Correlations between Immunoinflammatory Factor Levels and Cognitive Functions and Brain Structural Magnetic Resonance Imaging Features among Patients with Primary Schizophrenia.

BACKGROUND: Schizophrenia is associated with significant cognitive impairment. However, the pathophysiological mechanisms underlying cognitive dysfunction in schizophrenia remain unclear. Based on the latest concept of cognition, immunoinflammatory factors and structural magnetic resonance imaging (sMRI) features of the brain are considered markers of schizophrenia. This study explored the correlations between cognitive function and immunoinflammatory factors and sMRI in primary schizophrenia patients. METHODS: Non-interventional cross-sectional study was conducted, including 21 patients with primary schizophrenia, who were identified based on the Diagnostic and Statistical Manual, Fifth Edition (DSM-V) and grouped under the observation group. Thirty healthy volunteers with age, gender, hand dominance, and education duration matched with those of the primary schizophrenia patients were recruited to the control group. All subjects underwent sMRI examination. MATRICS consensus cognitive battery (MCCB) was employed to assess the cognitive functions among patients with primary schizophrenia. The levels of serum amyloid A (SAA), monocyte chemoattractant protein 1 (MCP-1), and chitinase-3-like protein 1 (YKL-40) were measured by means of enzyme-linked immunosorbent assay (ELISA). Pearson's correlation analysis was carried out to analyze the correlation between immunoinflammatory factor levels and cognitive functions as well as brain sMRI features. RESULTS: The scores for all MCCB items and the total score for the observation group were apparently lower than those for the control group (p < 0.001), while the YKL-40 and SAA levels were notably higher in the observation group (t = 3.406, p < 0.05; t = 5.656, p < 0.001). Compared to the control group, the observation group exhibited reduced volumes of left and right insular lobes, left and right anterior cingulate cortexes, left and right hippocampi, right parahippocampal gyrus, right amygdala, left inferior occipital lobe, left superior temporal lobe, left temporal pole, and left middle and inferior temporal lobes (p < 0.001). The levels of YKL-40 and SAA were both negatively correlated with MCCB score (r = -0.3668, p = 0.004; r = -0.8495, p < 0.001). The volumes of right insular lobe, left and right anterior cingulate cortexes, right parahippocampal gyrus, right amygdala, and gray matter in left middle temporal lobe were all negatively correlated with the levels of YKL-40 and SAA (p < 0.05). CONCLUSION: Cognitive impairment in patients with primary schizophrenia is associated with increased serum SAA and YKL-40 levels and decreased gray matter volume.

Relationship between triglyceride-glucose index and cognitive function among community-dwelling older adults: a population-based cohort study.

Background: The global increase in the aging population presents considerable challenges, particularly regarding cognitive impairment, a major concern for public health. This study investigates the association between the triglyceride-glucose (TyG) index, a measure of insulin resistance, and the risk of cognitive impairment in the elderly. Methods: This prospective cohort study enrolled 2,959 participants aged 65 and above from the 2015 and 2020 waves of the China Health and Retirement Longitudinal Study (CHARLS). The analysis employed a logistic regression model to assess the correlation between the TyG index and cognitive impairment. Results: The study included 2,959 participants, with a mean age of 71.2 ± 5.4 years, 49.8% of whom were female. The follow-up in 2020 showed a decrease in average cognitive function scores from 8.63 ± 4.61 in 2015 to 6.86 ± 5.45. After adjusting for confounding factors, a significant association was observed between TyG index quartiles and cognitive impairment. Participants in the highest quartile (Q4) of baseline TyG had a higher risk of cognitive impairment compared to those in the lowest quartile (Q1) (odds ratio [OR]: 1.97, 95% confidence intervals [CI]: 1.28-2.62, P<0.001). Conclusion: The study highlights a significant connection between elevated TyG index levels and cognitive impairment among older adults in China. These findings suggest that targeted interventions to reduce the TyG index could mitigate cognitive impairment and potentially lower the incidence of dementia.

A Multicenter Study of COPD and Cognitive Impairment: Unraveling the Interplay of Quantitative CT, Lung Function, HIF-1α, and Clinical Variables.

Purpose: The exact link between cognitive impairment (CI) and chronic obstructive pulmonary disease (COPD) is still limited. Thus, we aim to find the relationship and interaction of quantitative CT (QCT), lung function, HIF-1α, and clinical factors with the development of CI among COPD patients. Patients and Methods: A cross-sectional multicentre study was conducted from January 2022 to December 2023. We collected clinical data, spirometry, CT images, and venous blood samples from 114 COPD participants. Cognitive impairment assessment using the Montreal Cognitive Assessment Indonesian version (MoCA-Ina) with a cutoff value 26. The QCT analysis consists of lung density, airway wall thickness, pulmonary artery-to-aorta ratio (PA:A), and pectoralis muscles using 3D Slicer software. Serum HIF-1α analysis was performed using ELISA. Results: We found significant differences between %LAA-950, age, COPD duration, BMI, FEV1 pp, and FEV1/FVC among GOLD grades I-IV. Only education duration was found to correlate with CI (r = 0.40; p < 0.001). We found no significant difference in HIF-1α among GOLD grades (p = 0.149) and no correlation between HIF-1α and CI (p = 0.105). From multiple linear regression, we observed that the MoCA-Ina score was influenced mainly by %LAA-950 (p = 0.02) and education duration (p = 0.01). The path analysis model showed both %LAA and education duration directly and indirectly through FEV1 pp contributing to CI. Conclusion: We conclude that the utilization of QCT parameters is beneficial as it can identify abnormalities and contribute to the development of CI, indicating its potential utility in clinical decision-making. The MoCA-Ina score in COPD is mainly affected by %LAA-950 and education duration. Contrary to expectations, this study concludes that HIF-1α does not affect CI among COPD patients.

Plasma neurofilament light, glial fibrillary acid protein, and phosphorylated tau 181 as biomarkers for neuropsychiatric symptoms and related clinical disease progression.

BACKGROUND: Neuropsychiatric symptoms (NPS) are common in older people, may occur early in the development of dementia disorders, and have been associated with faster cognitive decline. Here, our objectives were to investigate whether plasma levels of neurofilament light chain (NfL), glial fibrillary acid protein (GFAP), and tau phosphorylated at threonine 181 (pTau181) are associated with current NPS and predict future NPS in non-demented older people. Furthermore, we tested whether the presence of NPS combined with plasma biomarkers are useful to predict Alzheimer's disease (AD) pathology and cognitive decline. METHODS: One hundred and fifty-one participants with normal cognition (n = 76) or mild cognitive impairment (n = 75) were examined in a longitudinal brain aging study at the Memory Centers, University Hospital of Lausanne, Switzerland. Plasma levels of NfL, GFAP, and pTau181 along with CSF biomarkers of AD pathology were measured at baseline. NPS were assessed through the Neuropsychiatric Inventory Questionnaire (NPI-Q), along with the cognitive and functional performance at baseline and follow-up (mean: 20 months). Different regression and ROC analyses were used to address the associations of interest. RESULTS: None of the three plasma biomarker was associated with NPS at baseline. Higher GFAP levels were associated with the presence of NPS at follow-up (OR = 2.8, p = .002) and both, higher NfL and higher GFAP with an increase in the NPI-Q severity score over time (ß = 0.25, p = .034 and ß = 0.30, p = .013, respectively). Adding NPS and the plasma biomarkers to a reference model improved the prediction of future NPS (AUC 0.72 to 0.88, p = .002) and AD pathology (AUC 0.78 to 0.87, p = .010), but not of cognitive decline (AUC 0.79 to 0.85, p = .081). CONCLUSION: Plasma NfL and GFAP are both associated with future NPS and NPS severity change. Considering the presence of NPS along with blood-based AD-biomarkers may improve the prediction of clinical progression of NPS over time and inform clinical decision-making in non-demented older people.

Circulating Angiogenic and Senescent T Lymphocytes in Ageing and Frailty.

BACKGROUND: There is a need to identify vascular and geroscience-relevant markers and mediators that can physiologically link ageing to vascular disease. There is evidence of specific T cell subsets, all influenced by age, that exert positive and negative effects on vascular health. CD31+, termed angiogenic T cells, have been linked to vascular repair whereas CD28null, termed senescent T cells, display pro-inflammatory and cytotoxic effector functions. OBJECTIVE: This study sought to determine the combined influence of increasing age and frailty status on these circulating CD31+ and CD28null T cell subsets. METHODS: This cross-sectional study recruited four different cohorts of men and women; young (20-30 years, n=22), older (65-75 years, n=17), robust non-frail (76+ years, n=17), and frail (76+ years, n=15) adults. Frailty was determined using the Fried Frailty method. T cell subsets were determined by whole blood flow cytometry based on the expression of CD3, CD4, CD8, CD31 and CD28. Cognitive impairment (CI) was measured via the Montreal Cognitive Assessment test. RESULTS: Whether expressed as circulating counts or as a % of total T cells, there was a progressive decrease (p<0.05) in CD31+ T cells with increasing age but paradoxically higher values (p<0.05) in the frail compared to the robust non-frail group. These changes were similar in the CD4+ and CD8+ fractions. CD28null T cells were considerably higher (p<0.05) in the frail compared to the robust non-frail group, including in the CD8+ (47% vs 29%, p<0.05) and CD4+ (4% vs 1%, p<0.05) fractions. CD28null T cell percentage was also higher (p<0.05) in those with moderate CI compared to mild CI and normal function. CONCLUSION: CD8+CD28null T cells are considerably elevated in frailty and with cognitive impairment and may serve as a useful target for intervention. Currently, the utility of CD31+ T cells as an ageing biomarker may be confined to healthy ageing cohorts.

[Correlations between serum BDNF, IL-18 and hs-CRP levels in patients with acute cerebral infarction and vascular cognitive impairment].

OBJECTIVE: To explore the correlations between serum levels of brain-derived neurotrophic factor (BDNF), interleukin-18 (IL-18) and hypersensitivity C-reactive protein (hs-CRP) in patients with acute cerebral infarction and vascular cognitive impairment (VCI), and to provide some clinical bases for early prevention of VCI. METHODS: A total of 160 patients with acute cerebral infarction admitted in Department of Neurology of Jincheng People' s Hospital from May 2019 to April 2020 were enrolled in this study and were devided into three groups according to whether or not combined with cognitive impairment, including no cognitive impairment group (NCI, 57 cases), vascular cognitive impairment no dementia group (VCIND, 56 cases) and vascular dementia group (VaD, 47 cases). The cognitive function of all the patients were evaluated by Montreal cognitive assessment (MoCA). The National Institute of Health stroke scale (NIHSS) was used to assess the degree of neurological deficit (mild-, moderate-, severe-neurologic deficit group). The infarct size was calculated by Pullicino' s method (small-, middle-, large-infarct group). The levels of serum BDNF and IL-18 were measured by enzyme-linked immunosorbent assay (ELISA), and serum levels of hs-CRP were measured by immunoturbidimetry during the acute phase (0-7 d), recovery period (15-30 d) and 6 months after cerebral infarction. The effects of varying degrees of neurological deficits and different size of infarction on BDNF, IL-18 and hs-CRP were observed. The levels of serum BDNF, IL-18 and hs-CRP in the patients of the three groups with acute, convalescent and six-month cerebral infarction were compared, and their correlations with VCI were analyzed. RESULTS: Serum BDNF level and MoCA scores in mild-neurologic deficit group and small-infarct group were significantly higher than those in moderate- and severe-deficit group, middle- and large-infarct group, respectively (P < 0.05). Their levels of IL-18 and hs-CRP were significantly lower than those in moderate- and severe-deficit group, middle- and large-infarct group, respectively (P < 0.05). The levels of serum BDNF in NCI group, VCIND group and VaD group during the acute phase, convalescence and 6 months after cerebral infarction were in a significant decline, and the differences during the acute phase and recovery period were statistically significant (P < 0.05). The levels of IL-18 and hs-CRP during the acute phase, recovery period and 6 months after cerebral infarction showed a significant increasing trend with significance (P < 0.05). Correlation analysis revealed that the levels of BDNF was positively correlated with MoCA scores but negatively correlated with the severity of cognitive impairment while the expression levels of IL-18 and hs-CRP were negatively correlated with MoCA scores but positively correlated with the severity of cognitive impairment. CONCLUSION: Serum BDNF, IL-18 and hs-CRP are involved in the pathological process of occurrence and development of VCI in the patients with acute cerebral infarction. BDNF has a protective effect on VCI while IL-18 and hs-CRP cause severe cognitive impairment. The levels of serum BDNF、IL-18 and hs-CRP in the patients with acute ischemic cerebral infarction are closely related to the severity of cognitive impairment and can be used as biomarkers of early diagnosis of VCI.

The Inflammasome Adaptor Protein ASC in Plasma as a Biomarker of Early Cognitive Changes.

Dementia is a group of symptoms including memory loss, language difficulties, and other types of cognitive and functional impairments that affects 57 million people worldwide, with the incidence expected to double by 2040. Therefore, there is an unmet need to develop reliable biomarkers to diagnose early brain impairments so that emerging interventions can be applied before brain degeneration. Here, we performed biomarker analyses for apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and amyloid-ß 42/40 (Aß42/40) ratio in the plasma of older adults. Participants had blood drawn at baseline and underwent two annual clinical and cognitive evaluations. The groups tested either cognitively normal on both evaluations (NN), cognitively normal year 1 but cognitively impaired year 2 (NI), or cognitively impaired on both evaluations (II). ASC was elevated in the plasma of the NI group compared to the NN and II groups. Additionally, Aß42 was increased in the plasma in the NI and II groups compared to the NN group. Importantly, the area under the curve (AUC) for ASC in participants older than 70 years old in NN vs. NI groups was 0.81, indicating that ASC is a promising plasma biomarker for early detection of cognitive decline.

Association of Changes in C-Reactive Protein Level Trajectories Through Early Adulthood With Cognitive Function at Midlife: The CARDIA Study.

BACKGROUND AND OBJECTIVES: Late-life inflammation has been linked to dementia risk and preclinical cognitive decline, but less is known about early adult inflammation and whether this could influence cognition in midlife. We aimed to identify inflammation levels through early adulthood and determine association of these trajectories with midlife cognition. METHODS: We used data from the Coronary Artery Risk Development in Young Adults study to identify inflammation trajectories (C-reactive protein [CRP] level <10 mg/L) over 18 years through early adulthood (age range 24-58) in latent class analysis and to assess associations with cognition 5 years after the last CRP measurement (age range 47-63). Six cognitive domains were evaluated from tests of verbal memory, processing speed, executive function, verbal and category fluency, and global cognition; poor cognitive performance was defined as a decline of ≥1 SD less than the mean on each domain. The primary outcome was poor cognitive performance. Logistic regression was used to adjust for demographics, smoking, alcohol use, physical activity, and APOE 4 status. RESULTS: Among 2,364 participants, the mean (SD) age was 50.2 (3.5) years; 55% were female, and 57% were White. Three CRP trajectories emerged over 18 years: lower stable (45%), moderate/increasing (16%), and consistently higher (39%). Compared with lower stable CRP, both consistently higher (adjusted odds ratio [aOR] 1.67, 95% CI 1.23-2.26) and moderately/increasing (aOR 2.04, 95% CI 1.40-2.96) CRP had higher odds of poor processing speed; consistently higher CRP additionally had higher odds of poor executive function (aOR 1.36, 95% CI 1.00-1.88). For memory (moderately/increasing aOR 1.36, 95% CI 1.00-1.88; consistently higher aOR 1.18, 95% CI 0.90-1.54), letter fluency (moderately/increasing aOR 1.00, 95% CI 0.69-1.43; consistently higher aOR 1.05, 95% CI 0.80-1.39), category fluency (moderately/increasing aOR 1.16, 95% CI 0.82-1.63; consistently higher aOR 1.11, 95% CI 0.85-1.45), or global cognition (moderately/increasing aOR 1.16, 95% CI 0.82-1.63; consistently higher aOR 1.11, 95% CI 0.85-1.45), no association was observed. DISCUSSION: Consistently higher or moderate/increasing inflammation starting in early adulthood may lead to worse midlife executive function and processing speed. Study limitations include selection bias due to loss to follow-up and reliance on CRP as the only inflammatory marker. Inflammation is important for cognitive aging and may begin much earlier than previously known.

Performance of Fully-Automated High-Throughput Plasma Biomarker Assays for Alzheimer's Disease in Amnestic Mild Cognitive Impairment Subjects.

INTRODUCTION: Novel plasma biomarkers are promising for identifying Alzheimer's disease (AD) pathological processes in vivo, but most currently employed assays have limitations precluding widespread use. METHODS: CSF and plasma samples were collected from seventy amnestic mild cognitive impairment (aMCI) subjects, stratified as A+ and A-. CSF Aß40, Aß42, p-tau181 and t-tau and plasma Aß40, Aß42 and p-tau181 quantification were conducted using the Lumipulse G assays (Fujirebio), to evaluate the diagnostic performance of plasma biomarkers and assess their associations with CSF biomarkers. RESULTS: All plasma biomarkers except Aß40 showed a very good accuracy in distinguishing A+ aMCI from A- aMCI, Aß42/p-tau181 ratio being the most accurate (AUC 0.895, sensitivity 95.1%, specificity 82.8%). Plasma biomarkers levels were significantly associated with CSF biomarkers concentration. DISCUSSION: High-throughput and fully-automated plasma assays could be helpful in discriminating with high accuracy between aMCI in the AD continuum and aMCI unlikely due to AD in clinical settings.

Mediation of depressive symptoms in the association between blood urea nitrogen to creatinine ratio and cognition among middle-aged and elderly adults: evidence from a national longitudinal cohort study.

BACKGROUND: The relationships between BUNCr (blood urea nitrogen and creatinine ratio) and cognitive function, as well as depressive symptoms, remain unclear. We aim to investigate the association between BUNCr and cognition, as well as depressive symptoms, and to identify the mechanisms underlying these relationships. METHODS: We utilized data from the China Health and Retirement Longitudinal Study (CHARLS) from 2015 to 2020. Cognitive function was assessed using the Telephone Interview of Cognitive Status (TICS) scale, while depressive symptoms were assessed using the 10-item Center for Epidemiologic Studies Depression Scale (CES-D-10). We employed multivariate linear regression models to examine the association between BUNCr and cognitive function, as well as depressive symptoms. Additionally, causal mediation analysis was conducted to identify potential mediation effects of depressive symptoms between BUNCr and cognition. RESULTS: We observed a negative association between BUNCr and cognitive function (coefficient: -0.192; 95% confidence interval [CI]: -0.326 ∼ -0.059) and a positive relationship between BUNCr and depressive symptoms (coefficient: 0.145; 95% CI: 0.006 ∼ 0.285). In addition, the causal mediation analysis revealed that depressive symptoms (proportion mediated: 7.0%) significantly mediated the association between BUNCr and cognition. CONCLUSION: Our study has unveiled that BUNCr is inversely associated with cognitive function and positively linked to depressive symptoms. Moreover, we found that depressive symptoms significantly mediated the association between BUNCr and cognition. These findings provide new evidence and insights for the prevention and management of cognitive function and dementia.

Non-linear association of liver enzymes with cognitive performance in the elderly: A cross-sectional study.

BACKGROUND: Although liver metabolic dysfunction has been found to potentially elevate susceptibility to cognitive impairment and dementia, there is still insufficient evidence to explore the non-linear association of liver enzymes with cognitive performance. Therefore, we aimed to elucidate the non-linear relationship between liver enzymes and cognitive performance. METHODS: In this cross-sectional study, 2764 individuals aged ≥ 60 who participated in the National Health and Nutrition Survey (NHANES) between 2011 and 2014 were included. The primary data comprised liver enzyme levels (alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), AST/ALT ratio, and gamma-glutamyl transferase (GGT)), and cognitive performance was the major measured outcome. The associations were analyzed using weighted multivariate logistic regression, subgroup analysis, a generalized additive model, smooth fitting curves, and threshold effects. RESULTS: The results of the fully adjusted model indicated that ALP was negatively associated with the animal fluency test (AFT) score (OR = 1.48, 95% CI: 1.11-1.98), whereas ALT demonstrated a positive association with the consortium to establish a registry for Alzheimer's disease (CERAD) test score (OR = 0.72, 95% CI: 0.53-0.97). Additionally, the AST/ALT ratio was negatively associated with the global cognitive test (OR = 2.39, 95% CI: 1.53-3.73), CERAD (OR = 2.61, 95% CI: 1.77-3.84), and digit symbol substitution test (DSST) scores (OR = 2.51, 95% CI: 1.57-4.02). GGT was also negatively associated with the AFT score (OR = 1.16, 95% CI: 1.01-1.33) in unadjusted model. A non-linear relationship was observed between liver enzymes and the risk of cognitive impairment as assessed by the global cognitive test. Specifically, when ALP > 60 U/L, 0.77 < AST/ALT < 1.76, and 25 < GGT < 94 U/L, higher liver enzyme levels were significantly associated with an elevated cognitive impairment risk, while a lower cognitive impairment risk when ALT level was > 17 U/L. CONCLUSIONS: There is a non-linear relationship between liver enzymes and cognitive performance, indicating that liver enzyme levels should be maintained within a certain level to mitigate the risk of cognitive impairment.

Association Between Subclinical Thyroid Dysfunction and Cognitive Decline: Findings From the ELSA-Brasil Study.

BACKGROUND: Thyroid dysfunction has been associated with cognitive decline and dementia. However, the role of subtle thyroid hormone alterations in cognitive function is still debatable. METHODS: Participants without overt thyroid dysfunction aged 35-74 years at baseline were evaluated in 3 study waves (2008-2010, 2012-2014, and 2017-2019). We assessed baseline thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3). Cognitive performance was evaluated every 4 years in each wave using 10-word immediate and late recall, word recognition, semantic (animals category) and phonemic (letter f) verbal fluency, and the trail-making B-version tests. A global composite z-score was derived from these tests. The associations of TSH, FT4, and FT3 levels with cognitive decline over time were evaluated using linear mixed-effect models adjusted for sociodemographic, clinical, and lifestyle variables. RESULTS: In 9 524 participants (mean age 51.2 ±â€…8.9 years old, 51% women, 52% White), there was no association between baseline TSH, FT4, and FT3 levels and cognitive decline during the follow-up. However, increase in FT4 levels over time was associated with faster memory (ß = -0.004, 95% CI = -0.007; -0.001, p = .014), verbal fluency (ß = -0.003, 95% CI = -0.007; -0.0005, p = .021), executive function (ß = -0.004, 95% CI = -0.011; -0.003, p < .001), and global cognition decline (ß = -0.003, 95% CI = -0.006; -0.001, p = .001). Decrease in FT4 levels over time was associated with faster verbal fluency (ß = -0.003, 95% CI = -0.007; -0.0004, p = .025) and executive function (ß = -0.004, 95% CI = -0.007; -0.0003, p = .031) decline. CONCLUSIONS: An increase or decrease in FT4 levels over time was associated with faster cognitive decline in middle-aged and older adults without overt thyroid dysfunction during 8 years of follow-up.

Relationship between serum levels of folic acid and homocysteine with cognitive impairment in patients diagnosed with multiple sclerosis.

Multiple Sclerosis (MS), one of the most common neurological diseases, plays a major role in the ailments of adults. Studies on the role of homocysteine (Hcy) and folic acid in causing cognitive disorders in patients diagnosed with MS are still ongoing. This study aimed to evaluate the serum levels of folic acid and Hcy related to cognitive impairment in patients with multiple sclerosis. This prospective clinical study was conducted on 57 patients diagnosed with MS who were referred to Firoozgar Hospital, Tehran, Iran (Between November 2019 and September 2021). Demographic information and clinical characteristics of enrolled patients were recorded in a predesigned checklist. These characteristics were comprised of outcomes related to the Brief International Cognitive Assessment for MS, and the patient's Hcy and acid folic levels. Data were analyzed using SPSS version 25. Out of 57 enrolled patients, 39 subjects (68.4%) were female and 18 subjects (31.6%) were male, with a mean age of 36.87 ±â€…9.40 years old. In terms of disease time span, there was a mean duration of 3.80 ±â€…4.94 years (range: 1-23 years). There were no significant differences between the mean score of Brief International Cognitive Assessment for MS scale with patient's sex (P value: .88), and disease duration of patients (P value: .86). There was no significant relationship between the serum levels of acid folic and Hcy with cognitive impairment (P value > .05). The study results revealed that there were no significant relationships between the folic acid, Hcy levels, disease duration, and the type of MS disease with the severity of cognitive impairment. More randomized controlled clinical trials are needed to confirm the relationships between the folic acid and Hcy levels with cognitive impairment in patients with MS.

Association between reduced plasma BDNF concentration and MMSE scores in both chronic schizophrenia and mild cognitive impairment.

Reduced brain derived neurotrophic factor (BDNF) concentration is reported to be associated with a cognitive decline in schizophrenia, depending on the stage of the disease. Aim of the study was to examine the possible association between plasma BDNF and cognitive decline in chronic stable schizophrenia and mild cognitive impairment (MCI). The study included 123 inpatients of both sexes with schizophrenia, 123 patients with MCI and 208 healthy control subjects. Cognitive abilities were assessed using mini mental state examination (MMSE), Clock Drawing test (CDT) and cognitive subscale of the Positive and Negative Syndrome Scale (PANSS). Plasma BDNF concentration was determined using ELISA. BDNF concentration was lower in patients with schizophrenia and MCI compared to age-matched healthy controls and was similar in carriers of different BDNF Val/66Met genotypes. The MMSE and CDT scores were lower in patients with schizophrenia compared to healthy controls and subjects with MCI. Reduced plasma BDNF was significantly associated with lower MMSE scores in all subjects. BDNF concentration in patients with schizophrenia was not affected by clinical and demographic factors. BDNF Val66Met polymorphism was not associated with the MMSE scores in all participants. Further studies should include longitudinal follow-up and other cognitive scales to confirm these results and offer cognition-improving strategies to prevent cognitive decline in chronic schizophrenia.

Serum dysregulation of serine and glycine metabolism as predictive biomarker for cognitive decline in frail elderly subjects.

Frailty is a common age-related clinical syndrome characterized by a decline in the function of multiple organ systems, increased vulnerability to stressors, and a huge socio-economic burden. Despite recent research efforts, the physiopathological mechanisms underlying frailty remain elusive and biomarkers able to predate its occurrence in the early stages are still lacking. Beyond its physical component, cognitive decline represents a critical domain of frailty associated with higher risk of adverse health outcomes. We measured by High-Performance Liquid Chromatography (HPLC) a pool of serum amino acids including L-glutamate, L-aspartate, glycine, and D-serine, as well as their precursors L-glutamine, L-asparagine, and L-serine in a cohort of elderly subjects encompassing the entire continuum from fitness to frailty. These amino acids are known to orchestrate excitatory and inhibitory neurotransmission, and in turn, to play a key role as intermediates of energy homeostasis and in liver, kidney, muscle, and immune system metabolism. To comprehensively assess frailty, we employed both the Edmonton Frail Scale (EFS), as a practical tool to capture the multidimensionality of frailty, and the frailty phenotype, as a measure of physical function. We found that D-serine and D-/Total serine ratio were independent predictors of EFS but not of physical frailty. Furthermore, higher levels of glycine, glycine/L-serine and D-/Total serine were associated with worse cognition and depressive symptoms in the frail group. These findings suggest that changes in peripheral glycine and serine enantiomers homeostasis may represent a novel biochemical correlate of frailty.

Insufficient Plasma Melatonin and Its Association With Neuropsychiatric Impairments in Patients With T2DM.

Purpose: Type 2 diabetes mellitus (T2DM) is associated with multiple neuropsychiatric impairments, including cognitive dysfunction, and melatonin (MLT) plays a crucial role in maintaining normal neuropsychiatric functions. This study is aimed at investigating the change in plasma MLT levels and its association with neuropsychiatric impairments in T2DM patients. Methods: One hundred twenty-six T2DM patients were recruited, and their demographics and clinical data were collected. Apart from the plasma glycated hemoglobin (HbA1c) levels and other routine metabolic indicators, the plasma concentrations of MLT, C-reactive protein (CRP), Interleukin 6 (IL-6), soluble myeloid triggered receptor 1 (sTREM 1), and receptor 2 (sTREM 2) were measured. Moreover, the executive function and depressive tendency were evaluated via the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) and the Epidemiological Research Center Depression Scale (CES-D), respectively. Result: Compared with the low HbA1c group, the T2DM patients in the high HbA1c group presented lower plasma MLT levels but higher plasma concentrations of inflammatory biomarker levels, together with higher scores in the BRIEF-A and CES-D scales. Moreover, results of the Pearson correlation test showed that the plasma MLT levels were negatively correlated with the BRIEF-A and CES-D scores, as well as plasma concentrations of HbA1c and inflammatory indications, indicating that MLT may mediate their neuroinflammation and neuropsychiatric impairments. Furthermore, the ROC curve results indicated that plasma MLT levels have a predictive effect on executive impairment and depressive status in T2DM patients. Conclusion: MLT levels decreased in patients with T2DM and were associated with neuropsychiatric impairments and inflammatory status, and MLT might be developed as a therapeutic agent and predictive indicator for T2DM-associated executive impairment and depression status.

Predicting Longitudinal Cognitive Decline and Alzheimer's Conversion in Mild Cognitive Impairment Patients Based on Plasma Biomarkers.

The increasing burden of Alzheimer's disease (AD) emphasizes the need for effective diagnostic and therapeutic strategies. Despite available treatments targeting amyloid beta (Aß) plaques, disease-modifying therapies remain elusive. Early detection of mild cognitive impairment (MCI) patients at risk for AD conversion is crucial, especially with anti-Aß therapy. While plasma biomarkers hold promise in differentiating AD from MCI, evidence on predicting cognitive decline is lacking. This study's objectives were to evaluate whether plasma protein biomarkers could predict both cognitive decline in non-demented individuals and the conversion to AD in patients with MCI. This study was conducted as part of the Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD), a prospective, community-based cohort. Participants were based on plasma biomarker availability and clinical diagnosis at baseline. The study included MCI (n = 50), MCI-to-AD (n = 21), and cognitively unimpaired (CU, n = 40) participants. Baseline plasma concentrations of six proteins-total tau (tTau), phosphorylated tau at residue 181 (pTau181), amyloid beta 42 (Aß42), amyloid beta 40 (Aß40), neurofilament light chain (NFL), and glial fibrillary acidic protein (GFAP)-along with three derivative ratios (pTau181/tTau, Aß42/Aß40, pTau181/Aß42) were analyzed to predict cognitive decline over a six-year follow-up period. Baseline protein biomarkers were stratified into tertiles (low, intermediate, and high) and analyzed using a linear mixed model (LMM) to predict longitudinal cognitive changes. In addition, Kaplan-Meier analysis was performed to discern whether protein biomarkers could predict AD conversion in the MCI subgroup. This prospective cohort study revealed that plasma NFL may predict longitudinal declines in Mini-Mental State Examination (MMSE) scores. In participants categorized as amyloid positive, the NFL biomarker demonstrated predictive performance for both MMSE and total scores of the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet (CERAD-TS) longitudinally. Additionally, as a baseline predictor, GFAP exhibited a significant association with cross-sectional cognitive impairment in the CERAD-TS measure, particularly in amyloid positive participants. Kaplan-Meier curve analysis indicated predictive performance of NFL, GFAP, tTau, and Aß42/Aß40 on MCI-to-AD conversion. This study suggests that plasma GFAP in non-demented participants may reflect baseline cross-sectional CERAD-TS scores, a measure of global cognitive function. Conversely, plasma NFL may predict longitudinal decline in MMSE and CERAD-TS scores in participants categorized as amyloid positive. Kaplan-Meier curve analysis suggests that NFL, GFAP, tTau, and Aß42/Aß40 are potentially robust predictors of future AD conversion.

Neutrophil-Lymphocytes Ratio as Potential Early Marker for Alzheimer's Disease.

Background: Neutrophil-lymphocyte ratio (NLR) is a noninvasive, inexpensive, and easily applicable marker of inflammation. Since immune dysregulation leading to inflammation is regarded as a hallmark of dementia, in particular Alzheimer's disease (AD), we decided to investigate the potentials of NLR as a diagnostic and predictive biomarker in this clinical setting. Materials and Methods: NLR was measured in the blood of patients with AD (n = 103), amnestic type mild cognitive impairment (aMCI, n = 212), vascular dementia (VAD, n = 34), and cognitively healthy Controls (n = 61). One hundred twelve MCI patients underwent a regular clinical follow-up. Over a 36-months median follow-up, 80 remained stable, while 32 progressed to overt dementia. Results: NLR was higher in patients with aMCI or dementia compared to Controls; however, the difference was statistically significant only for aMCI (+13%, p=0.04) and AD (+20%, p=0.03). These results were confirmed by multivariate logistic analysis, which showed that high NLR was associated with an increase in the likelihood of receiving a diagnosis of aMCI (odd ratio (OR): 2.58, 95% confidence interval (CI): 1.36-4.89) or AD (OR: 3.13, 95%CI: 1.47-6.70), but not of VAD. NLR did not differ when comparing stable vs. progressing aMCI. Conclusions: This is the first report showing that NLR is significantly increased in MCI and AD but not in VAD. We also found that NLR was unable to predict the conversion from aMCI to AD. Further research on larger cohorts is warranted to definitely ascertain the application of NLR as a possible marker for aMCI and AD.

Divergent Roles of APOAI and APOM in the Identification of Alcohol Use Disorder and Their Association With Inflammation and Cognitive Decline: A Pilot Study.

BACKGROUND: Alcohol use disorder (AUD) courses with inflammation and cognitive decline. Apolipoproteins have emerged as novel target compounds related to inflammatory processes and cognition. METHODS: A cross-sectional study was performed on abstinent AUD patients with at least 1 month of abstinence (n = 33; 72.7% men) and healthy controls (n = 34; 47.1% men). A battery of plasma apolipoproteins (APOAI, APOAII, APOB, APOCII, APOE, APOJ, and APOM), plasma inflammatory markers (LPS, LBP), and their influence on cognition and presence of the disorder were investigated. RESULTS: Higher levels of plasma APOAI, APOB, APOE, and APOJ, as well as the proinflammatory LPS, were observed in the AUD group, irrespective of sex, whereas APOM levels were lower vs controls. Hierarchical logistic regression analyses, adjusting for covariates (age, sex, education), associated APOM with the absence of cognitive impairment in AUD and identified APOAI and APOM as strong predictors of the presence or absence of the disorder, respectively. APOAI and APOM did not correlate with alcohol abuse variables or liver status markers, but they showed an opposite profile in their associations with LPS (positive for APOAI; negative for APOM) and cognition (negative for APOAI; positive for APOM) in the entire sample. CONCLUSIONS: The HDL constituents APOAI and APOM were differentially regulated in the plasma of AUD patients compared with controls, playing divergent roles in the disorder identification and associations with inflammation and cognitive decline.

Association between the serum uric acid/serum creatinine ratio and cognitive function in older adults: NHANES in the United States.

Cognitive impairment can potentially become a significant health concern in older adults. However, early effective diagnostic methods are still lacking. Therefore, we utilized the NHANES database in the US to investigate the relationship between serum uric acid to serum creatinine (SUA/SCR) ratio and cognitive impairment. In our study, a total of 3874 participants were included (2001-2002, 2011-2014). Weighted t tests or chi-square tests were utilized to analyze the basic characteristics of the population. Weighted logistic regression analysis, smooth-fit curves, threshold effects, and subgroup analysis were conducted to investigate the correlation between the SUA/SCR and cognitive impairment. In this study, the SUA/SCR was significantly lower in individuals with cognitive impairment. The logistic regression model, after adjusting for all covariates, revealed that the Q2-Q4 were 0.65 (95% CI 0.49, 0.86), 0.60 (95% CI 0.40, 0.90), 0.55 (95% CI 0.39, 0.77) respectively. This indicates that participants in the Q4 had a 45% reduced risk of cognitive impairment. Smooth-fit curves and threshold effect analysis revealed a nonlinear relationship between SUA/SCR and cognitive impairment, with a turning point at 4.13. Subgroup analysis showed no statistically significant differences in the relationship between SUA/SCR and cognitive impairment among different subgroups (P > 0.05). Our findings indicate a negative correlation between the SUA/SCR and the risk of cognitive impairment in the population of adults aged 60 and above in the US. This suggests that the SUA/SCR holds promise as a potential indicator for cognitive impairment.