impairment and risk for progression to dementia with plasma p-tau217.

Background: Mild cognitive impairment (MCI) is a clinical diagnosis representing early symptom changes with preserved functional independence. There are multiple potential etiologies of MCI. While often presumed to be related to Alzheimer's disease (AD), other neurodegenerative and non-neurodegenerative causes are common.

Longitudinal cognitive performance of participants with sporadic early onset Alzheimer's disease from LEADS.

Introduction: Early-onset Alzheimer's disease (EOAD) manifests prior to the age of 65, and affects 4%-8% of patients with Alzheimer's disease (AD). The current analyses sought to examine longitudinal cognitive trajectories of participants with early-onset dementia.

Methods: Data from 307 cognitively normal (CN) volunteer participants and those with amyloid-positive EOAD or amyloid-negative cognitive impairment (EOnonAD) were compared.

Differences in baseline cognitive performance between participants with early-onset and late-onset Alzheimer's disease: Comparison of LEADS and ADNI.

Introduction: Early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) share similar amyloid etiology, but evidence from smaller-scale studies suggests that they manifest differently clinically. Current analyses sought to contrast the cognitive profiles of EOAD and LOAD.

Methods: Z-score cognitive-domain composites for 311 amyloid-positive sporadic EOAD and 314 amyloid-positive LOAD participants were calculated from baseline data from age-appropriate control cohorts.

Predictors of Retention in the 1Florida Alzheimer's Disease Research Center (ADRC) Over Two Waves.

Attrition is a significant methodological concern in longitudinal studies. Sample loss can limit generalizability and compromise internal validity. Wave one ( = 346) and wave two follow-ups ( = 196) of the 1Florida ADRC clinical core were examined using a 24-month visit window.

The Association Between Plasma Amyloid-β 42/40 and Percentage of Semantic Intrusion Errors in Mild Cognitive Impairment.

Background: Semantic intrusion errors (SIEs) are both sensitive and specific to PET amyloid-β (Aβ) burden in older adults with amnestic mild cognitive impairment (aMCI).

Objective: Plasma Aβ biomarkers including the Aβ42/40 ratio using mass spectrometry are expected to become increasingly valuable in clinical settings. Plasma biomarkers are more clinically informative if linked to cognitive deficits that are salient to Alzheimer's disease (AD).

Neuroimaging and biofluid biomarkers across race and ethnicity in older adults across the spectrum of cognition.

Neuroimaging and biofluid biomarkers provide a proxy of pathological changes for Alzheimer's disease (AD) and are useful in improving diagnosis and assessing disease progression. However, it is not clear how race/ethnicity and different prevalence of AD risks impact biomarker levels. In this narrative review, we survey studies focusing on comparing biomarker differences between non-Hispanic White American(s) (NHW), African American(s) (AA), Hispanic/Latino American(s) (HLA), and Asian American(s) with normal cognition, mild cognitive impairment, and dementia.

Functional measures and AD biomarkers among Hispanic and White non-Hispanic older adults.

Introduction: Poorer baseline functioning is associated with long-term cognitive decline among Hispanic older adults, but little is known about associations of these factors with Alzheimer's disease (AD) neuroimaging biomarkers.

Methods: A total of 461 Hispanic and White non-Hispanic (NHW) older adults who are cognitively normal ( = 76), had impaired cognition without mild cognitive impairment (MCI) ( = 41), or carried a diagnosis of MCI ( = 253) or dementia ( = 91) completed neuropsychological and functional assessment, genetic testing, and brain magnetic resonance imaging (MRI). Structural equation modeling (SEM) was used to examine predictive associations between functional and cognitive measures of AD neuroimaging biomarkers.

A Protocol for the Inclusion of Minoritized Persons in Alzheimer Disease Research From the ADNI3 Diversity Taskforce.

Importance: Black or African American (hereinafter, Black) and Hispanic or Latino/a/x (hereinafter, Latinx) adults are disproportionally affected by Alzheimer disease, but most research studies do not enroll adequate numbers of both of these populations. The Alzheimer's Disease Neuroimaging Initiative-3 (ADNI3) launched a diversity taskforce to pilot a multipronged effort to increase the study inclusion of Black and Latinx older adults.

Objective: To describe and evaluate the culturally informed and community-engaged inclusion efforts to increase the screening and enrollment of Black and Latinx older adults in ADNI3.

Plasma p-tau217 concordance with amyloid PET among ethnically diverse older adults.

Introduction: Commercially available plasma p-tau217 biomarker tests are not well studied in ethnically diverse samples.

Methods: We evaluated associations between ALZPath plasma p-tau217 and amyloid-beta positron emission tomography (Aβ-PET) in Hispanic/Latino (88% of Cuban or South American ancestry) and non-Hispanic/Latino older adults. One- and two-cutoff ranges were derived and evaluated to assess agreement with Aβ-PET.

Clinicopathologic Heterogeneity and Glial Activation Patterns in Alzheimer Disease.

Importance: Factors associated with clinical heterogeneity in Alzheimer disease (AD) lay along a continuum hypothesized to associate with tangle distribution and are relevant for understanding glial activation considerations in therapeutic advancement.

Objectives: To examine clinicopathologic and neuroimaging characteristics of disease heterogeneity in AD along a quantitative continuum using the corticolimbic index (CLix) to account for individuality of spatially distributed tangles found at autopsy.

Design, Setting, And Participants: This cross-sectional study was a retrospective medical record review performed on the Florida Autopsied Multiethnic (FLAME) cohort accessioned from 1991 to 2020.

Neuropathology, Neuroimaging, and Fluid Biomarkers in Alzheimer's Disease.

An improved understanding of the pathobiology of Alzheimer's disease (AD) should lead ultimately to an earlier and more accurate diagnosis of AD, providing the opportunity to intervene earlier in the disease process and to improve outcomes. The known hallmarks of Alzheimer's disease include amyloid-β plaques and neurofibrillary tau tangles. It is now clear that an imbalance between production and clearance of the amyloid beta protein and related Aβ peptides, especially Aβ42, is a very early, initiating factor in Alzheimer's disease (AD) pathogenesis, leading to aggregates of hyperphosphorylation and misfolded tau protein, inflammation, and neurodegeneration.

Clinical utility of plasma Aβ42/40 ratio by LC-MS/MS in Alzheimer's disease assessment.

Introduction: Plasma Aβ42/40 ratio can help predict amyloid PET status, but its clinical utility in Alzheimer's disease (AD) assessment is unclear.

Methods: Aβ42/40 ratio was measured by LC-MS/MS for 250 specimens with associated amyloid PET imaging, diagnosis, and demographic data, and for 6,192 consecutive clinical specimens submitted for Aβ42/40 testing.

Results: High diagnostic sensitivity and negative predictive value (NPV) for Aβ-PET positivity were observed, consistent with the clinical performance of other plasma LC-MS/MS assays, but with greater separation between Aβ42/40 values for individuals with positive vs.

Diffusion MRI relates to plasma Aβ42/40 in PET negative participants without dementia.

Introduction: Magnetic resonance imaging (MRI) biomarkers are needed for indexing early biological stages of Alzheimer's disease (AD), such as plasma amyloid-β (Aβ42/40) positivity in Aβ positron emission tomography (PET) negative individuals.

Methods: Diffusion free-water (FW) MRI was acquired in individuals with normal cognition (NC) and mild cognitive impairment (MCI) with Aβ plasma-/PET- (NC = 22, MCI = 60), plasma+/PET- (NC = 5, MCI = 20), and plasma+/PET+ (AD dementia = 21) biomarker status. Gray and white matter FW and fractional anisotropy (FAt) were compared cross-sectionally and the relationships between imaging, plasma and PET biomarkers were assessed.

Multi-omics Characterization of Epigenetic and Genetic Risk of Alzheimer Disease in Autopsied Brains from two Ethnic Groups.

Background: Both genetic variants and epigenetic features contribute to the risk of Alzheimer's disease (AD). We studied the AD association of CpG-related single nucleotide polymorphisms (CGS), which act as the hub of both the genetic and epigenetic effects, in Hispanics decedents and generalized the findings to Non-Hispanic Whites (NHW) decedents.

Methods: First, we derived the dosage of the CpG site-creating allele of multiple CGSes in each 1 KB window across the genome and we conducted a sliding window association test with clinical diagnosis of AD in 7,155 Hispanics (3,194 cases and 3,961 controls) using generalized linear mixed models with the adjustment of age, sex, population structure, genomic relationship matrix, and genotyping batches.

Clinical utility of plasma Aβ42/40 ratio by LC-MS/MS in Alzheimer's disease assessment.

Introduction: Plasma Aβ42/40 ratio can be used to help predict amyloid PET status, but its clinical utility in Alzheimer's disease (AD) assessment is unclear.

Methods: Aβ42/40 ratio was measured by LC-MS/MS in 250 specimens with associated amyloid PET imaging, diagnosis, and demographic data, and 6,192 consecutive clinical specimens submitted for Aβ42/40 testing.

Results: High diagnostic sensitivity and negative predictive value (NPV) for Aβ-PET positivity were observed, consistent with the clinical performance of other plasma LC-MS/MS assays, but with greater separation between Aβ42/40 values for individuals with positive vs negative Aβ-PET results.

Cross-cultural Diagnostic Validity of the Multilingual Naming Test (MINT) in a Sample of Older Adults.

Objective: We aimed to evaluate the psychometric properties and diagnostic accuracy of the 32-item version of the Multilingual Naming Test (MINT) in participants from 2 ethnic groups (European Americans [EA; n = 106] and Hispanic Americans [HA; n = 175]) with 3 diagnostic groups (cognitively normal [CN], n = 94, mild cognitive impairment [MCI], n = 148, and dementia, n = 39).

Method: An Item Response Theory model was used to evaluate items across ethnicity and language groups (Spanish and English), resulting in a 24-item version. We analyzed the MINT discriminant and predictive validity across diagnostic groups.

Free-water imaging reveals unique brain microstructural deficits in hispanic individuals with Dementia.

Prior evidence suggests that Hispanic and non-Hispanic individuals differ in potential risk factors for the development of dementia. Here we determine whether specific brain regions are associated with cognitive performance for either ethnicity along various stages of Alzheimer's disease. For this cross-sectional study, we examined 108 participants (61 Hispanic vs.

Association of Physical Frailty and Cognitive Function in a Population-Based Cross-Sectional Study of American Older Adults.

Introduction: Cognitive impairment and frailty are prevalent in older persons. Physical frailty is associated with cognitive decline; however, the role of effect modifiers such as age, sex, race/ethnicity, and cognitive reserve is not well understood.

Methods: Cross-sectional data from the National Health and Nutrition Examination Survey (2011-2014) were obtained for participants aged ≥60 years.

Plasma Alzheimer's biomarkers and brain amyloid in Hispanic and non-Hispanic older adults.

Introduction: Alzheimer's disease studies often lack ethnic diversity.

Methods: We evaluated associations between plasma biomarkers commonly studied in Alzheimer's (p-tau181, GFAP, and NfL), clinical diagnosis (clinically normal, amnestic MCI, amnestic dementia, or non-amnestic MCI/dementia), and Aβ-PET in Hispanic and non-Hispanic older adults. Hispanics were predominantly of Cuban or South American ancestry.