Quality of life is decreased in bipolar disorders (BD) and contributes to poor prognosis. However, little is known about the causal pathways that may affect it. This study aimed to explore health-related QoL (HRQoL) in BD and investigate its relationship with cognition and psychosocial functioning.

This multicenter cross-sectional study used a neuropsychological battery to assess five cognition domains. Functioning was evaluated using global and domain-based tools, and health-related HRQoL was assessed using the EQ-5D-3L. Structural equation modeling was used to test whether the association between cognition and HRQoL would be mediated by functioning in BD while controlling for covariates such as residual depression, anxiety, antipsychotic medication, and psychotic features.

We included 1 190 adults with euthymic BD. The model provided a good fit for the data. In this model, the direct effect of cognition on HRQoL was not significant (β = − 0.03, z = −0.78, p = 0.433). The total effect of cognition on HRQoL was weak, albeit significant (β = 0.05, z = 3.6, p < 0.001), thus suggesting that cognition affected HRQoL only indirectly through functioning. Anxiety was associated with decreased functioning (β = −0.27, z = −7.4, p < 0.001) and QoL (β = −0.39, z = −11.8, p < 0.001).

These findings suggest that improving cognition may not directly lead to a higher HRQoL. Cognitive remediation is expected to improve HRQoL only through functioning enhancement. They also reveal the potential importance of functional remediation and reduction of comorbid anxiety symptoms in improving HRQoL in BD.

Identifying persons with HIV (PWH) at increased risk for Alzheimer’s disease (AD) is complicated because memory deficits are common in HIV-associated neurocognitive disorders (HAND) and a defining feature of amnestic mild cognitive impairment (aMCI; a precursor to AD). Recognition memory deficits may be useful in differentiating these etiologies. Therefore, neuroimaging correlates of different memory deficits (i.e., recall, recognition) and their longitudinal trajectories in PWH were examined.

We examined 92 PWH from the CHARTER Program, ages 45–68, without severe comorbid conditions, who received baseline structural MRI and baseline and longitudinal neuropsychological testing. Linear and logistic regression examined neuroanatomical correlates (i.e., cortical thickness and volumes of regions associated with HAND and/or AD) of memory performance at baseline and multilevel modeling examined neuroanatomical correlates of memory decline (average follow-up = 6.5 years).

At baseline, thinner pars opercularis cortex was associated with impaired recognition (p = 0.012; p = 0.060 after correcting for multiple comparisons). Worse delayed recall was associated with thinner pars opercularis (p = 0.001) and thinner rostral middle frontal cortex (p = 0.006) cross sectionally even after correcting for multiple comparisons. Delayed recall and recognition were not associated with medial temporal lobe (MTL), basal ganglia, or other prefrontal structures. Recognition impairment was variable over time, and there was little decline in delayed recall. Baseline MTL and prefrontal structures were not associated with delayed recall.

Episodic memory was associated with prefrontal structures, and MTL and prefrontal structures did not predict memory decline. There was relative stability in memory over time. Findings suggest that episodic memory is more related to frontal structures, rather than encroaching AD pathology, in middle-aged PWH. Additional research should clarify if recognition is useful clinically to differentiate aMCI and HAND.

22q11.2 deletion syndrome (22q11.2DS) is associated with cognitive impairments and an increased risk of psychopathology. Most of the research has been conducted in children and adolescents, although the majority of affected individuals live well into adulthood. Hence, limited data are available on functional outcomes in adults.

To provide more insight in cognitive and adaptive abilities, and daily life functioning (marital status, living situation and work situation) in adults with 22q11.2DS.

This retrospective study included 250 Dutch-speaking adults (16–69 years) with 22q11.2DS from three sites in The Netherlands and Belgium. Data on full-scale IQ (FSIQ) scores (assessed with the Wechsler Adult Intelligence Scale), adaptive functioning (assessed with the Vineland Adaptive Behavior Scale II), and functional outcomes including marital status, living and work situation were systematically collected from clinical files. In addition, we examined predictors of adaptive functioning.

The majority of individuals in our adult sample demonstrated a low level of adaptive functioning (65%). In contrast to previous findings in children and adolescents, the majority functioned at an intellectual disability level (56%). Male sex, lower FSIQ and autism spectrum disorder were predictors of lower adaptive functioning (P = 0.016, P < 0.001 and P = 0.16, respectively).

These results suggest that low levels of cognitive and adaptive functioning are common in adults with 22q11.2DS. Future longitudinal and multicentre studies including older patients (>40 years) are needed to further investigate cognitive and adaptive trajectories and their interactions with physical and psychiatric comorbidities.

There is a compelling need for innovative intervention strategies for patients with affective disorders, given their increasing global prevalence and significant associated disability and impaired functioning. This study aimed to investigate whether a comprehensive multimodule individualized intervention (AWARE), targeting known mediators of functioning, improves functioning in affective disorders.

AWARE was a randomized, controlled, rater-blind clinical trial conducted at two centers in the Capital Region of Denmark (Clinicaltrials.gov, NCT 04701827). Participants were adults with bipolar disorder or major depressive disorder and impaired functioning. Participants were randomized to the six-month AWARE intervention or treatment as usual (TAU). The AWARE intervention is based on the International Classification of Functioning, Disability and Health (ICF) Brief Core Set for Bipolar and Unipolar Disorder.

The primary outcome was observation-based functioning using the Assessment of Motor and Process Skills (AMPS). Secondary outcomes were functioning, QoL, stress, and cognition.

Between February 2021 and January 2023, 103 patients were enrolled; 50 allocated to AWARE treatment and 53 to TAU (96 included in the full analysis set). There was no statistically significant differential change over time between groups in the primary outcome (AMPS), however, both groups showed a statistically significant improvement at endpoint. The AWARE intervention had a statistically significant effect compared with TAU on secondary outcomes of patient-reported functioning, stress and cognition.

Compared with TAU, the AWARE intervention was ineffective at improving overall functioning on the primary outcome, presumably due to the short duration of the intervention. Further development of effective treatments targeting functioning is needed.

People with bipolar disorder (BD) often show inaccurate subjective ratings of their objective cognitive function. However, it is unclear what information individuals use to formulate their subjective ratings. This study evaluated whether people with BD are likely using information about their crystallized cognitive abilities (which involve an accumulated store of verbal knowledge and skills and are typically preserved in BD) or their fluid cognitive abilities (which involve the capacity for new learning and information processing in novel situations and are typically impaired in BD) to formulate their subjective cognitive ratings.

Eighty participants diagnosed with BD and 55 control volunteers were administered cognitive tests assessing crystallized and fluid cognitive abilities. Subjective cognitive functioning was assessed with the Cognitive Failures Questionnaire (CFQ), daily functioning was rated using the Multidimensional Scale of Independent Functioning (MSIF) and the Global Assessment of Functioning Scale (GAF), and quality of life was assessed with the Quality of Life in Bipolar Disorder scale (QoL.BD).

The BD group exhibited considerably elevated subjective cognitive complaints relative to controls. Among participants with BD, CFQ scores were associated with fluid cognitive abilities including measures of memory and executive function, but not to crystallized abilities. After controlling for objective cognition and depression, higher cognitive complaints predicted poorer psychosocial outcomes.

Cognitive self-reports in BD may represent a metacognitive difficulty whereby cognitive self-appraisals are distorted by a person’s focus on their cognitive weaknesses rather than strengths. Moreover, negative cognitive self-assessments are associated with poorer daily functioning and diminished quality of life.

Cognitive impairment, anxiety, depression, fatigue, and dependence in instrumental activities of daily living (ADL) are common after stroke; however, little is known about how these outcomes may differ following treatment with endovascular clot retrieval (ECR), intravenous tissue plasminogen activator (t-PA), or conservative management.

Patients were recruited after acute treatment and invited to participate in an outcome assessment 90–120 days post-stroke. The assessment included a cognitive test battery and several questionnaires. The COVID-19 pandemic led to significant disruptions in recruitment and data collection, and the t-PA and conservative management groups were combined into a standard medical care (SMC) group.

Sixty-two participants were included in the study (ECR = 31, SMC = 31). Mean age was 66.5 (20–86) years, and 35 (56.5%) participants were male. Participants treated with ECR had significantly higher National Institutes of Health Stroke Scale scores at presentation and significantly lower education. After adjusting for stroke severity, premorbid intellectual ability, and age, treatment with ECR was associated with significantly better performances on measures of cognitive screening, visual working memory, and verbal learning and memory. Participants treated with ECR also experienced less fatigue and were more likely to achieve independence in basic and instrumental ADLs. Despite this, cognitive impairment and fatigue were still common among participants treated with ECR and anxiety and depression symptoms were experienced similarly by both groups.

Cognitive impairment and fatigue were less common but still prevalent following treatment with ECR. This has important practical implications for stroke rehabilitation, and routine assessment of cognition, emotion, and fatigue is recommended for all stroke survivors regardless of stroke treatment and functional outcome.

3q29 deletion syndrome (3q29del) is a rare (~1:30 000) genomic disorder associated with a wide array of neurodevelopmental and psychiatric phenotypes. Prior work by our team identified clinically significant executive function (EF) deficits in 47% of individuals with 3q29del; however, the nuances of EF in this population have not been described.

We used the Behavior Rating Inventory of Executive Function (BRIEF) to perform the first in-depth assessment of real-world EF in a cohort of 32 individuals with 3q29del (62.5% male, mean age = 14.5 ± 8.3 years). All participants were also evaluated with gold-standard neuropsychiatric and cognitive assessments. High-resolution structural magnetic resonance imaging was performed on a subset of participants (n = 24).

We found global deficits in EF; individuals with 3q29del scored higher than the population mean on the BRIEF global executive composite (GEC) and all subscales. In total, 81.3% of study subjects (n = 26) scored in the clinical range on at least one BRIEF subscale. BRIEF GEC T scores were higher among 3q29del participants with a diagnosis of attention deficit/hyperactivity disorder (ADHD), and BRIEF GEC T scores were associated with schizophrenia spectrum symptoms as measured by the Structured Interview for Psychosis-Risk Syndromes. BRIEF GEC T scores were not associated with cognitive ability. The BRIEF-2 ADHD form accurately (sensitivity = 86.7%) classified individuals with 3q29del based on ADHD diagnosis status. BRIEF GEC T scores were correlated with cerebellar white matter and subregional cerebellar cortex volumes.

Together, these data expand our understanding of the phenotypic spectrum of 3q29del and identify EF as a core feature linked to both psychiatric and neuroanatomical features of the syndrome.

While inflammation is associated with cognitive impairment in severe mental illnesses (SMI), there is substantial heterogeneity and evidence of transdiagnostic subgroups across schizophrenia (SZ) and bipolar (BD) spectrum disorders. There is however, limited knowledge about the longitudinal course of this relationship.

Systemic inflammation (C-Reactive Protein, CRP) and cognition (nine cognitive domains) was measured from baseline to 1 year follow-up in first treatment SZ and BD (n = 221), and healthy controls (HC, n = 220). Linear mixed models were used to evaluate longitudinal changes separately in CRP and cognitive domains specific to diagnostic status (SZ, BD, HC). Hierarchical clustering was applied on the entire sample to investigate the longitudinal course of transdiagnostic inflammatory-cognitive subgroups.

There were no case-control differences or change in CRP from baseline to follow-up. We confirm previous observations of case-control differences in cognition at both time-points and domain specific stability/improvement over time regardless of diagnostic status. We identified transdiagnostic inflammatory-cognitive subgroups at baseline with differing demographics and clinical severity. Despite improvement in cognition, symptoms and functioning, the higher inflammation – lower cognition subgroup (75% SZ; 48% BD; 38% HC) had sustained inflammation and lower cognition, more symptoms, and lower functioning (SMI only) at follow-up. This was in comparison to a lower inflammation – higher cognition subgroup (25% SZ, 52% BD, 62% HC), where SMI participants showed cognitive functioning at HC level with a positive clinical course.

Our findings support heterogenous and transdiagnostic inflammatory-cognitive subgroups that are stable over time, and may benefit from targeted interventions.

We aimed to compare and link the total scores of the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), two common global cognitive screeners.

2,325 memory clinic patients (63.2 ± 8.6 years; 43% female) with a variety of diagnoses, including subjective cognitive decline, mild cognitive impairment, and dementia due to various etiologies completed the MMSE and MoCA concurrently. We described both screeners, including at the item level. Then, using linear regressions, we investigated how age, sex, education, and diagnosis affected total scores on both instruments. Next, in linear mixed models, we treated the two screeners as repeated measures and analyzed the influence of these characteristics on the relationship between the instruments’ total scores. Finally, we linked total scores using equipercentile equating, accounting for relevant patient characteristics.

MMSE scores (mean ± standard deviation: 25.0 ± 4.6) were higher than MoCA scores (21.2 ± 5.4), and MMSE items generally showed less variation than MoCA items. Both instruments’ scores were individually influenced by age, sex, education, and diagnosis. The relationship between the screeners was moderated by age (estimate = −0.01, 95% confidence interval = [−0.03, −0.00]), education (0.14 [0.10, 0.18]), and diagnosis. These were accounted for when producing crosswalk tables based on equipercentile equating.

Accounting for the influence of patient characteristics, we created crosswalk tables to convert MMSE scores to MoCA scores, and vice versa. These tables may facilitate collaboration between clinicians and researchers and could allow larger, pooled analyses of global cognitive functioning in older adults.

Identify which NIH Toolbox Cognition Battery (NIHTB-CB) subtest(s) best differentiate healthy controls (HC) from those with amnestic mild cognitive impairment (aMCI) and compare the discriminant accuracy between a model using a priori “Norm Adjusted” scores versus “Unadjusted” standard scores with age, sex, race/ethnicity, and education controlled for within the model. Racial differences were also examined.

Participants were Black/African American (B/AA) and White consensus-confirmed (HC = 96; aMCI = 62) adults 60–85 years old that completed the NIHTB-CB for tablet. Discriminant function analysis (DFA) was used in the Total Sample and separately for B/AA (n = 80) and White participants (n = 78).

Picture Sequence Memory (an episodic memory task) was the highest loading coefficient across all DFA models. When stratified by race, differences were noted in the pattern of the highest loading coefficients within the DFAs. However, the overall discriminant accuracy of the DFA models in identifying HCs and those with aMCI did not differ significantly by race (B/AA, White) or model/score type (Norm Adjusted versus Unadjusted).

Racial differences were noted despite the use of normalized scores or demographic covariates—highlighting the importance of including underrepresented groups in research. While the models were fairly accurate at identifying consensus-confirmed HCs, the models proved less accurate at identifying White participants with an aMCI diagnosis. In clinical settings, further work is needed to optimize computerized batteries and the use of NIHTB-CB norm adjusted scores is recommended. In research settings, demographically corrected scores or within model correction is suggested.

Anorexia nervosa (AN) is characterized by severe restriction of calorie intake, which persists despite serious medical and psychological sequelae of starvation. Several prior studies have identified impaired feedback learning among individuals with AN, but whether it reflects a disturbance in learning from positive feedback (i.e., reward), negative feedback (i.e., punishment), or both, and the extent to which this impairment is related to severity and duration of illness, has not been clarified.

Participants were female adolescents with AN (n = 76) and healthy teen volunteers (HC; n = 38) between the ages of 12–18 years who completed a probabilistic reinforcement learning task. A Bayesian reinforcement learning model was used to calculate separate learning rates for positive and negative feedback. Exploratory analyses examined associations between feedback learning and duration of illness, eating disorder severity, and self/parent reports of reward and punishment sensitivity.

Adolescents with AN had a significantly lower rate of learning from positive feedback relative to HC. Patients and HC did not differ in learning from negative feedback or on overall task performance measures. Feedback learning parameters were not significantly associated with duration of illness, eating disorder severity, or questionnaire-based reports of reward and punishment sensitivity.

Adolescents with AN showed a circumscribed deficit in learning from reward that was not associated with duration of illness or reported sensitivity to reward or punishment. Subsequent longitudinal research should explore whether differences in learning from positive feedback relate to course of illness in youth with AN.

Anxiety is a common comorbid feature of late-life depression (LLD) and is associated with poorer global cognitive functioning independent of depression severity. However, little is known about whether comorbid anxiety is associated with a domain-specific pattern of cognitive dysfunction. We therefore examined group differences (LLD with and without comorbid anxiety) in cognitive functioning performance across multiple domains.

Older adults with major depressive disorder (N = 228, ages 65–91) were evaluated for anxiety and depression severity, and cognitive functioning (learning, memory, language, processing speed, executive functioning, working memory, and visuospatial functioning). Ordinary least squares regression adjusting for age, sex, education, and concurrent depression severity examined anxiety group differences in performance on tests of cognitive functioning.

Significant group differences emerged for confrontation naming and visuospatial functioning, as well as for verbal fluency, working memory, and inhibition with lower performance for LLD with comorbid anxiety compared to LLD only, controlling for depression severity.

Performance patterns identified among older adults with LLD and comorbid anxiety resemble neuropsychological profiles typically seen in neurodegenerative diseases of aging. These findings have potential implications for etiological considerations in the interpretation of neuropsychological profiles.