Preoperative Serum Metabolites and Potential Biomarkers for Perioperative Cognitive Decline in Elderly Patients.
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ABSTRACT:
SUBMITTER: Lu W
PROVIDER: S-EPMC8174563 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:US studies suggest that leptin, a fat-derived hormone, may be protective against the development of dementia. OBJECTIVE:To investigate the complex relationship between leptin levels and cognitive decline in elderly Italians. METHODS:We studied circulating fasting leptin levels in 809 elderly adults free from dementia who participated in the prospective Italian population-based InCHIANTI study between 1998 and 2009 (mean follow-up of 8.0 years). Global cognitive decline was defined as a reduction of ?5 points on the Mini-Mental State Examination (MMSE). Trail-Making Tests A and B were also incorporated, with cognitive decline defined as discontinued testing or the worst 10% of change from baseline. We also investigated whether any association could be explained by midlife weight and whether cognitive decline was associated with changing leptin levels. RESULTS:The multivariate adjusted relative risk ([RR]; 95% confidence interval [CI]) of cognitive decline on the MMSE was 0.84 (95% CI 0.73-0.97) in relation to baseline sex-standardized log-leptin levels. High leptin levels showed a non-significant trend toward a reduced risk of decline on the Trail-Making Tests A (RR = 0.85, 95% CI 0.71-1.02) and B (RR = 0.90, 0.79-1.02). Adjusting for midlife weight or change in weight did not alter the pattern of results, and cognitive decline was not associated with changing leptin levels. CONCLUSIONS:High leptin levels were independently associated with a reduced risk of cognitive decline in elderly Italians.
| S-EPMC5873309 | biostudies-literature
Project description:IntroductionThe evidence on the impact of bladder antimuscarinics initiation on cognitive function in older adults is inconsistent.MethodsA retrospective analysis of data from the National Alzheimer's Coordinating Center (NACC) on enrollees 65 years and older evaluated the association between antimuscarinic initiation and cognitive decline. We defined decline from baseline (yes/no) for cognitive assessments included in the NACC Uniform Data Set 2.0 battery. New users were matched on year of enrollment and time in the cohort to randomly selected nonusers. Analyses were conducted using inverse probability of treatment weights based on baseline propensity scores.ResultsOur analyses included 698 new users and 7037 nonusers. The odds ratio (OR) and 95% confidence interval for cognitive decline in users as compared to nonusers was 1.4 (1.19-1.65) for Mini-Mental State Examination (MMSE), and 1.21 (1.03-1.42) for Clinical Dementia Rating; in addition, the odds of decline were 20% higher in users compared to nonusers for semantic memory/language and executive function. The effect estimate for MMSE was 1.94 (1.3-2.91) for those with mild cognitive impairment, 1.26 (0.99-1.62) in those with normal cognition, and 1.44 (1.04-1.99) in those with dementia at baseline.DiscussionOur results show that antimuscarinic initiation is associated with cognitive decline and raise questions about their use, especially in those with impaired cognition.
| S-EPMC5408467 | biostudies-literature
Project description:Plasma biomarkers of amyloid, tau, and neurodegeneration (ATN) need to be characterized in cognitively unimpaired (CU) elderly individuals. We therefore tested if plasma measurements of amyloid-β (Aβ)42/40, phospho-tau217 (P-tau217), and neurofilament light (NfL) together predict clinical deterioration in 435 CU individuals followed for an average of 4.8 ± 1.7 years in the BioFINDER study. A combination of all three plasma biomarkers and basic demographics best predicted change in cognition (Pre-Alzheimer's Clinical Composite; R2 = 0.14, 95% CI [0.12-0.17]; P < 0.0001) and subsequent AD dementia (AUC = 0.82, 95% CI [0.77-0.91], P < 0.0001). In a simulated clinical trial, a screening algorithm combining all three plasma biomarkers would reduce the required sample size by 70% (95% CI [54-81]; P < 0.001) with cognition as trial endpoint, and by 63% (95% CI [53-70], P < 0.001) with subsequent AD dementia as trial endpoint. Plasma ATN biomarkers show usefulness in cognitively unimpaired populations and could make large clinical trials more feasible and cost-effective.
| S-EPMC8196018 | biostudies-literature
Project description:Plasma-based biomarkers present a promising approach in the research and clinical practice of Alzheimer's disease as they are inexpensive, accessible and minimally invasive. In particular, prognostic biomarkers of cognitive decline may aid in planning and management of clinical care. Although recent studies have demonstrated the prognostic utility of plasma biomarkers of Alzheimer pathology or neurodegeneration, such as pTau-181 and NF-L, whether other plasma biomarkers can further improve prediction of cognitive decline is undetermined. We conducted an observational cohort study to determine the prognostic utility of plasma biomarkers in predicting progression to dementia for individuals presenting with mild cognitive impairment due to probable Alzheimer's disease. We used the Olink™ Proximity Extension Assay technology to measure the level of 460 circulating proteins in banked plasma samples of all participants. We used a discovery data set comprised 60 individuals with mild cognitive impairment (30 progressors and 30 stable) and a validation data set consisting of 21 stable and 21 progressors. We developed a machine learning model to distinguish progressors from stable and used 44 proteins with significantly different plasma levels in progressors versus stable along with age, sex, education and baseline cognition as candidate features. A model with age, education, APOE genotype, baseline cognition, plasma pTau-181 and 12 plasma Olink protein biomarker levels was able to distinguish progressors from stable with 86.7% accuracy (mean area under the curve = 0.88). In the validation data set, the model accuracy was 78.6%. The Olink proteins selected by the model included those associated with vascular injury and neuroinflammation (e.g. IL-8, IL-17A, TIMP-4, MMP7). In addition, to compare these prognostic biomarkers to those that are altered in Alzheimer's disease or other types of dementia relative to controls, we analyzed samples from 20 individuals with Alzheimer, 30 with non-Alzheimer dementias and 34 with normal cognition. The proteins NF-L and PTP-1B were significantly higher in both Alzheimer and non-Alzheimer dementias compared with cognitively normal individuals. Interestingly, the prognostic markers of decline at the mild cognitive impairment stage did not overlap with those that differed between dementia and control cases. In summary, our findings suggest that plasma biomarkers of inflammation and vascular injury are associated with cognitive decline. Developing a plasma biomarker profile could aid in prognostic deliberations and identify individuals at higher risk of dementia in clinical practice.
| S-EPMC9257670 | biostudies-literature
Project description: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.
| S-EPMC11233661 | biostudies-literature
Project description:BackgroundChronic postoperative pain affects approximately 20% of patients with knee osteoarthritis after total knee replacement. Circulating microRNAs can be found in serum and might act as biomarkers in a variety of diseases. The current study aimed to investigate the preoperative expression of circulating microRNAs as potential predictive biomarkers for the development of chronic postoperative pain in the year following total knee replacement.MethodsSerum samples, collected preoperatively from 136 knee osteoarthritis patients, were analyzed for 21 circulatory microRNAs. Pain intensity was assessed using a visual analog scale before and one year after total knee replacement. Patients were divided into a low-pain relief group (pain relief percentage <30%) and a high-pain relief group (pain relief percentage >30%) based on their pain relief one year after total knee replacement, and differences in microRNAs expression were analyzed between the two groups.ResultsWe found that three microRNAs were preoperatively dysregulated in serum in the low-pain relief group compared with the high-pain relief group. MicroRNAs hsa-miR-146a-5p, -145-5p, and -130 b-3p exhibited fold changes of 1.50, 1.55, and 1.61, respectively, between the groups (all P values < 0.05). Hsa-miR-146a-5p and preoperative pain intensity correlated positively with postoperative pain relief (respectively, R = 0.300, P = 0.006; R = 0.500, P < 0.001).DiscussionThis study showed that patients with a low postoperative pain relief present a dysregulation of circulating microRNAs. Altered circulatory microRNAs expression correlated with postoperative pain relief, indicating that microRNAs can serve as predictive biomarkers of pain outcome after surgery and hence may foster new strategies for preventing chronic postoperative pain after total knee replacement (TKR).
| S-EPMC7543153 | biostudies-literature
Project description:With ever-increasing elder populations, age-related cognitive decline, which is characterized as a gradual decline in cognitive capacity in the aging process, has turned out to be a mammoth public health concern. Since genetic information has become increasingly important to explore the biological mechanisms of cognitive decline, the search for genetic biomarkers of cognitive aging has received much attention. There is growing evidence that single-nucleotide polymorphisms (SNPs) within the ADAMTS9, BDNF, CASS4, COMT, CR1, DNMT3A, DTNBP1, REST, SRR, TOMM40, circadian clock, and Alzheimer's diseases-associated genes may contribute to susceptibility to cognitive aging. In this review, we first illustrated evidence of the genetic contribution to disease susceptibility to age-related cognitive decline in recent studies ranging from approaches of candidate genes to genome-wide association studies. We then surveyed a variety of association studies regarding age-related cognitive decline with consideration of gene-gene and gene-environment interactions. Finally, we highlighted their limitations and future directions. In light of advances in precision medicine and multi-omics technologies, future research in genomic medicine promises to lead to innovative ideas that are relevant to disease prevention and novel drugs for cognitive aging.
| S-EPMC5702307 | biostudies-literature
Project description:ObjectiveTo delineate the trajectories of Aβ42 level in cerebrospinal fluid (CSF), fludeoxyglucose F18 (FDG) uptake using positron emission tomography, and hippocampal volume using magnetic resonance imaging and their relative associations with cognitive change at different stages in aging and Alzheimer disease (AD).DesignCohort study.SettingThe 59 study sites for the Alzheimer's Disease Neuroimaging Initiative.ParticipantsA total of 819 participants 55 to 90 years of age with normal cognition, mild cognitive impairment, and AD who were followed up during the period from 2005 to 2007.Main outcome measuresRates of change in level of Aβ42 in CSF, FDG uptake, hippocampal volume, and the Alzheimer Disease's Assessment Scale-cognitive subscale score during up to 36 months of follow-up by diagnostic group as well as prediction of cognitive change by each biomarker.ResultsReductions in the level of Aβ42 in CSF were numerically greater in participants with normal cognition than in participants with mild cognitive impairment or AD; whereas both glucose metabolic decline and hippocampal atrophy were significantly slower in participants with normal cognition than in participants with mild cognitive impairment or AD. Positive APOE4 status accelerated hippocampal atrophic changes in participants with mild cognitive impairment or AD, but did not modify rates of change in level of Aβ42 in CSF or FDG uptake. The Alzheimer Disease's Assessment Scale-cognitive subscale scores were related only to the baseline level of Aβ42 in CSF and the baseline FDG uptake in participants with normal cognition, which were about equally associated with change in FDG uptake and hippocampal volume in participants with mild cognitive impairment and best modeled by change in FDG uptake in participants with AD.ConclusionTrajectories of Aβ42 level in CSF, FDG uptake, and hippocampal volume vary across different cognitive stages. The longitudinal patterns support a hypothetical sequence of AD pathology in which amyloid deposition is an early event before hypometabolism or hippocampal atrophy, suggesting that biomarker prediction for cognitive change is stage dependent.
| S-EPMC5604752 | biostudies-literature
Project description:IntroductionAny persistent degree of cognitive impairment in older adults is a concern as it can progress to dementia. This study aimed to determine the incidence and risk factors for early postoperative cognitive dysfunction (POCD) in elderly patients undergoing spine surgery.MethodsPatients were enrolled from a previous prospective observational study after screening for normal cognitive function using the Mini Mental State Examination (MMSE). Cognitive function was evaluated before surgery and at 1 week, month, and year post-surgery using MMSE and Montreal Cognitive Assessment scores (MoCA). Mild cognitive impairment (MCI) was determined using the MoCA scores adjusted for age. POCD was defined as a drop of three or more points on the MMSE 1 week post-surgery. Multivariate logistic analysis was performed to identify POCD risk factors.ResultsA total of 427 patients were included. Eighty-five (20%) had pre-existing MCI. The MCI group showed lower MoCA scores at each time point (baseline, 1 week after surgery, 1 month after surgery, 1 year after surgery) compared to the non-MCI group. Those in the MCI group had a higher rate of admission to intensive care unit after surgery, postoperative delirium, and POCD 1 week post-surgery, than those in the non-MCI group (16.5% vs. 6.7%, p = 0.008; 27.1% vs. 15.8%, p = 0.024; and 18.8% vs. 8.2%, p < 0.001, respectively). Among them, 10.3% were assessed for POCD on postoperative day 7 and self-reported poor social roles and physical functioning 1 week postoperatively.ConclusionPreoperative MCI was seen in ~20% of surgical patients aged >70 years. POCD was seen in ~20% of patients with pre-existing MCI, and ~ 10% of those without. Benzodiazepine use, significant comorbidities, pre-existing MCI, and depressive tendencies were risk factors for POCD.
| S-EPMC10811182 | biostudies-literature
Project description:Postoperative cognitive dysfunction (POCD) is one of the severe complications inducing low life quality and high mortality after surgery, especially in elderly patients.Here we probed differentially expressed circRNAs using microarray assay in POCD patients, aiming to find potential key circRNAs related to the occurrence of POCD. Subsequently, ten dysregulated circRNAs were confirmed via quantitative real-time polymerase chain reaction (qRT-PCR) in 10 paired samples. Then, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to probe the vital functions of dysregulated genes.
2020-07-14 | GSE147277 | GEO