Cognitive impairment is associated with language changes that emerge during verbal responses to neuropsychological assessments that traditional scoring does not capture. The current study investigated the utility of a linguistic analysis of paragraph recall responses for detecting cognitive impairment.

Digital voice recordings of logical memory (LM) were available from 598 Long Life Family Study participants with normal cognition and 112 with cognitive impairment. Linguistic polyfeature scores for immediate (PFS-IR) and delayed recall (PFS-DR) were created from weighted sums of features associated with cognitive impairment. Logistic regression models assessed the predictive value of each PFS for classifying cognitive impairment. Repeated measures models with generalized estimating equations assessed whether PFSs predict cognitive screener performance over time.

Twelve linguistic features and higher PFSs were associated with cognitive impairment (PFS-IR OR = 1.05; PFS-DR OR = 1.07). PFS-DR scores approximated the accuracy of traditional LM scoring (AUC-PR = 0.77 vs. 0.81, respectively). A higher PFS-DR was also associated with lower cognitive screener scores over an average of 7 years of follow-up (β = –0.08, 95% CI [–0.11, –0.06]).

Quantification of linguistic features from paragraph recall identified distinct linguistic markers that reflect differences in learning, retention, and self-monitoring. Summary feature scores detected cognitive impairment and predicted lower cognitive performance over time. This approach has potential implications for automated testing, recording, and scoring pipelines allowing for implementation of gold-standard neuropsychological assessments in broader clinical and research settings. Further studies are needed to validate these findings across clinical and community-based populations.

Cognitive dysfunction is a core feature of major depressive disorder (MDD). Although both repetitive transcranial magnetic stimulation (rTMS) and vortioxetine have demonstrated procognitive effects, direct comparative evidence remains limited. This study compared the clinical and cognitive outcomes of rTMS and vortioxetine in patients with MDD.

In this 8-week naturalistic study, 40 patients with MDD received either rTMS (n = 25) or vortioxetine (n = 15). Depressive symptoms were assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS). Cognitive performance was evaluated with the Perceived Deficits Questionnaire–Depression (PDQ-D), Trail Making Test Part B (TMT-B), Stroop Test, and Wisconsin Card Sorting Test (WCST). Longitudinal changes were analyzed using linear mixed-effects models. Week-8 outcomes were examined using ANCOVA adjusted for baseline cognitive performance and relevant clinical covariates.

Both groups showed significant improvements in depressive symptoms and cognitive performance over time, with no significant treatment × time interactions. Baseline cognitive performance strongly predicted week-8 outcomes. Domain-specific differences were observed in executive functioning: vortioxetine showed a modest advantage in WCST performance, whereas rTMS showed a non-significant trend toward better Stroop interference performance. No significant differences were detected in processing speed.

rTMS and vortioxetine were associated with comparable improvements in depressive symptoms and cognitive functioning in patients with MDD. Baseline cognitive status appeared to be a stronger predictor of outcome than treatment modality.

Cerebral microbleeds (CMBs) and cortical superficial siderosis (cSS) are increasingly recognized in patients with cognitive impairment and are considered markers of cerebral small vessel disease and cerebral amyloid angiopathy (CAA). However, their associated variable and cognitive impact remain under-characterized in memory clinic populations.

We retrospectively reviewed 2923 patients referred for cognitive complaints who underwent brain MRI at the University Health Network (Toronto, 2014–2022). Of these, 137 patients with CMBs and/or cSS were compared with 278 control patients without hemorrhagic findings, sampled at an approximately 2:1 ratio from the CMB/cSS-negative pool. We analyzed vascular-associated variable, Fazekas-rated white matter hyperintensities (WMH), lesion location and cognitive performance (Mini-Mental State Examination or Montreal Cognitive Assessment). Probable CAA was classified using Boston Criteria v2.0.

CMBs and/or cSS were present in 4.7% of the cohort. Of the 137 cases, 103 had CMBs only, 9 had cSS only and 25 had both. Thirty-one patients (22.6%) met criteria for probable CAA. The CMB/cSS group was older, had higher rates of hypertension and had greater WMH burden. Cognitive scores were lower in the CMB/cSS group, but in multivariable models, only lower education remained a significant predictor. WMH severity showed a stronger association with cognitive performance than the presence or topography of CMBs or cSS.

CMBs and cSS co-occur with vascular-associated variables and WMH burden, while their independent association with cognition is modest in cross-sectional analyses. The proportion meeting probable CAA supports diagnostic relevance. Considering hemorrhagic markers alongside WMH may better characterize vascular contributions to dementia in routine clinical assessment.

Childhood maltreatment has been associated with increased risk of cognitive impairment in later life, but little is known about whether distinct joint trajectories of social isolation and depression across midlife predict this risk.

Using a prospective cohort design with documented childhood maltreatment and matched controls (N = 1196) followed from ages 0 to 11 into late midlife, we modelled joint trajectories of social isolation and depression (ages 29–47) using group-based trajectory modelling (GBTM) and examined their associations with cognitive impairment with no dementia (CIND) at age 59 through modified Poisson regression, controlling for risk factors related to neurodegenerative outcomes (i.e., hypertension, diabetes, obesity, limited physical activity, hearing impairment, smoking, excessive alcohol consumption and traumatic brain injury).

GBTM identified four groups: ‘Not isolated or depressed’ (67.7%), ‘Moderately isolated’ (11.7%), ‘Moderately depressed’ (16.5%) and ‘Chronically isolated and depressed’ (4.1%). Using the ‘Not isolated or depressed’ group as the reference category, membership in the highest-risk trajectory (‘Chronically isolated and depressed’) was associated with a 41.5% higher risk of CIND, whereas the ‘Moderately isolated’ and ‘Moderately depressed’ groups did not differ significantly from the reference group. Black non-Hispanic participants and those with documented childhood maltreatment histories had 32.8% and 21.2% higher risk of CIND, respectively, and each additional year of education was associated with a 4.9% reduction in CIND risk.

Sustained co-occurring social isolation and depression from early to mid-adulthood predicted increased risk of CIND independent of established risk factors, highlighting prolonged social and emotional difficulties as modifiable targets for late midlife cognitive health.

Cognitive difficulties, including problems with attention and executive processing, are common in major depressive disorder (MDD), and strongly predict psychosocial and occupational functioning. Impairment in sustained attention contributes to increased intra-individual variability (IIV) in reaction times observed during cognitive tasks. Understanding brain network changes associated with IIV could guide novel neuromodulation strategies targeting cognitive difficulties.

We analyzed baseline resting-state fMRI data from 209 patients with moderate-to-severe treatment-resistant MDD who participated in the BRIGhTMIND neuromodulation trial. Following a preregistered analytic protocol, we examined associations between: functional connectivity across three core brain networks (executive control, ECN; default mode, DMN; and salience network, SN); components of IIV derived from a choice reaction time task (using a three-parameter ex-Gaussian model); and functioning.

Greater IIV was linked to increased ECN-DMN functional connectivity. The ECN supports top-down control and externally directed cognition, while the DMN supports internal mentation and rumination. ECN-DMN connectivity was modulated by the SN, which prioritizes salient internal and external stimuli. Higher SN-ECN connectivity was associated with lower ECN-DMN connectivity and with faster mean reaction times. Both IIV and mean reaction time predicted functioning, with poorer functioning related to a slowed and inflexible response pattern.

Distinct components of reaction time variability are associated with specific patterns of brain network connectivity, largely independent of mood severity. Connectivity between the salience and executive control networks may represent a promising target for neuromodulation interventions focused on cognitive deficits in MDD.

The development of cognitive impairment (CI) is a frequent and debilitating consequence of COVID-19 and can persist for more than 1 year after the acute infection stage. Previous neuroimaging studies in COVID-19 survivors with CI have revealed widespread alterations in functional connectivity (FC), particularly within fronto-parietal circuits and subcortical nuclei such as the hippocampus, basal ganglia, and thalamus. This study focuses on neural correlates of CI in subjects who recovered from COVID-19 and the relationship between FC patterns and discrete cognitive domains.

Resting-state functional MRI data from 136 subjects were analyzed using a ROI-to-ROI approach across 246 brain regions derived from the Human Brainnetome Atlas. Group comparisons were performed based on the presence or absence of CI, and correlation analyses were conducted between FC and scores obtained from a comprehensive neuropsychological test battery.

Whole-brain FC showed no difference between patients with and without CI. In the whole study sample, hypoconnectivity between two basal ganglia regions and two frontal motor regions was associated with impaired performance in the cognitive domain “Reasoning and Problem-Solving,” while hyperconnectivity between the prefrontal thalamus and the postcentral gyrus was associated with impaired performance in the same cognitive domain.

Our findings indicate that FC alterations within the cortico-striatal and thalamo-cortical circuits may subtend deficits in higher-order executive functions in post-COVID-19 patients and highlight the importance of examining discrete cognitive domains in relation to brain connectivity.

Lifestyle changes and unhealthy eating habits have led to a sharp rise in obesity rates worldwide. Obesity is closely associated with a range of complications, including cognitive impairment and dementia. Accumulating evidence indicates that obesity negatively affects cognitive function and may increase the risk of neurodegenerative diseases. Conversely, cognitive dysfunction may further contribute to the development and progression of obesity. With growing attention in this field, obesity-related cognitive impairment has emerged as an important research focus at the intersection of metabolic and neurological disorders.

This article reviews the potential mechanisms underlying obesity-related cognitive impairment and summarizes emerging therapeutic strategies.

The development and progression of obesity-related cognitive impairment involve multiple mechanisms, including insulin resistance, systemic and central inflammation, immune dysregulation, microcirculatory alterations and changes in neurotransmitters and synaptic plasticity. Recent studies have focused on the adipose tissue-brain axis and the microbiota–gut–brain axis, in particular, the targeted effects of extracellular vesicles released from adipose tissue and microbiota on the brain.

This article systematically reviews the mechanisms underlying obesity-related cognitive impairment and presents novel therapeutic strategies.

Cognitive impairment associated with schizophrenia (CIAS) is a prevalent, meaningful feature of schizophrenia with limited real-world data on its recognition and care setting impact. The LUCIA initiative is an international multi-stakeholder study that explored awareness, assessment practices, and the burden of CIAS to inform future care pathways.

A three phase, Delphi-informed design was applied, comprising expert interviews to frame the enquiry, qualitative interviews with health and social care professionals (HCPs; n = 74) and caregiver advocates (n = 11), two waves of a Delphi survey among HCPs (n=449 and 343, respectively) and one round among 61 patients and 112 caregivers across 15 countries (n = 964).

The results showed poor awareness of CIAS across stakeholders. Structured cognitive assessment was infrequent, and clinicians largely relied on the dementia oriented Mini-Mental State Examination (MMSE) rather than schizophrenia specific tools, citing time, training, and unclear actionability as key barriers. CIAS imposed broad humanistic, clinical, societal, and economic burden – poorer quality of life, social isolation, higher comorbidities, increased hospital days and health care costs, and heavy informal care. Consensus actions prioritized the development of brief, validated screening instruments, improved psychoeducation, and accelerated research into effective pharmacological and non pharmacological interventions.

These results provide additional evidence for the under-recognition of CIAS worldwide, despite its substantial multidimensional societal burden. The use of dementia-oriented cognitive tests carries significant risks of misclassification and inappropriate management. Therefore, improving awareness, implementing assessment guidelines, and accelerating therapeutic innovation is critical to improve the quality of life of CIAS patients and the wider community.

Substance use disorder (SUD) is frequently associated with cognitive impairment that negatively affects treatment adherence and clinical outcomes. Neuropsychological assessments provide detailed information but are often impractical in clinical settings, underscoring the value of brief but sensitive tools such as the Montreal Cognitive Assessment (MoCA).

This study aimed to evaluate the utility of MoCA in detecting cognitive impairment in SUD, examining cognitive recovery following sustained abstinence, exploring gender differences in cognitive progression and determining whether baseline cognitive performance predicts treatment dropout.

Ninety-five SUD patients and 57 healthy controls completed MoCA at baseline and were reassessed after 6 months.

At baseline, 72.60% of individuals demonstrated cognitive impairment compared with controls, with deficits evident in both global cognition and visuospatial/executive, attention, memory and language domains. Following 6 months of abstinence, deterioration rates decreased to 50%, indicating substantial but not complete recovery, because the improvement in overall cognition was moderate. Male patients showed significantly greater cognitive gains than female patients, particularly in visuospatial/executive and digit span performance. Patients impaired at baseline reported more severe alcohol use and earlier onset of cannabis use disorder. Patients with cocaine use disorder showed the poorest recovery and the highest rate of treatment dropout. Lower baseline language and fluency scores were strongly associated with treatment discontinuation. Language deficits, together with cocaine use disorder, predicted 69% of dropout cases.

Findings indicate MoCA as a practical screening tool for early detection of cognitive impairment, longitudinal monitoring and personalised treatment planning in SUD.

Extensive evidence links air pollution exposure to cognitive decline; however, it remains unclear whether cognitive reserve and brain reserve modify this association. We examined the moderating roles of cognitive reserve contributors and brain reserve in the association between air pollution and cognitive function in dementia-free adults.

Cross-sectional data were obtained from 650 participants who underwent 3T brain magnetic resonance imaging and completed the Montreal Cognitive Assessment (MoCA). Cognitive reserve contributors were assessed based on education, occupation, and social engagement. Brain reserve was quantified using the ventricle-to-brain ratio derived from brain scans. Five-year average concentrations of particulate matter with diameters ≤10 and ≤2.5 μm and nitrogen dioxide were estimated based on residential addresses. Partial least squares structural equation modeling was applied to construct latent variables representing the air pollution mixture and composite cognitive reserve (contributors). Analyses examined whether cognitive reserve contributors and brain reserve modified associations of air pollution with MoCA scores and suspected mild cognitive impairment.

In individuals with an average level of cognitive reserve, a 1–standard deviation increase in air pollution mixture was associated with a 0.24-point decrease in MoCA scores (95% confidence interval [CI]: −0.31 to −0.16). This association was attenuated in individuals with higher cognitive reserve (β = −0.12; 95% CI: −0.25 to 0.02) and intensified in those with lower cognitive reserve (β = −0.36; 95% CI: −0.37 to −0.35). The moderating effect of brain reserve was not significant.

Higher cognitive reserve may mitigate the effects of air pollution on cognitive function.