IntroductionAssessing attention and frontal lobe function is essential for diagnosing dementia. The Stroop test is widely used for these purposes, and its validity and reliability have been verified. Nevertheless, test-related burdens and procedural complexity have prevented their use as a screening tool. We developed a novel Stroop test using eye-tracking technology and evaluated its validity and utility in a clinical setting.MethodsThe study included 97 older adults at a memory clinic. Participants completed both the eye-tracking-based and conventional paper-based Stroop tests, along with MMSE, FAB, and TMT-A/B.ResultsScores on the eye-tracking-based Stroop test significantly correlated with the paper-based test (r = 0.634), FAB (r = 0.480), and TMT-B (r = −0.536). It achieved an AUC–ROC of 0.701 for frontal lobe dysfunction and 0.708 for dementia.DiscussionThe eye-tracking-based Stroop test has the potential to efficiently assess frontal lobe function and serve as a screening tool for dementia.

ObjectiveThis study aims to explore the associations of C-reactive protein-albumin-lymphocyte (CALLY) index with hemorrhagic transformation (HT), malignant cerebral edema (MCE), and 90-day unfavorable outcome and all-cause mortality in patients with acute ischemic stroke (AIS) following mechanical thrombectomy (MT).MethodsA retrospective study was conducted. The CALLY index was calculated as albumin × lymphocyte count/(CRP × 10). Unfavorable outcome was defined as the modified Rankin Scale score >2 at 90-day follow-up. Multivariable logistic analyses were performed to evaluate the associations between the CALLY index and clinical outcomes. The restricted cubic spines (RCS) curves were employed for pinpointing any nonlinear associations. In addition, mediation analysis was conducted to assess the potential mediating roles of HT and MCE linking the relationship between the CALLY index and 90-day outcomes.ResultsA total of 477 patients were enrolled, demonstrating the rates of HT, MCE, unfavorable outcome, and all-cause mortality were 29.8% (142), 22.9 (109), 54.5 (260), and 25.6 (122), respectively. Multivariable logistic analysis revealed that the CALLY index was associated with reduced risk of HT (odds ratio [OR] 0.843, 95% confidence interval [CI] 0.769–0.924, p < 0.001), MCE (OR 0.894, 95% CI 0.824–0.971, p = 0.008), unfavorable outcome (OR 0.895, 95% CI 0.840–0.954, p = 0.001), and mortality (OR 0.907, 95% CI 0.836–0.984, p = 0.019). RCS curves exhibited non-linear relationship between the CALLY index and HT (p-non-linear = 0.008), manifesting that CALLY index was associated with HT when its value below 2.681 (OR 0.530, 95% CI 0.357–0.785, p = 0.002). Mediation analysis indicated that the association between the CALLY index and unfavorable outcome may be partially mediated by HT (29.1%, p < 0.001) and MCE (28.1%, p = 0.003).ConclusionThe CALLY index is associated with reduced risk of HT, MCE, and 90-day unfavorable outcome and all-cause mortality. HT and MCE may be the mediators linking the CALLY index to 90-day unfavorable outcome.

Cognitive dysfunction is an increasingly recognized complication of diabetes, contributing substantially to morbidity in the aging population, yet disease-modifying therapies remain scarce. Dietary intervention, a cornerstone of diabetes management, may offer neuroprotective potential. Low-carbohydrate ketogenic diets (LCKDs), typically restricting carbohydrates to < 50 g/day, effectively improve glycemic control and metabolic health. Emerging preclinical and clinical evidence suggests that LCKDs may also confer cognitive benefits through mechanisms including enhanced mitochondrial bioenergetics, reduced neuro-inflammation, and modulation of the gut-brain axis. This narrative review critically evaluates the current evidence regarding the efficacy, mechanisms, and safety of LCKDs for managing diabetes-associated cognitive dysfunction, identifies key limitations in the existing literature, and proposes a framework for future research to enhance translational value.

Levodopa therapy effectively treats Parkinson's disease (PD) motor symptoms but causes Levodopa-Induced Dyskinesia (LID) in some patients long-term. Cerebellar changes exist in LID cases; however, radiomics models based on this region haven't been evaluated for diagnostic use. We built diagnostic model using cerebellar structural radiomics from 3D T1WI to non-invasively diagnose LID. In this study, we retrospectively collected 3D T1WI data from the Parkinson's Progression Markers Initiative (PPMI) database, including data from 69 LID patients and 142 non-LID (N-LID) patients. These data were randomly split into a training set and a testing set at an 8:2 ratio. Using Fastsurfer segmentation, we identified four regions of interest (ROIs) corresponding to the left and right cerebellar gray matter and white matter. Python scripts were employed to independently extract radiomic features from each ROI. Subsequent steps involved feature selection and model construction. After selecting the optimal model, its performance was evaluated and validated. Finally, the SHAP method was used for model visualization. Ultimately, the most representative 13 radiomic features were used for modeling. The model built based on the XGBoost algorithm achieved an AUC value of 0.962 on the training set and 0.849 on the testing set. The radiomic model extracted from the cerebellar gray and white matter effectively distinguishes between LID and N-LID patients. It offers a novel perspective on the heterogeneous characteristics of LID patients, significantly enhancing diagnostic performance and providing auxiliary support for clinical diagnosis.

This study aims to investigate the predictive value of the fibrinogen-to-high-density lipoprotein cholesterol ratio (FHR) in relation to sub-clinical diabetic peripheral neuropathy (sDPN) in individuals diagnosed with type 2 diabetes mellitus (T2DM). A cohort of 281 patients with T2DM was admitted to the Neurology Department of Jiangxi Provincial People's Hospital between January and December 2023. Within this population, 148 patients were diagnosed with sDPN. The clinical profiles, inflammatory biomarkers, and nerve conduction velocities or current perception thresholds (CPTs) were compared between the two distinct groups. A logistic regression analysis was performed to identify the risk factors for sDPN. The predictive performance of each factor was assessed using a receiver operating characteristic (ROC) curve analysis. The FHR was compared among three groups, which were based on the severity of peripheral neuropathy (PN). Patients with sDPN exhibited significantly elevated levels of fibrinogen (FIB), fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), the monocyte-to-lymphocyte ratio (MLR), and the platelet-to-lymphocyte ratio (PLR), along with diminished high-density lipoprotein cholesterol (HDL-C) levels, compared to patients without sDPN. Univariate and multivariate logistic regression analyses indicated that age, FIB levels, HbA1c, HDL-C, and MLR were significant risk factors that contributed to the onset of sDPN in T2DM patients. The ROC curve analysis indicated that the FHR had an area under the curve (AUC) of 65%. The optimal cutoff value for the FHR was 2.65, exhibiting a specificity of 62.4% and a sensitivity of 63.5%. The composite model incorporating the FHR demonstrated superior reclassification performance (net reclassification improvement (NRI) = 0.416, p = 0.001, 95% CI 0.180-0.650) and integrated discrimination improvement (IDI = 0.053, p < 0.001, 95% CI 0.001-0.015) compared to the basic model (age +HbA1c + MLR). Nonparametric test analysis showed significant differences in the FHR among the three groups. The more severe the PN, the higher the FHR. The FHR may serve as a valuable early diagnostic marker for sDPN in T2DM.

Non-pharmacological approaches are preferable to improve functional capacity and reduce emotional disorders for dementia patients with cognitive decline. This study aimed to assess the effectiveness of mindfulness-based stress reduction (MBSR) combined with reminiscence therapy (RT) on cognitive function and behavioral and psychological symptoms in older adults with mild cognitive impairment (MCI) or mild dementia due to Alzheimer's disease (AD). A total of 114 participants were randomly assigned to receive the reminiscence therapy combined with the MBSR program (n = 58) and to receive the reminiscence therapy only (n = 56) by using a computer-generated random table. The primary outcome measure was the Alzheimer's Disease Assessment Scale-Cognitive section (ADAS-Cog) scale for assessing cognitive impairment. The secondary outcome measures were scores of the Cornell Scale for Depression in Dementia (CSDD) scale, Neuropsychiatric Inventory (NPI) scale, and Spirituality Index of Well-Being (SIWB) scale to evaluate depressive symptoms, behavioral symptoms, and spiritual wellbeing, respectively. The RT+MBSR group exhibited lower scores in the ADAS-Cog scale, CSDD scale, and NPI scale, with a higher score in the SIWB scale than the RT group post intervention and 3 months post intervention, suggesting MBSR program combined with RT could improve cognitive function, depressive, behavioral symptoms, and spiritual wellbeing of older adults with MCI or mild dementia. The positive effects of MBSR program combined with RT on cognitive function and neuropsychiatric symptoms among patients with MCI or mild dementia suggest the need for more widespread use of this combination for older adults in geriatric care units.

Parkinson's disease (PD) is a neurodegenerative disorder for which no disease-modifying therapy currently exists, making it crucial to investigate alternative strategies that may slow its progression. The PRIME study will investigate the effects of combined dietary and physical activity interventions- performed in rehabilitative settings with health professional supervision and evaluation, versus single interventions on the gut microbiome in PD. The aim is to identify microbiome profiles - comparing traditional 16s rRNA gene sequencing with the third-generation method - as potential non-invasive, stage specific biomarkers of PD. In addition, the study will assess whether the combined intervention affects disease progression, symptoms, cognitive abilities, and quality of life. Eighty participants with PD will be randomized into four arms: a Mediterranean-diet intervention group; a structured physical-activity group; a combination group receiving both dietary and exercise interventions; a control group receiving standard care only. By integrating microbiome characterization with the evaluation of these interventions, the study aims to explore whether intervention-induced changes in the microbiota are associated with clinical improvement in PD, thus paving the way for the design of future non-pharmacological protocols to slow disease progression, mitigate symptom severity, and promote diagnosis. https://clinicaltrials.gov/, identifier NCT07097103.

Handwriting is a complex cognitive and motor skill supported by a distributed brain network involving cortical, subcortical, and cerebellar regions responsible for planning, execution, and sensorimotor integration. Beyond its communicative role, handwriting provides biologically meaningful information about brain function and motor control, serving as a sensitive marker of both normal and pathological changes. Age-related alterations, such as reduced fine motor precision, impaired sensory feedback, and cognitive slowing, contribute to the progressive decline in handwriting fluency and legibility. Importantly, distinctive handwriting patterns may be associated with early signs of neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease, and Multiple Sclerosis, reflecting disease-specific alterations in motor and cognitive circuits. Advances in digital technology now enable high-resolution, quantitative analysis of handwriting kinematics, offering promising and scalable tools for diagnosis, longitudinal monitoring, and personalized rehabilitation. Furthermore, interventions incorporating fine motor and visuomotor coordination exercises, adaptive writing, and cognitive training may help preserve handwriting abilities and promote adaptive neural changes. In this review, we synthesize current evidence on the neural, behavioral, and technological mechanisms underlying handwriting across aging and neurodegenerative conditions. We provide an integrated overview of neural substrates, age- and disease-related alterations, and emerging digital approaches for assessment and intervention, highlighting their relevance for research and clinical practice. Overall, handwriting has the potential to offer a powerful, non-invasive window into brain health, bridging neuroscience, aging research, and digital medicine.

BackgroundThis study investigated the association between liver fat, liver fibro-inflammation, and brain age, and assessed whether modifiable lifestyle factors modified the associations between liver markers and brain age.MethodsA total of 19,566 adults free from dementia and other neurological disorders were included from the UK Biobank. Liver fat and fibro-inflammation were quantified using proton density fat fraction (PDFF) and iron-corrected T1 mapping (cT1) derived from liver MRI scans. Brain age was estimated using a machine learning model based on 1,079 brain MRI phenotypes, and brain-predicted age difference (brain-PAD) was calculated.ResultsAmong participants, 4,634 (23.7%) had significant steatotic liver disease (PDFF ≥ 5.5%), and 938 (4.8%) had significant fibro-inflammation (cT1 ≥ 800 ms). Both significant liver fat accumulation (β = 0.4, 95% CI: 0.21–0.59) and fibro-inflammation (β = 1.09, 95% CI: 0.74–1.44) were associated with increased brain-PAD. Joint exposure analysis showed that the association between liver fat/fibro-inflammation and increased brain-PAD was attenuated among individuals with healthy lifestyle choices.ConclusionLiver fat accumulation and fibro-inflammation were associated with higher brain-PAD, with fibro-inflammation playing a key role. These associations may be attenuated in individuals with optimal lifestyle behaviors, suggesting a potentially modifiable target for intervention.

The high rate of comorbidity between metabolic diseases and neuropsychiatric disorders suggests a shared underlying pathogenic mechanism. However, the biological basis of this relationship remains unclear. This study aims to clarify the role of brain insulin resistance (BIR) in linking metabolic dysfunction to neuropsychiatric symptoms based on existing evidence. The analysis shows that BIR disrupts limbic system function through two primary molecular pathways: (1) impairment of the PI3K/Akt/mTOR pathway, which decreases the expression of synaptic plasticity-related proteins and causes deficits in long-term potentiation (LTP); (2) activation of the TLR4/MyD88 inflammatory axis, promoting pro-inflammatory cytokine release from glial cells. These changes result in characteristic neuropsychiatric phenotypes, including amygdala hyperactivity (emotional disorders), hippocampal atrophy (memory impairment), and decreased prefrontal cortex (PFC) function (executive dysfunction). This review highlights that interventions targeting BIR might simultaneously improve metabolic outcomes and neuropsychiatric symptoms, providing a theoretical foundation for trans-diagnostic treatment models. The findings support the view of BIR as a modifiable interface for metabolic- neuropsychiatric comorbidities and advocate for the development of a multidisciplinary collaborative framework to facilitate mechanism-based precision therapy.