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Kidney transplantation is the treatment of choice even for the elderly, as it improves quality of life and life expectancy, lowering the financial burden to the health care system compared to dialysis therapy. In Japan, kidney transplant recipients have become older due to the shift in demographics. Compared to community‐dwelling elderly adults, elderly kidney transplant recipients undergoing immunosuppressive therapy have a higher risk of age‐related outcomes including hospital readmissions, infections, dementia, malignancies, and fractures. In frailty, patients become vulnerable to adverse events after stressors due to a lack of physiologic reserve. Although it is often associated with aging, frailty can also occur in younger individuals with certain chronic illnesses or conditions including chronic kidney disease. Limited compensatory mechanisms result in functional impairment and adverse health outcomes, such as disability, falls, decreased mobility, hospitalization, and death. Although kidney transplant recipients can restore their kidney function after transplantation, most of them still have chronic kidney disease, as well as a gradual decline in graft function as a result of chronic allograft nephropathy. Wait‐listed candidates for kidney transplantation with frailty are more likely to experience wait‐list removal or death. Frailty at the time of transplantation is associated with complications after kidney transplantation such as delayed graft function, longer hospital stays, rehospitalizations, immunosuppression intolerance, surgical complications, and death. Nevertheless, kidney transplantation can be a viable intervention for frailty in dialysis patients. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusions People with cognitive impairment commonly use central nervous system‐active potentially inappropriate medications (CNS‐PIM), increasing risk of adverse outcomes. Patient portals may be a promising tool for facilitating medication‐related conversations. Little is known about portal use by this population related to medications.To target portal interventions, we sought to identify individuals with cognitive impairment and CNS‐PIM exposure who discussed medications through the portal and to determine how frequently their messages described possible adverse effects.We used electronic health record (EHR) data from an academic health system in Maryland (Site 1) from 2017 to 2022 and pharmacy and EHR data from an integrated health system in Colorado (Site 2) in 2022 to identify people with cognitive impairment and CNS‐PIM exposure who communicated about medications through the portal. At Site 1, message threads were manually categorized based on content. At Site 2, messages were categorized using natural language processing (NLP).The Site 1 cohort included 5543 patients aged ≥65 with cognitive impairment and ≥2 outpatient visits from 2017 to 2022. Over half (n = 3072; 55%) had CNS‐PIM prescriptions. Most with CNS‐PIM prescriptions had portal use (n = 1987; 65%); 1320 (66%) of those patients sent messages during possible CNS‐PIM exposure. Coding of a 5% random sample of message threads revealed that 3% mentioned CNS‐PIM and possible adverse effects, while 8% mentioned possible adverse effects without referencing CNS‐PIM. At Site 2, 4270 people had cognitive impairment and CNS‐PIM exposure in 2022; of these, 1984 (46%) had portal use and 1768 (41%) sent medication‐related messages during CNS‐PIM exposure. NLP identified 663 (8%) messages that mentioned CNS‐PIM and possible adverse effects, while 726 (41%) mentioned possible adverse effects without referencing CNS‐PIM.People with cognitive impairment and care partners frequently send portal messages about medications and possible adverse effects. Identifying such messages can help target deprescribing interventions. [ABSTRACT FROM AUTHOR]

Neuronal damage in the hippocampus induced by high glucose has been shown to promote the onset and development of cognitive impairment in diabetes, but the underlying molecular mechanism remains unclear. Guided by single-cell RNA sequencing, we here report that high glucose increases O-GlcNAcylation of Bmal1 in hippocampal neurons. This glycosylation promotes the binding of Clock to Bmal1, resulting in the expression of transcription factor Bhlhe41 and its target Dnajb4. Upregulated Dnajb4 in turn leads to ubiquitination and degradation of the mitochondrial Na + /Ca2+ exchanger NCLX, thereby inducing mitochondrial calcium overload that causes neuronal damage and cognitive impairment in mice. Notably, Bhlhe41 downregulation or treatment with a short peptide that specifically blocks O-GlcNAcylation of Bmal1 on Ser424 mitigated these adverse effects in diabetic mouse models. These data highlight the crucial role of O-GlcNAcylation in circadian clock gene expression and may facilitate the design of targeted therapies for diabetes-associated cognitive impairment. Synopsis: The molecular mechanism of high-glucose-induced cognitive impairment in diabetes remains unclear. This work demonstrates that high glucose levels increase Bmal1 O-GlcNAcylation and cause mitochondrial calcium overload and neuronal damage via a Bhlhe41/Dnajb4/NCLX signaling pathway. High- glucose-mediated Bmal1 O-GlcNAcylation upregulates expression of Bhlhe41 and Dnajb4, which promote ubiquitination and degradation of NCLX in hippocampal neurons. Decreased NCLX expression in high-glucose conditions promotes mitochondrial calcium overload and subsequent hippocampal neuron damage. A short synthetic peptide, S424-pe, protects against high-glucose-induced neuronal apoptosis and cognitive dysfunction in mice by inhibiting Bmal1 S424 O-GlcNAcylation. High-glucose-mediated Bmal1-OGlcNAcylation impairs cognitive function in diabetic mice by inducing mitochondrial calcium overload and neuronal damage. [ABSTRACT FROM AUTHOR]

Patients with Duchenne muscular dystrophy (DMD) commonly show specific cognitive deficits in addition to a severe muscle impairment caused by the absence of dystrophin expression in skeletal muscle. These cognitive deficits have been related to the absence of dystrophin in specific regions of the central nervous system, notably cerebellar Purkinje cells (PCs). Dystrophin has recently been involved in GABAA receptors clustering at postsynaptic densities, and its absence, by disrupting this clustering, leads to decreased inhibitory input to PC. We performed an in vivo electrophysiological study of the dystrophin‐deficient muscular dystrophy X‐linked (mdx) mouse model of DMD to compare PC firing and local field potential (LFP) in alert mdx and control C57Bl/10 mice. We found that the absence of dystrophin is associated with altered PC firing and the emergence of fast (~160–200 Hz) LFP oscillations in the cerebellar cortex of alert mdx mice. These abnormalities were not related to the disrupted expression of calcium‐binding proteins in cerebellar PC. We also demonstrate that cerebellar long‐term depression is altered in alert mdx mice. Finally, mdx mice displayed a force weakness, mild impairment of motor coordination and balance during behavioural tests. These findings demonstrate the existence of cerebellar dysfunction in mdx mice. A similar cerebellar dysfunction may contribute to the cognitive deficits observed in patients with DMD. [ABSTRACT FROM AUTHOR]

Approximately 50% of patients with chronic neuropathic pain experience cognitive impairment, which negatively impacts their quality of life. The cannabinoid type 2 receptor (CB2R) may be involved in hippocampal cognitive processes. However, its role in chronic neuropathic pain‐induced cognitive impairment remains elusive. Spared nerve injury (SNI) was used to induce chronic neuropathic pain in rats, while the novel‐object recognition test and the Y‐maze test were employed to assess cognitive function. Immunofluorescence, western blotting, and stereotaxic hippocampal microinjection were utilized to elucidate the potential mechanisms. We observed a reduction in mechanical pain threshold and cognitive impairment in SNI rats. This was accompanied by a tendency for hippocampal microglia to adopt pro‐inflammatory functions. Notably, no changes were detected in CB2R expression. However, downregulation of the endogenous ligands AEA and 2‐AG was evident. Hippocampal microinjection of a CB2R agonist mitigated cognitive impairment in SNI rats, which correlated with a tendency for microglia to adopt anti‐inflammatory functions. Additionally, SNI‐induced activation of the p‐ERK/NFκB pathway in the hippocampus. Activation of CB2R reversed this process by upregulating DUSP6 expression in microglia. The effects elicited by CB2R activation could be inhibited through the downregulation of microglial DUSP6 via hippocampal adeno‐associated virus (AAV) microinjection. Conversely, overexpression of hippocampal DUSP6 using AAV ameliorated the cognitive deficits observed in SNI rats, which remained unaffected by the administration of a CB2R antagonist. Our findings demonstrate that activation of hippocampal CB2R can mitigate chronic neuropathic pain‐induced cognitive impairment through the modulation of the DUSP6/ERK/NFκB pathway. [ABSTRACT FROM AUTHOR]

Background and purpose Methods Results Conclusions Affective disturbances and cognitive impairment are common sequelae of intracerebral hemorrhage (ICH), yet predictive models for these outcomes remain limited, especially for spontaneous supratentorial ICH with small hematomas (<30 mL). The aim of this study was to investigate predictors of affective disturbances and cognitive impairment following small spontaneous supratentorial intracerebral hemorrhage.We retrospectively analyzed 1692 patients with spontaneous supratentorial ICH between January 2018 and December 2020 at the First Affiliated Hospital of Harbin Medical University. Of these, 1563 patients completed a median follow‐up of 3.5 years. Cognitive function was evaluated using the modified Telephone Interview for Cognitive Status, and affective disturbances using the Hamilton Depression Scale and the Hamilton Anxiety Scale. Restricted cubic spline analyses were employed to examine the relationships between predictors and outcomes.In this cohort, 58.5% had cognitive impairment, 52.8% reported depressive symptoms, and 39.4% exhibited anxiety symptoms. Logistic regression models using Boruta's algorithm demonstrated strong predictive capacity, with areas under the curve of 0.82 for cognitive impairment, 0.78 for depressive symptoms, and 0.73 for anxiety symptoms. Hematoma volume was significantly linked to depressive symptoms (odds ratio [OR] 1.56, 95% confidence interval [CI] 1.38–1.76) and inversely to cognitive impairment (OR 0.67, 95% CI 0.59–0.77). Uric acid levels displayed a nonlinear relationship with cognitive impairment (OR 0.70, 95% CI 0.61–0.81). Hospitalization days significantly raised the risk of both depressive (OR 1.16, 95% CI 1.03–1.30) and anxiety symptoms (OR 1.17, 95% CI 1.04–1.31).The logistic regression model, enhanced by Boruta's algorithm, provides a valuable tool for predicting affective disturbances and cognitive impairment after ICH. It facilitates early identification and improves risk assessment for these neuropsychiatric outcomes in patients with small hematomas. [ABSTRACT FROM AUTHOR]

Background and purpose Methods Results Conclusions ‘Neurovascular coupling’ (NVC) alterations, assessing the interplay between local cerebral perfusion and neural activity within a given brain region or network, may reflect neurovascular unit impairment in amyotrophic lateral sclerosis (ALS). The aim was to explore NVC as a correlation between the functional connectivity and cerebral blood flow within the large‐scale resting‐state functional magnetic resonance imaging brain networks in a sample of ALS patients compared to healthy controls (HCs).Forty‐eight ALS patients (30 males; mean age 60.64 ± 9.62 years) and 32 HC subjects (14 males; mean age 55.06 ± 16 years) were enrolled and underwent 3 T magnetic resonance imaging. ALS patients were screened by clinical and neuropsychological scales and were retrospectively classified as very fast progressors (VFPs), fast progressors and slow progressors (SPs).Neurovascular coupling reduction within the default mode network (DMN) (p = 0.005) was revealed in ALS patients compared to HCs, observing, for this network, significant NVC differences between VFP and SP groups. Receiver operating characteristic curve analysis showed that impaired NVC in the DMN at baseline best discriminated VFPs and SPs (area under the curve 75%). Significant correlations were found between NVC and the executive (r = 0.40, p = 0.01), memory (r = 0.32, p = 0.04), visuospatial ability (r = 0.40, p = 0.01) and non‐ALS‐specific (r = 0.40, p = 0.01) subscores of the Edinburgh Cognitive and Behavioural ALS Screen.The reduction of brain NVC in the DMN may reflect largely distributed abnormalities of the neurovascular unit. NVC alterations in the DMN could play a role in anticipating a faster clinical progression in ALS patients, aiding patient selection and monitoring during clinical trials. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Eye movement tasks, especially anti‐saccade tasks, have been used to assess cognitive function in patients with neuropsychiatric disorders. Although it has been shown that individuals with cognitive impairment perform worse on anti‐saccades tasks, there is a lack of systematic evaluation of the sensitivity of parameters of anti‐saccades to assess different subtypes of cognitive impairment.A total of 158 participants were enrolled in this study, consisting of 66 men and 92 women, with an average age of 50.2 ± 10 years. The comparison of pro‐saccade reaction time, anti‐saccade reaction time, and error rates in the saccade task between individuals with cognitive impairments and a normal group was conducted. Furthermore, we systematically analyzed the correlations between the performance in neurological function tests (Mini‐Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Stroop) and these anti‐saccade parameters. Especially, the correlation between these parameters and cognitive function in different domains of the MoCA task were also evaluated.The pro‐saccade reaction time, anti‐saccade reaction time and error rate were negatively correlated with the MMSE and MoCA scores (P < 0.001), and positively correlated with the time used in Stroop tasks. Among them, the error rate had the strongest correlation with the performance of MMSE, MoCA and Stroop tasks (MoCA: P < 0.0001, r2 = −0.608; MMSE: P < 0.0001, r2 = −0.344; Stroop: P < 0.0001, r2 = 0.455). Among the seven cognitive domains examined by the MoCA task, error rates had relatively high correlations with visuospatial/executive (P < 0.0001, r2 = −0.4660) and delayed recall (P < 0.0001, r2 = −0.4228) compared to naming, language (P = 0.0004, r2 = −0.0788), attention (P = 0.0004, r2 = −0.0780), abstraction (P < 0.0001, r2 = −0.1515), orientation (P < 0.0001, r2 = −0.1075). Moreover, pro‐saccade reaction time, anti‐saccade reaction time and error rate of people with high MoCA scores were significantly higher than those of people with low MoCA scores, which can be used to identify people with mild cognitive impairment.Our study's results provide valuable clinical evidence supporting the effectiveness of anti‐saccades in assessing cognitive impairment, which is beneficial for screening and timely clinical intervention in individuals with specific cognitive impairment. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Chronic pain may be an important factor influencing cognitive impairment; however, there is limited research on that link in older adults with disabilities. We aimed to determine the association between chronic pain and cognitive impairment in older adults with disabilities.This 24‐month prospective cohort study involved 143 Japanese older adults (≥65 years of age) with long‐term care insurance. Chronic pain was defined as pain persisting for ≥3 months, and cognitive impairment was defined as a Mini‐Mental State Examination score ≤ 23. We employed logistic regression analysis with chronic pain as the independent variable and cognitive impairment as the dependent variable after propensity score matching (PSM).Sixty‐six participants were selected using PSM, and logistic regression analysis showed that chronic pain was significantly associated with cognitive impairment (odds ratio: 4.103, 95% confidence interval: 1.455–11.567, P = 0.008).To prevent cognitive impairment in older adults with disabilities, the management of chronic pain should be considered, as they are related. [ABSTRACT FROM AUTHOR]

Background Aim Study Design Result Conclusion Relevance to Clinical Practice Critically ill patients experience cognitive impairment throughout their intensive care unit trajectory, in the acute phase and the long‐term alike. Cognitive impairment may negatively impact patients' quality of life and rehabilitation outcomes.To provide an overall examination of literature concerning non‐pharmacological interventions that can enhance cognitive functioning in critically ill patients or facilitate their rehabilitation pathway during and after their intensive care unit stay.This study was conducted as an umbrella review. A systematic search was conducted in CINAHL, Embase, PubMed and PsychINFO, including all types of peer‐reviewed research syntheses published between 2008 and 2023. Eligible studies had to describe interventions capable of improving adult patients' cognitive functioning or supporting their cognitive rehabilitation process throughout the intensive care unit trajectory. All eligible research syntheses were screened systematically; those included were critically appraised.Based on 13 research syntheses, this review summarizes rehabilitative interventions that may be delivered during different phases of critical illness and recovery, in relation to content, delivery and timing. Interventions were: (1) cognitive activities and training, (2) mobilization and physical exercises, (3) emotional, psychological and social support and (4) information.Due to limited evidence, no definitive conclusion can be drawn about which type of intervention is most supportive or effective. Additionally, no recommendations can be made about the optimal timing for intervention delivery.Clinicians involved in developing and implementing cognitive rehabilitation measures should consider designing individualized, multicomponent interventions with a focus on content, delivery and timing. [ABSTRACT FROM AUTHOR]

Objective: Developmental and epileptic encephalopathies (DEEs) are neurological disorders characterized by developmental impairment and epilepsy. Our study aims to assess disease progression by comparing clinical findings, electroencephalography (EEG), and neuropsychological data from seizure onset to the last follow‐up evaluation. Methods: We retrospectively reviewed patients with genetic DEEs who were followed‐up at the epilepsy unit of Bambino Gesù Children's Hospital, Rome. We collected information regarding gender, family history, genetic variant, age at onset and at last follow‐up, neurological examination, type of seizure, drug resistance, occurrence of status epilepticus, and movement and cognitive and behavioral disorders. We compared EEG background activity, epileptiform abnormalities, and cognitive functions between seizure onset and the last follow‐up evaluation using the McNemar‐Bowker test (α = 5%). Results: A total of 160 patients (94 female) were included. Genetic analysis revealed a spectrum of pathogenic variants, with SCN1A being the most prevalent (25%). The median age at seizure onset and at the last follow‐up was 0.37 (interquartile range [IQR]: 0.09–0.75) and 8.54 years (IQR: 4.32–14.55), respectively. We documented a statistically significant difference in EEG background activity (p =.017) and cognitive impairment (p =.01) from seizure onset to the last follow‐up evaluation. No significant differences were detected for epileptiform abnormalities (p =.2). In addition, high prevalence rates were observed for drug resistance (81.9%), movement disorders (60.6%), behavioral and autism spectrum disorders (45%), neurological deficits (31.3%), and occurrence of status epilepticus (23.1%). Significance: Our study provides evidence that a clinical progression may appear in genetic DEEs, manifesting as development or worsening of cognitive impairment and disruption of EEG background activity. These results highlight the challenging clinical course and the importance of early intervention and personalized care in the management of patients with DEEs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairments are common in alcohol use disorder (AUD), but only a few studies have investigated the accuracy of the Montreal Cognitive Assessment (MoCA) in this population. We examined the accuracy and precision of the MoCA in detecting cognitive impairment in a sample of patients with AUD. In addition, we investigated whether the MoCA predicts premature discontinuation from treatment. Method: A sample of 126 persons with AUD undergoing treatment in specialist health services were administered the MoCA and a battery of 12 neuropsychological tests. Five cognitive domains were derived from the reference tests. A composite total score from these tests was used as a reference criterion for determining correct and incorrect classifications for the MoCA. We analyzed the optimal cut‐off score for the MoCA and the accuracy and agreement of classification between the MoCA and the reference tests. Results: Receiver operating characteristic (ROC) curve analyzes yielded an area under the curve (AUC) of 0.77 (95% CI [0.67, 0.87]). Applying 25 as the cut‐off, MoCA sensitivity was 0.77 and specificity 0.62. The PPV was 0.53. The NPV was 0.84. Using a cut‐off score of 24 yielded a lower sensitivity 0.60, but specificity was significantly better i.e., 0.79. PPV was 0.68. The NPV was 0.82. Kappa agreement between MoCA and the reference tests was fair to moderate, 0.38 for the cut‐off of 25, and 0.44 for the cut‐off of 24. MoCA did not predict discontinuation from treatment. Conclusions: Our findings indicate limitations in the classification accuracy of the MoCA in predicting cognitive impairment in AUD. Achieving the right balance between accurately identifying impaired cases without including too many false positives can be challenging. Further, MoCA does not predict discontinuation from treatment. Overall, the results do not support MoCA as a time‐efficient screening instrument. [ABSTRACT FROM AUTHOR]

Background: Family history of Parkinson's disease (PD) is a common finding in PD patients. However, a few studies have systematically examined this aspect. Objectives: We investigated the family history of PD patients, comparing demographic and clinical features between familial PD (fPD) and sporadic PD (sPD). Methods: A cross‐sectional study enrolling 2035 PD patients was conducted in 28 Italian centers. Clinical data and family history up to the third degree of kinship were collected. Results: Family history of PD was determined in 21.9% of patients. fPD patients had earlier age at onset than sporadic patients. No relevant differences in the prevalence of motor and nonmotor symptoms were detected. Family history of mood disorders resulted more prevalently in the fPD group. Conclusions: fPD was found to recur more frequently than previously reported. Family history collection beyond the core family is essential to discover disease clusters and identify novel risk factors for PD. [ABSTRACT FROM AUTHOR]

Aim: Driving cessation is strongly associated with adverse health outcomes in older adults. Although numerous studies have focused on driving skill interventions for safe driving, the effects of interventions on car accidents remain unclear. We designed a randomized controlled trial to examine the effects of driving skill training on the prevention of car accidents among community‐dwelling older adults using on‐road training. Methods: A total of 1408 community‐dwelling older drivers aged ≥65 years participated in the randomized controlled trial with blinded endpoint assessment. Participants randomized to the intervention group (n = 697) underwent four sessions, with 200 min re‐training focused on the problem of driving in the older people. Controls (n = 697) received one classroom education session. On‐road driving performance was assessed by certified driving school instructors in a driving school. The primary endpoint is an incident car accident, which will be detected based on the Japanese national car accident report data, after 24 months. Discussion: This study has the potential to provide the first evidence of the effectiveness of on‐road driving skill training regarding the prevention of car accidents. If our trial results show a lower number of car accidents due to driving skill training, this kind of intervention will provide an effective method for maintaining safe driving. These results will be disseminated to the appropriate national transportation agencies to improve or modify safe driving policies and possibly extend the validity of driver's licenses for older adults. Trial Registration: UMIN‐CTR (identification number: UMIN000034709). Registered 31 October 2018. Geriatr Gerontol Int 2024; 24: 1218–1222. [ABSTRACT FROM AUTHOR]

Background: The status of being unmarried is commonly associated with a higher tendency for loneliness and cognitive impairment. However, it has yet to be determined whether there is a link between loneliness and cognitive function among unmarried older people. Therefore, this study used longitudinal data to determine the link between loneliness and cognitive function, and the subjects were unmarried community‐dwelling older adults. Methods: The study follows up a sample of 733 unmarried older adults who were either never married, widowed, divorced or separated, from waves one and two of the 'Neuroprotective Model for Healthy Longevity among Malaysian Older Adults' study. The main statistical analysis used to answer the research question was the PROCESS macro (model 1) for SPSS. Results: The study found that increased loneliness was associated with a decline in cognitive function over a 3‐year period. Additionally, gender moderated the link between loneliness and cognitive function, with this association being particularly prominent in older men. Conclusions: Loneliness among unmarried older people should be given attention as it could lead to deteriorating cognitive function. Notably, older men experience a more substantial impact of loneliness on cognitive function than women. Therefore, special attention should be focused on this population, and more social services should be developed to reduce the incidence of cognitive impairment, improve their quality of life, and promote successful ageing. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment (CI) is common in older adults, especially those with renal dysfunction. We aimed to investigate the complex relationships among renal function, nutritional status, and CI in older people free from late chronic kidney disease (CKD) and severe CI. Methods: A study of older people (≥60 years old) with an estimated glomerular filtration rate (eGFR) of >30 mL/min/1.73 m2 and Montreal Cognitive Assessment (MoCA) scores of >10 (n = 237) was conducted at Beijing Tongren Hospital. Their eGFR was determined using the CKD‐EPI‐cr‐Cysc equation. Cognitive function was evaluated with the MoCA. We tested the relationship between eGFR and MoCA scores using Spearman correlation analysis and multivariate logistic regression analysis. We then conducted a mediation analysis to figure out the mediating roles of nutritional indicators (Mini Nutritional Assessment‐Short Form (MNA‐SF) scores, albumin (ALB), and haemoglobin (HGB)) between the eGFR and MoCA scores. Results: The incidence of CI was 48.5% (115/237) in older people. Spearman correlation analysis revealed that the better the kidney function, the better the cognitive function (R = 0.297, P < 0.001). Multivariate logistic regression analysis revealed that eGFR decrease per 15 mL/min/1.73 m2 (OR: 1.415, 95% confidence interval: 1.055–1.896, P = 0.020) was related to CI after adjusting for age and sex. However, the eGFR was not associated with cognitive decline after adjusting for nutritional indicators, behavioural risk factors, other biomarkers, and chronic conditions, suggesting that eGFR is not independently associated with CI. Mediation analysis revealed that the MNA‐SF scores (a*b = 0.006 (0.0002–0.012)) and HGB (a*b = 0.008 (0.001–0.017)) were mediating factors between the eGFR and MoCA scores. Conclusions: A decline in renal function can directly lead to CI and can also exacerbate cognitive deficits through intermediary factors such as MNA‐SF scores and HGB. Therefore, correcting anaemia and improving nutritional status are significantly important for enhancing cognitive function in older patients, especially those with renal dysfunction. [ABSTRACT FROM AUTHOR]

Aims/Introduction: To assess whether the sodium–glucose cotransporter 2 inhibitor, henagliflozin, improves cognitive impairment in patients with type 2 diabetes. Materials and Methods: We carried out a prospective study on 290 patients with type 2 diabetes and cognitive impairment. Montreal Cognitive Assessment scores and plasma phosphorylated tau181 levels were used to assess cognition. The association between henagliflozin use and changes in cognition was examined using multivariable logistic regression analysis. Results: Montreal Cognitive Assessment scores at enrollment and after 6 months were 21 (interquartile range [IQR]19–23) versus 22 (IQR 20–25; P < 0.0001) in all patients, 21 (IQR 19–23) versus 24 (IQR 22–26; P < 0.0001) in the henagliflozin group and 21 (IQR 19–22) versus 21 (IQR 19–23; P > 0.05) in the non‐sodium–glucose cotransporter 2 inhibitor group. Logistic regression analysis showed that henagliflozin treatment was associated with Montreal Cognitive Assessment score improvement independent of potential confounders (odds ratio [OR] 3.670, 95% confidence interval [CI] 2.224–6.056, P < 0.0001). Additionally, plasma phosphorylated tau181 levels significantly decreased at 6‐month follow up in all patients (OR 11.5, 95% CI 9.9–13.7 vs OR 10.1, 95% CI 7.8–12.9, P < 0.0001) and in the henagliflozin group (OR 11.5, 95% CI 10.3–13.0 vs OR 9.2, 95% CI 7.1–10.7, P < 0.0001), but not in the non‐sodium–glucose cotransporter 2 inhibitor group. Henagliflozin treatment was independently associated with decreased phosphorylated tau181 levels (OR 3.670, 95% CI 1.598–4.213, P < 0.0001). Conclusions: Henagliflozin treatment was independently associated with improvements in Montreal Cognitive Assessment scores and plasma phosphorylated tau181 levels, indicating significant beneficial effects on cognitive impairment in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

INTRODUCTION: This study aims to explore the current status of dementia‐specific diagnosis and treatment in China. METHODS: This national survey was conducted in mainland China from September 2022 to February 2023, with strong support from the Cognitive Disorders Group of the Chinese Society of Neurology, Chinese Medical Association. RESULTS: Among 2721 hospitals surveyed, 244 (8.97%) have dementia‐specific clinics (DSCs) and 166 (6.10%) have dementia‐specific inpatient departments (DSIDs). Almost all hospitals have brain structural imaging capabilities and basic hematological examinations, but dementia‐specific medical staff (DSMS) equipped for DSCs or DSIDs are rare. The proportion of patients with cognitive impairment receiving care through a DSCs or DSIDs is low, and most patients present with advanced (moderate to severe) disease. CONCLUSION: The survey shows that the proportion of DSCs and DSIDs is low, and the regional distribution varies significantly. Trained DSMS and specialized facilities for the diagnosis and treatment of dementia are inadequate. Highlights: This study was a multi‐center national research to comprehensively investigate the distribution and features of dementia‐specific clinics and inpatient departments in mainland China, given that the limited literature was available regarding the dementia‐specific centers.The study points to significant regional differences in the distribution of cognitive‐specific clinics and inpatient departments in mainland China. More centers in Eastern Regions compared to Western Regions, a greater presence in provincial capitals as opposed to other cities, and a predominance of tertiary hospitals over non‐tertiary ones. The aim is to provide data support for advancements in medical research within this field.Domestic dementia patients have inadequate access to specialized medical resources and expert assistance, which significantly contrasts with the growing number of dementia cases in China. [ABSTRACT FROM AUTHOR]

Blood‐based biomarkers (BBM) for Alzheimer's disease (AD) are being increasingly used in clinical practice to support an AD diagnosis. In contrast to traditional diagnostic modalities, such as amyloid positron emission tomography and cerebrospinal fluid biomarkers, BBMs offer a more accessible and lower cost alternative for AD biomarker testing. Their unique scalability addresses the anticipated surge in demand for biomarker testing with the emergence of disease‐modifying treatments (DMTs) that require confirmation of amyloid pathology. To facilitate the uptake of BBMs in clinical practice, The Global CEO Initiative on Alzheimer's Disease convened a BBM Workgroup to provide recommendations for two clinical implementational pathways for BBMs: one for current use for triaging and another for future use to confirm amyloid pathology. These pathways provide a standardized diagnostic approach with guidance on interpreting BBM test results. Integrating BBMs into clinical practice will simplify the diagnostic process and facilitate timely access to DMTs for eligible patients. [ABSTRACT FROM AUTHOR]

Diagnosing Alzheimer's disease (AD) poses significant challenges to health care, often resulting in delayed or inadequate patient care. The clinical integration of blood‐based biomarkers (BBMs) for AD holds promise in enabling early detection of pathology and timely intervention. However, several critical considerations, such as the lack of consistent guidelines for assessing cognition, limited understanding of BBM test characteristics, insufficient evidence on BBM performance across diverse populations, and the ethical management of test results, must be addressed for widespread clinical implementation of BBMs in the United States. The Global CEO Initiative on Alzheimer's Disease BBM Workgroup convened to address these challenges and provide recommendations that underscore the importance of evidence‐based guidelines, improved training for health‐care professionals, patient empowerment through informed decision making, and the necessity of community‐based studies to understand BBM performance in real‐world populations. Multi‐stakeholder engagement is essential to implement these recommendations and ensure credible guidance and education are accessible to all stakeholders. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Early detection of both objective and subjective cognitive impairment is important. Subjective complaints in healthy individuals can precede objective deficits. However, the differential associations of objective and subjective cognition with modifiable dementia risk factors are unclear. METHODS: We gathered a large cross‐sectional sample (N = 3327, age 18 to 84) via a smartphone app and quantified the associations of 13 risk factors with subjective memory problems and three objective measures of executive function (visual working memory, cognitive flexibility, model‐based planning). RESULTS: Depression, socioeconomic status, hearing handicap, loneliness, education, smoking, tinnitus, little exercise, small social network, stroke, diabetes, and hypertension were all associated with impairments in at least one cognitive measure. Subjective memory had the strongest link to most factors; these associations persisted after controlling for depression. Age mostly did not moderate these associations. DISCUSSION: Subjective cognition was more sensitive to self‐report risk factors than objective cognition. Smartphones could facilitate detecting the earliest cognitive impairments. Highlights: Smartphone assessments of cognition were sensitive to dementia risk factors.Subjective cognition had stronger links to most factors than did objective cognition.These associations were not fully explained by depression.These associations were largely consistent across the lifespan. [ABSTRACT FROM AUTHOR]

Background and Purpose Methods Results Conclusions Decompressive hemicraniectomy (DH) improves survival and functional outcome in large middle cerebral artery (MCA) infarcts. However, long‐term cognitive outcomes after DH remain underexplored. In a cohort of patients with large right‐hemisphere MCA infarction undergoing DH, we assessed the rates of long‐term cognitive impairment over 3‐year follow‐up.We prospectively evaluated consecutive patients included in the Lille Decompressive Surgery Database (May 2005–April 2022) undergoing DH according to existing guidelines for large hemisphere MCA infarction. We included patients with right‐sided stroke and screened with the Mini‐Mental State Examination (MMSE) in at least one of the prespecified follow‐ups (3‐month, 1‐year, 3‐year). Cognitive impairment was defined as an MMSE score < 24. We included only right‐hemisphere strokes to avoid testing biases related to severe aphasia. We compared clinical and neuroimaging data in patients with and without cognitive impairment.Three hundred four patients underwent DH during the study period. Among 3‐month survivors, 95 had a right‐hemisphere stroke and underwent at least one cognitive screening (median age = 51 years, 56.8% men). Forty‐four patients (46.3%) exhibited cognitive impairment at least once during the 3‐year follow‐up. Baseline characteristics did not significantly differ between patients with and without cognitive impairment. Regarding long‐term temporal trends, cognitive impairment was observed in 23 of 76 (30.3%), 25 of 80 (31.3%), and 19 of 66 (28.8%) patients at 3‐month, 1‐year, and 3‐year follow‐up, respectively, and it was associated with higher rates of functional disability (all p < 0.05).The persistently high rates of cognitive impairment after DH highlight the importance of cognitive monitoring to improve the long‐term management of survivors. [ABSTRACT FROM AUTHOR]

Introduction Methods Findings Discussion Cognitive impairment is common among patients with hemodialysis. Hemodialysis patients have theoretical risks for both deficiency and accumulation of trace elements. We aimed to investigate the relationship between cognitive dysfunction and whole blood levels of trace elements in hemodialysis patients. We also aimed to examine the effect of baseline trace element status and cognitive dysfunction on mortality.Maintenance hemodialysis patients and age‐and sex‐matched controls were included. The whole blood levels of trace elements were measured by inductively coupled plasma mass spectrometry. Cognitive impairment was defined as a score of ≤24 points on the Montreal Cognitive Assessment test. Executive dysfunction was also defined as Trails A score of more than 75 s and Trails B score of more than 180 s.Forty‐two patients and 35 controls were included. Cognitive impairment was detected in 69% of the patients and 45.7% of the controls (p = 0.039). Cognitively impaired patients had lower education years (p = 0.003) and higher whole blood levels of manganese (Mn) and lead (Pb) (p = 0.026, p = 0.019, respectively) compared to patients without cognitive impairment. Mn levels were also found statistically higher in patients with executive dysfunction compared to patients without executive dysfunction (p = 0.005). Lower education years and higher Pb levels were independent risk factors for cognitive impairment in hemodialysis patients (odds ratio [OR] 0.589 [95% confidence interval, CI 0.400–0.866, p = 0.007] and OR 1.047 [95% CI 1.001–1.096, p = 0.047, respectively]).Cognitive impairment, especially impaired executive function, is common among patients with hemodialysis patients. Cognitive impairment is not found to be associated in cross‐sectional analysis with several modifiable end‐stage renal disease‐ and dialysis‐associated factors. The accumulation of trace elements especially Mn and Pb might exacerbate the cognitive dysfunction in hemodialysis patients. [ABSTRACT FROM AUTHOR]

Objective Methods Results Significance Pathological amyloid‐β (Aβ) accumulation and hyperphosphorylated tau proteins have been described in resected temporal lobe specimens of epilepsy patients. We aimed to determine cerebrospinal fluid (CSF) Aβ1‐42 and p181‐tau levels and cerebral Aβ deposits on positron emission tomography (Aβ PET) and correlate these findings with cognitive performance in adults with drug‐resistant temporal lobe epilepsy (TLE).In this cross‐sectional study, we enrolled individuals with drug‐resistant TLE who were 25–55 years old. Each participant underwent 18F‐flutemetamol PET, determination of CSF Aβ1‐42, p181‐tau, and total tau, and a comprehensive neuropsychological assessment. We evaluated normalized standard uptake value ratios (SUVRs) for different brain regions on Aβ PET.Thirty patients (mean age = 41.9 ± SD 8.1 years, 57% men) were included. The median disease duration was 9.5 (interquartile range = 4–24) years. Twenty‐six patients (87%) had a clinically significant cognitive impairment on neuropsychological evaluation, 18 (69%) of the amnesic type. On Aβ PET, high uptake was observed in both mesial temporal regions (ipsilateral: SUVR z‐score = .90, 95% confidence interval [CI] = .60–1.20; contralateral: SUVR z‐score = .92, 95% CI = .57–1.27; p < .001), which was higher when compared to SUVR z‐scores in all the remaining regions (p < .001) and in the ipsilateral anterior cingulate (SUVR z‐score = .27, 95% CI = .04–.49, p = .020). No significant deposition was observed in other regions. Seven patients (23%) had low Aβ1‐42 levels, and two (7%) had elevated p181‐tau levels in CSF. Higher p181‐tau levels correlated with poorer verbal fluency (R = −.427, p = .044).Our findings reveal a considerable Aβ deposition in mesial temporal regions and ipsilateral anterior cingulate among adults with drug‐resistant TLE. Additionally, abnormal CSF Aβ1‐42 levels were observed in a significant proportion of patients, and p181‐tau levels were associated with verbal fluency. These results suggest that markers of neuronal damage can be observed in adults with TLE, warranting further investigation. [ABSTRACT FROM AUTHOR]

Background: Temporal lobe epilepsy (TLE), a prevalent chronic neurological disorder, affects millions of individuals and is often resistant to anti‐epileptic drugs. Increasing evidence has shown that acetylcholine (ACh) and cholinergic neurotransmission play a role in the pathophysiology of epilepsy. Tropisetron, an antiemetic drug used for chemotherapy in clinic, has displayed potential in the treatment of Alzheimer's disease, depression, and schizophrenia in animal models. However, as a partial agonist of α7 nicotinic acetylcholine receptors (α7nAChRs), whether tropisetron possesses the therapeutic potential for TLE has not yet been determined. Methods: In this study, tropisetron was intraperitoneally injected into pilocarpine‐induced epileptic rats for 3 weeks. Alpha‐bungarotoxin (α‐bgt), a specific α7nAChR antagonist, was applied to investigate the mechanism of tropisetron. Rats were assessed for spontaneous recurrent seizures (SRS) and cognitive function using video surveillance and Morris's water maze testing. Hippocampal impairment and synaptic structure were evaluated by Nissl staining, immunohistochemistry, and Golgi staining. Additionally, the levels of glutamate, γ‐aminobutyric acid (GABA), ACh, α7nAChRs, neuroinflammatory cytokines, glucocorticoids and their receptors, as well as synapse‐associated protein (F‐actin, cofilin‐1) were quantified. Results: The results showed that tropisetron significantly reduced SRS, improved cognitive function, alleviated hippocampal sclerosis, and concurrently suppressed synaptic remodeling and the m6A modification of cofilin‐1 in TLE rats. Furthermore, tropisetron lowered glutamate levels without affecting GABA levels, reduced neuroinflammation, and increased ACh levels and α7nAChR expression in the hippocampi of TLE rats. The effects of tropisetron treatment were counteracted by α‐bgt. Conclusion: In summary, these findings indicate that tropisetron exhibits an anti‐epileptic effect and provides neuroprotection in TLE rats through the activation of α7nAChRs. The potential mechanism may involve the reduction of glutamate levels, enhancement of cholinergic transmission, and suppression of synaptic remodeling. Consequently, the present study not only highlights the potential of tropisetron as an anti‐epileptic drug but also identifies α7nAChRs as a promising therapeutic target for the treatment of TLE. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic schizophrenia (SZ) have a high risk of suicide, and their cognition function is impaired. We aimed to explore the relationship between attention and suicidal ideation among patients with adult‐onset chronic SZ. Methods: A total of 416 patients with adult‐onset chronic SZ were enrolled in this study. We divided patients into suicidal ideation group and non‐suicidal ideation group according to the evaluation results of the Beck Scale for Suicide Ideation. Psychotic symptoms were measured by Positive and Negative Syndrome Scale (PANSS), and cognitive function was measured by Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Insomnia symptoms were measured by Insomnia Severity Index (ISI). Results: Age was significantly different (44.28 ± 10.58 vs. 48.46 ± 12.23, t = 10.64, p = 0.001) between the two groups, and the patients with suicidal ideation were younger than patients without suicidal ideation. The positive symptom scores of the PANSS, the scores of ISI, and attention scores of RBANS were higher in patients with suicidal ideation than patients without suicidal ideation (17.30 ± 5.67 vs. 15.58 ± 4.90, t = 9.633, p = 0.002; 3.00 [1.00–6.00] vs. 2.00 [1.00–3.50], Z = −2.048, p = 0.041; 81.80 ± 14.99 vs. 76.91 ± 13.88, t = 10.101, p = 0.002). In the logistic regression analysis, age (odds ratio [OR], 0.973; 95% confidence interval [95%CI], [0.955–0.992]; p = 0.005), positive symptom scores of PANSS (OR, 1.063; 95%CI, [1.019–1.109]; p = 0.005), ISI scores (OR, 1.098; 95%CI, [1.037–1.163]; p = 0.001), and attention scores of RBANS (OR, 1.029; 95%CI, [1.013–1.047]; p = 0.001) were independently associated with the occurrence of suicidal ideation among patients with adult‐onset chronic SZ. Conclusions: High attention scores of RBANS were a risk factor for suicidal ideation among patients with adult‐onset chronic SZ. [ABSTRACT FROM AUTHOR]

Objectives: In older U.S. nursing home residents with suicidal ideation (SI), limited studies have longitudinally investigated their health changes as related to cognitive function. This study aimed to identify the health profiles and the transitions between profiles at admission and 90‐days and examine the associations with cognitive impairment. Methods: Using Minimum Data Set 3.0 (2011–15), we identified 10,079 older residents without severe cognitive impairment who reported SI on Patient Health Questionnaire‐9. Health profile indicators included at‐admission and 90‐day post‐admission depressive symptoms, frailty, and pain frequency and intensity. Using latent transition analysis, we identified distinct health profiles, examined the transitions between profiles over time, and estimated their associations with cognitive impairment. Results: One third of residents continued to report SI at 90 days. The five health profiles identified at admission were distinctive with varying levels of frailty, depressive symptoms, and pain, from the most severe Profile 1 characterized by frailty, all depressive symptoms, and horrible or frequent pain, to the least severe Profile 5 characterized by pre‐frailty, depressed mood, and no pain. The 90‐day profiles were mostly consistent. Most residents remained in a similar profile over time. Relative to residents with intact cognition/mild cognitive impairment, those with moderate impairment were less likely to belong to profiles characterized by more depressive symptoms and pain. Conclusions: Residents with SI had heterogeneous health profiles, which varied by cognitive impairment levels, but showed minimal changes despite being in a medically supervised setting. Findings highlighted the critical need for adequate recognition and management of SI in nursing homes. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a devastating disorder with a multifaceted aetiology characterized by dementia, which later progresses to cognitive impairment. Significant efforts have been made to develop pharmacological interventions that slow down the pathogenesis of AD. However, conventional drugs have failed to satisfactorily treat AD and are more focussed towards symptomatic management. Thus, there is a gap in the literature regarding novel targets and modulators targeting them for the effective treatment of AD. Recent studies have demonstrated that modulation of transient receptor potential (TRP) channels has the potential to halt AD pathogenesis at an early stage and rescue hippocampal neurons from death. Amongst several members, TRP channels like TRPA1, TRPC6, TRPM2 and TRPV2 have shown promising results in the attenuation of neurobehavioural cognitive deficits as well as signalling pathways governing such cognitive decline. Furthermore, as these channels govern the ionic balance in the cell, their beneficial effects have also been known to maintain the homeostasis of Ca2+, which is the major culprit eliciting the vicious cycle of excitotoxicity, mitochondrial dysfunction, ROS generation and neurodegeneration. Despite such tremendous potential of TRP channel modulators, their clinical investigation remains elusive. Therefore, in the present review, we have discussed such agents in the light of TRP channels as molecular targets for the amelioration of AD both at the preclinical and clinical levels. [ABSTRACT FROM AUTHOR]

This article discusses a case study of a 23-year-old male with juvenile parkinsonism and cognitive impairment due to compound heterozygous variants in the BTD gene, leading to biotinidase deficiency. The patient showed symptoms of stiffness, tremors, delayed development milestones, and cognitive impairments. Treatment with biotin supplementation and dopaminergic therapy showed improvement in motor symptoms but not in cognitive functions. The study highlights the importance of considering biotinidase deficiency in cases of juvenile parkinsonism, especially when accompanied by developmental delays, cognitive impairments, and specific MRI findings. [Extracted from the article]

Backgroud: Cancer‐related cognitive impairment is one of the common complications in children with cancer, but our understanding of their experience with cognitive deficits remains limited. From the perspective of parents, this study aimed to explore the distress and demands faced by children with cancer‐related cognitive impairment, to provide references for developing targeted intervention strategies for cancer children. Methods: We used a purposeful sampling method to conduct semi‐structured interviews with the parents of 18 children with cancer‐related cognitive impairment. The transcripts were analyzed using Colaizzi's method. Results: Three categories and 11 subcategories were obtained from the data analysis, including diverse levels of cognitive impairment in children (speech communication difficulties, impaired executive function, attention deficit, and intellectual disability), persistent negative emotions (anxiety and worry, complaints and resentment, negative avoidance and positive experiences after psychological adjustment), multiple needs (need for disease information, need for professional management, and an urgent need for more external support). Conclusion: Parents of children with cancer‐related cognitive impairment face a significant psychological burden, coupled with confusion and numerous inquiries regarding the symptoms and management of their children's cognitive impairment. It is imperative for medical professionals to strengthen the dissemination of information related to cancer‐associated cognitive impairments, while promptly recognizing and intervening in related symptoms. Rational allocation of resources, establishment of targeted support systems, and enhancement of social acceptance may be the key points that policymakers could consider. These efforts hold immense significance, as they play a pivotal role in elevating cognitive capabilities and enhancing the overall quality of life for children with cancer. [ABSTRACT FROM AUTHOR]

Background and purpose: Although air pollution (AP) has been associated with stroke and dementia, data regarding its relationship with covert cerebrovascular disease (cCVD) and cognition over time are sparse. The aim of this study was to explore these relationships. Methods: A prospective population‐based study of 976 stroke‐free and non‐demented individuals living in Barcelona, Spain, was conducted during 2010–2016. A land use regression model was used to estimate the exposure of each participant to AP: NOx, NO2, PM2.5, PM10, PMcoarse and PM2.5 absorbance. Cognitive function and cCVD were assessed at baseline (n = 976) and 4 years after (n = 317). Multivariate‐adjusted models were developed. Results: At baseline, 99 participants (10.1%) had covert brain infarcts and 91 (9.3%) had extensive periventricular white matter hyperintensities (WMHs). Marked subcortical WMH progression was seen in 19.7%; the incidence of other covert cerebrovascular lessons ranged between 5% and 6% each. PM2.5 was related to higher odds of having a covert brain infarct (odds ratio [OR] 2.21; 95% confidence interval [CI] 1.06–4.60). PM2.5 absorbance was related to higher odds of having extensive subcortical WMHs (OR 1.72; 95% CI 1.13–2.60), whereas NO2 was related to higher odds of having extensive subcortical (OR 1.66; 95% CI 1.17–2.35) or periventricular (OR 1.96; 95% CI 1.10–3.50) WMHs and to higher odds of developing marked subcortical WMH progression (OR 1.40; 95% CI 1.05–1.90). NOx was related to incident cerebral microbleeds (OR 1.36; 95% CI 1.04–1.79). There was no association between AP and cognition. Conclusions: Air pollutant predicts the presence and accumulation of cCVD. Its impact on cognitive impairment remains to be determined. [ABSTRACT FROM AUTHOR]

This article explores the relationship between diabetes, cognitive impairment, and continuous glucose monitoring (CGM). It highlights the increasing prevalence of cognitive impairment in older adults with diabetes and the negative impact of hypoglycemia on cognition and mortality. The study focuses on the use of CGM in older patients with diabetes and cognitive impairment, aiming to assess its association with all-cause mortality. The results indicate that CGM users had better glycemic control and lower mortality rates compared to non-users. The study suggests that CGM could be beneficial in identifying hypoglycemia and calls for further research to validate these findings. [Extracted from the article]

INTRODUCTION: CD33 rs3865444 and hypertension (HTN) are related to cognitive impairment, individually. However, little is known about their combined effects on cognitive function in older adults. METHODS: This population‐based study included 4368 dementia‐free participants (age ≥65 years) in the Multimodal Interventions to Delay Dementia and Disability in Rural China (MIND‐China), with data available in 1044 persons for gray matter volume and 85 persons for cerebral blood flow (CBF). We used general linear regression and mediation models to examine the associations of rs3865444 and HTN with cognition, brain atrophy, and CBF. RESULTS: Among rs3865444 CC carriers, HTN and late‐life HTN were significantly associated with impaired cognition. Midlife and late‐life HTN were correlated with brain atrophy. CD33 rs3865444 CC moderated the mediation effect of gray matter volume on the association between HTN and global cognition. HTN was correlated with low CBF in rs3865444 CC carriers. DISCUSSION: There are synergistic associations of CD33 rs3865444 and HTN with brain and cognitive aging in dementia‐free older adults. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Best practices for conducting advance care planning (ACP) among persons with cognitive impairment exist, but evidence‐based models are lacking for the primary care setting. METHODS: We tested a remote multicomponent ACP model (SHARE) versus minimally enhanced usual care in 273 person–family dyads from eight primary care practices. RESULTS: Mean patient age was 88.0 years, 85 (31.1%) were Black/Latino; 189 (69.2%) had moderate‐to‐severe cognitive impairment. Most (101/145; 69.6%) intervention dyads engaged in ACP. At follow‐up, no treatment effect was observed for care partner–reported quality of communication about end‐of‐life care at 6 or 12 months, but intervention patients reported better quality of communication about end‐of‐life care at 12 months. Intervention care partners and patients reported greater readiness to engage in ACP at 6 and 12 months, respectively, and increased completion of key aspects of ACP. DISCUSSION: SHARE supported key aspects of ACP processes and communication about end‐of‐life care. Highlights: Primary care–based models of ACP for persons with dementia are lacking.Involving persons with cognitive impairment in remote ACP is feasible with care partner involvement.Results indicate benefit for aspects of ACP processes and communication about end‐of‐life care. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Clonal hematopoiesis of indeterminate potential (CHIP) and dementia disproportionately burden patients with chronic kidney disease (CKD). The association between CHIP and cognitive impairment in CKD patients is unknown. METHODS: We conducted time‐to‐event analyses in up to 1452 older adults with CKD from the Chronic Renal Insufficiency Cohort who underwent CHIP gene sequencing. Cognition was assessed using four validated tests in up to 6 years mean follow‐up time. Incident cognitive impairment was defined as a test score one standard deviation below the baseline mean. RESULTS: Compared to non‐carriers, CHIP carriers were markedly less likely to experience impairment in attention (adjusted hazard ratio [HR] [95% confidence interval {CI}] = 0.44 [0.26, 0.76], p = 0.003) and executive function (adjusted HR [95% CI] = 0.60 [0.37, 0.97], p = 0.04). There were no significant associations between CHIP and impairment in global cognition or verbal memory. DISCUSSION: CHIP was associated with lower risks of impairment in attention and executive function among CKD patients. Highlights: Our study is the first to examine the role of CHIP in cognitive decline in CKD.CHIP markedly decreased the risk of impairment in attention and executive function.CHIP was not associated with impairment in global cognition or verbal memory. [ABSTRACT FROM AUTHOR]

Objective: In this research, we examine perceptions of couple relationships and intimacy among older couples when one partner is diagnosed with mild cognitive impairment (MCI), based on ambiguous loss theory. Background: Many studies have examined couples with one partner affected by dementia, yet few have explored intimacy when the affected partner is diagnosed with MCI. Method: A qualitative‐phenomenological approach in which data were collected through in‐depth, semistructured, face‐to‐face interviews with 16 men and women aged 67–90. Results: The nondiagnosed partners live in the present while acknowledging the changes caused by aging and the diagnosis. In contrast, the diagnosed partners tend to live in the past. In line with ambiguous loss theory, the nondiagnosed partners reported that their diagnosed spouses are physically present yet many aspects of their personalities are partially absent. Conclusion: The findings reveal two patterns of coping with the consequences of loss. Understanding these relationships offers insights into how to care for individuals with MCI. Implications: The results highlight that individuals with MCI and their partners do not invariably constitute a homogenous group, necessitating a critical appraisal of partners' roles and expectations before initiating therapeutic interventions. [ABSTRACT FROM AUTHOR]

Aims: Cognitive impairment (CI) is a common, yet frequently unrecognized co‐morbidity in chronic heart failure (HF). We quantified trajectories of cognitive performance, brain volume, and related clinical outcome over a time course of 6 years. Methods and results: The Cognition.Matters‐HF cohort study recruited patients with stable HF of any aetiology and severity. Beyond cardiological assessment, the workup included cognitive testing and brain magnetic resonance imaging (MRI). Of 148 recruited patients, 70% exhibited CI at baseline. During the median follow‐up time of 69 months (quartiles: 68, 70), indicators of HF severity remained essentially unaltered. CI was also stable, with the exception of intensity of attention, where age‐adjusted t‐scores decreased from 42 (38, 46) to 38 (34, 44; P < 0.001). Complete sets of four serial brain MRI scans were available in 47 patients (32% of total sample). Total brain volume shrank by 0.4% per year, from 1103 (1060, 1143) cm3 to 1078 (1027, 1117) cm3, which was within limits observed in non‐diseased ageing individuals. During follow‐up, 29 study participants (20%) died, and 26 (18%) were at least once hospitalized due to worsening HF. The presence of CI was not associated with overall (P = 0.290) or hospitalization‐free (P = 0.450) survival. Conclusions: In patients with stable HF patients receiving guideline‐directed pharmacologic treatment and regular medical care, the presence of CI did not affect overall and hospitalization‐free 6‐year survival. The loss of brain parenchyma observed in patients with stable HF did not exceed that of normal ageing. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Atrial fibrillation is associated with several comorbidities, particularly cognitive impairment and dementia, especially in older patients. Non‐vitamin K oral anticoagulants (NOACs) or vitamin K antagonists (VKAs) were used to prevent thromboembolic events. However, data on the real benefit of these drugs on cognitive function decline remains controversial. In this study we evaluated the effect of NOACs compared to VKAs on the absolute and relative decline in cognitive function over time.Nine hundred and eighty‐three older patients with nonvalvular AF were enrolled (76 ± 6 years; 291 on VKAs and 692 on NOACs). The cognitive function was assessed with Mini Mental State examination (MMSE) score. The between‐arms difference of cognitive evolution over time was investigated by Linear Mixed Models and group‐based trajectory model analyses.In the whole multicenter observational study, after a long follow‐up of 7.2 ± 3.4 years, the patients of the NOACs versus VKAs group had lowest absolute reduction of the MMSE score between baseline and follow‐up (−0.3 ± 0.03 vs.−1.7 ± 0.1, p < 0.001). After stratification into five subgroups according to trajectories of MMSE score over time, the probability to belong to trajectories with lower decline in cognitive functions was higher in patients on NOACs than in those on VKAs (3.93–13.88 times).In older patients with atrial fibrillation, the use of NOACs was associated with a smaller decline of cognitive function over time compared to the VKAs, regardless that patients in the NOACs group were older and with a higher burden of comorbidities. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Life‐space mobility captures the daily, enacted mobility of older adults. We determined cross‐sectional associations between life‐space mobility and cognitive impairment (CI) among community‐dwelling women in the 9th and 10th decades of life.A total of 1375 (mean age 88 years; 88% White) community‐dwelling women enrolled in a prospective cohort of older women. Life‐space score was calculated with range 0 (daily restriction to one's bedroom) to 120 (daily trips leaving town without assistance) and categorized (0–20, 21–40, 41–60, 61–80, 81–120). The primary outcome was adjudicated CI defined as mild cognitive impairment or dementia; scores on a 6‐test cognitive battery were secondary outcomes.Compared to women with life‐space scores of 81–120 and after adjustment for demographics and depressive symptoms, the odds of CI was 1.4‐fold (OR 1.36, 95% CI 0.91–2.03) higher for women with life‐space scores of 61–80, twofold (OR 1.98, 95% CI 1.33–2.94) higher for women with life‐space scores of 41–60, 2.6‐fold (OR 2.62, 95% CI 1.71–4.01) higher for women with life‐space scores of 21–40, and 2.7‐fold (OR 2.71, 95% CI 1.27–5.79) higher for women with life‐space scores of 0–20. The association of life‐space scores with adjudicated CI was primarily due to higher odds of dementia; the odds of dementia versus normal cognition was eightfold (OR 8.63, 95% CI 3.20–23.26) higher among women with life‐space scores of 0–20 compared to women with life‐space scores of 81–120. Lower life‐space scores were associated in a graded manner with lower mean scores on tests of delayed recall (California Verbal Learning Test‐II delayed recall) and language and executive function (phonemic fluency, category fluency, and Trails B). Life‐space score was not associated with scores on tests of attention and working memory (forward and backward digit span).Lower life‐space mobility is associated in a graded manner with CI among community‐dwelling White women in the 9th and 10th decades of life. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common age‐related neurodegenerative disorder leading to cognitive decline. Excessive cytosolic calcium (Ca2+) accumulation plays a critical role in the pathogenesis of AD since it activates the NOD‐like receptor family, pyrin domain containing 3 (NLRP3), switches the endoplasmic reticulum (ER) unfolded protein response (UPR) toward proapoptotic signaling and promotes Aβ seeding. Herein, a liposomal nanodrug (felodipine@LND) is developed incorporating a calcium channel antagonist felodipine for Alzheimer's disease treatment through a low‐intensity pulse ultrasound (LIPUS) irradiation‐assisted blood brain barrier (BBB)‐crossing drug delivery. The multifunctional felodipine@LND is effectively delivered to diseased brain through applying a LIPUS irradiation to the skull, which resulted in a series of positive effects against AD. Markedly, the nanodrug treatment switched the ER UPR toward antioxidant signaling, prevented the surface translocation of ER calreticulin (CALR) in microglia, and inhibited the NLRP3 activation and Aβ seeding. In addition, it promoted the degradation of damaged mitochondria via mitophagy, thereby inhibiting the neuronal apoptosis. Therefore, the anxiety‐like behavior and cognitive impairment of 5xFAD mice with AD is significantly ameliorated, which manifested the potential of LIPUS – assisted BBB‐crossing delivery of felodipine@LND to serve as a paradigm for AD therapy based on the well‐recognized clinically available felodipine. [ABSTRACT FROM AUTHOR]

This research aimed to determine the sensitivity and clinical validity of the OCS‐Plus, a stroke‐specific tablet‐based cognitive screening tool, in comparison with the MoCA, a routinely used screening tool, after stroke. Eighty‐six patients were recruited from Oxfordshire stroke wards over a 22‐month period and completed both screens. Overall, we found that the OCS‐Plus has good convergent validity and excellent sensitivity when compared with the MoCA. The OCS‐Plus is therefore of potential benefit to those seeking a sensitive screening tool. [ABSTRACT FROM AUTHOR]

Background: Persistent cognitive impairment is a serious consequence of the post‐COVID condition. However, there have been no established effective treatments for this pathophysiology supported by sufficient evidence. Case Presentation: A 32‐year‐old woman became aware of difficulty in word recalling, reading, and writing as well as difficulty in completing various household multitasks 3 weeks after the COVID‐19 infection. Although blood tests, magnetic resonance imaging, electroencephalography, and Kohs block design test were all within normal limits, completion time by trail making test (TMT) A or B was markedly delayed. Finally, she was referred to our hospital 3 months after the infection. At baseline, the THINC integrated tool (THINC‐it), a digital battery consisting of the five‐item version of the perceived deficit questionnaire (PDQ‐5), choice reaction time (CRT), 1‐back test, digit symbol substitution test (DSST), and TMT‐B, revealed poor capability in attention, working memory, and executive function. Also, near‐infrared spectroscopy (NIRS) demonstrated no activation in frontal or temporal regions during verbal fluency task. Extended‐release guanfacine (GXR) 2 mg/day was initiated and a month later was elevated up to 4 mg/day as a maintenance dose. The PDQ‐5, CRT, 1‐back test, DSST, and TMT‐B were dramatically improved 1 month after GXR treatment. NIRS finding was also normalized after 2 months of treatment. These effects were successfully maintained throughout the 6‐month follow‐up period. Conclusion: GXR may be helpful in improving subjective/objective cognitive functioning and frontotemporal brain activity in long‐COVID patients manifesting apparent cognitive impairment. [ABSTRACT FROM AUTHOR]

Though previous studies revealed the potential associations of elevated levels of plasma fibrinogen with dementia, there is still limited understanding regarding the influence of Alzheimer's disease (AD) biomarkers on these associations. We sought to investigate the interrelationships among fibrinogen, cerebrospinal fluid (CSF) AD biomarkers, and cognition in non‐demented adults. We included 1996 non‐demented adults from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) study and 337 from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The associations of fibrinogen with AD biomarkers and cognition were explored using multiple linear regression models. The mediation analyses with 10 000 bootstrapped iterations were conducted to explore the mediating effects of AD biomarkers on cognition. In addition, interaction analyses and subgroup analyses were conducted to assess the influence of covariates on the relationships between fibrinogen and AD biomarkers. Participants exhibiting low Aβ42 were designated as A+, while those demonstrating high phosphorylated tau (P‐tau) and total tau (Tau) were labeled as T+ and N+, respectively. Individuals with normal measures of Aβ42 and P‐tau were categorized as the A−T− group, and those with abnormal levels of both Aβ42 and P‐tau were grouped under A+T+. Fibrinogen was higher in the A+ subgroup compared to that in the A− subgroup (p = 0.026). Fibrinogen was higher in the A+T+ subgroup compared to that in the A−T− subgroup (p = 0.011). Higher fibrinogen was associated with worse cognition and Aβ pathology (all p < 0.05). Additionally, the associations between fibrinogen and cognition were partially mediated by Aβ pathology (mediation proportion range 8%–28%). Interaction analyses and subgroup analyses showed that age and ApoE ε4 affect the relationships between fibrinogen and Aβ pathology. Fibrinogen was associated with both cognition and Aβ pathology. Aβ pathology may be a critical mediator for impacts of fibrinogen on cognition. [ABSTRACT FROM AUTHOR]

Background: Intracranial atherosclerotic stenosis (ICAS) is one of the most important independent risk factors for stroke that is closely related to the occurrence of cognitive impairment. The relationship between ICAS and vascular cognitive impairment (VCI) remains unclear. Cerebral hemodynamic changes are one of the main causes of cognitive impairment. Computed tomographic perfusion (CTP) imaging can quantitatively analyze cerebral blood perfusion and quantify cerebral hemodynamic changes. Previous research on the relationship between hypoperfusion induced by ICAS and cognitive impairment, as well as its underlying mechanisms, remains relatively insufficient. This study is dedicated to elucidating the characteristics and potential mechanisms of cognitive impairment in ICAS patients with abnormal perfusion, utilizing CTP imaging as our primary investigative tool. Methods: This study recruited 82 patients who suffer from non‐disabling ischemic stroke (IS group) and 28 healthy controls. All participants underwent comprehensive neuropsychological assessments both collectively and individually, in addition to CTP imaging. Within the patient group, we further categorized individuals into two subgroups: the ischemic penumbra group (IP, N = 28) and the benign oligemia group (BO, N = 54), based on CTP parameters—Tmax. The correlations between cognitive function and abnormal perfusion were explored. Results: The cognitive function, including the overall cognitive, memory, attention, executive functions, and language, was significantly impaired in the IS group compared with that in the control group. Further, there are statistical differences in the stroop color–word test‐dot (Stroop‐D) and Montreal Cognitive Assessment (MoCA) sub‐items (memory + language) between the BO and IP groups. In the BO group, the score of Stroop‐D is lower, and the MoCA sub‐items are higher than the IP group. There is no correlation between CTP parameters and cognitive function. Conclusion: Cognitive function is significantly impaired in patients with ICAS, which is related to cerebral perfusion. Executive, memory, and language function were better preserved in ICAS patients without IP. Hence, this study posits that managing hypoperfusion induced by ICAS may play a pivotal role in the development of VCI. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to develop and validate an eMCI‐CHD tool based on clinical data to predict mild cognitive impairment (MCI) risk in patients with coronary heart disease (CHD). Methods: This cross‐sectional study prospectively collected data from 400 patients with coronary heart disease (aged 55–90 years, 62% men) from July 2022 to September 2023 and randomized (7:3 ratio) them into training and validation sets. After determining the modeling variables through least absolute shrinkage and selection operator regression analysis, four ML classifiers were developed: logistic regression, extreme gradient boosting (XGBoost), support vector machine, and random forest. The performance of the models was evaluated using area under the ROC curve, accuracy, sensitivity, specificity, and F1 score. Decision curve analysis was used to assess the clinical performance of the established models. The SHapley Additive exPlanations (SHAP) method was applied to determine the significance of the features, the predictive model was visualized with a nomogram, and an online web‐based calculator for predicting CHD‐MCI risk scores was developed. Results: Of 400 CHD patients (average age 70.86 ± 8.74 years), 220 (55%) had MCI. The XGBoost model demonstrated superior performance (AUC: 0.86, accuracy: 78.57%, sensitivity: 0.74, specificity: 0.84, F1: 0.79) and underwent validation. An online tool (https://mr.cscps.com.cn/mci/index.html) with seven predictive variables (APOE gene typing, age, education, TyG index, NT‐proBNP, C‐reactive protein, and occupation) assessed MCI risk in CHD patients. Conclusion: This study highlights the potential for predicting MCI risk among CHD patients using an ML model‐driven nomogram and risk scoring tool based on clinical data. [ABSTRACT FROM AUTHOR]

Background: Previous studies using emerging diffusion MRI techniques have revealed damage to the white matter (WM) microstructure in amyotrophic lateral sclerosis (ALS), particularly the influence of crossed fibers, but there is a lack of subgroup analyses. Purpose: To detect WM microstructural changes in ALS patients using fixel‐based analysis (FBA) and neurite orientation dispersion and density imaging (NODDI) MRI. Study Type: Prospective. Population: Thirty‐six ALS patients (aged 60.50 ± 9.5 years) and 25 healthy controls (HCs) (aged 58.90 ± 8.1 years). Field Strength/Sequence: 3 T; NODDI and FBA (b‐values = 0, 1000, and 2500 seconds/mm2). Assessment: Subgroups were performed according to progression rate and cognition, including fast and slow progression (FP/SP), ALS with and without cognitive impairment (ALS‐ci/ALS‐nci). Fiber density (FD), fiber‐bundle cross‐section (FC), combined fiber density and cross‐section (FDC), neurite density index (NDI), orientation dispersion index (ODI), isotropic volume fraction (ISO), and fractional anisotropy (FA) were calculated and their correlation with clinical variables examined. Statistical Testing: Chi‐square test, Mann–Whitney U test, two‐sample t test, partial correlation analysis, and false discovery rate (FDR) corrected. A P‐value <0.05 was considered significant. Results: ALS patients had lower FD and FDC values predominantly in the corticospinal tract (CST) and corpus callosum (CC) regions, as well as lower NDI value in the CC, radial crown, and internal capsule compared to HCs. Subgroup analysis based on progression rate and cognitive function showed significant differences in FBA results. The FC in the right CST region was significantly lower in the FP than SP, and the FD in the CC region was significantly lower in the ALS‐ci than ALS‐nci. Furthermore, a negative correlation was found between the mean FC value and the rate of progression in ALS patients (r = −0.408). Data Conclusion: FBA is a powerful tool for detecting complex cerebral WM microstructural damage for evaluating ALS cognition and disease progression. [ABSTRACT FROM AUTHOR]

Background: Resting‐state functional MRI (rs‐fMRI) has identified static changes of local brain activity among patients with intracerebral hemorrhage (ICH). However, the dynamic and concordance‐related characteristics of brain activity remain unclear. Purpose: To investigate static, dynamic, and concordance‐related features of the regional brain activity of young non‐disabled ICH patients. Study Type: Prospective. Subjects: Thirty‐three ICH patients (modified Rankin Scale score ≤2, 21% female, 46.36 ± 6.53) and 33 matched healthy controls (HCs) (21% female, 47.64 ± 6.16). Field Strength/Sequence: 3‐T, rs‐fMRI using gradient echo‐planar imaging, T1‐weighted imaging. Assessment: Neuropsychological and rs‐fMRI data were acquired from all participants. Amplitude of low‐frequency fluctuations (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), voxel‐mirrored homotopic connectivity, global signal correlation (GSCorr) and degree centrality (DC), and their dynamic and concordance‐related changes with sliding window analysis were calculated based on rs‐fMRI data at a whole‐brain level. The burden of cerebral small vascular diseases (cSVD) was assessed by cSVD scores. All hemorrhage lesions were delineated on normalized T1 images. Statistical Tests: Multiple regression models, a voxel‐level uncorrected P < 0.001, a cluster‐level false discovery rate (FDR) corrected q < 0.05, a re‐corrected qFDR <0.05 were considered significant. Pearson or Spearman correlation analyses between fMRI data and neurocognitive performance were performed. Results: Compared to HCs, ICH patients showed significant abnormal changes of ALFF, dynamic ALFF, fALFF, ReHo, dynamic ReHo, GSCorr, DC, and voxel‐wise concordance in multiple brain regions mainly including the bilateral cerebellar hemispheres, ipsilesional thalamus, and bilateral middle cingulum gyrus. The ALFF in the cerebellar posterior lobe and thalamus were significantly associated with attention (r = −0.481) and executive function (rho = −0.521) in ICH patients. Data Conclusion: Young non‐disabled ICH patients exhibit static, dynamic, and concordance‐related alterations of local brain activity, part of which shows associations with cognitive functions. These findings may help comprehensively understand the mechanism of cognitive impairment after ICH. Level of Evidence: 2 Technical Efficacy: Stage 3 [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment is increasingly recognized as an important comorbidity and complication of type 2 diabetes (T2D), affecting patients' quality of life and diabetes management. Dynamic brain activity indicators can reflect changes in key neural activity patterns of cognition and behavior. Purpose: To investigate dynamic functional connectivity (DFC) changes and spontaneous brain activity based on resting‐state functional magnetic resonance imaging (rs‐fMRI) in patients with T2D, exploring their correlations with clinical features. Study Type: Retrospective. Subjects: Forty‐five healthy controls (HCs) (22 males and 23 females) and 102 patients with T2D (57 males and 45 females). Field Strength/Sequence: 3.0 T/T1‐weighted imaging and rs‐fMRI with gradient‐echo planar imaging sequence. Assessment: Functional networks were created using independent component analysis. DFC states were determined using sliding window approach and k‐means clustering. Spontaneous brain activity was assessed using dynamic regional homogeneity (dReHo) variability. Statistical Tests: One‐way analysis of variance and post hoc analysis were used to compare the essential information including demographics, clinical data, and features of DFC and dReHo among groups. Diagnostic performance was assessed using receiver operating characteristic (ROC) curve. P‐values <0.05 were taken to indicate statistical significance. Results: T2D group had significantly decreased mean dwell time and fractional windows in state 4 compared to HC. T2D with mild cognitive impairment showed significantly increased dReHo variability in left superior occipital gyrus compared to T2D with normal cognition. Mean dwell time and number of fractional windows of state 4 both showed significant positive correlations with the Montreal cognitive assessment scores (r = 0.309; r = 0.308, respectively) and the coefficient of variation of dReHo was significantly positively correlated with high‐density lipoprotein cholesterol (r = 0.266). The integrated index had an area under the curve of 0.693 (95% confidence interval = 0.592–0.794). Data Conclusion: Differences in DFC and dynamic characteristic of spontaneous brain activity associated with T2D‐related functional impairment may serve as indicators for predicting symptom progression and assessing cognitive dysfunction. Level of Evidence: 2 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Liver, an important regulator of metabolic homeostasis, is critical for healthy brain function. In particular, age‐related neurodegenerative diseases seriously reduce the quality of life for the elderly. As population aging progresses rapidly, unraveling the mechanisms that effectively delay aging has become critical. Appropriate exercise is reported to improve aging‐related cognitive impairment. Whereas current studies focused on exploring the effect of exercise on the aging brain itself, ignoring the persistent effects of peripheral organs on the brain through the blood circulation. The aim of this paper is to summarize the communication and aging processes of the liver and brain and to emphasize the metabolic mechanisms of the liver–brain axis about exercise ameliorating aging‐related neurodegenerative diseases. A comprehensive understanding of the potential mechanisms about exercise ameliorating aging is critical for improving adaptation to age‐related brain changes and formulating effective interventions against age‐related cognitive decline. [ABSTRACT FROM AUTHOR]