There is limited research on neurocognitive outcome and associated risk factors in long-term, adult survivors of childhood acute lymphoblastic leukemia (ALL), without treatment of cranial radiation therapy. Moreover, the impact of fatigue severity and pain interference on neurocognition has received little attention. In this cross-sectional study, we examined neurocognitive outcome and associated factors in this population.

Intellectual abilities, verbal learning/memory, processing speed, attention, and executive functions were compared to normative means/medians with one sample t tests or Wilcoxon signed-rank tests. Associations with risk factors, fatigue severity, and pain interference were analyzed with linear regressions.

Long-term, adult survivors of childhood ALL (N = 53, 51% females, mean age = 24.4 years, SD = 4.4, mean = 14.7 years post-diagnosis, SD = 3.4) demonstrated above average intellectual abilities, but performed below average in attention, inhibition, processing speed, and shifting (p < 0.001). Executive functioning complaints were significantly higher than normative means, and positively associated with fatigue (p < 0.001). There was no interaction between sex and fatigue and no neurocognitive impairments were associated with pain interference, risk group, age at diagnosis, or sex.

Long-term, adult survivors of ALL treated without cranial radiation therapy, demonstrate domain-specific performance-based neurocognitive impairments. However, continued research on the neurocognitive outcome in this population as they age will be important in the coming years. Executive functioning complaints were frequently in the clinical range, and often accompanied by fatigue. This suggests a need for cognitive rehabilitation programs.

Symptoms and cognition are both utilized as indicators of recovery following pediatric concussion, yet their interrelationship is not well understood. This study aimed to investigate: 1) the association of post-concussion symptom burden and cognitive outcomes (processing speed and executive functioning [EF]) at 4 and 12 weeks after pediatric concussion, and 2) the moderating effect of sex on this association.

This prospective, multicenter cohort study included participants aged 5.00–17.99 years with acute concussion presenting to four Emergency Departments of the Pediatric Emergency Research Canada network. Five processing speed and EF tasks and the Post-Concussion Symptom Inventory (PCSI; symptom burden, defined as the difference between post-injury and retrospective [pre-injury] scores) were administered at 4 and 12 weeks post-concussion. Generalized least squares models were conducted with task performances as dependent variables and PCSI and PCSI*sex interaction as the main predictors, with important pre-injury demographic and injury characteristics as covariates.

311 children (65.0% males; median age = 11.92 [IQR = 9.14–14.21 years]) were included in the analysis. After adjusting for covariates, higher symptom burden was associated with lower Backward Digit Span (χ2 = 9.85, p = .043) and Verbal Fluency scores (χ2 = 10.48, p = .033) across time points; these associations were not moderated by sex, ps ≥ .20. Symptom burden was not associated with performance on the Coding, Continuous Performance Test, and Color-Word Interference scores, ps ≥ .17.

Higher symptom burden is associated with lower working memory and cognitive flexibility following pediatric concussion, yet these associations were not moderated by sex. Findings may inform concussion management by emphasizing the importance of multifaceted assessments of EF.

The present study asked if bilinguals who are immersed in their nondominant language are more likely to know some words only in their nondominant language.

The either-language scoring benefit (ELSB) reflects how many more points bilinguals get when credited for pictures named regardless of which language is used. We asked if the ELSB varies with self-rated proficiency level of the nondominant language in young English-dominant (n = 68) compared to Spanish-dominant (n = 33) bilinguals, and in older English-dominant (n = 36) compared to Spanish-dominant (n = 32) bilinguals. All bilinguals were immersed in English (in the USA) at the time of testing.

Spanish-dominant bilinguals showed a larger ELSB than English-dominant bilinguals (in both young and older groups), but simple correlations showed that the degree of Spanish dominance was associated with a higher ELSB only in young bilinguals. Additionally, the ELSB was larger for bilinguals with more years of immersion and for more balanced bilinguals, whether measured by naming scores or self-rated balance (in both age groups). Nearly half (n = 14/33) of the young bilinguals who said they were Spanish-dominant scored higher in English than in Spanish, and on average these participants had similar naming scores in English and Spanish.

Either-language scoring benefits bilinguals with higher proficiency level in the nondominant language, which is more likely in bilinguals with extended immersion in the nondominant language, who also tend to be more balanced bilinguals, and for young adult bilinguals who may be in the process of a switch in which language is dominant.

White matter hyperintensity (WMH) volume is a neuroimaging marker of lesion load related to small vessel disease that has been associated with cognitive aging and Alzheimer’s disease (AD) risk.

The present study sought to examine whether regional WMH volume mediates the relationship between APOE ε4 status, a strong genetic risk factor for AD, and cognition and if this association is moderated by age group differences within a sample of 187 healthy older adults (APOE ε4 status [carrier/non-carrier] = 56/131).

After we controlled for sex, education, and vascular risk factors, ANCOVA analyses revealed significant age group by APOE ε4 status interactions for right parietal and left temporal WMH volumes. Within the young-old group (50-69 years), ε4 carriers had greater right parietal and left temporal WMH volumes than non-carriers. However, in the old-old group (70-89 years), right parietal and left temporal WMH volumes were comparable across APOE ε4 groups. Further, within ε4 non-carriers, old-old adults had greater right parietal and left temporal WMH volumes than young-old adults, but there were no significant differences across age groups in ε4 carriers. Follow-up moderated mediation analyses revealed that, in the young-old, but not the old-old group, there were significant indirect effects of ε4 status on memory and executive functions through left temporal WMH volume.

These findings suggest that, among healthy young-old adults, increased left temporal WMH volume, in the context of the ε4 allele, may represent an early marker of cognitive aging with the potential to lead to greater risk for AD.

Associations have been found between five-factor model (FFM) personality traits and risk of developing specific predementia syndromes such as subjective cognitive decline (SCD) and mild cognitive impairment (MCI). The aims of this study were to: 1) Compare baseline FFM traits between participants who transitioned from healthy cognition or SCD to amnestic MCI (aMCI) versus non-amnestic MCI (naMCI); and 2) Determine the relationship between FFM traits and risk of transition between predementia cognitive states.

Participants were 562 older adults from the Einstein Aging Study, 378 of which had at least one follow-up assessment. Baseline data collected included levels of FFM personality traits, anxiety and depressive symptoms, medical history, performance on a cognitive battery, and demographics. Follow-up cognitive diagnoses were also recorded.

Mann–Whitney U tests revealed no differences in baseline levels of FFM personality traits between participants who developed aMCI compared to those who developed naMCI. A four-state multistate Markov model revealed that higher levels of conscientiousness were protective against developing SCD while higher levels of neuroticism resulted in an increased risk of developing SCD. Further, higher levels of extraversion were protective against developing naMCI.

FFM personality traits may be useful in improving predictions of who is at greatest risk for developing specific predementia syndromes. Information on these personality traits could enrich clinical trials by permitting trials to target individuals who are at greatest risk for developing specific forms of cognitive impairment. These results should be replicated in future studies with larger sample sizes and younger participants.

To determine whether poorer performance on the Boston Naming Test (BNT) in individuals with transactive response DNA-binding protein 43 pathology (TDP-43+) is due to greater loss of word knowledge compared to retrieval-based deficits.

Retrospective clinical-pathologic study of 282 participants with Alzheimer’s disease neuropathologic changes (ADNC) and known TDP-43 status. We evaluated item-level performance on the 60-item BNT for first and last available assessment. We fit cross-sectional negative binomial count models that assessed total number of incorrect items, number correct of responses with phonemic cue (reflecting retrieval difficulties), and number of “I don’t know” (IDK) responses (suggestive of loss of word knowledge) at both assessments. Models included TDP-43 status and adjusted for sex, age, education, years from test to death, and ADNC severity. Models that evaluated the last assessment adjusted for number of prior BNT exposures.

43% were TDP-43+. The TDP-43+ group had worse performance on BNT total score at first (p = .01) and last assessments (p = .01). At first assessment, TDP-43+ individuals had an estimated 29% (CI: 7%–56%) higher mean number of incorrect items after adjusting for covariates, and a 51% (CI: 15%–98%) higher number of IDK responses compared to TDP-43−. At last assessment, compared to TDP-43−, the TDP-43+ group on average missed 31% (CI: 6%–62%; p = .01) more items and had 33% more IDK responses (CI: 1% fewer to 78% more; p = .06).

An important component of poorer performance on the BNT in participants who are TDP-43+ is having loss of word knowledge versus retrieval difficulties.

We investigated how well a visual associative learning task discriminates Alzheimer’s disease (AD) dementia from other types of dementia and how it relates to AD pathology.

3,599 patients (63.9 ± 8.9 years old, 41% female) from the Amsterdam Dementia Cohort completed two sets of the Visual Association Test (VAT) in a single test session and underwent magnetic resonance imaging. We performed receiver operating curve analysis to investigate the VAT’s discriminatory ability between AD dementia and other diagnoses and compared it to that of other episodic memory tests. We tested associations between VAT performance and medial temporal lobe atrophy (MTA), and amyloid status (n = 2,769, 77%).

Patients with AD dementia performed worse on the VAT than all other patients. The VAT discriminated well between AD and other types of dementia (area under the curve range 0.70–0.86), better than other episodic memory tests. Six-hundred forty patients (17.8%) learned all associations on VAT-A, but not on VAT-B, and they were more likely to have higher MTA scores (odds ratios range 1.63 (MTA 0.5) through 5.13 for MTA ≥ 3, all p < .001) and to be amyloid positive (odds ratio = 3.38, 95%CI = [2.71, 4.22], p < .001) than patients who learned all associations on both sets.

Performance on the VAT, especially on a second set administered immediately after the first, discriminates AD from other types of dementia and is associated with MTA and amyloid positivity. The VAT might be a useful, simple tool to assess early episodic memory deficits in the presence of AD pathology.

Normative data for older adults may be tainted by inadvertent inclusion of undiagnosed individuals at the very early stage of a neurodegenerative process. To avoid this pitfall, we developed norms for a cohort of older adults without MCI/dementia at 3-year follow-up.

A randomly selected sample of 1041 community-dwelling individuals (age ≥ 65) received a full neurological and neuropsychological examination on two occasions [mean interval = 3.1 (SD = 0.9) years].

Of these, 492 participants (Group 1; 65–87 years old) were without dementia on both evaluations (CDR=0 and MMSE ≥ 26); their baseline data were used for norms development. Group 2 (n = 202) met the aforementioned criteria only at baseline, but not at follow-up. Multiple linear regressions included demographic predictors for regression-based normative formulae and raw test scores as dependent variables for each test variable separately. Standardized scaled scores and stratified discrete norms were also calculated. Group 2 performed worse than Group 1 on most tests (p-values < .001–.021). Education was associated with all test scores, age with most, and sex effects were consistent with the literature.

We provide a model for developing sound normative data for widely used neuropsychological tests among older adults, untainted by potential early, undiagnosed cognitive impairment, reporting regression-based, scaled, and discrete norms for use in clinical settings to identify cognitive decline in older adults. Additionally, our co-norming of a variety of tests may enable intra-individual comparisons for diagnostic purposes. The present work addresses the challenge of developing robust normative data for neuropsychological tests in older adults.

Symptom clustering research provides a unique opportunity for understanding complex medical conditions. The objective of this study was to apply a variable-centered analytic approach to understand how symptoms may cluster together, within and across domains of functioning in mild cognitive impairment (MCI) and dementia, to better understand these conditions and potential etiological, prevention, and intervention considerations.

Cognitive, motor, sensory, emotional, and social measures from the NIH Toolbox were analyzed using exploratory factor analysis (EFA) from a dataset of 165 individuals with a research diagnosis of either amnestic MCI or dementia of the Alzheimer’s type.

The six-factor EFA solution described here primarily replicated the intended structure of the NIH Toolbox with a few deviations, notably sensory and motor scores loading onto factors with measures of cognition, emotional, and social health. These findings suggest the presence of cross-domain symptom clusters in these populations. In particular, negative affect, stress, loneliness, and pain formed one unique symptom cluster that bridged the NIH Toolbox domains of physical, social, and emotional health. Olfaction and dexterity formed a second unique cluster with measures of executive functioning, working memory, episodic memory, and processing speed. A third novel cluster was detected for mobility, strength, and vision, which was considered to reflect a physical functioning factor. Somewhat unexpectedly, the hearing test included did not load strongly onto any factor.

This research presents a preliminary effort to detect symptom clusters in amnestic MCI and dementia using an existing dataset of outcome measures from the NIH Toolbox.

The Amsterdam Instrumental Activities of Daily Living Questionnaire (A-IADL-Q) is well validated and commonly used to assess difficulties in everyday functioning regarding dementia. To facilitate interpretation and clinical implementation across different European countries, we aim to provide normative data and a diagnostic cutoff for dementia.

Cross-sectional data from Dutch Brain Research Registry (N = 1,064; mean (M) age = 62 ± 11 year; 69.5% female), European Medial Information Framework-Alzheimer’s Disease 90 + (N = 63; Mage = 92 ± 2 year; 52.4% female), and European Prevention of Alzheimer’s Dementia Longitudinal Cohort Study (N = 247; Mage = 63 ± 7 year; 72.1% female) were used. The generalized additive models for location, scale, and shape framework were used to obtain normative values (Z-scores). The beta distribution was applied, and combinations of age, sex, and educational attainment were modeled. The optimal cutoff for dementia was calculated using area under receiver operating curves (AUC-ROC) and Youden Index, using data from Amsterdam Dementia Cohort (N = 2,511, Mage = 64 ± 8 year, 44.4% female).

The best normative model accounted for a cubic-like decrease of IADL performance with age that was more pronounced in low compared to medium/high educational attainment. The cutoff for dementia was 1.85 standard deviation below the population mean (AUC = 0.97; 95% CI [0.97–0.98]).

We provide regression-based norms for A-IADL-Q and a diagnostic cutoff for dementia, which help improve clinical assessment of IADL performance across European countries.