Preclinical Alzheimer disease (AD) has been associated with subtle changes in memory, attention, and spatial navigation abilities. The current study examined whether self- and informant-reported domain-specific cognitive changes are sensitive to AD-associated biomarkers.

Clinically normal adults aged 56–93 and their informants completed the memory, divided attention, and visuospatial abilities (which assesses spatial navigation) subsections of the Everyday Cognition Scale (ECog). Reliability and validity of these subsections were examined using Cronbach’s alpha and confirmatory factor analysis. Logistic regression was used to examine the ability of ECog subsections to predict AD-related biomarkers (cerebrospinal fluid (CSF) ptau181/Aβ42 ratio (N = 371) or hippocampal volume (N = 313)). Hierarchical logistic regression was used to examine whether the self-reported subsections continued to predict biomarkers when controlling for depressive symptomatology if available (N = 197). Additionally, logistic regression was used to examine the ability of neuropsychological composites assessing the same or similar cognitive domains as the subsections (memory, executive function, and visuospatial abilities) to predict biomarkers to allow for comparison of the predictive ability of subjective and objective measures.

All subsections demonstrated appropriate reliability and validity. Self-reported memory (with outliers removed) was the only significant predictor of AD biomarker positivity (i.e., CSF ptau181/Aβ42 ratio; p = .018) but was not significant when examined in the subsample with depressive symptomatology available (p = .517). Self-reported memory (with outliers removed) was a significant predictor of CSF ptau181/Aβ42 ratio biomarker positivity when the objective memory composite was included in the model.

ECog subsections were not robust predictors of AD biomarker positivity.

Most neuropsychological tests were developed without the benefit of modern psychometric theory. We used item response theory (IRT) methods to determine whether a widely used test – the 26-item Matrix Reasoning subtest of the WAIS-IV – might be used more efficiently if it were administered using computerized adaptive testing (CAT).

Data on the Matrix Reasoning subtest from 2197 participants enrolled in the National Neuropsychology Network (NNN) were analyzed using a two-parameter logistic (2PL) IRT model. Simulated CAT results were generated to examine optimal short forms using fixed-length CATs of 3, 6, and 12 items and scores were compared to the original full subtest score. CAT models further explored how many items were needed to achieve a selected precision of measurement (standard error ≤ .40).

The fixed-length CATs of 3, 6, and 12 items correlated well with full-length test results (with r = .90, .97 and .99, respectively). To achieve a standard error of .40 (approximate reliability = .84) only 3–7 items had to be administered for a large percentage of individuals.

This proof-of-concept investigation suggests that the widely used Matrix Reasoning subtest of the WAIS-IV might be shortened by more than 70% in most examinees while maintaining acceptable measurement precision. If similar savings could be realized in other tests, the accessibility of neuropsychological assessment might be markedly enhanced, and more efficient time use could lead to broader subdomain assessment.

Valid estimates of premorbid cognitive functioning (PMIQ) are crucial for the assessment of older adults at risk for Alzheimer’s disease. We investigated the relationship between the NIH Toolbox-Cognition Battery’s (NIHTB-CB) Oral Reading Recognition (ORR) subtest and Wechsler Test of Adult Reading scores (WTAR, convergent validity). We also compared ORR to NIHTB-CB Flanker scores, where null relationships were expected (discriminant validity).

The WTAR and NIHTB-CB were administered to 130 cognitively normal (CN) and 113 participants with mild cognitive impairment (MCI). Participants were community-dwelling, older Black and White adults, ages 55–88 years. Data analysis used uncorrected standard scores and Bayesian bivariate correlations. Supplemental materials include intraclass correlations.

ORR and WTAR scores were strongly positively associated, while ORR and Flanker scores were unrelated. This pattern held when restricting analyses to the two cognitive status groups, the two racial groups, and the four race-by-diagnosis subgroups.

The findings demonstrate convergent and discriminant validity and support NIHTB-CB ORR scores as valid estimates of scores on a PMIQ measure in older Black and White adults with and without MCI.

Verbal fluency tests are quick and easy to administer neuropsychological measures and are regularly used in neuropsychological assessment. Additionally, phonological fluency is a widely used paradigm that is sensitive to cognitive impairment. This paper offers normative data of phonological verbal fluency (letters P, M, R) for Spanish middle- and older-aged adults, considering sociodemographic factors, and different measures such as the total number of words, errors (perseveration and intrusions), and 15 sec-segmented scores.

A total of 1165 cognitively unimpaired participants aged between 50 and 89 years old, participated in the study. Data for P were obtained for all participants. Letters M and R were also administered to a subsample of participants (852) aged 60 to 89 years. In addition, errors and words produced every 15 seconds were collected in the subsample. To verify the effect of sociodemographic variables, linear regression was used. Adjustments were calculated for variables that explained at least 5% of the variance (R2 ≥ .05).

Means and standard deviations by age, scaled scores, and percentiles for all tests across different measures are shown. No determination coefficients equal to or greater than .05 were found for sex or age. The need to establish adjustments for the educational level was only found in some of the measures.

The current norms provide clinically useful data to evaluate Spanish-speaking natives from Spain aged from 50 to 89 years. Specific patterns of cognitive impairment can be analyzed using these normative data and may be important in neuropsychological assessment.

The Harmonized Cognitive Assessment Protocol (HCAP) describes an assessment battery and a family of population-representative studies measuring neuropsychological performance. We describe the factorial structure of the HCAP battery in the US Health and Retirement Study (HRS).

The HCAP battery was compiled from existing measures by a cross-disciplinary and international panel of researchers. The HCAP battery was used in the 2016 wave of the HRS. We used factor analysis methods to assess and refine a theoretically driven single and multiple domain factor structure for tests included in the HCAP battery among 3,347 participants with evaluable performance data.

For the eight domains of cognitive functioning identified (orientation, memory [immediate, delayed, and recognition], set shifting, attention/speed, language/fluency, and visuospatial), all single factor models fit reasonably well, although four of these domains had either 2 or 3 indicators where fit must be perfect and is not informative. Multidimensional models suggested the eight-domain model was overly complex. A five-domain model (orientation, memory delayed and recognition, executive functioning, language/fluency, visuospatial) was identified as a reasonable model for summarizing performance in this sample (standardized root mean square residual = 0.05, root mean square error of approximation = 0.05, confirmatory fit index = 0.94).

The HCAP battery conforms adequately to a multidimensional structure of neuropsychological performance. The derived measurement models can be used to operationalize notions of neurocognitive impairment, and as a starting point for prioritizing pre-statistical harmonization and evaluating configural invariance in cross-national research.

Adverse childhood experiences (ACEs) have been associated with worse cognitive health in older adulthood. This study aimed to extend findings on the specificity, persistence, and pathways of associations between two ACEs and cognition by using a comprehensive neuropsychological battery and a time-lagged mediation design.

Participants were 3304 older adults in the Health and Retirement Study Harmonized Cognitive Assessment Protocol. Participants retrospectively reported whether they were exposed to parental substance abuse or experienced parental physical abuse before age 18. Factor scores derived from a battery of 13 neuropsychological tests indexed cognitive domains of episodic memory, executive functioning, processing speed, language, and visuospatial function. Structural equation models examined self-reported years of education and stroke as mediators, controlling for sociodemographics and childhood socioeconomic status.

Parental substance abuse in childhood was associated with worse later-life cognitive function across all domains, in part via pathways involving educational attainment and stroke. Parental physical abuse was associated with worse cognitive outcomes via stroke independent of education.

This national longitudinal study in the United States provides evidence for broad and persistent indirect associations between two ACEs and cognitive aging via differential pathways involving educational attainment and stroke. Future research should examine additional ACEs and mechanisms as well as moderators of these associations to better understand points of intervention.

The Stricker Learning Span (SLS) is a computer-adaptive digital word list memory test specifically designed for remote assessment and self-administration on a web-based multi-device platform (Mayo Test Drive). We aimed to establish criterion validity of the SLS by comparing its ability to differentiate biomarker-defined groups to the person-administered Rey’s Auditory Verbal Learning Test (AVLT).

Participants (N = 353; mean age = 71, SD = 11; 93% cognitively unimpaired [CU]) completed the AVLT during an in-person visit, the SLS remotely (within 3 months) and had brain amyloid and tau PET scans available (within 3 years). Overlapping groups were formed for 1) those on the Alzheimer’s disease (AD) continuum (amyloid PET positive, A+, n = 125) or not (A-, n = 228), and those with biological AD (amyloid and tau PET positive, A+T+, n = 55) vs no evidence of AD pathology (A−T−, n = 195). Analyses were repeated among CU participants only.

The SLS and AVLT showed similar ability to differentiate biomarker-defined groups when comparing AUROCs (p’s > .05). In logistic regression models, SLS contributed significantly to predicting biomarker group beyond age, education, and sex, including when limited to CU participants. Medium (A− vs A+) to large (A−T− vs A+T+) unadjusted effect sizes were observed for both SLS and AVLT. Learning and delay variables were similar in terms of ability to separate biomarker groups.

Remotely administered SLS performed similarly to in-person-administered AVLT in its ability to separate biomarker-defined groups, providing evidence of criterion validity. Results suggest the SLS may be sensitive to detecting subtle objective cognitive decline in preclinical AD.

Few studies have evaluated in-home teleneuropsychological (teleNP) assessment and none, to our knowledge, has evaluated the National Alzheimer’s Coordinating Center’s (NACC) Uniform Data Set version 3 tele-adapted test battery (UDS v3.0 t-cog). The current study evaluates the reliability of the in-home UDS v3.0 t-cog with a prior in-person UDS v3.0 evaluation.

One hundred and eighty-one cognitively unimpaired or cognitively impaired participants from a longitudinal study of memory and aging completed an in-person UDS v3.0 and a subsequent UDS v3.0 t-cog evaluation (∼16 months apart) administered either via video conference (n = 122) or telephone (n = 59).

We calculated intraclass correlation coefficients (ICCs) between each time point for the entire sample. ICCs ranged widely (0.01–0.79) but were generally indicative of “moderate” (i.e., ICCs ranging from 0.5–0.75) to “good” (i.e., ICCs ranging from 0.75–0.90) agreement. Comparable ICCs were evident when looking only at those with stable diagnoses. However, relatively stronger ICCs (Range: 0.35–0.87) were found between similarly timed in-person UDS v3.0 evaluations.

Our findings suggest that most tests on the UDS v3.0 t-cog battery may serve as a viable alternative to its in-person counterpart, though reliability may be attenuated relative to the traditional in-person format. More tightly controlled studies are needed to better establish the reliability of these measures.

This study was designed to evaluate the effect of limited English proficiency (LEP) on neurocognitive profiles.

Romanian (LEP-RO; n = 59) and Arabic (LEP-AR; n = 30) native speakers were compared to Canadian native speakers of English (NSE; n = 24) on a strategically selected battery of neuropsychological tests.

As predicted, participants with LEP demonstrated significantly lower performance on tests with high verbal mediation relative to US norms and the NSE sample (large effects). In contrast, several tests with low verbal mediation were robust to LEP. However, clinically relevant deviations from this general pattern were observed. The level of English proficiency varied significantly within the LEP-RO and was associated with a predictable performance pattern on tests with high verbal mediation.

The heterogeneity in cognitive profiles among individuals with LEP challenges the notion that LEP status is a unitary construct. The level of verbal mediation is an imperfect predictor of the performance of LEP examinees during neuropsychological testing. Several commonly used measures were identified that are robust to the deleterious effects of LEP. Administering tests in the examinee’s native language may not be the optimal solution to contain the confounding effect of LEP in cognitive evaluations.

Aging of the population encourages research on how to preserve cognition and quality of life. Many studies have shown that Physical Activity (PA) positively affects cognition in older adults. However, PA carried out throughout the individual’s lifespan may also have an impact on cognition in old age. We hypothesize the existence of Motor Reserve (MR), a flexible and dynamic construct that increases over time and compensates for age-related motor and cognitive loss.

Two questionnaires were developed and validated to estimate MR (Physical Activity carried out throughout the individual’s lifespan) and Current Physical Activity (CPA, PA carried out in the previous 12 months). They were administered to 75 healthy individuals over 50 to verify the relation with cognition. MR and CPA include physical exercise (i.e., structured activities to improve or maintain physical fitness) and incidental PA, which we consider as any movement that leads to a metabolic cost above baseline (e.g., housekeeping, walking). In addition, the Cognitive Reserve Index questionnaire (CRI), a reliable predictor of cognitive performance, was used to measure each participant’s Cognitive Reserve.

The factors that most influenced performance are Age and Cognitive Reserve, but also MR and CPA together and MR when it is the only factor.

Cognitive variability in adult and elderly populations is explained by both MR and CPA. PA training could profitably be included in new preventive and existing interventions.

The ‘attentional spotlight’ can be adjusted depending on the task requirements, resulting in processing information at either the local or global level. Stroke can lead to local or global processing biases, or the inability to simultaneously attend both levels. In this study, we assessed the (1) prevalence of abnormal local and global biases following stroke, (2) differences between left- and right-sided brain damaged patients, and (3) relations between local and global interference, the ability to attend local and global levels simultaneously, and lateralized attention, search organization, search speed, visuo-construction, executive functioning, and verbal (working) memory.

Stroke patients admitted for inpatient rehabilitation completed directed (N = 192 total; N = 46 left-sided/N = 48 right-sided lesion) and divided (N = 258 total; N = 67 left-sided/N = 66 right-sided lesion) local–global processing tasks, as well as a conventional neuropsychological assessment. Processing biases and interference effects were separately computed for directed and divided tasks.

On the local–global tasks, 7.8–10.9% of patients showed an abnormal local bias and 6.3–8.3% an abnormal global bias for directed attention, and 5.4–10.1% an abnormal local bias and 6.6–15.9% an abnormal global bias for divided attention. There was no significant difference between patients with left- and right-sided brain damage. There was a moderate positive relation between local interference and search speed, and a small positive relation between global interference and neglect.

Abnormal local and global biases can occur after stroke and might relate to a range of cognitive functions. A specific bias might require a different approach in assessment, psycho-education, and treatment.

Research shows that cognitively healthy older adults with mild executive function (EF) weaknesses are vulnerable to the negative impacts of life complexity (or daily busyness) when performing instrumental activities of daily living (IADLs). However, past research assessed life complexity only at one timepoint, not capturing daily fluctuations. Importantly, fluctuations in busyness can themselves have deleterious impacts on functioning. This study extended past research by examining whether (1) variability in daily busyness would be more detrimental than level of busyness to performance of IADLs, and (2) EF assessed at home would moderate deleterious impact of busyness on IADLs.

Fifty-two community-dwelling older adults aged 60 to 95 completed daily IADL tasks and daily measures of EF and busyness via ecological momentary assessment, independently at home for 18 days.

(1) In a subset of participants with mild EF weaknesses, high variability in busyness across days was associated with fewer tasks completed correctly; and (2) across all participants (regardless of EF), high levels of daily busyness were associated with fewer tasks completed on time.

Findings indicate that high variability in daily busyness, potentially reflecting a lack of daily routine, was associated with IADL errors among cognitively healthy older adults with mild EF weaknesses. Additionally, consistently high levels of busyness were associated with failures to complete tasks, or failures to complete them on time, regardless of EF. These results further support the Contextually Valid Executive Assessment (ConVExA) model, which posits that EF and contextual factors interact to predict functional outcomes.

The developmental absence (agenesis) of the corpus callosum (AgCC) is a congenital brain malformation associated with risk for a range of neuropsychological difficulties. Inhibitory control outcomes, including interference control and response inhibition, in children with AgCC are unclear. This study examined interference control and response inhibition: 1) in children with AgCC compared with typically developing (TD) children, 2) in children with different anatomical features of AgCC (complete vs. partial, isolated vs. complex), and 3) associations with white matter volume and microstructure of the anterior (AC) and posterior commissures (PC) and any remnant corpus callosum (CC).

Participants were 27 children with AgCC and 32 TD children 8–16 years who completed inhibitory control assessments and brain MRI to define AgCC anatomical features and measure white matter volume and microstructure.

The AgCC cohort had poorer performance and higher rates of below average performance on inhibitory control measures than TD children. Children with complex AgCC had poorer response inhibition performance than children with isolated AgCC. While not statistically significant, there were select medium to large effect sizes for better inhibitory control associated with greater volume and microstructure of the AC and PC, and with reduced volume and microstructure of the remnant CC in partial AgCC.

This study provides evidence of inhibitory control difficulties in children with AgCC. While the sample was small, the study found preliminary evidence that the AC (f2=.18) and PC (f2=.30) may play a compensatory role for inhibitory control outcomes in the absence of the CC.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, in which cognitive dysfunction is common, but poorly understood. This study aims to characterize the prevalence and patterns of cognitive dysfunction in SLE.

SLE patients (n = 95) and demographically matched healthy controls (n = 48) underwent cross-sectional cognitive testing using the 1-hr conventional neuropsychological test battery recommended by the American College of Rheumatology for use in SLE. We used standard deviations (SD) from the healthy control group to define impairment. For each cognitive test we compared SLE and control groups using independent samples t-tests (or alternatives when needed). We performed cluster analysis using a machine learning algorithm to look for patterns of cognitive dysfunction.

The SLE group performed significantly worse than healthy controls on every cognitive test. The largest differences were in the domains of verbal fluency, working memory and attention, while fine motor and psychomotor speed were the least affected domains. As expected, the prevalence of cognitive dysfunction varied depending on the SD cut-off used, with 49% of participants being >1.5 SD below the healthy control mean in at least two cognitive domains. Heat mapping showed variability in the pattern of dysfunction between individual patients and cluster analysis confirmed the presence of two clusters of patients, which were those significantly impaired versus those having preserved cognition.

Cognitive dysfunction is common in SLE but markedly heterogeneous across both cognitive domains and across the SLE group. Cluster analysis supports the use of a binary definition of cognitive dysfunction in SLE.

Mild cognitive impairment (MCI) is an etiologically nonspecific diagnosis including a broad spectrum of cognitive decline between normal aging and dementia. Several large-scale cohort studies have found sex effects on neuropsychological test performance in MCI. The primary aim of the current project was to examine sex differences in neuropsychological profiles in a clinically diagnosed MCI sample using clinical and research diagnostic criteria.

The current study includes archival data from 349 patients (age M = 74.7; SD = 7.7) who underwent an outpatient neuropsychological evaluation and were diagnosed with MCI. Raw scores were converted to z-scores using normative datasets. Sex differences in neurocognitive profiles including severity, domain-specific composites (memory, executive functioning/information processing speed, and language), and modality-specific learning curves (verbal, visual) were examined using Analysis of Variance, Chi-square analyses, and linear mixed models. Post hoc analyses examined whether sex effects were uniform across age and education brackets.

Females exhibit worse non-memory domain and test-specific cognitive performances compared to males with otherwise comparable categorical MCI criteria and global cognition measured via screening and composite scores. Analysis of learning curves showed additional sex-specific advantages (visual Males>Females; verbal Females >Males) not captured by MCI subtypes.

Our results highlight sex differences in a clinical sample with MCI. The emphasis of verbal memory in the diagnosis of MCI may result in diagnosis at more advanced stages for females. Additional investigation is needed to determine whether these profiles confer greater risk for progressing to dementia or are confounded by other factors (e.g., delayed referral, medical comorbidities).

The U.S. population is aging and increasing numbers of older adults are using cannabis. Cognitive decline is common in older age and subjective memory complaints (SMC) have been associated with increased risk for dementia. While residual cognitive effects of cannabis use at younger ages are well understood, the links between cannabis use and cognition in older adults is less clear. The present study represents the first population-level analysis of cannabis use and SMC in older adults in the U.S.

We used the National Survey of Drug Use and Health (NSDUH) dataset to evaluate SMC in respondents over age 50 (N = 26,399) according to past-year cannabis use.

Results revealed that 13.2% (95%CI: 11.5%−15.0%) of those who reported cannabis use also reported SMC, compared to 6.4% (95%CI: 6.1%–6.8%) among individuals with no cannabis use. Logistic regression revealed a two-fold increase (OR = 2.21, 95%CI: 1.88–2.60) of reporting SMC in respondents who had used cannabis in the past year, which was attenuated (OR = 1.38, 95%CI: 1.10–1.72) when controlling for additional factors. Other covariates, including physical health conditions, misuse of other substances, and mental illness also significantly contributed to SMC outcomes.

Cannabis use represents a modifiable lifestyle factor that has potential for both risk and protective properties that may impact the trajectory of cognitive decline in older age. These hypothesis generating results are important for characterizing and contextualizing population-level trends related to cannabis use and SMC in older adults.

Physical activity (PA) may help maintain brain structure and function in aging. Since the intensity of PA needed to effect cognition and cerebrovascular health remains unknown, we examined associations between PA and cognition, regional white matter hyperintensities (WMH), and regional cerebral blood flow (CBF) in older adults.

Forty-three older adults without cognitive impairment underwent magnetic resonance imaging (MRI) and comprehensive neuropsychological assessment. Waist-worn accelerometers objectively measured PA for approximately one week.

Higher time spent in moderate to vigorous PA (MVPA) was uniquely associated with better memory and executive functioning after adjusting for all light PA. Higher MVPA was also uniquely associated with lower frontal WMH volume although the finding was no longer significant after additionally adjusting for age and accelerometer wear time. MVPA was not associated with CBF. Higher time spent in all light PA was uniquely associated with higher CBF but not with cognitive performance or WMH volume.

Engaging in PA may be beneficial for cerebrovascular health, and MVPA in particular may help preserve memory and executive function in otherwise cognitively healthy older adults. There may be differential effects of engaging in lighter PA and MVPA on MRI markers of cerebrovascular health although this needs to be confirmed in future studies with larger samples. Future randomized controlled trials that increase PA are needed to elucidate cause-effect associations between PA and cerebrovascular health.

Executive functioning (EF) can be one of the earliest, despite under-detected, impaired cognitive domains in patients with multiple sclerosis (pwMS). However, it is still not clear the role of EF on verbal fluency tests given the presence of information processing speed (IPS) deficits in pwMS.

Performance of a group of 43 pwMS without IPS impairment as measured with the Symbol Digit Modalities Test (SDMT) and a group of 32 healthy controls (HC) was compared on the Phonemic and Semantic Fluency Tests. For each group, we scored the number of words generated (i) in the early time interval (i.e., first 15 sec, semi-automatic process) and (ii) in the late time interval (i.e., from 15 to 60 sec, controlled process).

Globally, pwMS produced significantly fewer words than HC on the Phonemic but not on the Semantic Fluency Test. Crucially, in the Phonemic Fluency Test pwMS generated significantly fewer words than HC in the late time interval, whereas no significant difference between the two groups emerged in the early time interval.

These findings suggest that executive dysfunction is the core element on the Phonemic Fluency Test also in pwMS and it deserves attention in both research and clinical practice.

Stroke can cause cognitive impairment, which can lead to challenges returning to day-to-day activities. Knowing what factors are associated with cognitive impairment post-stroke can be useful for predicting outcomes and guiding rehabilitation. One such factor is gender: previous studies are inconclusive as to whether gender influences cognitive outcomes post-stroke. Accounting for key variables, we examined whether there are gender differences in cognitive outcomes after stroke.

We analyzed data from neuropsychological assessments of 237 individuals tested in the chronic epoch (≥ 3 months) following ischemic stroke. Using ANCOVA and linear mixed modeling, we examined gender as a predictor of cognition as measured by general cognitive ability (g), Full-Scale IQ, and 18 cognitive tests, controlling for age at stroke onset, education, premorbid intelligence, and lesion volume.

There were no significant gender differences in overall cognitive outcomes as measured by g (p = .887) or Full-Scale IQ (p = .801). There were some significant gender differences on specific cognitive tests, with women outperforming men on scores from the Rey Auditory Verbal Learning Test (ps < .01) and men outperforming women on the Wechsler Adult Intelligence Scale Arithmetic and Information subtests (ps < .01).

Our findings indicate that men and women have similar overall cognitive outcomes after stroke, when demographic and lesion factors are accounted for. Although men and women differed in their performance on some individual cognitive tests, neither gender performed systematically better or worse. However, for learning, working memory, and verbal knowledge/comprehension, gender may be an important predictor of outcome post-stroke.