Adaptive measurement of cognitive function based on multidimensional item response theory.

Introduction: Up to 20% of older adults in the United States have mild cognitive impairment (MCI), and about one-third of people with MCI are predicted to transition to Alzheimer's disease (AD) within 5 years. Standard cognitive assessments are long and require a trained technician to administer. We developed the first computerized adaptive test (CAT) based on multidimensional item response theory (MIRT) to more precisely, rapidly, and repeatedly assesses cognitive abilities across the adult lifespan.

Biological effects of sodium phenylbutyrate and taurursodiol in Alzheimer's disease.

Introduction: Sodium phenylbutyrate and taurursodiol (PB and TURSO) is hypothesized to mitigate endoplasmic reticulum stress and mitochondrial dysfunction, two of many mechanisms implicated in Alzheimer's disease (AD) pathophysiology.

Methods: The first-in-indication phase 2a PEGASUS trial was designed to gain insight into PB and TURSO effects on mechanistic targets of engagement and disease biology in AD. The primary clinical efficacy outcome was a global statistical test combining three endpoints relevant to disease trajectory (cognition [Mild/Moderate Alzheimer's Disease Composite Score], function [Functional Activities Questionnaire], and total hippocampal volume on magnetic resonance imaging).

Characterizing cognitive profiles in diverse middle-aged and older Hispanics/Latinos: Study of Latinos-Investigation of Neurocognitive Aging (HCHS/SOL).

Introduction: We investigated cognitive profiles among diverse, middle-aged and older Hispanic/Latino adults in the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) cohort using a cross-sectional observational study design.

Methods: Based on weighted descriptive statistics, the average baseline age of the target population was 56.4 years, slightly more than half were women (54.

Cardiometabolic disease, cognitive decline, and brain structure in middle and older age.

Introduction: The presence of multiple cardiometabolic diseases (CMDs) has been linked to increased dementia risk, but the combined influence of CMDs on cognition and brain structure across the life course is unclear.

Methods: In the UK Biobank, 46,562 dementia-free participants completed a cognitive test battery at baseline and a follow-up visit 9 years later, at which point 39,306 also underwent brain magnetic resonance imaging. CMDs (diabetes, heart disease, and stroke) were ascertained from medical records.

Normative data for the Digit Symbol Substitution for diverse Hispanic/Latino adults: Results from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA).

Introduction: Executive functioning and processing speed are crucial elements of neuropsychological assessment. To meet the needs of the Hispanic/Latino population, we aimed to provide normative data for the Digit Symbol Substitution (DSS) test.

Methods: The target population for the Study of Latinos-Investigation of Neurocognitive Aging included six heritage backgrounds ( = 6177).

Stability and change in acculturation-related characteristics in older Latinos: Implications for culturally compatible ADRD research.

Introduction: Acculturation-related characteristics, that is, factors directly connected to culture and familial relationships, are associated with engaged research participation within Latino communities. Despite this, little empirical data exists on whether acculturation changes over time in older Latinos, which has potential implications for Alzheimer's disease and related dementias (ADRD) research study design including longer duration clinical trial implementation.

Methods: Self-identified Latinos ( = 222; mean age = 71, 76% female) participating in one of three ongoing longitudinal community-based cohort studies of aging who reported their nativity outside of the United States/District of Columbia (US/DC) contributed, on average, 4.

Grip strength, gait speed, and trajectories of cognitive function in community-dwelling older adults: A prospective study.

Introduction: This study investigated whether grip strength and gait speed predict cognitive aging trajectories and examined potential sex-specific associations.

Methods: Community-dwelling older adults ( = 19,114) were followed for up to 7 years, with regular assessment of global function, episodic memory, psychomotor speed, and executive function. Group-based multi-trajectory modeling identified joint cognitive trajectories.

Combination of gait speed and grip strength to predict cognitive decline and dementia.

Introduction: To determine whether slowed gait and weakened grip strength independently, or together, better identify risk of cognitive decline or dementia.

Methods: Time to walk 3 meters and grip strength were measured in a randomized placebo-controlled clinical trial involving community-dwelling, initially cognitively healthy older adults (N = 19,114).

Results: Over a median 4.

Retinal arteriolar parameters as a surrogate marker of intracranial vascular pathology.

Introduction: Development of novel diagnostic tools is a top research priority in vascular dementia. A major obstacle is the lack of a simple, non-invasive method to visualize cerebral arteriolar walls in vivo. Retinal arterioles offer a window into the cerebral circulation.

Marine n-3 fatty acids and cognitive change among older adults in the VITAL randomized trial.

Introduction: : Few large, randomized trials have evaluated marine n-3 supplements and cognition in healthy older adults.

Methods: : Healthy community-dwelling participants aged 60+ years (mean [standard deviation] = 70.9 [5.

Instrumental validation of free water, peak-width of skeletonized mean diffusivity, and white matter hyperintensities: MarkVCID neuroimaging kits.

Introduction: To describe the protocol and findings of the instrumental validation of three imaging-based biomarker kits selected by the MarkVCID consortium: free water (FW) and peak width of skeletonized mean diffusivity (PSMD), both derived from diffusion tensor imaging (DTI), and white matter hyperintensity (WMH) volume derived from fluid attenuation inversion recovery and T1-weighted imaging.

Methods: The instrumental validation of imaging-based biomarker kits included inter-rater reliability among participating sites, test-retest repeatability, and inter-scanner reproducibility across three types of magnetic resonance imaging (MRI) scanners using intra-class correlation coefficients (ICC).

Results: The three biomarkers demonstrated excellent inter-rater reliability (ICC >0.

10-year frailty trajectory is associated with Alzheimer's dementia after considering neuropathological burden.

Main Problem: Frailty is an established risk factor for cognitive decline and Alzheimer's disease. Few studies have examined the longitudinal relationship between frailty and cognition.

Methods: Participants of Rush Memory and Aging project ( = 625, 67.

Normative data for the Brief Spanish-English Verbal Learning Test for representative and diverse Hispanics/Latinos: Results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

Introduction: Episodic learning and memory performance are crucial components of cognitive assessment. To meet the needs of a diverse Hispanic/Latino population, we aimed to provide normative data on the Brief Spanish-English Verbal Learning Test (B-SEVLT).

Methods: The target population for the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) included individuals 45+ years old from Central American, Cuban, Dominican, Mexican, Puerto Rican, and South American backgrounds.

Neuropsychiatric symptoms in Brazilians with mild cognitive impairment and dementia.

Introduction: Knowledge is limited about behavioral and psychological symptoms of mild cognitive impairment (MCI) and dementia in racial and ethnic minorities.

Methods: As part of the Pathology, Alzheimer's and Related Dementias Study (PARDoS), we interviewed knowledgeable informants of 2319 older Brazilian decedents (67% white, 11% black, 22% mixed) using the informant portion of the Clinical Dementia Rating Scale to classify MCI and dementia and the Neuropsychiatric Inventory to assess behavioral and psychological symptoms.

Results: We identified four clusters of neuropsychiatric symptoms: agitation, affect/apathy, psychosis, and behavioral problems.

Longitudinal cognitive performance of Alzheimer's disease neuropathological subtypes.

Introduction: Alzheimer's disease (AD) neuropathological subtypes (limbic predominant [lpAD], hippocampal sparing [HpSpAD], and typical [tAD]), defined by relative neurofibrillary tangle (NFT) burden in limbic and cortical regions, have not been studied in prospectively characterized epidemiological cohorts with robust cognitive assessments.

Methods: Two hundred ninety-two participants with neuropathologically confirmed AD from the Religious Orders Study and Memory and Aging Project were categorized by neuropathological subtype based on previously specified diagnostic criteria using quantitative regional NFT counts. Rates of cognitive decline were compared across subtypes using linear mixed-effects models that included subtype, time, and a subtype-time interaction as predictors and four cognitive domain factor scores (memory, executive function, language, visuospatial) and a global score as outcomes.

Feasibility study for detection of retinal amyloid in clinical trials: The Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) trial.

Introduction: The retina and brain exhibit similar pathologies in patients diagnosed with neurodegenerative diseases. The ability to access the retina through imaging techniques opens the possibility for non-invasive evaluation of Alzheimer's disease (AD) pathology. While retinal amyloid deposits are detected in individuals clinically diagnosed with AD, studies including preclinical individuals are lacking, limiting assessment of the feasibility of retinal imaging as a biomarker for early-stage AD risk detection.

Polygenic score modifies risk for Alzheimer's disease in ε4 homozygotes at phenotypic extremes.

Introduction: Diversity in cognition among apolipoprotein E () ε4 homozygotes can range from early-onset Alzheimer's disease (AD) to a lifetime with no symptoms.

Methods: We evaluated a phenotypic extreme polygenic risk score (PRS) for AD between cognitively healthy ε4 homozygotes aged ≥75 years (n = 213) and early-onset ε4 homozygote AD cases aged ≤65 years (n = 223) as an explanation for this diversity.

Results: The PRS for AD was significantly higher in ε4 homozygote AD cases compared to older cognitively healthy ε4/ε4 controls (odds ratio [OR] 8.

Trajectories of cognitive function in community-dwelling older adults: A longitudinal study of population heterogeneity.

Introduction: This study aimed to investigate cognitive aging trajectories, the associated sociodemographic characteristics, and the association of these trajectories with dementia.

Methods: Generally healthy older adults (n = 19,114) were followed for up to 7 years, with regular cognitive assessments. Group-based trajectory modeling identified distinct cognitive trajectories.

Differentiating among stages of cognitive impairment in aging: Version 3 of the Uniform Data Set (UDS) neuropsychological test battery and MoCA index scores.

Introduction: Federally funded Alzheimer's Disease Centers in the United States have been using a standardized neuropsychological test battery as part of the National Alzheimer's Coordinating Center Uniform Data Set (UDS) since 2005. Version 3 (V3) of the UDS replaced the previous version (V2) in 2015. We compared V2 and V3 neuropsychological tests with respect to their ability to distinguish among the Clinical Dementia Rating (CDR) global scores of 0, 0.

Blood DNA methylation signatures to detect dementia prior to overt clinical symptoms.

Introduction: This study determined whether blood DNA methylation (DNAm) patterns differentiate individuals with presymptomatic dementia compared to controls.

Methods: DNAm was measured in 73 individuals prior to dementia diagnosis and 87 cognitively healthy controls matched for age, sex, smoking, education, and baseline cognition. DNAm was also measured at 3 years follow-up in 25 dementia cases, and 24 controls.

Lower practice effects as a marker of cognitive performance and dementia risk: A literature review.

Background: Practice effects (PEs) are improvements in performance after repeated exposure to test materials, and typically viewed as a source of bias in repeated cognitive assessments. We aimed to determine whether characterizing PEs could also provide a useful marker of early cognitive decline.

Methods: We conducted a systematic review of the literature, searching PsycInfo (Ebsco) and PubMed databases for articles studying PEs in aging and dementia populations.