Cognitive Changes Research Articles (Page 1)

Abstract Background Management of isocitrate dehydrogenase (IDH) mutated gliomas is multidisciplinary and current guidelines support early multimodal treatment. The effects of this treatment approach on cognition are less studied. We aimed to study changes in cognitive functioning the first year following treatment in these patients and explore predictors of cognitive deterioration. Methods Patients with a first-time diagnosis of IDH mutated glioma were neuropsychologically assessed before and one year after surgery. Results were compared to published norms, and impairment defined as z <-1.645. Matched controls were assessed at corresponding times, and reliable change indices (RCIs) were calculated to account for practice effects. Logistic regression models investigated predictors for cognitive declines. Tumor locations for declined versus non-declined patients were visualized using heatmaps. Results Of the 127 included patients, 104 underwent multi-modal treatment. Pre-operative impairments ranged from 3% to 24 %, depending on the specific test. Cognitive declines according to RCI domains were largest in tests of executive functioning (24%), learning/memory (23%) and language (21%). Tests of inhibition/flexibility (32%), naming speed (29%), verbal memory (28%), object naming (28%) and verbal fluency (22%) showed the largest proportions of declines. Regression models revealed that older age and chemoradiotherapy predicted declines in specific domains as well as in individual tests (P<0.05). Conclusions Significant changes occurred in several cognitive domains after guideline-based treatment. Older age and chemoradiotherapy increased the risk of cognitive declines one year after surgery, but to which extent the deficits are persistent or progressing remains unknown.

ABSTRACTLong-term survivors (LTS) of HIV are people diagnosed before the advent of highly active antiretroviral therapy in 1996 or who have lived with HIV for more than ten years. As they age, many experience comorbidities and effects of lifelong therapy, yet they remain underrepresented in research, which limits person-centered strategies. We examined priorities related to health, aging, safer antiretroviral therapy, community, mental health, and research engagement among LTS in the United States, and explored how social determinants shaped outcomes and access. In 2023 to 2024, we conducted qualitative interviews with 32 LTS aged 60 and above across the country, recruited through community partners and purposively sampled by gender, race, and region. Most participants were community advocates with a mean of 27.4 years since diagnosis. Thematic analysis identified priorities for integrated care addressing HIV alongside age-related comorbidities including cardiovascular disease and cognitive change. Participants emphasized mental health needs including survivor guilt, depression, and anxiety, and called for safer long term antiretroviral options and involvement in research. Housing, food security, and financial stability were social determinants. Findings support person-centered models integrating geriatric expertise, mental health services, and social supports to improve quality of life and resilience among LTS.

Abstract Repetitive head impacts are common in contact and collision sports and are linked to structural brain changes and an elevated risk of neurodegenerative diseases such as Chronic Traumatic Encephalopathy. Identifying early in vivo structural markers remains challenging. Although diagnosis currently requires postmortem confirmation, clinical symptoms, including cognitive impairment and behavioral changes, are reflected in the diagnosis of Traumatic Encephalopathy Syndrome. These symptoms align with dysfunction in key brain regions—amygdala, hippocampus, and thalamus—which support memory, emotion, and behavior, and commonly show tau pathology in Chronic Traumatic Encephalopathy. This study uses shape analysis to examine structural differences in these regions between former American football players and unexposed asymptomatic controls and evaluates the influence of age, head impact exposure, and clinical diagnosis on brain structure. We analyzed brain morphology in former American football players (n = 163) and unexposed, asymptomatic controls (n = 53). Structural segmentation was performed with FreeSurfer 7.1, and the shape analysis pipeline was used to generate subregional reconstructions. Vertex-level morphometry, based on the logarithm of the Jacobian determinant and radial distance, quantified local surface area dilation and thickness. Group differences were examined with covariate-adjusted linear regression models contrasting football players and controls, as well as participants with and without a Traumatic Encephalopathy Syndrome diagnosis. Partial correlations examined the influence of age, age of first football exposure, and cumulative head impact index metrics, including frequency, linear acceleration, and rotational force. Models were adjusted accordingly for age, body mass index, education, race, imaging site, apolipoprotein ε4 status, and total intracranial volume. Former football players exhibited bilateral surface area contractions in the hippocampus and amygdala, along with reduced amygdala thickness, compared to controls. Older age was associated with widespread surface contractions and thinning across all regions, except for preserved thickness in the left hippocampus. An earlier age of first exposure to football correlated with surface contractions in the thalamus and left hippocampus. Greater cumulative linear acceleration was linked to bilateral hippocampal surface contractions and reduced thickness in the left thalamus, while greater rotational force exposure was associated with hippocampal thinning. No significant structural differences were found between players with and without a diagnosis of Traumatic Encephalopathy Syndrome. These findings extend volume-based research by revealing localized alterations in surface area dilation and thickness and emphasize the roles of age and repetitive head impact exposure in long-term brain changes.

A new theoretical measurement framework for assessing active elements in cognitive behavioral therapies (CBT) emphasizes distinguishing various aspects of therapeutic components, and differentiating processes occurring within and between sessions. In this article, we apply the framework to data analyzed prior to its introduction. In Study 1, a panel of CBT experts evaluated items from the Cognitive Change scales (immediate and sustained) to determine whether they assess CBT skills (active elements) or cognitive change (mechanisms). In Study 2, we applied the framework to data from 125 CBT clients undergoing treatment for depression. Using disaggregated within- and between-patient components, we tested mediation models using framework-informed scores. In Study 1, experts achieved high interrater reliability and identified skill and cognitive change items using the framework. In Study 2, findings revealed that cognitive change mediated the relationship between skill use and symptom improvement. Results were similar using different subscales, consistent with the subscales being driven by a single underlying factor. Our results suggest that the pattern of findings was similar whether a distinction between skills and cognitive change was made or not. Considering previous factor analytic results and the present findings, we call into question whether the distinction between active elements and mechanisms is as essential or important as the framework suggests. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Objectives The present study aimed to identify immune, metabolic, and hematological biomarkers, among those commonly monitored in clinical practice, that are predictive of age-related behavioral and cognitive changes in clinically healthy elderly cats, with the objective of highlighting potential patterns of inflammaging. Methods A cross-sectional observational study was conducted at two veterinary institutions and involved 90 clinically healthy, privately owned domestic cats aged 7–16 years. All cats underwent physical examinations, laboratory, and behavioral screenings. Serum concentrations of the pro-inflammatory cytokine interleukin-1beta (IL-1β) and the anti-inflammatory cytokine IL-10 were measured using ELISA as markers of peripheral inflammation. Behavioral and cognitive changes were assessed using the Feline Behavioral Assessment and Research Questionnaire and Feline Cognitive Dysfunction Rating Chart, respectively. Multivariate regression analysis was used to assess the association between behavioral and cognitive outcomes and immune, metabolic, and biochemical predictors ( p < 0.05). Results Significant associations were identified between immune, hematological, and metabolic phenotypes indicative of chronic inflammation and cognitive changes assessed using the FCDRS Sleep–wake cycle disturbances were strongly and positively predicted by increased body condition score (BCS), alanine aminotransferase (ALT), creatinine, white blood cells (WBCs), globulin, and IL-1β levels, and negatively predicted by albumin and neutrophils. Anxiety was positively associated with higher BCS, creatinine, and IL-10, and negatively associated with IL-1β. Activity levels were positively predicted by IL-10. Altered social interactions and house-soiling were significantly associated with increased BCS. Conclusion and relevance Findings suggest that changes in physiological parameters describing patterns of chronic inflammation are associated with measurable cognitive changes in aging cats, in the absence of overt clinical disease, which is consistent with the concept of inflammaging. Routine monitoring of standard bloodwork and BCS may offer an accessible means of tracking chronic subclinical inflammation and predicting cognitive aging in senior feline patients. These results highlight the importance of proactive cognitive screening and client education to preserve welfare and the human-animal bond in aging cats.

Minimal hepatic encephalopathy (MHE) is the initial stage of hepatic encephalopathy (HE), MHE patients have associated with widespread neuro-psychological impairment. Liver transplantation (LT) can restore metabolic abnormalities but the mechanisms are unclear. This study aimed to longitudinally evaluate brain function alteration in MHE patients one month after LT and their correlation with cognitive changes by using resting-state functional magnetic resonance imaging (rs-fMRI). Rs-fMRI data was collected from 32 healthy controls and 27 MHE before and 1 month after LT. Between-group comparisons of demographic data and neuropsychological scores were analyzed using SPSS 25.0. Functional imaging data were analyzed using RESTplus and SPM12 software based on MATLAB 2017b. Gender, age, and years of education were used as covariates to obtain low-frequency fluctuationd (ALFF) and dynamic low-frequency fluctuation (dALFF) dindices. Correlation analyses were performed to explore the relationship between the change of ALFF and dALFF with the change of clinical indexes pre- and post-LT. Compared to controls, ALFF values increased in the Left Cerebelum 8, right orbital part of the inferior frontal gyrus (ORBinf), right superior occipital gyrus (SOG) and decreased in right PreCG and left middle frontal gyrus (MFG) in patients post-LT; dALFF values increased in the right temporal pole and middle temporal gyrus (TPOmid), right ORBinf, left caudate nucleus (CAU), right SOG and decreased in left PreCG, left PCUN, left ANG, left SMA and left MFG in patients post-LT. Compared to pre-LT, ALFF values of post-LT patients increased in the right calcarine fissure and surrounding cortex (CAL), right MOG and decreased in right cerebelum 8, left PCUN; dALFF values of post-LT patients decreased in right thalamus (THA), left posterior cingulate gyrus (PCG) and left MFG. The changes of ALFF in the left PCUN, right CAL and right MOG were correlated with change of digit symbol test (DST) scores ( P < 0.05). In summary, this study not only showcases the potential of ALFF/dALFF algorithms for assessing alterations in spontaneous neural activity in MHE, but also provides new insights into the altered brain functions in MHE patients 1 month after LT, which may facilitate the elucidation of elucidation of mechanisms underlying cognitive restoration post-LT in MHE patients.

In the context of a health condition affecting their partner's autonomy, spouses may perceive changes in their partner. Due to the affective bond between partners, the increase in perceived change in the partner may lead to a shift from the identity of spouse to caregiver. However, although the literature hypothesis that the identification to the caregiver role may be a protective factor against the negative outcomes of caregiving negative, it remains unclear how this change in identification affects spouse caregivers' happiness and health. In this cross-sectional study, 102 spouse caregivers completed an online survey measuring their perception of their partner's changes, identification with the caregiver role, and the perceived impact of caregiving on their health and happiness. Path analysis revealed that only the perception of cognitive and relational changes in the spouse predicted identification to the caregiver role (standardised β ranged from -0.31 to 0.44; p ≤ 0.05). A higher level of identification with the caregiver role explained less happiness (standardised β = -0.37, p ≤ 0.01) but a smaller perceived impact of caregiving on health (standardised β = -0.39, p ≤ 0.001). Due to its influence on happiness and health, caregivers' identity and its personal meaning should be considered a determining factor in the experience of caregiving for a spouse and should be taken into account by the professionals supporting them.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is common in older adults and associated with systemic metabolic dysfunction, potentially contributing to cognitive decline and brain structural abnormalities. The fibrosis-4 (FIB-4) index, a widely used non-invasive marker for liver fibrosis risk, has not been investigated in relation to cognitive impairment. This study examined the association between elevated FIB-4 index scores, cognitive impairment, and hippocampal and amygdala changes in older adults with MASLD. This cross-sectional study included 384 participants with MASLD from the Japanese Arao Cohort, comprising 1577 individuals aged ≥ 65 years. Participants were stratified by FIB-4 index scores (< 2.67 vs. ≥ 2.67). Cognitive function was evaluated using the Mini-Mental State Examination, and brain magnetic resonance imaging was used to measure hippocampal and amygdala volumes. The association between the FIB-4 index and cognitive impairment was examined using logistic regression, while its relationship with brain volume was analyzed with linear regression. Participants with elevated FIB-4 scores (≥ 2.67) had significantly higher odds of cognitive impairment (adjusted odds ratio: 2.60, 95% CI: 1.11-6.05), even after adjusting for confounders, for example, sex, hypertension, diabetes, and hyperlipidemia. They also showed smaller hippocampal and amygdala volumes, with a linear relationship between the FIB-4 index score and hippocampal/amygdala volume. Elevated FIB-4 index scores were significantly associated with cognitive impairment and structural brain changes. These findings suggest that the FIB-4 index may serve as a useful, non-invasive marker of liver-related and systemic health burdens contributing to cognitive decline in older adults with MASLD.

Introduction: Cerebrovascular disease and vascular risk factors have important contributions to Alzheimer’s disease (AD) risk, and greater understanding of cognitive changes in vascular versus non-vascular populations may help reveal complementary and overlapping clinical changes. The aim of this work was to evaluate how cognitive changes in middle to later aged vascular and non-vascular cohorts are related to AD pathology. Methods: A subset of the National Alzheimer’s Coordinating Center (NACC) cohort with pTau217 testing available (ages 50-90, n=444) was included as a general population cohort. The first 167 participants enrolled in our prospective Carotid and Minds (CAM) study (participants aged 50-85 with ≥2 vascular comorbidities with/without asymptomatic carotid stenosis were included as a vascular disease cohort. Both cohorts were assessed using a full UDS neurocognitive battery and compared to plasma pTau217 adjusting for demographics and APOE ε4 status. Dementia and other neurological disorders were exclusionary. Results: Demographics of NACC cohort shown (Table1). When adjusted for age, sex, education, race, ethnicity and APOE ε4 status, pTau217 was associated with significantly worse memory (β=-0.15, p=0.003) while no significant association with domains of language, executive function, visuospatial and processing speed was seen. Demographics of CAM are shown (Table 2). Within CAM, pTau217 was associated with significantly worse non-amnestic domains including language (β=-0.18, p=0.02), executive function (β=-0.19, p=0.013) and processing speed (β=-0.18, p=0.02), but not memory (β=-0.07, p=0.36) independent of age, sex, education, race, ethnicity and APOE ε4 status. Poorer cognition was associated with age, sex and education in both cohorts; in contrast, worse processing speed and executive function in CAM cohort is associated with carotid stenosis (β=-0.24, p&lt;0.001) and a history of stroke (β=-0.47, p=0.02), but not APOE ε4 status or cerebral white matter lesion volumes. Conclusion: Within a vascular disease cohort, association of AD pathology with non-amnestic domains of processing speed, executive function and language complements and contrasts with memory domain impacts often associated with the classic notion of AD. Further assessment of these pathways associated with AD pathology could help understand unique and potentially complimentary cognitive changes relevant in understanding vascular contributions to cognitive impairment and dementia.

Alzheimer’s disease (AD), the leading cause of dementia, could potentially be mitigated through early detection and interventions. However, it remains challenging to assess subtle cognitive changes in the early AD continuum. Computational modeling is a promising approach to explain a generative process underlying subtle behavioral changes with a number of putative variables. Nonetheless, internal models of the patient remain underexplored in AD. Determining the states of an internal model between measurable pathological states and behavioral phenotypes would advance explanations about the generative process in earlier disease stages beyond assessing behavior alone. Previously, Gershman et al., 2017b proposed the latent cause model, which provides a normative account of memory modification phenomena in Pavlovian fear conditioning. Here, we assumed the latent cause model as an internal model and estimated internal states defined by the model parameters being in conjunction with measurable behavioral phenotypes. The 6- and 12-month-old App NL-G-F knock-in AD model mice and the age-matched control mice underwent memory modification learning, which consisted of classical fear conditioning, extinction, and reinstatement. The results showed that App NL-G-F mice exhibited a lower extent of reinstatement of fear memory. Computational modeling revealed that the deficit in the App NL-G-F mice would be due to their internal states being biased toward overgeneralization or overdifferentiation of their observations, and consequently, the competing memories were not retained. This deficit was replicated in another type of memory modification learning in the reversal Barnes maze task. Following reversal learning, App NL-G-F mice, given spatial cues, failed to infer coexisting memories for two goal locations during the trial. We concluded that the altered internal states of App NL-G-F mice illustrated their misclassification in the memory modification process. This novel approach highlights the potential of investigating internal states to precisely assess cognitive changes in early AD and multidimensionally evaluate how early interventions may work.

Alzheimer’s disease (AD), the leading cause of dementia, could potentially be mitigated through early detection and interventions. However, it remains challenging to assess subtle cognitive changes in the early AD continuum. Computational modeling is a promising approach to explain a generative process underlying subtle behavioral changes with a number of putative variables. Nonetheless, internal models of the patient remain underexplored in AD. Determining the states of an internal model between measurable pathological states and behavioral phenotypes would advance explanations about the generative process in earlier disease stages beyond assessing behavior alone. Previously, Gershman et al., 2017b proposed the latent cause model, which provides a normative account of memory modification phenomena in Pavlovian fear conditioning. Here, we assumed the latent cause model as an internal model and estimated internal states defined by the model parameters being in conjunction with measurable behavioral phenotypes. The 6- and 12-month-old AppNL-G-F knock-in AD model mice and the age-matched control mice underwent memory modification learning, which consisted of classical fear conditioning, extinction, and reinstatement. The results showed that AppNL-G-F mice exhibited a lower extent of reinstatement of fear memory. Computational modeling revealed that the deficit in the AppNL-G-F mice would be due to their internal states being biased toward overgeneralization or overdifferentiation of their observations, and consequently, the competing memories were not retained. This deficit was replicated in another type of memory modification learning in the reversal Barnes maze task. Following reversal learning, AppNL-G-F mice, given spatial cues, failed to infer coexisting memories for two goal locations during the trial. We concluded that the altered internal states of AppNL-G-F mice illustrated their misclassification in the memory modification process. This novel approach highlights the potential of investigating internal states to precisely assess cognitive changes in early AD and multidimensionally evaluate how early interventions may work.

Introduction: Older patients with chronic kidney disease (CKD) are at high risk of cognitive impairment. We have previously demonstrated that a 6-month home-based exercise training program improves cognition in older adults with CKD and mild cognitive impairment. Research Questions: 1) What is the impact of a 6-month home-based exercise compared to usual care on arterial stiffness measures? 2) What is the association between changes in arterial stiffness and cognition? Hypothesis: An increased pulse wave velocity will be significantly associated with lower cognitive performance. Methods: Participants (n=32, mean age of 68.4 (5.0) years; 65.6% women, 71.9% Black) were randomized to intervention or usual care. The intervention included a wearable activity monitor, weekly didactic phone meetings, interactive tools (e.g., reminders), and monthly coach-delivered feedback. Carotid-femoral pulse wave velocity was obtained via the Sphygmocor. Results: The compliance rate was 78%, the mean minutes of exercise per week was 174 (155) minutes/week. ANCOVA adjusting for baseline, sex, and age indicating an improvement in PWV in the intervention group of -.20 m/s versus +.41 in the control with a mean difference of -.61 m/s (95% IC -1.2 to .006, p=.05). The effect size was large at η 2 =.14. PWV was strongly correlated with improved global cognition at 6-months (r=-.52, p=.04), learning and memory (r=-.55, p =.03) in the intervention group, but not in the control group. Conclusion: These findings suggest that the observed improvement in cognition following exercise training may be related to an improvement in arterial stiffness providing insight into potential mechanisms of the vascular contribution of improved cognition following exercise training.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) are cardioprotective glucose-lowering therapies, but their impact on dementia risk in type 2 diabetes remains underexplored. Methods: We searched PubMed, Scopus, and Embase from inception to May 1, 2025, for randomized controlled trials (RCTs) comparing GLP-1RAs or SGLT2is with controls, reporting dementia or cognitive score changes. Included trials featured guideline-recommended drugs for cardiovascular risk reduction. A Bayesian network meta-analysis estimated risk ratios (RR) with 95% credible intervals (CrI) using Markov Chain Monte Carlo methods, with Gelman-Rubin diagnostics for convergence. Surface under the cumulative ranking curve (SUCRA) ranked treatments. Results: From 22 RCTs with 156,697 patients, therapies showed varied dementia risk reductions. For all-cause dementia versus control according to the SUCRA: albiglutide (RR: 0.03, 95% CrI: 0.00 to 0.08; SUCRA: 94.4%), lixisenatide (RR: 0.08, 95% CrI: 0.00 to 0.20; SUCRA: 93.62%), efpeglenatide (RR: 0.24, 95% CrI: 0.00 to 1.38; SUCRA: 70.09%), canagliflozin (RR: 0.31, 95% CrI: 0.01 to 1.47; SUCRA: 61.81%), semaglutide (RR: 0.50, 95% CrI: 0.03 to 1.98; SUCRA: 50.06%), liraglutide (RR: 2.12, 95% CrI: 0.02 to 9.89; SUCRA: 41.91%), empagliflozin (RR: 0.68, 95% CrI: 0.05 to 2.35; SUCRA: 39.63%), exenatide (RR: 4.13, 95% CrI: 0.02 to 20.28; SUCRA: 35.41%), dulaglutide (RR: 3.38, 95% CrI: 0.03 to 15.72; SUCRA: 32.89%), dapagliflozin (RR: 1.19, 95% CrI: 0.09 to 4.96; SUCRA: 30.37%), ertugliflozin (RR: 6.79, 95% CrI: 0.02 to 29.23; SUCRA: 30.1%), control (SUCRA: 19.67%). For vascular dementia versus control: dapagliflozin (RR: 0.01, 95% CrI: 0.00 to 0.08; SUCRA: 86.65%), ertugliflozin (RR: 0.03, 95% CrI: 0.00 to 0.16; SUCRA: 85.98%), dulaglutide (RR: 0.05, 95% CrI: 0.00 to 0.32; SUCRA: 84.35%), while semaglutide (RR: 3.83, 95% CrI: 0.05 to 21.72; SUCRA: 17.4%), and control (SUCRA: 13.2%). For Alzheimer’s dementia versus control: dulaglutide showed the lowest (RR: 0.87, 95% CrI: 0.01 to 4.68; SUCRA: 77.64%), while exenatide the highest (RR: 60.62, 95% CrI: 0.21 to 185.09; SUCRA: 23.36%), and control (SUCRA: 50.29%). Conclusions: GLP-1RAs and SGLT2is reduce dementia risk, with albiglutide and lixisenatide excelling for all-cause dementia, dapagliflozin and ertugliflozin for vascular dementia, and dulaglutide for Alzheimer’s. Higher risks with some drugs highlight tailored therapy needs.

Background/Objectives: Fragile X-associated tremor/ataxia syndrome (FXTAS) is characterized by tremor, gait ataxia, and cerebellar white matter degeneration, along with possible cognitive and cerebral changes. Although diagnostic criteria were originally developed in males, emerging evidence suggests that FXTAS may present differently in females. The present study examined sensorimotor and memory features of aging in female premutation carriers with (FXTAS+) and without FXTAS (FXTAS+). Methods: We studied 51 female premutation carriers (FXTAS+ = 16, FXTAS− = 35) and 24 age-matched female controls. Participants ranged in age from 47–80 years. All participants completed genetic testing, clinical evaluations, T2-weighted MRIs, and quantitative assessments of sensorimotor (precision grip force task) and memory (reading span; visual paired associates task) functions. Results: During precision grip testing, FXTAS+ carriers showed higher sustained force regularity than FXTAS− carriers (p = 0.03, d = 1.0) and controls (p = 0.004, d = 1.1) at low gain levels only. FXTAS+ participants were slower than controls on motor reaction time (p = 0.009, d = 0.82). Initial force output was higher in FXTAS+ than FXTAS− carriers (p = 0.03, d = 1.0) and controls (p = 0.03, d = 1.0) but at low gain only. FXTAS+ carriers exhibited poorer working memory than FXTAS− carriers (p = 0.03, d = 0.91) and controls (p = 0.02, d = 1.0). During a long-term memory task, FXTAS+ participants were less accurate than FXTAS− carriers (p = 0.04, d = 0.86) and controls (p = 0.004, d = 1.1) and showed increased reaction times relative to FXTAS− carriers (p = 0.03, d = −0.82) and controls (p = 0.01, d = −1.2). Conclusions: Together, these findings indicate that FXTAS+ females exhibit distinct motor and cognitive impairments, underscoring the value of quantitative behavioral measures for detecting and tracking neurodegenerative progression in female premutation carriers.

The long-term trajectory of cognitive changes in isolated REM sleep behavior disorder (iRBD) remains unclear. Increasing evidence suggests potential heterogeneity in disease progression. Patients who maintained an iRBD diagnosis without phenoconversion for at least five years were included. Cognitive changes over time were assessed using linear mixed models. Subgroup analyses were conducted for men and women separately, and for longstanding iRBD patients. A total of 318 neuropsychological assessments from 162 patients with iRBD (28% women) were analyzed. The mean age at diagnosis was 65.6 years, with an average follow-up duration of 7.7 years. Significant linear declines were observed across attention/working memory and memory domains, with notable decreases in Digit Symbol ($\boldsymbol{\beta}$= -0.084, 95% confidence intervals (CI) -0.102 to -0.066), Stroop Test color naming ($\boldsymbol{\beta}$= -0.054, 95% CI -0.074 to -0.054), and Word List Recall ($\boldsymbol{\beta}$= -0.054, 95% CI -0.078 to -0.030) as representative examples. In the longstanding iRBD subgroup (n = 33) and among men, cognitive decline patterns largely mirrored those observed in the full cohort, with significant declines in attention/working memory and memory. In contrast, women exhibited a more restricted decline, limited to Digit Span Forward ($\boldsymbol{\beta}$= -0.055, 95% CI -0.102 to -0.008) and Digit Symbol ($\boldsymbol{\beta}$= -0.082, 95% CI -0.121 to -0.043). Gradual cognitive decline in attention/working memory and memory may represent a natural course of neurodegeneration in men with iRBD, without necessarily indicating imminent phenoconversion. Women with iRBD appeared to show greater resilience to cognitive decline compared to men.

Introduction Implantable neural devices, including brain–computer interfaces and spinal cord stimulators, hold significant therapeutic promise for conditions such as paralysis and chronic pain. However, the novelty of these technologies introduces unique ethical challenges. While much of the existing literature emphasizes development-related concerns such as device safety, the ethical issues surrounding explantation remain relatively underexplored. Methods We conducted a systematic review to identify ethical, legal, and sociocultural considerations relevant to the explantation of neural devices. The review applied the IEEE BRAIN Neuroethics framework as a guiding structure for the categorization of the themes. A subsequent thematic analysis was performed to categorize and synthesize findings across studies. Results Thematic analysis revealed that medical motives were the predominant factor in discussions of explantation, with 83% of studies citing medical complications as a central concern. Additional themes identified included changes in cognition and behavior, emotional well-being, lack of therapeutic benefit, identity, financial issues, autonomy, post-trial considerations, and neurorights. Discussion Our findings underscore the multifaceted nature of neural device explantation, extending beyond purely medical considerations to include psychological, financial, legal, and sociocultural dimensions. These results highlight the necessity of interdisciplinary approaches to adequately address the broad spectrum of challenges associated with explantation.

Aging is a dynamic process across a dog's lifespan, with age-related changes impacting how dogs function in their companion and working roles. However, the impact of aging on key sensory modalities, such as olfaction, is not well understood. The current study aimed to characterize age-related changes in canine olfactory abilities via an adaptation of the Natural Detection Task. Data were collected on 65 dogs aged 5years or older, with 44 dogs completing all components of the task. We found age-related decrements in olfactory performance, but only under certain conditions and with differential effects as a function of training level. Age also affected whether dogs completed the entirety of the task, indicative of non-olfactory (e.g., physical or motivational) factors. Additionally, dogs completed the Cylinder Reversal Task (CRT) to determine whether olfactory changes were correlated with cognitive changes. We found no age-related changes in CRT performance and no significant associations between cognitive and olfactory task performance. These findings indicate that dogs' olfactory capabilities decrease with age but, critically, training experience may have protective effects against age-related declines, and effects may only be apparent under certain conditions. Future studies should continue to consider olfaction when studying aging impacts upon the dog.

Background: Aβ1-42 and APOE concentrations, as well as Aβ42/40 ratio, may be considered as a link between hypertension (HTN) or diabetes mellitus (DM), brain amyloidosis, and dementia. HTN and DM are associated with cognitive impairment and may contribute to the development of Alzheimer’s disease (AD). This preliminary study aimed to evaluate the impact of vascular risk factors on the concentration of biochemical AD markers and cognitive state. As it is a cross-sectional study in nature, causal relationships cannot be established. Methods: The study was conducted in the south of Poland among a rural population over 65 years of age. A total of 58 patients qualified into the study were divided into groups according to the presence of HTN (n = 18) or HTN coexisting with DM (n = 40). A healthy control group was also formed (n = 20), resulting in 78 study participants. The study population was also divided based on M-ACE results, forming a normal cognition group (NC) and a deteriorated cognition group (DC). Biochemical tests, neurological scales assessments, and ultrasound examinations were conducted. Results: Patients who scored in the normal range on the M-ACE had higher Aβ1-42 (median 38.52 vs. 27.35 pg/mL, p = 0.02) and apoE concentrations (median 125.0 vs. 65.73 μg/mL, p = 0.002), and a higher Aβ42/40 ratio (median 0.39 vs. 0.29 p &lt; 0.000) compared to the DC group. Considering the study groups, the highest Aβ42/40 ratio was found among the HC group (median 0.47). The median score for the M-ACE scale was 3 points lower when HTN and DM coexisted, compared to the sole diagnosis of HTN (25 points and 28 points, respectively). A higher number of years of education correlated with better M-ACE results. Lipid and uric acid concentrations were not related to M-ACE or MMSE scores. An inverse relationship connected Aβ1-40 and Aβ1-42 to BMI, the duration of HTN treatment, and glycated hemoglobin. Conclusions: Aβ1-42, APOE, and Aβ42/40 are not only correlated with cognition but also related to patient’s disease profile. The coexistence of DM and HTN was associated with the most significant decline in cognitive functioning. However, a higher number of years of education may protect against the development of dementia in old age. The roles of cholesterol and uric acid in cognitive decline are still inconclusive.

The brainstem is a vital component of the cerebro-cerebellar network underlying cognition, however it remains unclear whether brainstem volumes are associated with cognitive functioning in MS. Investigate the relationship between brainstem volumes and cognitive impairment in MS, as assessed by the BICAMS battery (processing speed, verbal and visuospatial memory). We analyzed data from the VOLUMS (Volumetry in MS) study, including 143 MS patients. Magnetic resonance imaging (1.5/3.0T, 3DT1-weighted images) was used for brain volumetrics and brainstem lesion counts. Cognitive data were collected using the "Brief International Assessment of Cognition for Multiple Sclerosis" (BICAMS). Correlation and stepwise logistic regression explored associations between brain volumes and cognitive performance. In a subset of 35 patients with 3-year follow-up, longitudinal changes in brain volumes and cognition were also assessed. Cognitive impairment (≥ 2 standard deviations below predicted scores on at least one test) was present in 30.1% of participants. No significant correlations were found between brainstem volume and cognitive scores. Hippocampus (p = .046), thalamus (p = .024), cortex (p < .001), and gray matter (p < .001) volumes were significantly lower in cognitively impaired patients. Processing speed correlated with cortex (R = .217, p = .009) and GM (R = .206, p = .013), while verbal memory correlated with hippocampus (R = .218, p = .009), cortex (R = .251, p = .003) and GM (R = .275, p = .001) volumes. Disease duration was the only significant predictor of cognitive impairment (p < .001). In the longitudinal subset, no clear evidence of progressive volumetric decline or related cognitive deterioration was observed. While no link was found between brainstem volumes and cognitive impairment, this analysis underscores the importance of considering various brain structures in understanding cognitive impairment in MS.

Plasticity is a fundamental property of the brain that enables the nervous system to respond appropriately to internal and external stimuli. It primarily involves changes at the synaptic level, mediated by a wide array of molecules, ultimately leading to cognitive and behavioral changes. This review critically contrasts the developmental timing and mechanisms of plasticity in Autism spectrum disorder (early hyperplasticity and excitation–inhibition imbalance) versus Schizophrenia (adolescent overpruning and NMDAR hypofunction) and evaluates evidence for interventions that harness plasticity to improve cognitive and behavioral outcomes. Preclinical and small clinical studies suggest that interventions targeting plasticity-related pathways may improve specific cognitive and behavioral domains. However, effects appear to be symptom-domain-specific and protocol-dependent and larger randomized controlled trials are needed to confirm efficacy. Cognitive remediation for Schizophrenia has been associated with improved executive function and increased hippocampal volume, while virtual reality-based training for Autism spectrum disorder has shown gains in attention and planning skills. By highlighting both molecular mechanisms and therapeutic strategies, this review aims to provide an integrated perspective on how plasticity-targeted interventions could be optimized across neurodevelopmental and neuropsychiatric disorders.