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Chronic pain is prevalent among aging adults. Epidemiologic evidence has demonstrated that individuals with chronic pain have accelerated memory decline and increased probability of dementia. Neurophysiologic, molecular, and pharmacologic hypotheses have been proposed to explain the relationship between chronic pain and cognitive decline, but there remains currently limited evidence supporting any of these. Here, we integrate multi-omic data across human cohorts and rodent species and demonstrate that methylation in the prefrontal cortex induced by chronic pain specifically targets transcriptional networks associated with cognitive ability, memory, and Alzheimer's disease in humans. We validate this with multiple independent data sets and identify cortical microglia as a likely mechanism by which chronic pain can increase dementia risk. Our analyses support the molecular hypothesis for the role of chronic pain in cognitive decline and identifies several potential therapeutic targets., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.)

Parkinson's Disease (PD) exhibits heterogeneous cognitive deficits that may represent different cognitive phenotypes. While previous studies have described them in a "macro" manner, only one study has applied Network Analysis (NA) in PD. NA represents a model to explore relationships between cognitive abilities, aiding in understanding cognitive phenotypes. This study aims to verify whether the cognitive system undergoes reorganization in PD with Mild Cognitive Impairment (PD-MCI) patients. To explore this, a Level II cognitive assessment was administered to 275 PD patients, who were classified into two diagnostic categories: PD-Cognitive Unimpaired (CU) (n = 171) and PD-MCI (n = 104). NA was applied to construct Gaussian Graphical Models for each diagnostic group, where nodes represent cognitive tests and demographic factors, and edges represent their interconnections. The NA revealed substantial differences between the cognitive networks of PD-CU and PD-MCI patients. Specifically, the network of PD-MCI patients appears less sparse, with some weakened relationships between nodes. Overall, the results support the presence of a cognitive reorganization in PD-MCI patients, potentially indicating a functional compensation mechanism. In conclusion, this study enhances the understanding of the cognitive mechanisms underlying cognitive decline in patients with PD., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Age-related cognitive impairment is a prevalent issue in developed societies. Gamma oscil2lations at 40 Hz have been identified as a potential therapeutic approach for age-related cognitive decline and can be induced through various modalities, including auditory, visual, electrical, and magnetic stimulation. In this study, we investigated a novel modality of stimulation: whole-body vibration at 40 Hz. We examined the effects of 40 Hz vibration on cognitive performance and associated neuronal activity in the brains of aged male rats. Our findings revealed that only vibration at 40 Hz, rather than 20 Hz or 80 Hz, elicited cortical gamma oscillations in aged male rats. Additionally, following 8 weeks of prolonged treatment, the implementation of 40 Hz whole-body vibration significantly augmented the cognitive function of aged male rats as evidenced by behavioral assessments. Mechanistic studies demonstrated that these beneficial effects were attributed to the reduction of neuronal apoptosis in hippocampal CA1 through regulation of synaptic connections between astrocytes and neurons via 40 Hz gamma oscillations. Collectively, this suggests a promising intervention for age-related cognitive decline and identifies neuron-astrocyte synapses as potential therapeutic targets., Competing Interests: Declarations Conflict of interest The authors declare no competing interests. Ethical approval All experimental procedures received approval from Guilin Medical College's Animal Ethics Committee (Approval Number: GLMC202105081) and adhered to guidelines outlined by European Union Council Directive (86/609/European Economic Community)., (© 2024. The Author(s).)

Introduction: We evaluated the relationship between baseline enlarged perivascular space (ePVS) burden and later cognitive decline., Methods: 83 community-dwelling, older adults (aged 56-86) completed three annual cognitive assessments that included the Clinical Dementia Rating (CDR®) Dementia Staging Instrument Sum of Boxes (CDR-SB) and composite measures of executive function and episodic memory. An MRI scan at baseline was used to count ePVS in the basal ganglia and centrum semiovale. Mixed effects models were run with ePVS as the predictor variable and cognitive measures as the dependent variable. Covariates included age, sex, education, cerebral small vessel disease (cSVD) risk factors, and cSVD neuroimaging biomarkers., Results: At baseline, high basal ganglia ePVS counts were associated with lower executive function scores and episodic memory scores. Moreover, baseline basal ganglia ePVS predicted worse longitudinal CDR-SB scores over the study period., Discussion: Basal ganglia ePVS burden is a promising biomarker for cSVD-related cognitive and functional decline., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

The cognitive reserve (CR) hypothesis posits that individuals can differ in how their brain function is disrupted by pathology associated with aging and neurodegeneration. Here, we test this hypothesis in the continuum from cognitively normal to at-risk stages for Alzheimer's Disease (AD) to AD dementia using longitudinal data from 490 participants of the DELCODE multicentric observational study. Brain function is measured using task fMRI of visual memory encoding. Using a multivariate moderation analysis, we identify a CR-related activity pattern underlying successful memory encoding that moderates the detrimental effect of AD pathological load on cognitive performance. CR is mainly represented by a more pronounced expression of the task-active network encompassing deactivation of the default mode network (DMN) and activation of inferior temporal regions including the fusiform gyrus. We devise personalized fMRI-based CR scores that moderate the impact of AD pathology on cognitive performance and are positively associated with years of education. Furthermore, higher CR scores attenuate the effect of AD pathology on cognitive decline over time. Our findings primarily provide evidence for the maintenance of core cognitive circuits including the DMN as the neural basis of CR. Individual brain activity levels of these areas during memory encoding have prognostic value for future cognitive decline., Competing Interests: Competing interests The authors declare the following competing interests: Y.S. consults for Eisai, Lilly, and Arcadia. Columbia University licenses the Dependence Scale, and in accordance with university policy, Y.S. is entitled to royalties through this license. B.H.S. is involved in clinical studies by Roche, Biogen, and Hummingbird Diagnostics, but does not receive personal funds from any of them. S.T. is member of the DSMB of the study ENVISION (Biogen). J.W. acted as a consultant for Immungenetics, Noselab, and Roboscreen. J.W. further served on a scientific advisory board for Abbott, Biogen, Boehringer Ingelheim, Lilly, Immungenetics, MSD Sharp-Dohme, Noselab, Roboscreen, and Roche. J.W. received honoraria for presentations from Beijing Yibai Science and Technology Ltd, Eisai, Gloryren, Janssen, Pfizer, Med Update GmbH, Roche, and Lilly. The remaining authors declare no competing interests., (© 2024. The Author(s).)

Background and Objectives: Patients with multiple sclerosis (MS) often experience cognitive impairment, and this is related to structural disconnection and subsequent functional reorganization. It is unclear how specific patterns of functional reorganization might make it harder for cognitively impaired (CI) patients with MS to dynamically adapt how brain regions communicate, which is crucial for normal cognition. We aimed to identify dynamic functional network patterns that are relevant to cognitive impairment in MS and investigate whether these patterns can be explained by altered energy costs., Methods: Resting-state functional and diffusion MRI was acquired in a cross-sectional design, as part of the Amsterdam MS cohort. Patients with clinically definitive MS (relapse-free) were classified as CI (≥2/7 domains Z < -2), mildly CI (MCI) (≥2/7 domains Z < -1.5), or cognitively preserved (CP) based on an expanded Brief Repeatable Battery of Neuropsychological Tests. Functional connectivity states were determined using k -means clustering of moment-to-moment cofluctuations (i.e., edge time series), and the resulting state sequence was used to characterize the frequency of transitions. Control energy of the state transitions was calculated using the structural network with network control theory., Results: Imaging and cognitive data were available for 95 controls and 330 patients (disease duration: 15 years; 179 CP, 65 MCI, and 86 CI). We identified a "visual network state," "sensorimotor network state," "ventral attention network state," and "default mode network state." CI patients transitioned less frequently between connectivity states compared with CP (β = -5.78; p = 0.038). Relative to the time spent in a state, CI patients transitioned less from a "default mode network state" to a "visual network state" (β = -0.02; p = 0.004). The CI patients required more control energy to transition between states (β = 0.32; p = 0.007), particularly for the same transition (β = 0.34; p = 0.049)., Discussion: This study showed that it costs more energy for MS patients with cognitive impairment to dynamically change the functional network, possibly explaining why these transitions occur less frequently. In particular, transitions from a default mode network state to a visual network state were relevant for cognition in these patients. To further study the order of events leading to these network disturbances, future work should include longitudinal data across different disease stages.

Type 1 diabetes mellitus (T1D) is associated with cognitive impairments in humans. A well-established animal model of T1D is induced through the administration of streptozotocin (STZ), a glucose analog that induces pancreatic β-cell death, resulting in hyperglycemia and cognitive impairment linked to neuroinflammation and oxidative stress. Tumor necrosis factor (TNF)-α, a key inflammatory mediator, is elevated in the central nervous system (CNS) of diabetic animals. In this study, we utilized TNFR1 knockout mice to investigate the role of TNFR1 signaling in short-term T1D-related cognitive impairment. Our findings showed that diabetic animals did not develop cognitive damage within the first 2 weeks of T1D but exhibited reduced exploration in all behavioral tests. Our findings suggest that this reduction in exploration was attributable to motor impairment, as there was no reduction in motivated novelty-seeking behavior. Additionally, deletion of TNFR1 signaling attenuated gait speed impairment in diabetic mice, but did not affect other motor-related or exploratory behaviors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.)

Parkinson's disease (PD) is characterized by motor and non-motor symptoms. Cognitive decline is crucial in disease progression and affect quality of life; however, their underlying mechanisms in PD remain unclear. We explored the relationship between cognitive impairment and functional connectivity (FC) using resting-state functional magnetic resonance imaging in 26 patients with sporadic PD, focusing on the changes in FC between on and off states. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) score. The correlation between MMSE scores and changes in FC values during on and off states was assessed using Pearson's correlation coefficient. The correlation between changes in FC during the on and off periods and cognitive function differed for each cognitive function item. MMSE memory scores were positively correlated with FC between the brainstem and the left cerebral hemisphere. MMSE attention scores were positively correlated with FC between the bilateral thalamus and frontal lobes and negatively correlated with FC between the left cerebral hemispheres. These findings may facilitate our understanding of the neural correlates underlying cognitive impairment in PD and help develop treatment strategies to preserve cognitive function., (© 2024. The Author(s).)

Diffuse axonal injury (DAI) results in aberrant functional connectivity and is significantly linked to cognitive impairment. Nevertheless, the network mechanisms influencing neurocognitive function following DAI remain unclear. This study aimed to examine the characteristics of static and dynamic functional network connectivity (FNC) in patients with DAI. Resting-state functional magnetic resonance imaging data were collected from 26 patients with DAI and 27 healthy controls. Resting-state networks were extracted using independent component analysis. We evaluated the connectivity strength through spatial maps and static FNC, and then further dynamic properties were identified using a sliding time-window approach and k-means clustering, and investigated their associations with clinical variables. Patients with DAI showed stronger intra-network spatial maps in the default mode network and subcortical network than healthy controls, but static inter-network functional connectivity remained stable. Furthermore, three recurring states for dynamic connectivity were identified in all participants, and state 1 occurred most frequently in patients with DAI and exhibited higher fractional time, and as well as longer mean dwell time, which was positively associated with MMSE scores. Meanwhile, patients with DAI exhibited mostly increased functional connectivity strength of dynamic FNC in all states, particularly within the default mode network and visual network. These findings suggest that patients with DAI are characterized by altered dynamic FNC and temporal properties, which provide distinct complementary information different from static functional connectivity, and new insights into the neural pathophysiology of DAI associated with cognitive impairment., (© 2024. The Author(s).)

A primary aim of computational psychiatry is to establish predictive models linking individual differences in brain functioning with symptoms. In particular, cognitive impairments are transdiagnostic, treatment resistant, and associated with poor outcomes. Recent work suggests that thousands of participants may be necessary for the accurate and reliable prediction of cognition, questioning the utility of most patient collection efforts. Here, using a transfer learning framework, we train a model on functional neuroimaging data from the UK Biobank to predict cognitive functioning in three transdiagnostic samples (ns = 101 to 224). We demonstrate prediction performance in all three samples comparable to that reported in larger prediction studies and a boost of up to 116% relative to classical models trained directly in the smaller samples. Critically, the model generalizes across datasets, maintaining performance when trained and tested across independent samples. This work establishes that predictive models derived in large population-level datasets can boost the prediction of cognition across clinical studies.

Background and Hypothesis: Zinc finger protein 804A (ZNF804A) was the first genome-wide associated susceptibility gene for schizophrenia (SCZ) and played an essential role in the pathophysiology of SCZ by influencing neurodevelopment regulation, neurite outgrowth, synaptic plasticity, and RNA translational control; however, the exact molecular mechanism remains unclear., Study Design: A nervous-system-specific Zfp804a (ZNF804A murine gene) conditional knockout (cKO) mouse model was generated using clustered regularly interspaced short palindromic repeat/Cas9 technology and the Cre/loxP method., Results: Multiple and complex SCZ-like behaviors, such as anxiety, depression, and impaired cognition, were observed in Zfp804a cKO mice. Molecular biological methods and targeted metabolomics assay validated that Zfp804a cKO mice displayed altered SATB2 (a cortical superficial neuron marker) expression in the cortex; aberrant NeuN, cleaved caspase 3, and DLG4 (markers of mature neurons, apoptosis, and postsynapse, respectively) expressions in the hippocampus and a loss of glutamate (Glu)/γ-aminobutyric acid (GABA) homeostasis with abnormal GAD67 (Gad1) expression in the hippocampus. Clozapine partly ameliorated some SCZ-like behaviors, reversed the disequilibrium of the Glu/GABA ratio, and recovered the expression of GAD67 in cKO mice., Conclusions: Zfp804a cKO mice reproducing SCZ-like pathological and behavioral phenotypes were successfully developed. A novel mechanism was determined in which Zfp804a caused Glu/GABA imbalance and reduced GAD67 expression, which was partly recovered by clozapine treatment. These findings underscore the role of altered gene expression in understanding the pathogenesis of SCZ and provide a reliable SCZ model for future therapeutic interventions and biomarker discovery., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: To provide precision cognitive remediation therapy (CR) for schizophrenia, we need to understand whether the mechanism for improved functioning is via cognition improvements. This mechanism has not been rigorously tested for potential moderator effects., Study Design: We used data (n = 377) from a randomized controlled trial using CIRCuiTS, a therapist-supported CR, with participants from first-episode psychosis services. We applied structured equation modeling to test whether: (1) CR hours explain the goal attainment functional outcome (GAS) at posttreatment, (2) global cognitive improvement mediates GAS, and if (3) total symptoms moderate the CR hours to cognitive improvement pathway, and/or negative symptoms moderate the cognition to functioning pathway, testing moderator effects via the mediator or directly on CR hours to functioning path., Study Results: CR produced significant functioning benefit for each therapy hour (Coeff = 0.203, 95% CI 0.101-0.304, P < .001). The mediated path from CR hours to cognition and cognition to functioning was small and nonsignificant (Coeff = 0.014, 95% CI = -0.010, 0.037, P = .256). Total symptoms did not moderate the path to cognition (P = .211) or the direct path to outcome (P = .896). However, negative symptoms significantly moderated the effect of cognitive improvements on functioning (P = .015) with high negative symptoms reducing the functional gains of improved cognition., Conclusions: Although cognitive improvements were correlated with functioning benefit, they did not fully explain the positive effect of increased therapy hours on functioning, suggesting additional CR factors also contribute to therapy benefit. Negative symptoms interfere with the translation of cognitive improvements into functional gains so need consideration., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Background and Hypothesis: Cognitive control deficits are prominent in individuals with psychotic psychopathology. Studies providing evidence for deficits in proactive control generally examine average performance and not variation across trials for individuals-potentially obscuring detection of essential contributors to cognitive control. Here, we leverage intertrial variability through drift-diffusion models (DDMs) aiming to identify key contributors to cognitive control deficits in psychosis., Study Design: People with psychosis (PwP; N = 122), their first-degree biological relatives (N = 78), and controls (N = 50) each completed 120 trials of the dot pattern expectancy (DPX) cognitive control task. We fit full hierarchical DDMs to response and reaction time (RT) data for individual trials and then used classification models to compare the DDM parameters with conventional measures of proactive and reactive control., Study Results: PwP demonstrated slower drift rates on proactive control trials suggesting less efficient use of cue information. Both PwP and relatives showed protracted nondecision times to infrequent trial sequences suggesting slowed perceptual processing. Classification analyses indicated that DDM parameters differentiated between the groups better than conventional measures and identified drift rates during proactive control, nondecision time during reactive control, and cue bias as most important. DDM parameters were associated with real-world functioning and schizotypal traits., Conclusions: Modeling of trial-level data revealed that slow evidence accumulation and longer preparatory periods are the strongest contributors to cognitive control deficits in psychotic psychopathology. This pattern of atypical responding during the DPX is consistent with shallow basins in attractor dynamic models that reflect difficulties in maintaining state representations, possibly mediated by excess neural excitation or poor connectivity., (Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center 2024.)

Background: Mild cognitive impairment (MCI) may lead to difficulty maintaining postural stability and balance during locomotion. This heightened susceptibility to falls is particularly evident during tasks such as obstacle negotiation, which demands efficient motor planning and reallocation of attentional resources. This study proposed a multi-objective optimal control (MOOC) technique to assess the changes in motor control strategies during obstacle negotiation in older people affected by amnestic MCI., Methods: Motion data from 12 older adults with MCI and 12 controls when crossing obstacles were measured using a motion capture system, and used to obtain the control strategy of obstacle-crossing as the best compromise between the conflicting objectives of the MOOC problem, i.e., minimising mechanical energy expenditure and maximising foot-obstacle clearance. Comparisons of the weighting sets between groups and obstacle heights were performed using a two-way analysis of variance with a significance level of 0.05., Results: Compared to the controls, the MCI group showed significantly lower best-compromise weightings for mechanical energy expenditure but greater best-compromise weightings for both heel- and toe-obstacle clearances. This altered strategy involved a trade-off, prioritising maximising foot-obstacle clearance at the expense of increased mechanical energy expenditure. The MCI group could successfully navigate obstacles with a normal foot-obstacle clearance but at the cost of higher mechanical energy expenditure., Conclusions: MCI alters the best-compromise strategy between minimising mechanical energy expenditure and maximising foot-obstacle clearances for obstacle-crossing in older people. These findings provide valuable insights into how MCI impacts motor tasks and offer potential strategies for mitigating fall risks in individuals with MCI. Moreover, this approach could serve as an assessment tool for early diagnosis and a more precise evaluation of disease progression. It may also have applications for individuals with impairments in other cognitive domains., (© 2024. The Author(s).)

Background: The Stroop task was used to investigate differences in cognitive function between Long COVID (LC), Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) and healthy control subjects., Methods: Subjects viewed four color words or neutral (XXXX) stimuli with the same (congruent) or different color ink (incongruent). Cognitive conflict was inferred from response times for pairings of prestimuli and subsequent stimuli. Overall effects were assessed by univariate analysis with time courses determined for binned response times., Results: LC and ME/CFS had significantly longer response times than controls indicating cognitive dysfunction. Initial response times were ranked LC > ME > HC, and decreased according to power functions. At the end of the task (900s), times were ranked LC = ME > HC. Response times were significantly slower for stimuli following an incongruent prestimulus. Time series for Stroop effect, facilitation, interference, surprise index and practice power law parameters were generally similar in LC, ME/CFS and HC suggesting comparable patterns for recruitment of cognitive resources. The prestimulus data were analyzed and generated positive Stroop and interference effects that were distinct from stimulus effects., Conclusion: LC and ME/CFS have global slowing of response times that cannot be overcome by practice suggesting impaired communications between network nodes during problem solving. Analysis of matched prestimulus - stimulus effects adds a new dimension for understanding cognitive conflict., Brief Summary: Cognitive dysfunction in Long COVID and ME/CFS was demonstrated using the Stroop task which found global slowing of response times and limitations of practice effects., (© 2024. The Author(s).)

Background: This study aimed to examine whether baseline atherosclerosis was associated with subsequent short-term domain-specific cognitive decline., Methods and Results: This research was based on the BRAVE (Beijing Research on Aging and Vessel) study, a population-based prospective cohort study of adults aged 40 to 80 years, free of dementia. At baseline (wave 1, 2019), cognitive assessments and atherosclerosis measures, including carotid intima-media thickness, carotid plaques, coronary artery calcification, and brachial-ankle pulse wave velocity were conducted. Cognitive function was reassessed in wave 2 (2022-2023) using linear mixed models for analysis. A total of 932 participants (63.7% women; mean age, 60.0±6.9 years) were included. Compared with the lowest tertile of carotid intima-media thickness, carotid plaques, and brachial-ankle pulse wave velocity, or a coronary artery calcification score=0, the highest tertile of carotid intima-media thickness (β=-0.065 SD/y [95% CI, -0.112 to -0.017]; P =0.008), carotid plaques (β=-0.070 SD/y [95% CI, -0.130 to -0.011]; P =0.021), and brachial-ankle pulse wave velocity (β=-0.057 SD/y [95% CI, -0.105 to -0.010]; P =0.018), and a coronary artery calcification score≥400 (β=-0.081 SD/y [95% CI, -0.153 to -0.008]; P =0.029) were significantly associated with a faster decline in semantic fluency after multivariable adjustment. Moreover, greater carotid intima-media thickness, coronary artery calcification, and brachial-ankle pulse wave velocity were significantly associated with a faster decline in global cognition., Conclusions: More significant atherosclerosis was associated with faster semantic fluency and global cognition declines.

Background: Short sleep duration has been associated with an increased risk of cognitive impairment and dementia. Short sleep is associated with elevated blood pressure, yet the combined insult of short sleep and hypertension on brain health remains unclear. We assessed whether the association of sleep duration with cognition and vascular brain injury was moderated by hypertensive status., Methods and Results: A total of 682 dementia-free participants (mean age, 62±9 years; 53% women) from the Framingham Heart Study completed assessments of cognition, office blood pressure, and self-reported habitual and polysomnography-derived sleep duration; 637 underwent brain magnetic resonance imaging. Linear regressions were performed to assess effect modification by hypertensive status on total sleep time (coded in hours) and cognitive and magnetic resonance imaging outcomes. There was a significant interaction between sleep duration and hypertensive status when predicting executive function/processing speed (Trail Making B-A) and white matter hyperintensities. When results were stratified by hypertensive status, longer sleep duration was associated with better executive functioning/processing speed scores in the hypertensive group (meaning that shorter sleep duration was associated with poorer executive function/processing speed scores) (self-report sleep: β=0.041 [95% CI, 0.012-0.069], P =0.005; polysomnography sleep: β=0.045 [95% CI, 0.002-0.087], P =0.038), but no association was observed for the normotensive group. Similarly, shorter subjective sleep duration was associated with higher white matter hyperintensity burden in the hypertensive group (β=-0.115 [95% CI, -0.227 to -0.004], P =0.042), but not in the normotensive group., Conclusions: In individuals with hypertension, shorter sleep duration was associated with worse cognitive performance and greater brain injury.

This study investigated the association between cognitive function and facial emotion recognition (FER) in patients with Parkinson's disease (PD) and mild cognitive impairment (PD-MCI). We enrolled 126 participants from Taiwan, including 63 patients with idiopathic PD and 63 matched healthy controls. The PD group was divided into two groups: those with normal cognitive function (PD-NC) and those with MCI (PD-MCI). Participants underwent a modality emotion recognition test and comprehensive cognitive assessment. Our findings reveal that patients with PD-MCI exhibit significantly impaired FER, especially in recognizing "disgust," compared with patients with PD-NC and healthy adults (P = .001). This deficit correlates with executive function, attention, memory, and visuospatial abilities. Attention mediates the relationship between executive function and "disgust" FER. The findings highlight how patients with PD-MCI are specifically challenged when recognizing "disgust" and suggest that cognitive training focusing on cognitive flexibility and attention may improve their FER abilities. This study contributes to our understanding of the nuanced relationship between cognitive dysfunction and FER in patients with PD-MCI, emphasizing the need for targeted interventions., (© The Author(s) 2024. Published by Oxford University Press.)

Background: The purpose of this study was to identify patterns of structural disconnection and multivariate lesion-behaviour relationships associated with post-stroke deficits across six commonly impacted cognitive domains: executive function, language, memory, numerical processing, praxis, and visuospatial attention., Methods: Stroke survivors (n = 593) completed a brief domain-specific cognitive assessment (the Oxford Cognitive Screen (OCS)) during acute hospitalisation. Network-level and multivariate (sparce canonical correlation) lesion mapping analyses were conducted to identify focal neural correlates and distributed patterns of structural disconnection associated with impairment on each of the 16 OCS measures., Results: Network-level and multivariate lesion mapping analyses identified significant correlates for 12/16 and 10/16 OCS measures, respectively which were largely consistent with correlates reported in past work. Language impairments were reliably localised to network- and voxel-level correlates centred in left fronto-temporal regions. Memory impairments were associated with disconnection in a large network of left hemisphere regions. Number processing deficits were associated with damage to voxels centred in the left insular/opercular cortex, as well as disconnection within the surrounding white matter tracts. Within the domain of attention, different subtypes of visuospatial neglect were linked to distinct but partially overlapping patterns of disconnection and voxel-level damage. Praxis impairment was not linked to any voxel-level regions but was significantly associated with disconnection within the left hemisphere dorsal attention network., Conclusion: These results highlight the utility of routine, domain-specific cognitive assessment and imaging data for theoretically-driven lesion mapping analyses, while providing novel insight into the complex anatomical correlates of common and debilitating post-stroke cognitive impairments., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cerebral small vessel disease (SVD) is known to contribute to cognitive impairment, apathy and gait dysfunction. Although associations between cognitive impairment and either apathy or gait dysfunction have been shown in SVD, the inter-relations among these three clinical features and their potential common neural basis remain unexplored. The dopaminergic meso-cortical and meso-limbic pathways have been known as the important brain circuits for both cognitive control, emotion regulation and motor function. Here, we investigated the potential inter-relations between cognitive impairment, apathy and gait dysfunction, with a specific focus on determining whether these clinical features are associated with damage to the meso-cortical and meso-limbic pathways in SVD. In this cross-sectional study, we included 213 participants with SVD for whom MRI and comprehensive neurobehavioural assessments were performed. These assessments comprised six clinical measures: processing speed, executive function, memory, apathy (based on the Apathy Evaluation Scale) and gait function (based on the time and steps in the Timed Up and Go Test). We reconstructed five tracts connecting the ventral tegmental area (VTA) and dorsolateral prefrontal cortex (PFC), ventral lateral PFC, medial orbitofrontal cortex, anterior cingulate cortex (ACC) and nucleus accumbens within meso-cortical and meso-limbic pathways using diffusion weighted imaging. The damage along the five tracts was quantified using the free water (FW) and FW-corrected mean diffusivity indices. Furthermore, we explored the inter-correlations among the six clinical measures and identified their common components using principal component analysis (PCA). Linear regression analyses showed that higher FW values of tracts within meso-cortical pathways were related to these clinical measures in cognition, apathy, and gait (all P-corrected values < 0.05). The PCA showed strong inter-associations among these clinical measures and identified a common component wherein all six clinical measures loaded on. Higher FW values of tracts within meso-cortical pathways were related to the PCA-derived common component (all P-corrected values < 0.05). Moreover, FW values of the VTA-ACC tract showed the strongest contribution to the PCA-derived common component over all other neuroimaging features. In conclusion, our study showed that the three clinical features (cognitive impairment, apathy, and gait dysfunction) of SVD are strongly inter-related and that the damage in meso-cortical pathway could be the common neural basis underlying the three features in SVD. These findings advance our understanding of the mechanisms behind these clinical features of SVD and have the potential to inform novel management and intervention strategies for SVD., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Single-value scores reflecting the deviation from (FADE score) or similarity with (SAME score) prototypical novelty-related and memory-related functional MRI activation patterns in young adults have been proposed as imaging biomarkers of healthy neurocognitive ageing. Here, we tested the utility of these scores as potential diagnostic and prognostic markers in Alzheimer's disease (AD) and risk states like mild cognitive impairment (MCI) or subjective cognitive decline (SCD). To this end, we analysed subsequent memory functional MRI data from individuals with SCD, MCI and AD dementia as well as healthy controls and first-degree relatives of AD dementia patients (AD-rel) who participated in the multi-centre DELCODE study (n = 468). Based on the individual participants' whole-brain functional MRI novelty and subsequent memory responses, we calculated the FADE and SAME scores and assessed their association with AD risk stage, neuropsychological test scores, CSF amyloid positivity and APOE genotype. Memory-based FADE and SAME scores showed a considerably larger deviation from a reference sample of young adults in the MCI and AD dementia groups compared to healthy controls, SCD and AD-rel. In addition, novelty-based scores significantly differed between the MCI and AD dementia groups. Across the entire sample, single-value scores correlated with neuropsychological test performance. The novelty-based SAME score further differed between Aβ-positive and Aβ-negative individuals in SCD and AD-rel, and between ApoE ɛ4 carriers and non-carriers in AD-rel. Hence, FADE and SAME scores are associated with both cognitive performance and individual risk factors for AD. Their potential utility as diagnostic and prognostic biomarkers warrants further exploration, particularly in individuals with SCD and healthy relatives of AD dementia patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance (IR) and is often accompanied by mild cognitive impairment (MCI). The detrimental effects of T2DM and IR on the hippocampus have been extensively demonstrated. Few studies have examined the effects of IR on structure and function of hippocampal subfields in T2DM-MCI patients., Method: A total of 104 T2DM patients were recruited in this prospective study and divided into four groups (T2DM-MCI-higherIR, n = 17; T2DM-MCI-lowerIR, n = 32; T2DM-nonMCI-higherIR, n = 19; T2DM-nonMCI-lowerIR, n = 36). Structure and function MRI data were captured. Clinical variables and neuropsychological scores were determined for all participants. Hippocampal subfield volume and functional connectivity were compared among four groups. Partial correlation analysis was performed between imaging indicators, clinical variables, and neuropsychological scores in all patients., Results: T2DM-MCI-higher IR group had the smallest volumes of bilateral hippocampal tail, right subiculum-body, right GC-ML-DG-body, and right CA4-body. IR in right hippocampal tail, right subiculum-body, and right GC-ML-DG-body exerted main effect. Furthermore, elevated functional connectivity was found between right subiculum-body and bilateral dorsolateral prefrontal cortex and right anterior cingulate-medial prefrontal cortex. Hippocampal subfield volume positively correlates with total cholesterol and triglycerides and negatively correlates with fasting insulin., Conclusion: The present study found that T2DM-MCI patients have structural and functional alterations in hippocampal subfields, and IR is a negative factor influencing the alteration of hippocampal subfields volume. These findings support the importance of IR in T2DM-MCI patients and might be potential neuroimaging biomarkers of cerebral impairment in T2DM-MCI patients., (© 2024 The Author(s). Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Cognitive decline in Parkinson's disease (PD) varies widely. While models to predict cognitive progression exist, comparing traditional probabilistic models to deep learning methods remains understudied. This study compares sequential modeling techniques to identify cognitive progression in individuals with and without PD. Using data from the Parkinson's Progression Marker Initiative, shallow Markov, deep recurrent (long short-term memory [LSTM]), and nonrecurrent (temporal fusion transformer [TFT]) models were compared to predict cognitive status over time. Cognitive status was categorized into normal cognition (NC), mild cognitive impairment (MCI), and dementia. Predictions were made annually for up to 3 years using clinical data, including demographics, cognitive assessments, PD severity, and medical history. Each approach was evaluated using inverse probability weighted (IPW-) F1 scores. An ensemble method combined outputs from the Markov, LSTM, and TFT models. The dataset included 917 individuals (53% PD; 30% at risk for PD; 17% Healthy Controls). The TFT model outperformed others across all annual periods (IPW-F1 = 0.468) compared to the Markov (IPW-F1 = 0.349) and LSTM (IPW-F1 = 0.414) models, with improved performance using an ensemble approach (IPW-F1 = 0.502). For MCI and dementia predictions, which were rarer occurrences compared to NC status (ratios: 50:8:1), the TFT model consistently outperformed competing models, achieving IPW-F1 scores of 0.496 and 0.533 for MCI and dementia, respectively. In conclusion, sequential deep learning models like TFT, which mitigate long-term memory loss and can interpret complex, high-dimensional data, perform best overall in predicting clinically important cognitive transitions. These methods should be further explored for predicting degenerative conditions., (© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Objective: To summarize and evaluate evidence pertaining to the clinical, genetic, histopathological, and neuroimaging correlates of cognitive and behavioral dysfunction in amyotrophic lateral sclerosis (ALS)., Methodology: We comprehensively reviewed the literature on cognitive and behavioral manifestations of ALS, narrating findings from both cross-sectional and longitudinal studies. We discussed knowledge gaps in the evidence base and key limitations affecting studies to date, before formulating a framework for future research paradigms aimed at investigating clinicopathological correlates of neuropsychological dysfunction in ALS., Results: Studies have demonstrated clinical associations with cognitive dysfunction in ALS e.g., bulbar-onset of symptoms, pathological associations (extramotor TDP-43 deposition), and imaging associations (frontotemporal involvement). The most common behavioral deficit, apathy, is highly associated with verbal fluency, but longitudinal studies assessing behavioral dysfunction in ALS are comparatively lacking., Conclusion: Longitudinal studies have been helpful in identifying several potential correlates of cognitive and behavioral dysfunction but have frequently been confounded by selection bias and inappropriate testing platforms. This review provides a framework for more robust assessment of clinicopathological associations of neuropsychological abnormalities in ALS in the future, advocating for greater utilization of pre-symptomatic C9orf72 repeat expansion-carrying cohorts., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

Sensory deprivation theory is an important hypothesis involving potential pathways between hearing loss and cognitive impairment in patients with presbycusis. The theory suggests that prolonged auditory deprivation in presbycusis, including neural deafferentation, cortical reallocation, and atrophy, causes long-lasting changes and reorganization in brain structure and function. However, neurophysiological changes underlying the cognition-ear link have not been explored. In this study, we recruited 98 presbycusis patients and 60 healthy controls and examined the differences between the two groups in gamma-aminobutyric acid (GABA) and glutamate (Glu) levels in bilateral auditory cortex, excitation-inhibition (E/I) balance (Glu/GABA ratio), dynamic functional network connectivity (dFNC), hearing ability and cognitive performance. Then, correlations with each other were investigated and variables with statistical significance were further analyzed using the PROCESS Macro in SPSS. GABA levels in right auditory cortex and Glu levels in bilateral auditory cortex were lower but E/I balance in right auditory cortex were higher in presbycusis patients compared to healthy controls. Hearing assessments and cognitive performance were worse in presbycusis patients. Three recurring connectivity states were identified after dFNC analysis: State 1 (least frequent, middle-high dFNC strength with negative functional connectivity), State 2 (high dFNC strength), and State 3 (most frequent, low dFNC strength). The occurrence and dwell time of State 3 were higher, on the other hand, the dwell time of State 2 decreased in patients with presbycusis compared to healthy controls. In patients with presbycusis, worse hearing assessments and cognition were correlated with decreased GABA levels, increased E/I balance, and aberrant dFNC, decreased GABA levels and increased E/I balance were correlated with decreased occurrence and dwell time in State 3. In the mediation model, the fractional windows, as well as dwell time in State 3, mediated the relationship between the E/I balance in right auditory cortex and episodic memory (Auditory Verbal Learning Test, AVLT) in presbycusis. Moreover, in patients with presbycusis, we found that worse hearing loss contribute to lower GABA levels, higher E/I balance, and further impact aberrant dFNC, which caused lower AVLT scores. Overall, the results suggest that a shift in E/I balance in right auditory cortex plays an important role in cognition-ear link reorganization and provide evidence for sensory deprivation theory, enhancing our understanding the connection between neurophysiological changes and cognitive impairment in presbycusis. In presbycusis patients, E/I balance may serve as a potential neuroimaging marker for exploring and predicting cognitive impairment., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

The cerebellum has been largely overlooked in Alzheimer's disease, despite increasing evidence implicating its cognitive capacities and functional networks, which interacts with cerebral cortex to subserve cognition. A study by Lin et al. has indicated that the cerebellum is part of the integrated network in amnestic mild cognitive impairment (aMCI), a prodromal state of Alzheimer's disease. The aMCI patients exhibited weaker cerebello-parietal functional connectivity but stronger cerebellar coupling with precuneus cortex, posterior cingulate gyrus, and caudate nucleus. These alterations in cerebello-cortical connectivity correlated with cognitive performance, suggesting a dynamic change of cerebello-cortical network related to cognitive change in aMCI., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Cognitive decline is a common challenge faced by older individuals with presbycusis; their performance on dual-task (DT) activities is generally lower compared to those without hearing loss. However, the influence of hearing aids on nonauditory cognitive decline in this population remains unclear. This study aims to investigate the effect of hearing aids on nonauditory DT performance in older adults with presbycusis., Material and Methods: This study included older people with presbycusis who used hearing aids (P&HA group), those with presbycusis who did not use hearing aids (PoHA group), and a control group of healthy adults. Forward and backward digit span tests and timed up and go test (TUG) were administered to all individuals. TUG and motor and cognitive (forward and backward digit span) tasks were applied simultaneously to evaluate the participants' DT performance., Results: The study comprised 60 individuals with presbycusis (19 females, 41 males; mean age: 73.23 ± 6.49 years) and 30 healthy adults (15 females, 15 males; mean age: 35.93 ± 8.57 years). Healthy adults performed better than the P&HA and PoHA groups in all the administered tests (p < 0.05). There was a moderate negative relationship between the severity of hearing loss and the forward and backward digit span test performances (p < 0.05). The P&HA group performed better than the PoHA group on the DT cognitive forward and backward digit span tests., Conclusion: The use of hearing aids and their proper fitting are important not only for improving communication skills and reducing listening effort but also for supporting nonauditory cognitive functions, minimizing the risk of falls during DT activities, and enhancing the overall quality of life., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

Introduction: Patients with Alzheimer's disease (AD), namely at an initial stage like amnestic cognitive impairment (aMCI), typically present with memory complaints. They also have difficulties regarding self-knowledge about their cognitive deficits. In clinical practice, a formal neuropsychological assessment is often done. The present study aimed to understand whether patients with aMCI retain the ability to monitor the success or failure in their performance during the neuropsychological assessment and adjust the report of memory complaints accordingly, as compared to healthy controls., Methods: Participants were patients with aMCI and healthy controls who were questioned about their own memory abilities using the Subjective Memory Complaints (SMC) scale, applied before and after the neuropsychological assessment protocol. A repeated measures General Linear Model was performed to analyze changes in SMC (within-subjects effects) after the neuropsychological assessment, in patients with aMCI and healthy controls (between-subjects effects)., Results: Eighty volunteers, 40 patients with aMCI and 40 healthy controls, participated in the study. Patients with aMCI showed lower MMSE scores, more depressive symptoms, and deficits in memory and learning, language and executive domains. Patients with aMCI had higher SMC scores [9.4(3.6)] than healthy controls [4.4(2.3)] before the neuropsychological assessment. A statistically significant interaction was found between the SMC and the diagnostic group, meaning that healthy controls decreased SMC [3.4(1.9)] after the neuropsychological assessment, whereas patients with aMCI kept high levels of SMC [9.6(3.9)]. In patients with aMCI, an inverse correlation between logical memory and the change in SMC was found, so that patients with lower scores in the logical memory test tended to increase their memory complaints after the assessment., Conclusions: Both patients with aMCI and healthy controls can monitor and update the impression about their memory abilities following a formal neuropsychological assessment. Patients with aMCI maintain a high SMC level, which is inversely associated with their memory performance. In practical terms, SMC should be measured consistently at a particular moment in time, preferably preceding the objective neuropsychological assessment., (© 2024 John Wiley & Sons Ltd.)

Purpose: Cognitive impairment is prevalent among individuals with epilepsy, and increasing evidence indicates that genetic factors can underlie this relationship. However, the extent to which epilepsy subtypes differ in their genetic relationship with cognitive function, and information about the specific genetic variants involved remain largely unknown., Methods: We investigated the genetic relationship between epilepsies and general cognitive ability (COG) using complementary statistical tools, including linkage disequilibrium score (LDSC) regression, MiXeR and conjunctional false discovery rate (conjFDR). We analyzed genome-wide association study data on COG (n = 269,867) and common epilepsies (n = 27,559 cases, 42,436 controls), including the broad phenotypes 'all epilepsy', focal epilepsies and genetic generalized epilepsies (GGE), as well as specific subtypes. We functionally annotated the identified loci using several biological resources and validated the results in independent samples., Results: Using MiXeR, COG (11.2k variants) was estimated to be almost four times more polygenic than 'all epilepsy', GGE, juvenile myoclonic epilepsy (JME), and childhood absence epilepsy (CAE) (2.5k - 2.9k variants). The other epilepsy phenotypes were insufficiently powered for MiXeR analysis. We quantified extensive genetic overlap between COG and epilepsy types, but with varying negative genetic correlations (-0.23 to -0.04). COG was estimated to share 2.9k variants with both GGE and 'all epilepsy', and 2.3k variants with both JME and CAE. Using conjFDR, we identified 66 distinct loci shared between COG and epilepsies, including novel associations for GGE (27), 'all epilepsy' (5), JME (5) and CAE (5). The implicated genes were significantly expressed in multiple brain regions. The results were validated in independent samples (COG: p = 3.62 × 10 -7 ; 'all epilepsy': p = 2.58 × 10 -3 )., Conclusion: Our study further dissects the substantial genetic basis shared between epilepsies and COG and identifies novel shared loci. An improved understanding of the genetic relationship between epilepsies and COG may lead to the development of novel comorbidity-targeted epilepsy treatments., Competing Interests: Declaration of competing interest O.A.A. has received speaker's honorarium from Lundbeck, Sunovion, Takeda, Janssen and is a consultant for CorTechs.ai and Precision Health AS. A.M.D. is a founder of and holds equity interest in CorTechs Labs and serves on its scientific advisory board. He is also a member of the Scientific Advisory Board of Healthlytix and receives research funding from General Electric Healthcare (GEHC). The terms of these arrangements have been reviewed and approved by the University of California, San Diego in accordance with its conflict-of-interest policies. Remaining authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To explore changes in cerebral cortex activation and functional connectivity during resting-state and verbal fluency tasks in patients with different types of dementia., Methods: We recorded oxygenated hemoglobin concentration (HbO) signals detected by functional near-infrared spectroscopy (fNIRS) from the prefrontal cortex, partial parietal cortex, and cortex of the temporal lobe in four groups of participants: mild cognitive impairment (MCI), Lewy body dementia (LBD), Alzheimer's disease (AD), and cognitively normal (CN)., Results: The study recruited 120 older adults with MCI (n = 30), LBD (n = 28), AD (n = 30), or CN (n = 32). The mean functional connectivity of the frontal and temporal lobe in resting state was significantly less in the AD (0.19 ± 0.11) group than in the MCI (0.23 ± 0.11), LBD (0.29 ± 0.12), and CN (0.40 ± 0.11) groups (p < 0.001). Further, the mean HbO concentrations in the brain regions and channels were significantly lower in the AD group than in the LBD and MCI groups (p < 0.001). Cognitive levels correlated significantly with the mean HbO concentrations in the resting state and verbal fluency task conditions., Conclusion: The fNIRS HbO signals significantly differed in the cerebral cortex regions in participants with different types of dementia. These findings suggest that fNIRS can effectively enhance the differential diagnosis and assessment of dementia., Competing Interests: Declaration of competing interest All authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Recent research has revolutionized our understanding of memory consolidation by emphasizing the critical role of astrocytes, microglia, and immune cells in through cytokine signaling. Cytokines, compact proteins, play pivotal roles in neuronal development, synaptic transmission, and normal aging. This review explores the cellular mechanisms contributing to cognitive decline in inflammaging and Alzheimer's disease, highlighting the paradoxical effects of most studied cytokines (IL-1, IL-6, TNF-α) in brain function, which act as a double-edged sword in brain physiology, acting both as facilitators of healthy cognitive function and as a potential contributor to cognitive decline., Competing Interests: Declaration of Competing Interest All the authors declare there is no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Age-related cognitive decline is a pervasive problem in the aging population. Daoyin therapy is a mind-body movement characteristic of traditional Chinese medicine (TCM). Increasing evidence has reported its usefulness in improving cognitive function among different populations. However, there is no systematic review to assess the effect and mechanism of Daoyin therapy on mild cognitive dysfunction (MCI) in older adults., Objective: To systematically review the evidence on the effect and mechanism of Daoyin therapy on MCI in older adults., Results: Taichi, Baduanjin, and Yijinjing can improve cognitive function. Qigong and Wuqinxi can enhance the physical and cognitive functions related to balance, muscle strength, physical endurance, postural control, and flexibility. Taichi, Baduanjin, and Wuqinxi can improve the cognitive function of older adults and alleviate the symptoms associated with MCI through multiple mechanisms. The underlying mechanisms include activating the expression of signals and changing their connections in different brain regions, increasing brain capacity, and regulating brain-derived neurotropic and inflammatory factors., Conclusion: In summary, the existing evidence from RCTs suggests that traditional Daoyin therapy, such as Taichi, Baduanjin, and Wuqinxi, is a promising strategy that can improve cognitive function and delay the onset of dementia in older adults with MCI by altering structural and neural activities and modulating other factors., Competing Interests: Declaration of Competing Interest The author declares that there is no conflict of interest, (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Obesity is one of the most prevalent and increasing metabolic disorders and is considered one of the twelve risk factors for dementia. Numerous studies have demonstrated that obesity induces pathophysiological changes leading to cognitive decline; however, the underlying molecular mechanisms are yet to be fully elucidated. Various biochemical processes, including chronic inflammation, oxidative stress, insulin resistance, dysregulation of lipid metabolism, disruption of the blood-brain barrier, and the release of adipokines have been reported to contribute to the accumulation of senescent neurons during obesity. These senescent cells dysregulate neuronal health and function by exhibiting a senescence-associated secretory phenotype, inducing neuronal inflammation, deregulating cellular homeostasis, causing mitochondrial dysfunction, and promoting microglial infiltration. These factors act as major risks for the occurrence of neurodegenerative diseases and cognitive decline. This review aims to focus on how obesity upregulates neuronal senescence and explores both pharmacological and non-pharmacological interventions for preventing cognitive impairments, thus offering new insights into potential therapeutic strategies., Competing Interests: Declaration of Competing Interest All authors have no potential conflicts of interest to be disclosed or relevant financial interest in this manuscript., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: A recently developed mild behavioral impairment (MBI) diagnostic framework standardizes the early characterization of neuropsychiatric symptoms in older adults. However, the joint contributions of Alzheimer's disease (AD) pathology and brain function to MBI remain unclear., Methods: We test a novel model assessing direct relationships between AD biomarker status and MBI symptoms, as well as mediated effects through segregation of the salience and default-mode networks, using data from 128 participants with diagnosis of amnestic mild cognitive impairment or mild dementia-AD type., Results: We identified a mediated effect of tau positivity on MBI through functional segregation of the salience network from the other high-level, association networks. There were no direct effects of AD biomarkers status on MBI., Discussion: Our findings suggest that tau pathology contributes to MBI primarily by disrupting salience network function and emphasize the role of the salience network in mediating relationships between neuropathological changes and behavioral manifestations., Highlights: Network segregation mediates Alzheimer's disease (AD) pathology impact on mild behavioral impairment (MBI). The salience network is pivotal in linking tau pathology and MBI. This study used path analysis with AD biomarkers and network integrity. The study evaluated the roles of salience, default mode, and frontoparietal networks. This is the first study to integrate MBI with AD biomarkers and network functionality., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Evidence suggests that neuropsychiatric symptoms and deficits in attentional control and executive function can impair time discrimination, demonstrating the intricate link between cognitive processes, subjective well-being, and perception of time. However, the relationship between sleep quality and time discrimination remains elusive. This study aimed to understand differences in the temporal bisection task (TBT) performance. We expected that individuals with impaired cognition, executive function, quality of life, or sleep quality would have reduced time sensitivity. At the same time, those with stress, anxiety, or depression would show a shift in the point of subjective equality. Data were collected from 97 female participants (ranging from 20 to 72 years of age) in more than one moment, resulting in 163 measurements used for the analysis. Participants' neuropsychiatric status was assessed using a battery of tests and scales, including the Mini-Mental State Examination (MMSE), the Frontal Assessment Battery (FAB), the World Health Organization Quality of Life Questionnaire (WHOQOL), the Pittsburgh Sleep Quality Index (PSQI), and the Depression, Anxiety, and Stress Scale-21 items (DASS-21). The results showed that attention and executive control significantly affect time discrimination. In addition, the research indicated that better sleep quality is associated with improved time discrimination sensitivity., (© 2024 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Background: Sleep macro and microstructural features have a relevant role for cognition. Although alterations in sleep macrostructure have been reported in persons with neurodegenerative disorders, including Parkinson's disease (PD), it is unknown whether there is a relationship between alterations in microstructure (sleep spindles) and global cognitive deficits in this disease., Objective: To explore the association between the macro and microstructure of sleep (sleep spindles) and the general cognitive state in persons with PD., Methods: Thirty-three patients with idiopathic PD underwent a one-night polysomnography (PSG) and a global cognitive assessment using the Montreal Cognitive Assessment (MoCA) test. PSG-based macrostructural sleep values and quantification and spectral estimation of sleep spindles were obtained., Results: We found increases in total sleep time, latency to rapid eye movement (REM) sleep, and percentage of N1 stage, as well as a decrease in percentage of REM sleep and sleep efficiency compared to values reported in healthy adults. Compared to expected values, a decrease in the number of sleep spindles was found at frontal regions. Participants with cognitive impairment showed an even lower count of sleep spindles, as well as an increase in the amplitude of underlying sigma (12-16 Hz) waves (fast spindles). When exploring MoCA subdomains, we found a consistent relationship between the number and amplitude of sleep spindles and attention capacity., Conclusions: Decreased number and increased amplitude of sleep spindles are linked to cognitive impairment in persons with PD, especially in attention capacity. Therefore, sleep spindles characteristics could serve as prognostic indicators of cognitive deterioration in PD., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Heterozygous variants in the glucocerebrosidase (GBA1) gene are the most common genetic risk factor for Parkinson's Disease (PD). GBA1-PD patients exhibit earlier disease onset, severe motor impairment, and heightened cognitive decline. Deep Brain Stimulation (DBS) offers motor improvement for PD patients, but its cognitive effects, particularly in GBA1-PD, are debated., Methods: This study involved 96 PD patients who underwent subthalamic nucleus DBS at Hospital de la Santa Creu i Sant Pau between 2004 and 2023. Clinical and neuropsychological assessments were conducted pre- and post-surgery, focusing on Mattis Dementia Rating Scale (MDRS) and Frontal Systems Behavior Scale (FrSBe). Patients were categorized into GBA1-PD and non-GBA1-PD groups, with non-GBA1-PD further divided into cognitive fast-progressors and slow-progressors., Results: GBA1 variants were present in 13.5 % of patients. GBA1-PD patients showed greater cognitive decline over time, particularly in attention, conceptualization, and memory, compared to non-GBA1-PD. Non-GBA1-PD fast-progressors exhibited significant cognitive deterioration in initiation and conceptualization within the first year post-DBS. Motor outcomes improved similarly across all groups, but slow-progressors showed a greater reduction in Levodopa Equivalent Daily Dose (LEDD)., Conclusions: GBA1-PD patients experience more rapid cognitive decline, particularly in posterior-cortical and fronto-striatal functions. Additionally, a subset of non-GBA1-PD patients shows significant early cognitive decline post-DBS, especially in executive functions. Baseline MDRS scores do not predict cognitive outcomes, highlighting the need for further research to refine prognostic tools. Despite cognitive challenges, GBA1-PD patients benefit from DBS in terms of motor outcomes, underscoring the importance of individualized assessments for DBS suitability, regardless of genetic status., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Neuropsychology is an integral component of health care assessment for persons with vascular contributions to cognitive impairment and dementia. Since syndromes of vascular cognitive decline have multiple and varying pathophysiologies, anatomic brain locations, and levels of severity, neuropsychological assessment can be critical to clarify the cognitive manifestations of the disease, potential consequences for the patient and family, as well as the prognosis for future life planning. Cognitive profiles of vascular cognitive declines and relevant neuropsychological literature are reviewed here to provide the practicing physician with guidance for best clinical care practices., Competing Interests: Disclosure Preparation of this manuscript was supported in part by a grant from NIH, United States to J.S. Paulsen (RF1AG074608)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Diabetes is associated with cognitive impairment, but the underlying mechanism remains unclear. Methylglyoxal (MGO), a precursor to advanced glycation endproducts (AGEs), is elevated in diabetes and linked to microvascular dysfunction. In this study, overexpression of the MGO-detoxifying enzyme glyoxalase 1 (Glo1) was used in a mouse model of diabetes to explore whether MGO accumulation in diabetes causes cognitive impairment. Diabetes was induced with streptozotocin. Fasting blood glucose, cognitive function, cerebral blood flow, neurovascular coupling (NVC), Glo1 activity, MGO and AGEs were assessed. In diabetes, MGO-derived hydroimidazolone-1 increased in the cortex, and was decreased in Glo1-overexpressing mice compared to controls. Visuospatial memory was decreased in diabetes, but not in Glo1/diabetes. NVC response time was slightly increased in diabetes, and normalised in the Glo1-overexpressing group. No impact of diabetes or Glo1 overexpression on blood-brain barrier integrity or vascular density was observed. Diabetes induced a mild visuospatial memory impairment and slightly reduced NVC response speed and these effects were mitigated by Glo1. This study shows a link between MGO-related AGE accumulation and cerebrovascular/cognitive functions in diabetes. Modulation of the MGO-Glo1 pathway may be a novel intervention strategy in patients with diabetes who have cerebrovascular complications. KEY POINTS: Diabetes is associated with an increased risk of stroke, cognitive decline, depression and Alzheimer's disease, but the underlying mechanism remains unclear. Methylglyoxal (MGO), a highly reactive by-product of glycolysis, plays an important role in the development of diabetes-associated microvascular dysfunction in the periphery and is detoxified by the enzyme glyoxalase 1. Diabetes reduced visuospatial memory in mice and slowed the neurovascular coupling response speed, which was improved by overexpression of glyoxalase 1. MGO formation and MGO-derived advanced glycation endproduct (AGE) accumulation in the brain of diabetic mice are associated with a slight reduction in neurovascular coupling and mild cognitive impairment. The endogenous formation of MGO, and the accumulation of MGO-derived AGEs, might be a potential target in reducing the risk of vascular cognitive impairment in people with diabetes., (© 2024 The Author(s). The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Background: Mild cognitive impairment (MCI) is a critical time window for implementing prevention strategies to attenuate or delay cognitive decline. Non-invasive brain stimulation (NIBS) techniques are promising non-pharmacological therapies for improving the cognitive function of MCI, but it is unclear which type of NIBS protocol is most effective. This study aimed to compare and rank the beneficial effect of different NIBS methods/protocols on cognitive function and examine the acceptability of NIBS in patients with MCI., Methods: Electronic search of PubMed, Cochrane Library, EMBASE, China National Knowledge Infrastructure, Wanfang Database, and Chongqing VIP Database up to November 2023. Patients with diagnosis of MCI were included. The primary outcomes were acceptability and pre-post treatment changes in global cognitive function, and the secondary outcomes were specific cognitive domains (language and executive function). All network meta‑analysis procedures were performed under the frequentist model. A protocol for this systematic review was registered in PROSPERO (Registration number: CRD42023441448)., Results: A network meta-analysis was conducted on 19 eligible RCTs consisting of 599 subjects. Compared with the sham stimulation, Repetitive Transcranial Magnetic Stimulation over the Bilateral dorsolateral prefrontal cortex (rTMS-F3F4) showed the strongest improvement in global cognitive function in MCI patients (SMD =1.52[95 %CIs =0.49-2.56]), followed by rTMS over the left dorsolateral prefrontal cortex (rTMS-F3) (SMD =1.25[95 %CIs =0.57-1.93]); Moreover, rTMS-F3F4 showed more significant efficacy in language function (SMD =0.96[95 %CIs = 0.20-1.72]); No statistically significant differences were found among the other cognitive domains. Compared with the rTMS-F4, rTMS-F3F4 showed a stronger improvement in global cognitive function in MCI patients (SMD =1.80[95 %CIs =0.02-3.59]). Similar results were obtained in subgroup analyses of cognitive function. All the methods were well-tolerated with an acceptable safety profile., Conclusion: The present findings provide evidence of the benefits of NIBS, especially TMS stimulating the bilateral dorsolateral prefrontal cortex, for the beneficial effect on cognitive and language function in patients with MCI. However, because few studies were available for inclusion, additional well-designed, large-scale RCTs are warranted to support exploring longer-term dynamic effects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In recent years, there has been a growing interest in exploring the non-classical symptoms of multiple sclerosis (MS), with a particular focus on cognitive impairments associated with the disease's progression. These cognitive symptoms are now recognized as crucial elements in the assessment of disease activity. In this context, neurophysiology has emerged as a valuable and accessible tool for studying and addressing cognitive decline in individuals with MS. This scoping literature review investigates the role of neurophysiology in assessing and treating cognitive impairment in MS patients. The review focuses on Electroencephalography (EEG), Non-Invasive Brain Stimulation (NIBS), and magnetoencephalography (MEG) to assess cognitive decline in MS patients. Moreover, we discuss all the papers that tried to treat this cognitive impairment with NIBS techniques. While several neurophysiological markers show potential, standardization of protocols is essential for enhancing the reliability and consistency of these approaches. Further research is warranted to explore other NIBS techniques and deepen our understanding of the neurophysiological underpinnings of cognitive deficits in MS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Magnetic resonance imaging (MRI)-determined atrophy of the nucleus basalis of Meynert (Ch4) predicts cognitive decline in Parkinson's disease (PD). However, interactions with other brain regions causing the decline remain unclear. This study aimed to describe how MRI-determined Ch4 atrophy leads to cognitive decline in patients with PD., Methods: We evaluated 137 patients with PD and 39 healthy controls using neuropsychological examinations, MRI, and 123 I-ioflupane single-photon emission computed tomography. First, we explored brain areas with regional gray matter loss correlated with Ch4 volume reduction using voxel-based morphometry (VBM). We then assessed the correlation between Ch4 volume reduction and cognitive impairments in PD using partial correlation coefficients (r par ). Finally, we examined whether the regional gray matter loss mediated the association between Ch4 volume reduction and cognitive impairments using mediation analysis., Results: Our PD cohort was "advanced-stage enriched." VBM analyses revealed that Ch4 volume loss was correlated with volume reduction in the medial temporal lobe in PD (P < 0.05, family-wise error corrected, >29 voxels). Ch4 volume reduction was significantly correlated with verbal memory deficits in PD when adjusted for age, sex, total brain volume, and 123 I-ioflupane uptake in the caudate (r par  = 0.28, P < 0.001). The mediation analysis revealed that the hippocampus mediated the effects of Ch4 volumes on verbal memory (average causal mediation effect = 0.013, 95 % CI = 0.006-0.020, P < 0.001)., Conclusion: Particularly in advanced-stage PD, Ch4 atrophy was associated with medial temporal lobe atrophy, which played an intermediary role in the relationship between Ch4 atrophy and verbal memory impairments., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ryosuke Takahashi received a research grant from Nihon Medi-Physics Co., Ltd., a manufacturer of (123)Iioflupane., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Animal and computational models of Alzheimer's disease (AD) indicate that early amyloid-β (Aβ) deposits drive neurons into a hyperactive regime, and that subsequent tau depositions manifest an opposite, suppressive effect as behavioral deficits emerge. Here we report analogous changes in macroscopic oscillatory neurophysiology in the human brain. We used positron emission tomography and task-free magnetoencephalography to test the effects of Aβ and tau deposition on cortical neurophysiology in 104 cognitively unimpaired older adults with a family history of sporadic AD. In these asymptomatic individuals, we found that Aβ depositions colocalize with accelerated neurophysiological activity. In those also presenting medial-temporal tau pathology, linear mixed effects of Aβ and tau depositions indicate a shift toward slower neurophysiological activity, which was also linked to cognitive decline. We conclude that early Aβ and tau depositions relate synergistically to human cortical neurophysiology and subsequent cognitive decline. Our findings provide insight into the multifaceted neurophysiological mechanisms engaged in the preclinical phases of AD., (© 2024. The Author(s).)

Objective: To define the clinical usability of an affect recognition (AR) battery-the Comprehensive Affect Testing System (CATS)-in an Italian sample of patients with amyotrophic lateral sclerosis (ALS)., Methods: 96 ALS patients and 116 healthy controls underwent a neuropsychological assessment including the AR subtests of the abbreviated version of the CATS (CATS-A). CATS-A AR subtests and their global score (CATS-A AR Quotient, ARQ) were assessed for their factorial, convergent, and divergent validity. The diagnostic accuracy of each CATS-A AR measure in discriminating ALS patients with cognitive impairment from cognitively normal controls and patients was tested via receiver-operating characteristics analyses. Optimal cut-offs were identified for CATS-A AR measures yielding an acceptable AUC value (≥ .70). The ability of CATS-A ARQ to discriminate between different ALS cognitive phenotypes was also tested. Gray-matter (GM) volumes of controls, ALS with normal (ALS-nARQ), and impaired ARQ score (ALS-iARQ) were compared using ANCOVA models., Results: CATS-A AR subtests and ARQ proved to have moderate-to-strong convergent and divergent validity. Almost all considered CATS-A measures reached acceptable accuracy and diagnostic power (AUC range = .79-.83). ARQ showed to be the best diagnostic measure (sensitivity = .80; specificity = .75) and discriminated between different ALS cognitive phenotypes. Compared to ALS-nARQ, ALS-iARQ patients showed reduced GM volumes in the right anterior cingulate, right middle frontal, left inferior temporal, and superior occipital regions., Conclusions: The AR subtests of the CATS-A, and in particular the CATS-A ARQ, are sound measures of AR in ALS. AR deficits may be a valid marker of frontotemporal involvement in these patients., Competing Interests: Declarations Conflicts of interest V. Castelnovo has nothing to disclose; E. Canu has received research supports from the Italian Ministry of Health; E.N. Aiello serves as an Editorial Board Member for BMC Neurology; B. Curti, E. Sibilla, S.Torre, F. Freri, C. Tripodi, and L. Lumaca have nothing to disclose; E. G. Spinelli, P. Schito, T. Russo, and Y. Falzone have nothing to disclose; F. Verde is Associated Editor for Journal of Alzheimer’s Disease; V. Silani received compensation for consulting services and/or speaking activities from AveXis, Cytokinetics, Italfarmaco, Liquidweb S.r.l., Novartis Pharma AG, Amylyx Pharmaceuticals, Biogen, and Zambon Biotech SA; receives or has received research supports from the Italian Ministry of Health, AriSLA, and E-Rare Joint Transnational Call. He is in the Editorial Board of Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, European Neurology, American Journal of Neurodegenerative Diseases, Frontiers in Neurology; N. Ticozzi received compensation for consulting services from Amylyx Pharmaceuticals and Zambon Biotech SA. He is Associate Editor for Frontiers in Aging Neuroscience; V.E. Sturm, K.P. Rankin, and M.L. Gorno-Tempini have nothing to disclose; B. Poletti received compensation for consulting services and/or speaking activities from Liquidweb S.r.l. She is Associate Editor for Frontiers in Neuroscience; M. Filippi is the Editor-in-Chief of the Journal of Neurology, Associate Editor of Human Brain Mapping, Neurological Sciences, and Radiology, received compensation for consulting services from Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi, speaking activities from Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA, participation in Advisory Boards for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme, Takeda, scientific direction of educational events for Biogen, Merck, Roche, Celgene, Bristol-Myers Squibb, Lilly, Novartis, Sanofi-Genzyme, and he receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla; F. Agosta is Associate Editor of NeuroImage: Clinical, has received speaker honoraria from Biogen Idec, Italfarmaco, Roche, Zambon and Eli Lilly, and receives or has received research supports from the Italian Ministry of Health, the Italian Ministry of University and Research, AriSLA (Fondazione Italiana di Ricerca per la SLA), the European Research Council, the EU Joint Programme—Neurodegenerative Disease Research (JPND), and Foundation Research on Alzheimer Disease (France). Ethical approval Before participating, all participants provided written informed consent according to the Declaration of Helsinki. The local ethical standards committee on human experimentation approved the study protocol., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Pediatric onset multiple sclerosis (POMS) patients are at risk for cognitive impairment (CI). Nevertheless, the underlying mechanisms and relationship with paramagnetic rim lesions (PRLs) are not fully understood. We aimed to explore CI with clinical and neuroimaging correlates in POMS., Methods: We analyzed 10 patients with POMS and 16 healthy controls, evaluating cognitive, clinical, and neuroimaging variables., Results: Fifty percent of POMS had CI and ninety percent had at least one PRL. A higher percentage of PRLs was associated with worse information processing speed performance., Conclusion: CI is frequent in POMS and may be related to higher PRL percentage., Competing Interests: Declaration of Competing Interest No conflict of Interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: To apply susceptibility separation on quantitative susceptibility mapping (QSM) images of Parkinson's disease (PD) patients to obtain more accurate images and gain pathophysiological insights., Methods: This retrospective study included subjects who underwent head MRI, including QSM between March 2016 and March 2018. Patients with PD were categorized as having mild cognitive impairment (PD-MCI), or normal cognition (PD-CN); healthy controls (HC) were also enrolled. Susceptibility separation generated positive (QSM+) and negative susceptibility (QSM-) labels. Voxel-based whole-brain susceptibility and atlas-based susceptibility were compared among groups on white matter. Correlations between susceptibility and Montreal Cognitive Assessment (MoCA) scores were analyzed., Results: Overall, 65 subjects (mean age 72 years ±6, 35 men) were included. White-matter regions with significant (P < 0.05) group differences were found for QSM+ (HC > PD-MCI, PD-CN > PD-MCI) and QSM- (PD-MCI > HC, PD-MCI > PD-CN). In the atlas-based analyses, PD-MCI exhibited lower QSM + values (vs. HC; P = 0.002, vs. PD-CN; P = 0.001), and higher QSM-values (vs. HC; P = 0.02, vs. PD-CN; P = 0.03) in the genu of corpus callosum (gCC). QSM+ and QSM-showed significant positive and negative correlations with MoCA (P < 0.05). In the gCC, partial correlation analyses revealed a positive correlation between QSM+ and MoCA (R = 0.458, P < 0.001) and a negative correlation between QSM- and MoCA (R = -0.316, P = 0.01)., Conclusion: QSM utilizing susceptibility separation is valuable for assessing white matter in PD patients, where nerve fiber loss potentially influences cognitive function., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: An association between lipid measures and cognitive decline in patients with multiple sclerosis (MS) has been suggested., Objectives: This study aimed to investigate relationships between lipid profile and cognitive performance in a large observational cohort of MS patients., Materials and Methods: We included 211 patients with 316 available pairs of lipid and cognitive measures performed over follow-up. The time between lipid and cognitive measures did not exceed 90 days. Baseline data were analyzed by non-parametric Spearman rank correlation test. Repeated measures were analyzed using linear mixed models adjusted for sex, age, education level, disease-modifying therapy status, and depression., Results: Baseline analyses showed a correlation between higher low-density lipoprotein cholesterol (LDL-C) and lower Categorical Verbal Learning Test (CVLT) (rho=-0.15; p = 0.04), lower Symbol Digit Modalities Test (SDMT) (rho=-0.16; p = 0.02) and lower Brief Visuospatial Memory Test-Revised (BVMT-R) scores (rho=-0.12; p = 0.04). Higher high-density lipoprotein cholesterol (HDL-C) was negatively correlated with lower SDMT scores (rho=-0.16; p = 0.02) and lower Paced Auditory Serial Addition Test-3 (PASAT-3) scores (rho=-0.24; p = 0.03). Mixed model analyses of repeated measures showed a negative association between higher LDL-C and lower CVLT (B=-0.02; p < 0.001, Cohen´s d = 0.08) and lower BVMT-R (B=-0.01; p = 0.03, Cohen´s d=-0.12). Also, the negative association between HDL-C and PASAT-3 was confirmed in the mixed model analysis (B=-0.18; p = 0.01, Cohen´s d = 0.07). Additional adjustments of the models for disability assessed by Expanded Disability Status Scale or Normalized Brain Volume did not change the results of the models substantially., Conclusions: Our results suggest a mild negative impact of dyslipidemia on cognitive performance in patients with MS. We propose that dyslipidemia contributes, at least in part, to cognitive decline in MS patients, independent of brain atrophy., Competing Interests: Declaration of competing interest Balazs Lorincz received financial support for conference travel from Merck, Medtronic, Bayer and speaker honoraria from Sandoz. Jiri Motyl received compensation for traveling, conference fees and speaker honoraria from Sanofi Genzyme, Biogen, Novartis, and Merck. Lucie Friedova has nothing to disclose Daniel Hrych has received financial support for conference travel from Biogen. Eva Kubala Havrdova received speaker honoraria and consultant fees from Biogen Idec, Merck Serono, Novartis, Genzyme and Teva, as well as support for research activities from Biogen, and Merck Serono. Dana Horakova received compensation for travel, speaker honoraria and consultant fees from Biogen, Novartis, Merck, Bayer, Sanofi Genzyme, Roche, and Teva, as well as support for research activities from Biogen. Manuela Vaneckova received speaker honoraria, consultant fees, and travel expenses from Biogen Idec, Novartis, Roche, Genzyme, and Teva, as well as support for research activities from Biogen Idec. Jan Krasensky received financial support for research activities from Biogen Idec. Tobias Kober and Bénédicte Maréchal are Siemens Healthineers International AG employees. Tadeas Urbas has nothing to disclose. Michal Vrablik reports fees for clinical trials, consultancy and presentations from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Lilly, Mylan, Novartis, Novo Nordisk, Sanofi and Zentiva. Tomas Uher received financial support for conference travel and honoraria from Biogen Idec, Novartis, Roche, Genzyme, and Merck Serono, as well as support for research activities from Biogen Idec and Sanofi., (Copyright © 2024. Published by Elsevier B.V.)

Objective: To construct a predictive model for the improvement of cognitive function in patients with depressive disorder treated with SNRIs, based on emotional regulation abilities, and to provide personalized treatment for depressed patients., Methods: Clinical data from 170 patients with depressive disorder treated with SNRIs at Tongji Hospital, Shanghai, from December 2017 to May 2023 were collected. Based on whether the MoCA-B total score at 3-6 months post-treatment was at least 2 points higher than at baseline, patients were divided into the cognitive function improved group (n = 80) and the cognitive function not improved group (n = 90). Stepwise logistic regression and LASSO regression were used to select predictive factors, and logistic regression analysis was applied to construct predictive models solely based on emotional regulation abilities, combined with executive functions and HAMD scores. The models were further validated through Bootstrap internal validation, calibration curve plotting, and C-index calculation, and a comparison between the two models was performed., Results: An ER model with an area under the ROC curve of 0.817was established using four emotional regulation ability indicators: the valence of reappraised images, the arousal of negative images, the arousal of neutral images, and the success of reappraisal (arousal). Internal validation using Bootstrap showed a C index of 0.817, and clinical decision curves indicated that this model has a significant net benefit with a probability of improved cognitive function ranging from about 20 to 85%. Additionally, an EREH model including emotional regulation ability, executive function, and HAMD score as predictors was constructed using Lasso and logistic regression methods. This model reached an area under the ROC curve of 0.859and clinical decision curves showed high net benefits with probabilities of improved cognitive function ranging from 10 to 100%. The calibration curves of both models coincided well with the actual curves, with the latter having a higher AUC and significant statistical differences between the two models., Conclusion: This study suggests that emotional regulation ability may serve as a predictor for the improvement of cognitive functions in patients with depression depressive disorder treated with SNRIs. However, it is important to note that there may be other factors not covered or included in this study.The predictive model that includes executive functions and HAMD scores offers better differentiation and consistency and is more feasible in clinical practice., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Motoric cognitive risk syndrome (MCR) is defined as the presence of slow gait-speed and subjective cognitive decline in older individuals without mobility disability or dementia. While some studies suggest that MCR is a pre-dementia syndrome and may help predict the risk of cognitive impairment and dementia, not all studies concur. The objective of this study is to comprehensively summarize and synthesize evidence to assess the association between MCR and cognitive impairment and dementia., Methods: Following a pre-specified protocol, two authors systematically searched PubMed, Embase, and The Cochrane Library from inception to 19 August 2024 for observational or randomized studies pertaining to the association between MCR and cognitive impairment and dementia. We favoured maximally adjusted hazards and odds ratios to determine the longitudinal and cross-sectional risk of cognitive impairment and dementia. We investigated for potential sources of heterogeneity and also conducted sensitivity and subgroup analyses by continent and the type of cognitive outcome. The quality of evidence was assessed using the Newcastle-Ottawa Scale (NOS) and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework., Results: We included 20 studies comprising a combined cohort of 1206,782 participants, of which 17 studies were included in the quantitative analysis. The pooled analysis outlined that individuals with MCR exhibited 2.20-fold higher risk of cognitive impairment and dementia, compared to controls (RR=2.20; 95 %CI=1.91-2.53). These findings remained robust across all subgroup analyses, sensitivity analyses and assessments of publication bias., Conclusion: MCR may be considered a predictive factor for long-term cognitive impairment and dementia. This should be taken into consideration when clinically evaluating the risk of cognitive impairment and dementia but further research is required to lend greater clarity to this association., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)