Cognitive intra-individual variability (IIV) is a neuropsychological marker reflecting divergent performance across cognitive domains. In this brief communication, we examined whether clinical severity, apolipoprotein E (APOE) ε4 carriers, and higher polygenic risk were associated with higher cognitive IIV, and whether higher polygenic risk and cognitive IIV synergistically influence clinical severity.

This large study involved up to 24,248 participants (mean age = 72) from the National Alzheimer’s Coordinating Center (NACC) and multiple regression controlling for age, sex, and education was used to analyze the data.

We found that disease severity (B = 0.055, SE = 0.001, P < 0.001), APOE ε4 carriers (B = 0.02, SE = 0.003, P < 0.001), and higher polygenic risk (B = 0.02, SE = 0.004, P < 0.001) were associated with higher cognitive IIV. Polygenic risk and cognitive IIV also interacted to influence clinical severity, beyond APOE ε4 (B = 0.11, SE = 0.05, P = 0.02), such that individuals with high polygenic risk and cognitive IIV had the greatest clinical severity.

Heightened polygenic risk and increased cross-domain cognitive variation are implicated in dementia and may impact clinical decline in tandem.

We investigated differences in cognition between variants of progressive supranuclear palsy (PSP) including PSP-Richardson (PSP-RS) and subcortical and cortical variants using updated diagnostic criteria and comprehensive neuropsychological assessment.

We recruited 140 participants with PSP (age = 71.3 ± 6.9 years; education = 15.0 ± 2.8 years; 49.3% female) who completed neurological and neuropsychological assessment. Participants received diagnoses of PSP clinical variants at their evaluation (or retrospectively if evaluated before 2017) according to the Movement Disorder Society PSP criteria. We grouped variants as PSP-RS (62 participants), PSP-Cortical (25 with PSP-speech/language and 9 with PSP-corticobasal syndrome), and PSP-Subcortical (27 with PSP-parkinsonism, 11 with PSP-progressive gait freezing, and 6 with PSP-postural instability). Analysis of covariance adjusted for age assessed for differences in neuropsychological performance between variants across cognitive domains.

PSP-Cortical participants performed worst on measures of visual attention/working memory (Spatial Span Forward/Backward/Total), executive function (Frontal Assessment Battery), and language (Letter Fluency). PSP-RS participants performed worst on verbal memory (Camden Words). There were no significant group differences for the MoCA or indices of visuospatial function. There were no sex or education differences between PSP groups; however, there were differences in age at visit and disease duration.

In a large sample of participants with PSP, there were differences in cognition across PSP-RS, PSP-Subcortical, and PSP-Cortical variants, with PSP-Cortical and, to a lesser extent, PSP-RS, performing worse on tests of attention and executive function. These findings suggest cognitive distinctions among PSP clinical variants and highlight the value of neuropsychological assessment in differential diagnosis of PSP subtypes for more accurate and timely clinical classification.

This study examined three neurocognitive patterns or “clinical pearls” historically viewed as evidence for executive dysfunction in Parkinson disease (PD): 1) letter < category fluency; 2) word list < story delayed recall; 3) word list delayed recall < recognition. The association between intraindividual magnitudes of each neuropsychological pattern and individual performance on traditional executive function tests was examined.

A clinical sample of 772 individuals with PD underwent neuropsychological testing including tests of verbal fluency, word list/story recall, recognition memory, and executive function. Raw scores were demographically normed (Heaton) and converted to z-scores for group-level analyses.

Letter fluency performance was worse than category fluency (d = −0.12), with 28% of participants showing a discrepancy of ≥ −1.0 SD. Delayed recall of a list was markedly poorer than story recall (d = −0.86), with 52% of the sample exhibiting ≥ −1.0 SD deficits. Lastly, delayed free recall was worse than recognition memory (d = −0.25), with 24% showing a discrepancy of ≥ −1.0 SD. These patterns did not consistently correlate with executive function scores. The word list < story recall pattern was more common in earlier than later PD stages and durations.

Among the three pearls, the most pronounced was stronger memory performance on story recall than word lists, observed in more than half the sample. Only ¼ the participants exhibited all three neurocognitive patterns simultaneously. The variability in patterns across individuals highlights the heterogeneity of cognitive impairment in PD and suggests that intra-individual comparisons may offer a more nuanced insight into cognitive functioning.

Cognitive impairment represents a central component of major depressive disorder (MDD), affecting a large proportion of people living with MDD and showing a consistent negative impact on social, interpersonal, and occupational functioning and subjective quality of life. Cognitive remediation (CR) is a training-based psychosocial intervention targeting cognitive performance and psychosocial functioning that has shown consistent evidence of effectiveness in individuals with schizophrenia and that could provide significant benefits also in people with MDD: this study aimed to assess the effects of a computerized CR intervention in adults living with MDD.

Participants recruited in this single blind multicentric randomized controlled trial were allocated to receive a computerized CR intervention delivered by an active and trained therapist or to an active control condition (computer games – CG). Outcomes were measured with validated instruments by blind assessors and included cognitive performance, depressive symptoms, and psychosocial functioning. Outcomes were assessed using mixed models for repeated measures, considering baseline and end-of-treatment scores.

Hundred and one participants (CR=52 and CG=49) were included and 81 (CR=45 and CG=36) completed the study. CR produced superior results in clinician-rated depressive symptoms (p=0.023, d=042), global clinical severity (p=0.025, d=0.39), subjective depressive symptoms (p=0.005, d=0.45), working memory performance (p=0.004, d=0.34), executive functions/cognitive flexibility (p=0.020, d=0.43), and subjective cognitive impairment (p=0.006, d=0.48).

CR represents an effective intervention in MDD, improving clinical outcomes and cognitive performance in a clinician-rated and in a subjective manner, which should be more consistently implemented in clinical practice and included in MDD treatment recommendations.

Obstetric complications (OCs) are associated with cognitive and brain abnormalities observed in patients with schizophrenia. Gyrification, a measure of cortical integrity sensitive to events occurring during the prenatal and perinatal periods, is also altered in first-episode psychosis (FEP). We examined the relationship between OCs and gyrification in FEP, as well as whether gyrification mediates the relationship between OCs and cognition.

We examined differences in the Local Gyrification Index (LGI) for the frontal, parietal, temporal, occipital, and cingulate cortices between 139 FEP patients and 125 healthy controls (HCs). Regression analyses explored whether OCs and diagnosis interact to explain LGI variation. Parametric mediation analyses were conducted to assess the effect of LGI on the relationship between OCs and cognition for FEP and HC.

Significant LGI differences were observed between FEP patients and HC in the left parietal and bilateral cingulate and occipital cortices. There was a significant interaction between OCs and diagnosis on the left cingulate cortex (LCC) that was specific to males (p = 0.04) and was driven by gestational rather than intrauterine OCs.

In HCs, OCs had a direct effect on working memory (WM) (p = 0.048) in the mediation analysis, whereas in FEP, we observed no significant effect of OCs on either verbal or WM.

OCs interact with diagnosis to predict LCC gyrification, such that males with FEP exposed to OCs exhibit the lowest LGI. OCs influence WM, and LCC gyrification may mediate this relation only in HC, suggesting a differential neurodevelopmental process in psychosis.

Most cognitive studies of bipolar disorder (BD) have examined case–control differences on cognitive tests using measures of central tendency, which do not consider intraindividual variability (IIV); a distinct cognitive construct that reliably indexes meaningful cognitive differences between individuals. In this study, we sought to characterize IIV in BD by examining whether it differs from healthy controls (HCs) and is associated with other cognitive measures, clinical variables, and white matter microstructure.

Two hundred and seventeen adults, including 100 BD outpatients and 117 HCs, completed processing speed, sustained attention, working memory, and executive function tasks. A subsample of 55 BD participants underwent diffusion tensor imaging. IIV was operationalized as the individual standard deviation in reaction time on the Continuous Performance Test-Identical Pairs version.

BD participants had significantly increased IIV compared to age-matched controls. Increased IIV was associated with poorer mean performance scores on processing speed, sustained attention, working memory, and executive function tasks, as well as two whole-brain white matter indices: fractional anisotropy and radial diffusivity.

IIV is increased in BD and appears to correlate with other cognitive variables, as well as white matter measures that index reduced structural integrity and demyelination. Thus, IIV may represent a neurobiologically informative cognitive measure for BD research that is worthy of further investigation.

The cerebellar cognitive affective syndrome (CCAS) scale has been developed to screen for possible cognitive and affective impairments in cerebellar patients, but previous studies stressed concerns regarding insufficient specificity of the scale. Also, direct comparisons of CCAS scale performance between cerebellar patients with and without CCAS are currently lacking. The aim of this study was to evaluate the validity of the CCAS scale in cerebellar patients.

In this study, cerebellar patients with CCAS (n = 49), without CCAS (n = 30), and healthy controls (n = 32) were included. The Dutch/Flemish version of the CCAS scale was evaluated in terms of validity and reliability using an extensive neuropsychological assessment as the gold standard for CCAS. Correlations were examined between the CCAS scale and possible confounding factors. Additionally, a correction for dysarthria was applied to timed neuropsychological tests to explore the influence of dysarthria on test outcomes.

Cerebellar patients with CCAS performed significantly worse on the CCAS scale compared to cerebellar controls. Sensitivity was acceptable, but specificity was insufficient due to high false-positive rates. Correlations were found between outcomes of the scale and both education and age. Although dysarthria did not affect the validity of the CCAS scale, it may influence timed neuropsychological test outcomes.

Evaluation of the CCAS scale revealed insufficient specificity. Our findings call for age- and education-dependent reference values, which may improve the validity and usability of the scale. Dysarthria might be a confounding factor in timed test items and should be considered to prevent misclassification.

Children born very preterm (VPT; ≤32 weeks’ gestation) are at higher risk of developing behavioural problems, encompassing socio-emotional processing and attention, compared to term-born children. This study aimed to examine multi-dimensional predictors of late childhood behavioural and psychiatric outcomes in very preterm children, using longitudinal clinical, environmental, and cognitive measures.

Participants were 153 VPT children previously enrolled in the Evaluation of Preterm Imaging study who underwent neuropsychological assessments at 18–24 months, 4–7 years and 8–11 years as part of the Brain Immunity and Psychopathology following very Preterm birth (BIPP) study. Predictors of late childhood behavioural and psychiatric outcomes were investigated, including clinical, environmental, cognitive, and behavioural measures in toddlerhood and early childhood. Parallel analysis and exploratory factor analysis were conducted to define outcome variables. A prediction model using elastic-net regularisation and repeated nested cross-validation was applied to evaluate the predictive strength of these variables.

Factor analysis revealed two key outcome factors in late childhood: externalising and internalising-socio-emotional problems. The strongest predictors of externalising problems were response inhibition, effortful control and internalising symptoms in early childhood (cross-validated R2=.256). The strongest predictors of internalising problems were autism traits and poor cognitive flexibility in early childhood (cross-validated R2=.123). Cross-validation demonstrated robust prediction models, with higher accuracy for externalising symptoms.

Early childhood cognitive and behavioural outcomes predicted late childhood behavioural and psychiatric outcomes in very preterm children. These findings underscore the importance of early interventions targeting cognitive development and behavioural regulation to mitigate long-term psychiatric risks in very preterm children.

Normative data of neuropsychological tests in the Vietnamese population is considerably lacking. We aim to evaluate the effects of age, education, and sex on the performance of common neuropsychological tests, and to generate normative data for these tests in cognitively normal Vietnamese adults.

Participants were recruited from two hospitals in Ho Chi Minh City, with inclusion criteria as follows: age ≥ 40 years, normal cognition and function, and Mini-Mental State Examination (MMSE) scores ≥ 26. Neuropsychological tests were administered in a paper-and-pencil format, including the CERAD Word List, Trail Making Tests, Digit Span, Animal Naming, and Clock Drawing Test. Effects of age, education, and sex on test performance were evaluated using multiple linear regression analyses. Normed scores were reported as regression-based and discrete norms tables.

Participants included 385 cognitively normal Vietnamese, with age 61.4 ± 10.9 years (range 40 – 89), female 56%, who were relatively highly educated (42% attended college and beyond, 36% attended high school or equivalent institutions, 22% had less than high school education), and had MMSE scores 27.8 ± 1.0. Trail Making Test Part B was completed within 300 s by only 204/385 (53%) participants. Regression analyses demonstrated significant associations between age and education with performance on all or most tests, and between sex and all CERAD Word List measures and Clock Drawing Test.

The present work provides the first known normative data for a relatively comprehensive neuropsychological battery in Vietnamese adults. Performance on all tests was significantly influenced by age and education.