Cognitive complaints are common in multiple sclerosis, but their relationship to non-cognitive symptoms such as fatigue, sleep dysfunction and psychopathology has not been systematically examined in patients referred for specialist cognitive evaluation. These potentially modifiable symptoms may warrant attention in a clinical context.

This study aimed to characterise common patterns of cognitive and non-cognitive symptoms in a referred patient cohort and determine whether cognitive complaints are associated with clinically significant fatigue, sleep dysfunction and psychopathology.

Cognitive complaints were captured using (a) a binary classification derived from clinical impression and (b) a severity rating from a self-report instrument. Objective cognitive performance was measured across five cognitive domains. Patients also completed self-report measures of fatigue, sleep dysfunction and psychopathology.

Fifty-one patients were included. Although 98% had cognitive complaints, only 29% had objective cognitive impairment. Most (90%) had significant non-cognitive symptoms, primarily fatigue (86%), sleep dysfunction (28%) and depression (26%). Pattern analysis revealed that the most common symptom phenotype was cognitive complaints with significant non-cognitive symptoms, occurring in the absence of objective cognitive impairment. More severe cognitive complaints were associated with greater psychopathology (r = 0.57, BF10 = 2188.48), fatigue (r = 0.53, BF10 = 366.44) and sleep dysfunction (r = 0.47, BF10 = 69.27).

Cognitive complaints in multiple sclerosis may reflect broader non-cognitive symptom burden rather than objective cognitive impairment, even among patients referred for specialist evaluation. Their presence should prompt consideration of fatigue, sleep disturbance and psychopathology as potential targets for intervention.

Predicting suicide risk remains a challenge. We examined whether neurocognitive performance on implicit associations toward suicide, motor speed, response inhibition, and executive functioning predicts suicide attempt and behavior in high-risk psychiatric patients.

Our sample (N = 298) consisted of inpatients (n = 161) and outpatients (n = 83) admitted for a suicide attempt (SA; n = 78), for suicidal ideation (SI; n = 76), or were non-suicidal psychiatric controls (PC; n = 90), and healthy controls (HC; n = 54). Participants were followed for 12 months, with follow-up assessments at 3-, 6-, and 12-months. Neurocognitive tasks were administered at baseline. Clinical symptom measures, suicidality, and electronic health record data were collected at each timepoint. ANCOVA was used to compare groups on neurocognitive performance, and logistic and Cox regressions examined whether neurocognitive performance predicted future actual suicide attempt and suicidal behaviors.

Participants had a mean age of 24.34 years (SD = 3.71). A total of 19 participants made an actual suicide attempt during the study. On neurocognitive tasks at baseline, the SA group had stronger implicit associations with death- and suicide-related words compared to the HC (d = 0.88, p < 0.001) and SI (d = 0.63, p = 0.005) groups and poorer executive functioning than the SI (d = 0.44, p = 0.043) group in multivariate models. Stronger implicit associations with death/suicide predicted higher risk of suicide attempts at the univariate (HR = 1.68 p = 000), but not multivariate level (HR = 1.17 p = 000), while slower motor speed predicted actual suicide attempts (HR = 1.81 p = 000) at the multivariate level.

Slower motor speed predicts actual suicide attempt and may help identify psychiatric patients who are at high risk for suicidal behavior.

Cognitive reserve (CR) is a protective factor in first-episode psychosis (FEP), influencing cognitive, clinical, and functional outcomes. CR is shaped by a combination of genetic, clinical, and environmental factors, yet the extent of their respective contributions remains unclear. This study investigates the influence of polygenic risk scores (PRS), clinical and environmental variables on CR in FEP.

A cohort of 174 individuals with non-affective FEP, aged 25.5 (SD=5.3), was analyzed. CR was assessed using a socio-behavioral proxy. PRS for educational attainment (PRSEA), intelligence (PRSIQ), cognitive performance (PRSCP), occupational attainment (PRSOA), physical activity (PRSPA), and schizophrenia (PRSSZ) were calculated. Age at onset, socioeconomic status, birth weight, and family history of psychosis were considered. Multiple regression models were employed to evaluate the impact of the different predictors on CR.

PRSEA (p=0.002), age at onset (p=5.32x10-5), and family history of psychosis (p=0.001) emerged as the strongest contributors to CR. Higher PRSEA was associated with higher levels of CR, while earlier age at onset and positive family history were associated with lower CR. The model incorporating environmental, clinical, and genetic variables explained 17.7% of the variance in CR, and the one without PRS explained 13.5%. The inclusion of PRSEA in the model improved the explanatory power (Δadj.R2=0.042) and predictive accuracy (ΔRMSE=−0.288).

These findings highlight the role of precision psychiatry in better understanding CR. Early identification of individuals with earlier onset, family history of psychosis, and lower genetic predisposition to educational attainment may help characterize those with lower CR.

Working memory (WM) impairment is a core cognitive deficit in schizophrenia, associated with dysfunction of large-scale brain networks, particularly the triple-network system comprising the default mode, frontoparietal, and salience networks. Given the role of environmental risks like childhood trauma (CT) in cognitive deficits, we investigated whether trauma relates to altered triple-network flexibility and WM in schizophrenia.

We enrolled 190 patients with schizophrenia (SZ) and 117 healthy controls (HCs). Among them, 162 SZ and 99 HCs underwent n-back task-based functional magnetic resonance imaging. We computed temporal variability (TV) in the triple-network connectivity, defining ΔTV as the change between 0-back and 2-back conditions. Subgroup comparisons of ΔTV were conducted within each group based on trauma status. Associations of ΔTV with WM performance and clinical symptoms were examined in SZ, followed by mediation analyses testing whether ΔTV mediates the relationship between trauma and WM.

Among HCs, individuals with childhood trauma showed reduced ΔTV across triple-network connections, whereas no such differences appeared in SZ. In SZ, greater ΔTV within the frontoparietal network (FPN) was correlated with lower positive symptom severity (r = −0.211, p-fdr = 0.046) and better n-back target accuracy (r = 0.303, p-fdr = 0.002). Furthermore, ΔTV within the FPN partially mediated the association between trauma and n-back accuracy.

Our findings highlight the central role of FPN flexibility in mediating childhood trauma’s effect on working memory in schizophrenia. This outlines a key pathway through which an early environmental risk (trauma) translates into cognitive and clinical manifestations in schizophrenia.

Paranoia is a transdiagnostic symptom and is associated with cognitive and social impairments. Attentional bias toward threat is thought to maintain paranoia.

Despite many studies, attentional biases in paranoia have not been systematically summarised, which was the aim of the current work.

We conducted a systematic review and meta-analysis, identifying 10 964 studies, of which 35 met inclusion criteria for review and 15 for meta-analysis.

Findings showed a significant negative attentional bias (average standardised effect size 0.26; 95% CI 0.01–0.52; p = 0.046). Preliminary indications suggested bias was strongest for paranoia-related stimuli (average effect size 0.30; 95% CI 0.03–0.57; p = 0.027) and stronger for words than faces (average effect size 0.41; 95% CI 0.05–0.77; p = 0.027), but more data is needed to confirm these effects. Limitations were primarily statistical and included likely underestimation of the overall effect size of the association between negative attentional bias and paranoia and a lack of sufficient studies to robustly examine moderators.

Summarising this literature provides a rationale for existing and new interventions for paranoia that target biased attentional mechanisms.

This study examines how multiple dimensions of socio-emotional well-being relate to cognitive functioning in older adults, and whether the associations vary by cognitive status, depression, and socio-demographic factors.

Data from the Harmonized Cognitive Assessment Protocol of the Survey of Health, Ageing and Retirement in Europe (n = 2,650; mean age = 76; 54.5% females) were used to test associations between life satisfaction, meaning in life, social connectedness, and loneliness with global, domain-specific cognitive performance, and informant-rated cognitive decline.

Linear mixed models, with individuals nested within five countries, found that higher life satisfaction, meaning in life, and social connectedness were associated with better cognitive outcomes, whereas greater loneliness was associated with worse performance and greater informant-rated decline. The largest effect sizes were observed for meaning in life (median β = .10) and loneliness (median β = −.09) across cognitive measures. The associations generally remained significant adjusting for well-known clinical (e.g., diabetes), behavioral (e.g., physical inactivity), and psychological (depressive symptomatology) risk factors for dementia. Moderation and sensitivity analyses suggested that associations with global cognition hinged on the inclusion of participants classified with cognitive impairment, while some domain-specific associations (e.g., loneliness and episodic memory) were observed only in individuals without cognitive impairment. Overall, evidence for moderation by cognitive status, depression and age was limited, and no moderation was observed for sex or education.

The results underscore the importance of socio-emotional well-being in cognitive aging and highlight the need for longitudinal research to clarify mechanistic pathways and inform targeted interventions.

Idiopathic normal pressure hydrocephalus (iNPH) is a neurological disorder affecting older adults for which symptoms may improve following shunting; however, the criteria for surgical referral remain unclear. While most studies rely on fixed cut-off scores for cognitive and gait tests, the present study examined decision-making based on clinical judgment to identify which factors influence referral. A secondary objective was to compare pre- and post-CSF tap test (CSF-TT) changes between the shunt and no shunt groups.

This retrospective study included 175 patients assessed at CHU de Québec – Hôpital de l’Enfant-Jésus. Based on a combination of objective test results and clinical judgment, patients were categorized as referred (n = 119) or not referred (n = 56) for shunt surgery. Logistic regression identified the variables influencing referral decisions. Mixed-effects ANOVA models for repeated measures were conducted to compare pre- and post-CSF-TT changes in gait and cognitive performance between shunt and no shunt groups.

Three change indices significantly predicted referral: the 10-Meter Walk Test (normal pace), the Trail Making Test Condition 5 and the Berg Balance Scale. Higher education positively influenced referral. While most gait and balance measures showed significant improvement following CSF-TT, cognitive tests appeared less responsive to the procedure.

Although this study employed a clinically grounded approach based on clinical judgment rather than fixed thresholds, the findings align with prior literature identifying gait and balance as robust indicators. This study reinforces the need to shift from rigid threshold-based criteria toward individualized, clinically grounded decision-making models that can better capture the heterogeneity of iNPH presentations.

Schizophrenia (SZ) is a debilitating psychiatric disorder where patients experience cognitive decline. Antipsychotic drugs alleviate positive symptoms but do not improve cognitive performance. We previously demonstrated that Toll-like receptors (TLRs), involved in cytokine production, can predict cognitive deficits in SZ patients. In this study, we aim to investigate the potential moderating effects of antipsychotic drugs on the associations between cytokines, TLRs, and cognition.

In total, 280 participants (201 controls and 79 cases of SZ) were recruited in Ireland. Venous blood from the participants was stimulated with TLR ligands. Levels of cytokines were measured from plasma and post-blood stimulation. The participants were administered a battery of cognitive tasks using the Cambridge Neuropsychological Test Automated Battery and Wechsler Adult Intelligence Scale-IIIR. Olanzapine equivalents were calculated using the defined daily dose method.

The results indicate that antipsychotic drug dose does not predict TLR activity or cognition, indicating that antipsychotic drug dose does not have a direct effect on cognition or TLR activity. However, the relationship between TLR4 activity and visual learning and memory is moderated by the antipsychotic drug dose (B = −0.065; p < 0.001), where increasing doses have a decreasing impact on their relationship.

Our data indicate that the dose of antipsychotic drugs alone cannot predict changes in cognitive performance and TLR4-activity. It also suggests that antipsychotic drug doses significantly affect TLR activity and its relationship with cognition. These effects are more pronounced on some domains than others. These findings open up new avenues for understanding the complex interplay between antipsychotic drugs, TLRs, and cognitive deficits in SZ.

Subjective cognitive complaints (SCC) can precede cognitive decline and are associated with demographic, exposure, lifestyle, and psychological factors. Prevalences of SCC and their correlates in individuals with repetitive head impacts (RHI) are poorly understood. This study characterized SCC in former elite American football players by frequency, mood and behavioral correlates, concordance with informant reports, and associations with neuropsychological test performance, cerebrospinal fluid (CSF), and magnetic resonance imaging (MRI) markers of neurodegeneration.

Former American football players (n = 180) completed measures of global and domain-specific SCC, neuropsychiatric symptom questionnaires, neuropsychological testing, lumbar puncture, and MRI. Elastic net regression evaluated the relative importance of potential SCC correlates. Intraclass correlation coefficients measured concordance between self and informant reports. Multiple linear regressions tested associations between SCC and verbal memory and executive functioning scores. CSF Aβ1-42, p-tau181, t-tau, neurofilament light (NfL), hippocampal volume, and regional cortical thickness were examined for their potential associations with SCC.

Rates of SCC ranged from 43 to 77% depending on the domain. Symptoms of depression, impulsivity, and anxiety were strongly associated with SCC. Self- and informant-reported SCC showed moderate inter-rater agreement. Adjusting for age, race, education, APOE ϵ4 carrier status, and depressive symptoms, SCC were associated with lower objective verbal memory and executive functioning performance. SCC were associated with lower parahippocampal cortical thickness but not with hippocampal volume or any of the measured CSF tests.

SCC are strongly associated with neuropsychiatric factors in former American football players. SCC may also be a marker of cognitive decline and neurodegeneration.