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.

Long-term neurobehavioral and neuroimaging outcomes in athletes with prior concussion(s) and head impact exposure.

The long-term health of former athletes with a history of multiple concussions and/or repetitive head impact (RHI) exposure has been of growing interest among the public. The true proportion of dementia cases attributable to neurotrauma and the neurobehavioral profile/sequelae of multiple concussion and RHI exposure among athletes has been difficult to determine. Across three exposure paradigms (i.

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.

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.

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.

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.

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.

Stability in cognitive classification as a function of severity of impairment and ethnicity: A longitudinal analysis.

Objective: The interaction of ethnicity, progression of cognitive impairment, and neuroimaging biomarkers of Alzheimer's Disease remains unclear. We investigated the stability in cognitive status classification (cognitively normal [CN] and mild cognitive impairment [MCI]) of 209 participants (124 Hispanics/Latinos and 85 European Americans).

Methods: Biomarkers (structural MRI and amyloid PET scans) were compared between Hispanic/Latino and European American individuals who presented a change in cognitive diagnosis during the second or third follow-up and those who remained stable over time.

Plasma inflammation for predicting phenotypic conversion and clinical progression of autosomal dominant frontotemporal lobar degeneration.

Background: Measuring systemic inflammatory markers may improve clinical prognosis and help identify targetable pathways for treatment in patients with autosomal dominant forms of frontotemporal lobar degeneration (FTLD).

Methods: We measured plasma concentrations of IL-6, TNFα and YKL-40 in pathogenic variant carriers () and non-carrier family members enrolled in the ARTFL-LEFFTDS Longitudinal Frontotemporal Lobar Degeneration consortium. We evaluated associations between baseline plasma inflammation and rate of clinical and neuroimaging changes (linear mixed effects models with standardised (z) outcomes).

Newer glucose-lowering drugs and risk of dementia: A systematic review and meta-analysis of observational studies.

Background: Preclinical studies have suggested potential beneficial effects of newer glucose-lowering drugs (GLDs) including dipeptidyl peptidase (DPP)-4 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and sodium glucose co-transporter-2 (SGLT2) inhibitors, in protecting humans against cognitive decline and dementia. However, population studies aiming to demonstrate such cognitive benefits from newer GLDs have produced mixed findings. This meta-analysis aimed to evaluate the association between newer GLDs and risk of dementia in adults with type 2 diabetes (T2D).

Association of longitudinal cognitive decline with diffusion MRI in Gray Matter, Amyloid, and Tau deposition.

Extracellular amyloid plaques in gray matter are the earliest pathological marker for Alzheimer's disease (AD), followed by abnormal tau protein accumulation. The link between diffusion changes in gray matter, amyloid and tau pathology, and cognitive decline is not well understood. We first performed cross-sectional analyses on T1-weighted imaging, diffusion MRI, and amyloid and tau PETs from the ADNI 2/3 database.

Culture, Ethnicity, and Level of Education in Alzheimer's Disease.

Alzheimer's disease (AD) is the most frequent cause of dementia, where the abnormal accumulation of beta-amyloid (Aβ) and tau lead to neurodegeneration as well as loss of cognitive, behavioral, and functional abilities. The present review analyzes AD from a cross-cultural neuropsychological perspective, looking at differences in culture-associated variables, neuropsychological test performance and biomarkers across ethnic and racial groups. Studies have found significant effects of culture, preferred language, country of origin, race, and ethnicity on cognitive test performance, although the definition of those grouping terms varies across studies.

The relationship of semantic intrusions to different etiological subtypes of MCI and cognitively healthy older adults.

Introduction: There is increasing evidence that susceptibility to proactive semantic interference (PSI) and the failure to recover from PSI (frPSI) as evidenced by intrusion errors may be early cognitive markers of both preclinical and prodromal Alzheimer's disease (AD).

Methods: One hundred forty-five participants were administered extensive clinical and neuropsychological evaluations including the Loewenstein-Acevedo Scales for Semantic Interference and Learning (LASSI-L), a sensitive cognitive stress test measuring PSI and frPSI. Participants also underwent structural magnetic resonance imaging (MRI) and amyloid positron emission tomography/computed tomography (PET/CT) imaging.

Semantic intrusion errors as a function of age, amyloid, and volumetric loss: a confirmatory path analysis.

Objective: To examine the direct and indirect effects of age, APOE ϵ4 genotype, amyloid positivity, and volumetric reductions in AD-prone brain regions as it relates to semantic intrusion errors reflecting proactive semantic interference (PSI) and the failure to recover from proactive semantic interference (frPSI) on the Loewenstein-Acevedo Scales of Semantic Interference and Learning (LASSI-L), a cognitive stress test that has been consistently more predictive of preclinical and prodromal Alzheimer's disease (AD) than traditional list-learning tests.

Design: Cross-sectional study.

Setting: 1Florida Alzheimer's Disease Research Center baseline study.

A Brief Version of the LASSI-L Detects Prodromal Alzheimer's Disease States.

Background: The Loewenstein-Acevedo Scales for Semantic Interference and Learning (LASSI-L) is an increasingly utilized cognitive stress test designed to identify early cognitive changes associated with incipient neurodegenerative disease.

Objective: To examine previously derived cut-points for cognitively unimpaired older adults that were suggestive of performance impairment on multiple subscales of the LASSI-L. These cut-points were applied to a new sample of older adults who were cognitive healthy controls (HC: n = 26) and those on the Alzheimer's disease (AD) continuum from early stage mild cognitive impairment (EMCI: n = 28), late stage MCI (LMCI: n = 18) to mild AD (AD: n = 27).

The Association Between Functional Assessment and Structural Brain Biomarkers in an Ethnically Diverse Sample With Normal Cognition, Mild Cognitive Impairment, or Dementia.

Objective: To investigate the association between the functional activities questionnaire (FAQ) and brain biomarkers (bilateral hippocampal volume [HV], bilateral entorhinal volume [ERV], and entorhinal cortical thickness [ERT]) in cognitively normal (CN) individuals, mild cognitive impairment (MCI), or dementia.

Method: In total, 226 participants (137 females; mean age = 71.76, SD = 7.