Alogliptin attenuates diabetes-associated cognitive impairment in rats via HMGB1/RAGE/TLR4-NFκB pathway modulation.

Alzheimer's disease is an age-related neurodegenerative disorder characterized by progressive cognitive decline and multiple biochemical and structural abnormalities in the brain. Accumulating evidence suggests that aluminum exposure may contribute to neurodegenerative process including those observed in AD and was linked to neuronal damage and cognitive impairment. Melatonin (Mel) is a neurohormone that regulates circadian rhythm and possesses antioxidant, anti-inflammatory and neuroprotective properties. The current study investigated the potential protective roles of Mel in a rat model of AD induced by aluminum chloride (AlCl3). Forty adult male rats were divided into 4 experimental groups: a control group, an AlCl3-treated group, an AlCl3+Mel-treated group, and a Mel-only group. AlCl3 was administered orally for four weeks. Cognitive performance and spatial learning were assessed using Morris water maze test. Plasma levels of the pro inflammatory cytokines; interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were measured using enzyme linked immunosorbent assay. Histopathological examination of the frontal cortex was performed using hematoxylin and eosin staining, and immunohistochemistry was conducted using the neuronal marker NeuN, microglial marker Iba1, and inflammatory markers IL-6 and TNF-α. Mel treatment significantly improved learning and memory performance in the Morris water maze test. It also reduced plasma levels of IL-6 and TNF-α. Using immunohistochemistry, Mel increased NeuN expression, while reducing Iba1, IL-6 and TNF-α expression. These findings showed that Mel attenuated frontal cortical neurodegeneration and neuroinflammation in this model of AD, suggesting that Mel may represent a promising neuroprotective therapeutic strategy for AD.

Heterogeneity in working memory performance caused by different positions of the visual cue in the visual field.

Anxiety influences working memory performance, but the effects on clinical neuropsychological assessments of working memory are not well known. We examined the effect of anxiety, induced using the 7.5% carbon dioxide model of anxiety on standardized clinical neuropsychological tests of working memory and executive function in a single-blind, placebo-controlled, randomized, crossover within-subjects design. The CO2-challenge reduced spatial working memory performance and verbal working memory performance accuracy when task demands were high. The CO2-challenge increased effort and reduced processing efficiency across all verbal and spatial working memory tasks. The CO2-challenge resulted in significant reductions in working memory performance and processing efficiency. These results encourage the routine assessment of anxiety when administering and interpreting neuropsychological measures of working memory function in clinical practice.

Chronic pain is a prevalent condition often associated with cognitive impairments, including memory deficits. The dorsal raphe nucleus (DRN) is implicated in both pain processing and memory regulation, yet the role of DRN dopaminergic (DAergic) neurons in chronic pain-induced memory impairment remains unclear. This study aimed to investigate whether DRN-DA neurons and their projections to the bed nucleus of the stria terminalis (BNST) contribute to memory deficits in a mouse model of chronic neuropathic pain. Chronic constrictive injury (CCI) was induced in male C57BL/6J and DAT-Cre mice to establish neuropathic pain. Memory function was assessed using the novel object recognition (NOR) and fear conditioning tests (FCT). Neuronal activity was evaluated via c-Fos immunohistochemistry and whole-cell patch-clamp recordings. Chemogenetic and optogenetic techniques were employed to selectively manipulate DRN-DA neurons and their projections to the BNST. CCI mice exhibited significant memory impairments alongside reduced activity of DRN-DA neurons. Chemogenetic or optogenetic activation of DRN-DA neurons alleviated memory deficits in CCI mice. Optogenetic stimulation of DRN-DA terminals in the BNST similarly rescued memory performance, confirming the involvement of the DRNDA-BNST pathway in pain-related cognitive dysfunction. Our findings demonstrate that DRN-DA neurons play a critical role in regulating memory impairment induced by chronic pain, partly through projections to the BNST. Targeted activation of this pathway may represent a potential therapeutic strategy for alleviating cognitive deficits in chronic pain conditions.

BackgroundThere is an evident interrelationship between stroke and Alzheimer's disease (AD). Post-stroke cognitive impairment (PSCI) is a frequently encountered and potentially disabling outcome of stroke. Memory impairment is an important component of the post-stroke cognitive syndrome, and high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has been widely used for memory in patients with PSCI.ObjectiveIn this study, we systematically evaluated the therapeutic effects of HF-rTMS on memory function in patients with PSCI, offering insights that may also inform the treatment of AD.MethodsAll relevant publications in Chinese and English were systematically searched from ten databases up to March 20, 2025. Retrieved articles were carefully screened. The quality of the included studies was assessed using the Cochrane Collaboration's risk of bias tool. The Review Manager 5.4 software was adopted for meta-analysis.ResultsTwenty-one studies of 1746 participants with PSCI were included. Meta-analysis revealed that HF-rTMS ameliorated memory of PSCI patients according to several outcome indicators: Rivermead Behavioural Memory Test [mean difference (MD) = 2.59, 95% confidence interval (CI) (2.08, 3.11), p < 0.00001], forward digit span [MD = 1.79, 95% CI (1.36, 2.22), p < 0.00001] and backward digit span [MD = 1.18, 95% CI (0.77, 1.59), p < 0.00001] of digit span test, Delayed Recall of the Montreal Cognitive Assessment [MD = 0.53, 95% CI (0.47, 0.59), p < 0.00001]; all p < 0.05.ConclusionsThe HF-rTMS might enhance memory in patients with PSCI, with the left dorsolateral prefrontal cortex being the most common stimulation site.

Early life is essential for establishing memory T cells, which rapidly populate mucosal sites during infancy, although these nascent memory T cells are less protective than their adult counterparts. Here we used single-cell RNA sequencing of resting and CD3+CD28 antibody-stimulated T cells from lymphoid and mucosal tissues of infant (2-9 months) and adult (40-63 years) organ donors to investigate age-dependent mechanisms for functional regulation of human memory T cells. Infant CCL5+ effector memory T cells exhibited reduced effector function compared to adults. Transcription factor network analysis identified HELIOS and KLF6 as regulators of memory T cell states in infant and adult tissues, respectively. Using single-nucleus RNA sequencing, assay for transposase-accessible chromatin sequencing and CRISPR-Cas9 knockout, we defined HELIOS (IKZF2) as a critical regulator of the infant-specific transcriptional program in CCL5+ effector memory T cells and restricted effector function in SELL+CCR7+ naive and/or central memory T cells. Our findings reveal key mechanisms controlling T cell functional states in early life.

Design, synthesis, and biological evaluation of pyranone-carbamate hybrids as selective butyrylcholinesterase inhibitors with anti-neuroinflammatory activity for Alzheimer's disease.

Compensatory cognitive training for unstably housed, post-9/11 veterans in residential mental health treatment: A randomized controlled trial.

Because critical illness, sedation, and ICU treatment commonly disrupt attention, memory, and executive function, early cognitive rehabilitation during the ICU stay may preserve or restore these capacities, reduce the delirium burden, and support engagement and recovery. Our primary aim was to identify and describe cognitive rehabilitation interventions delivered during the ICU stay and describe the healthcare professionals providing them. Secondarily, we summarized patient-important outcomes associated with these interventions and appraised study quality to inform future research. We performed a systematic integrative review with searches in Medline, EMBASE, CINAHL, and CENTRAL. Eligible studies included adult ICU patients receiving or healthcare professionals delivering early cognitive rehabilitation initiated in the ICU. Data synthesis followed PRISMA guidelines, and risk of bias was assessed using RoB2 and ROBINS-I and narratively described. We included 27 studies: 10 randomized clinical trials, six cross-sectional studies, five cohort studies, three qualitative studies, three non-randomized trials, and one mixed-methods study. Four categories of interventions were identified: (1) orientation and multisensory stimulation, (2) activities of daily living (ADL)-focused functional occupational therapy, (3) early mobilization and physical rehabilitation, and (4) technology-based sensory and affective stimulation (music or virtual reality). Interventions were provided by nurses, physiotherapists, occupational therapists, research staff, and family members. Multi-component programs combining cognitive and physical elements indicated possible benefits for selected cognitive measures. Effects estimates on delirium and ADL were inconsistent and, in several studies, were based on secondary or exploratory outcomes analyses. Outcomes related to ventilator-free days, health-related quality of life, and survival were also inconsistent, with substantial heterogeneity in outcome definitions, measurement tools, and assessment time points. Multi-component cognitive rehabilitation appeared clinically applicable, but effects on patient-important outcomes were uncertain. High-quality research is needed to assess whether interventions targeting the improvement of cognitive function benefit ICU patients. This systematic review presents and update of published work on cognitive rehabilitation performed during ICU care and then also with assessments after critical illness in ICU survivors. The findings support the idea that this field need more robust clinical research to assess these different interventions in the ICU and their possible benefit and cost.

Biological subtypes of cognitive impairment in first-episode medication-naïve MDD linking individualized functional connectome, cognition, and symptom.

Cognitive impairment in antibody-mediated autoimmune encephalitis: subtype-specific clinical features and mechanistic insights from anti-NMDAR encephalitis.

Cognitive impairment in intensive care unit (ICU) survivors is multifactorial and can affect especially memory, attention, and executive functions. This study aimed to determine the cognitive functioning of patients with circulatory shock immediately after ICU discharge and 3 months later. This study, ASSESS-SHOCK 2, is a preplanned sub-study of the observational ASSESS-SHOCK study conducted at Helsinki University Hospital ICU. We included adults with circulatory shock, defined as hypotension requiring vasopressor infusion and concomitant signs of hypoperfusion. We excluded patients with severe neurological or psychiatric diagnoses, impairment of hearing or vision, developmental disability, and language barriers. Cognitive functioning of patients was assessed within 3 days of ICU discharge and 3 months thereafter with the Montreal Cognitive Assessment (MoCA) test. We defined cognitive impairment as MoCA score < 26 points. We also included data of 48 volunteer controls, tested once, to analyses. Fifty-five patients underwent an assessment within 3 days of ICU discharge, and 36 of them completed a follow-up assessment at 3 months. At discharge median MoCA-score was 22 (IQR 17-25). At the 3 months follow-up, the median MoCA-score was 26.5 points (IQR 24.25-28) showing improvement from discharge to follow-up (p < 0.001). The prevalence of cognitive impairment at discharge was 78.2%, and, at the 3-month follow-up 44.4%. In the control group, the median MoCA score was 27 points (IQR 25-28) and the prevalence of cognitive impairment 33%. We found cognitive impairment in more than three out of four ICU survivors immediately after ICU treatment for circulatory shock. We observed an improvement in cognitive functioning between ICU discharge and 3 months follow-up. These results have importance considering the optimal timing of information given to patients and when involving patients in decision-making. This study used the MoCA score to investigate the change in cognitive impairment in patients who survived circulatory shock, from the time of discharge from intensive care to 3 months after discharge. Scores indicated more severe cognitive dysfunction compared to controls at the time of discharge, but these improved to match control scores 3 months later. The findings have important implications for strategies to inform and support newly discharged ICU survivors who have experienced circulatory shock.

Discrepancies in loneliness and social isolation predict cognitive impairment through chronic disease burden.

Linking neuroinflammation and neurodegeneration to cognitive decline in HIV.

BackgroundThe logopenic variant of primary progressive aphasia (lvPPA) is a language-led neurodegenerative syndrome commonly associated with Alzheimer's disease pathology and temporo-parietal degeneration. Although acalculia has been reported in lvPPA, numerical cognition has not been systematically investigated, and the specific profile of impairment remains poorly defined.ObjectiveTo characterize numerical cognition impairment in lvPPA using a comprehensive, theory-driven assessment battery and to examine its clinical relevance for diagnosis and cognitive characterization.MethodsFourteen individuals with lvPPA and twenty-eight demographically matched healthy controls completed the dCALQ, a standardized battery assessing number recognition and comprehension, number production (transcoding), and calculation. Participants also underwent global cognitive screening (Montreal Cognitive Assessment), language assessment (Detection Test for Language Impairments in Adults and the Aged), and measures of working memory and executive functioning. Group comparisons, intra-group domain analyses, correlation analyses, and receiver operating characteristic (ROC) analyses were performed.ResultsIndividuals with lvPPA showed significant impairments across all numerical domains compared with controls, with the most severe deficits in calculation, followed by transcoding, and milder impairment in number recognition and comprehension. Within the lvPPA group, performance differed significantly across domains, revealing a graded pattern of impairment. ROC analyses demonstrated excellent diagnostic accuracy for the dCALQ total score and strong discrimination for the calculation and transcoding domains.ConclusionsNumerical impairment is a robust and systematic feature of lvPPA rather than an incidental finding. The distinct numerical profile identified highlights the contribution of parietal-based cognitive dysfunction and supports the clinical utility of structured numerical assessment for cognitive characterization and diagnosis in dementia syndromes.

Sarsasapogenin ameliorates Alzheimer's disease by dual inhibition of RIPK1-mediated necroptosis and pyroptosis.

Nonlinear shift along the sensorimotor-association-axis in brain responses to task performance.

Bacopa monnieri confers neuroprotection against middle cerebral artery occlusion (MCAO)-induced neurobehavioral and biochemical dysregulation in the frontal cortex and hippocampus of male Wistar rats.

Chronic pain and post-traumatic stress symptoms (PTSS) frequently co-occur. However, how they interact in the brain to influence cognition and emotion is not well understood. In this study, we examined how PTSS affects working memory-related networks during an N-back task. In addition, we examined how these networks interact with subcortical threat regions and influence working memory and pain symptoms. Fifty-three chronic low back pain participants completed the N-back task during fMRI. Brain activation was analyzed in relation to PTSS as both a continuous measure and a high-versus-low group, using whole-brain parcellation across task loads (FDR corrected). We also examined whether abnormally activated regions were functionally connected to periaqueductal gray subregions, the amygdala, or hippocampus, and how these connections related to PTSS. Although higher PTSS did not affect task performance, it was associated with reduced activation in dorsal and inferior lateral frontal regions during the 3-back condition. Post-traumatic stress symptoms were also associated with increased functional connectivity between the dorsolateral prefrontal cortex and periaqueductal gray, but not with the amygdala or hippocampus. Reduced prefrontal activations and high connectivity with periaqueductal gray predicted higher depression and catastrophizing symptoms. Thus, in chronic pain, PTSS selectively disrupts prefrontal circuits, suggesting that higher trauma symptoms interact with prefrontal circuits when cognitive demand is high. Post-traumatic stress symptoms strengthen coupling between prefrontal regions and brainstem threat/pain circuits, suggesting cognitive-affective coupling. These neural alterations occur even when working memory performance is intact and are linked to higher depression and pain catastrophizing. Larger studies are needed to confirm and clarify these mechanisms.