scholarly journals Neurofilament light: a possible prognostic biomarker for treatment of vascular contributions to cognitive impairment and dementia

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Christina Hoyer-Kimura ◽  
John P. Konhilas ◽  
Heidi M. Mansour ◽  
Robin Polt ◽  
Kristian P. Doyle ◽  
...  

Abstract Background Decreased cerebral blood flow and systemic inflammation during heart failure (HF) increase the risk for vascular contributions to cognitive impairment and dementia (VCID) and Alzheimer disease-related dementias (ADRD). We previously demonstrated that PNA5, a novel glycosylated angiotensin 1–7 (Ang-(1–7)) Mas receptor (MasR) agonist peptide, is an effective therapy to rescue cognitive impairment in our preclinical model of VCID. Neurofilament light (NfL) protein concentration is correlated with cognitive impairment and elevated in neurodegenerative diseases, hypoxic brain injury, and cardiac disease. The goal of the present study was to determine (1) if treatment with Ang-(1–7)/MasR agonists can rescue cognitive impairment and decrease VCID-induced increases in NfL levels as compared to HF-saline treated mice and, (2) if NfL levels correlate with measures of cognitive function and brain cytokines in our VCID model. Methods VCID was induced in C57BL/6 male mice via myocardial infarction (MI). At 5 weeks post-MI, mice were treated with daily subcutaneous injections for 24 days, 5 weeks after MI, with PNA5 or angiotensin 1–7 (500 microg/kg/day or 50 microg/kg/day) or saline (n = 15/group). Following the 24-day treatment protocol, cognitive function was assessed using the Novel Object Recognition (NOR) test. Cardiac function was measured by echocardiography and plasma concentrations of NfL were quantified using a Quanterix Simoa assay. Brain and circulating cytokine levels were determined with a MILLIPLEX MAP Mouse High Sensitivity Multiplex Immunoassay. Treatment groups were compared via ANOVA, significance was set at p < 0.05. Results Treatment with Ang-(1–7)/MasR agonists reversed VCID-induced cognitive impairment and significantly decreased NfL levels in our mouse model of VCID as compared to HF-saline treated mice. Further, NfL levels were significantly negatively correlated with cognitive scores and the concentrations of multiple pleiotropic cytokines in the brain. Conclusions These data show that treatment with Ang-(1–7)/MasR agonists rescues cognitive impairment and decreases plasma NfL relative to HF-saline-treated animals in our VCID mouse model. Further, levels of NfL are significantly negatively correlated with cognitive function and with several brain cytokine concentrations. Based on these preclinical findings, we propose that circulating NfL might be a candidate for a prognostic biomarker for VCID and may also serve as a pharmacodynamic/response biomarker for therapeutic target engagement.

2003 ◽  
Vol 33 (6) ◽  
pp. 1029-1038 ◽  
Author(s):  
A. BUSSE ◽  
J. BISCHKOPF ◽  
S. G. RIEDEL-HELLER ◽  
M. C. ANGERMEYER

Background. Mild cognitive impairment (MCI) is associated with an increased risk of developing dementia. Recently published results of the Current Concepts in MCI Conference suggested subclassifications for MCI (MCI-amnestic, MCI-multiple domains slightly impaired, MCI-single nonmemory domain) based on the recognized heterogeneity in the use of the term. These subclassifications have not been empirically validated to date.Method. A community sample of 1045 dementia-free individuals aged 75 years and over was examined by neuropsychological testing in a three-wave longitudinal study. The prevalences and the predictive validities for the subclassifications of MCI and their modifications (original criteria except for the report of subjective decline in cognitive function) were determined.Results. The prevalence was 1 to 15% depending on the subset employed. Subjects with a diagnosis of MCI progressed to dementia at a rate of 10 to 55% over 2·6 years, depending on the subset employed. MCI-amnestic achieved the highest positive predictive power (PPP). ROC curves of the subclassifications for MCI indicate that all but one subset for MCI failed to predict dementia (MCI-multiple domains slightly impaired-modified: AUC=0·585, P<0·01, 95% CI, 0·517–0·653). The use of modified criteria for MCI (original criteria except for the report of subjective decline in cognitive function) is associated with a higher diagnostic sensitivity but also with a reduction in diagnostic specificity and PPP.Conclusions. Modified criteria should be applied if a concept for MCI with a high sensitivity is required and the original criteria (including subjective cognitive complaint) if a concept with high specificity and high PPP is required.


Stroke ◽  
2020 ◽  
Vol 51 (5) ◽  
pp. 1604-1607 ◽  
Author(s):  
Leonie H.A. Broersen ◽  
Bob Siegerink ◽  
Pia S. Sperber ◽  
Regina von Rennenberg ◽  
Sophie K. Piper ◽  
...  

Background and Purpose— Our study aim was to assess whether high-sensitivity cardiac troponin T (hs-cTnT), a specific biomarker for myocardial injury, is associated with cognitive function in patients after mild-to-moderate first-ever ischemic stroke. Methods— We used data from PROSCIS-B (Prospective Cohort With Incident Stroke Berlin). Cognitive function was assessed by Mini-Mental-State-Examination at baseline, and Telephone Interview for Cognitive Status–modified after 1 to 3 years of follow-up. Patients were categorized according to hs-cTnT quartiles. We performed generalized linear regression to calculate risk ratios of cognitive impairment (Mini-Mental-State-Examination <27; Telephone Interview for Cognitive Status–modified <32). Association of hs-cTnT with cognitive function over time was estimated using a linear mixed model. Results— We included 555 patients (mean age, 67 years, 62% male, median National Institutes of Health Stroke Scale 2 [interquartile range, 1–5], hs-cTnT above upper reference limit 40%, baseline cognitive impairment 28%). Baseline Mini-Mental-State-Examination score and rate of cognitive impairment were lower in patients in the highest versus lowest hs-cTnT quartile (median Mini-Mental-State-Examination 27 versus 29, and 15.3% versus 43.0%, adjusted risk ratio, 1.76 [95% CI, 1.07–2.90], respectively). If anything, cognition seemed to improve in all groups, yet Telephone Interview for Cognitive Status–modified scores were consistently lower in patients within the highest versus lowest hs-cTnT quartile (adjusted β, −1.33 [95% CI, −2.65 to −0.02]), without difference in the rate of change over time. Conclusions— In patients with mild-to-moderate first-ever ischemic stroke without dementia, higher hs-cTnT was associated with higher prevalence of cognitive impairment at baseline and lower Telephone Interview for Cognitive Status–modified during 3-year follow-up. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01363856.


2020 ◽  
Vol 49 (3) ◽  
pp. 235-242
Author(s):  
Fang Ran ◽  
Feng Liu ◽  
Ying Zhang ◽  
Linyun Chen

<b><i>Background:</i></b> Cognitive impairment induced by cerebral infarction has become a devastating health problem. More efficient predictors are required to evaluate the potential cognitive decline after cerebral infarction in clinic. Serum uric acid (UA) and high-sensitivity C-reactive protein (hs-CRP) are two factors reported to correlate with cognitive impairment. However, the understanding on serum UA and hs-CRP with cognitive dysfunction remains unclear. <b><i>Methods:</i></b> Serum UA and hs-CRP were evaluated in patients with cerebral infarction (<i>n</i> = 197) using single factor analysis and multivariate logistic regression analysis. Clinical and pathological characteristics were analyzed by logistic regression, respectively, and the results demonstrated the correlation between the pathological characteristics and the cognitive impairment post cerebral infarction. Montreal Cognitive Assessment (MoCA) was used to evaluate the patients’ cognitive function, and patients with a MoCA score &#x3c;26 were recognized as with cognitive impairment. <b><i>Results:</i></b> Clinical characteristics related to cognitive impairment, including age, gender, blood pressure, serum UA, and hs-CRP were collected and analyzed. Serum UA and hs-CRP were identified to be potential predictors for post-stroke cognitive dysfunction, with higher serum UA levels correlated with better cognitive function and higher hs-CRP levels correlated with worse cognitive impairment. <b><i>Conclusion:</i></b> Serum UA and hs-CRP are two predictors for cognitive impairment post cerebral infarction.


2016 ◽  
Vol 24 (2) ◽  
pp. 161-176 ◽  
Author(s):  
Simona Cernea ◽  
Floredana-Laura Şular ◽  
Adina Huţanu ◽  
Septimiu Voidăzan

Abstract Background. The study aimed to evaluate the correlations of cognitive function with metabolic, nutritional, hormonal and immunologic parameters in patients with type 2 diabetes (T2D), in order to identify markers of cognitive impairment. Material and methods. This cross-sectional study included 216 T2D patients and 23 healthy individuals (HC). The cognitive status was evaluated by the MoCA test. From HC and 145 T2D patients several parameters were also determined: C-peptide, vitamin B12, high-sensitivity CRP (by chemiluminescent immunometric assay), HbA1c, lipids, cortisol, TSH, Mg (by a Cobas 6000 analyzer), glucose (by glucose-oxidase method) and leptin and adiponectin (by ELISA method). Statistical significance was set at p < 0.05. Results. There was a significant difference in the MoCA scores between HC and T2D groups (26.0(17.0-29.0) vs. 23.0(13.0- 31.0) points; p: 0.004). T2D patients with cognitive dysfunction were significantly older and less formally educated (p < 0.0001). Age negatively correlated with MoCA scores (-0.31; 95%CI:-0.42,-0.18; p < 0.0001). T2D patients had significantly lower visuospatial/executive (4.0(0.0-5.0) vs. 5.0(2.0-5.0) points; p: 0.04) and delayed recall scores (2.0(0.0- 5.0) vs. 3.0(1.0-5.0) points; p: 0.03) and lower serum Mg concentrations (0.81(0.12-0.99) vs. 0.92(0.41-1.35) mmol/l, p < 0.0001). Serum Mg levels positively correlated with MoCA scores (0.24, 95%CI: 0.07, 0.39; p: 0.003) and with visuospatial/ executive (0.30; 95%CI: 0.14, 0.45; p: 0.0002) and naming functions (0.18; 95%CI: 0.01, 0.34; p: 0.02). Conclusions. Patients with T2D had significant cognitive impairment, with decrements in the visuospatial/executive and delayed recall domains. Younger age and higher education correlated with better cognitive function. Serum Mg levels correlated positively with overall cognitive function and with visuospatial/executive and naming domains.


2016 ◽  
Vol 64 (2) ◽  

Strategies to improve cognitive aging are highly needed. Among those, promotion of exercise and physical activity appears as one of the most attractive and beneficial intervention. Indeed, results from basic and clinical studies suggest that exercise and physical activity have positive effects on cognition in older persons without cognitive impairment, as well as in those with dementia. Despite inconsistent results, aerobic exercise appears to have the strongest potential to enhance cognition. However, even limited periods of walking (45 minutes, three times a week, over a 6-month period) have also been shown to enhance cognition, particularly executive functions. Changing long-term lifestyle habits in these older persons remains a critical challenge and attractive programs susceptible to gain adherence are needed to succeed in achieving improved cognitive aging.


Author(s):  
Mattia Chini ◽  
Jastyn A. P&ouml;pplau ◽  
Christoph Lindemann ◽  
Laura Carol-Perdiguer ◽  
Marilena Hnida ◽  
...  

2020 ◽  
Vol 17 (6) ◽  
pp. 556-565
Author(s):  
Yujie Guo ◽  
Pengfei Li ◽  
Xiaojun Ma ◽  
Xiaochen Huang ◽  
Zhuoheng Liu ◽  
...  

Background: The present study was designed to examine the association of circulating cholesterol with cognitive function in non-demented community aging adults. Methods: This was a cross-sectional study including 1754 Chinese adults aged 55-80 years. The association between serum cholesterol levels and cognitive function was examined. Participants were categorized into four groups according to the quartile of circulating TC (total cholesterol), High Density Lipoprotein Cholesterol (HDL-c), Low Density Lipoprotein Cholesterol (LDL-c) levels and HDLc/ LDL-c ratio. The difference in cognitive performance among the groups was compared. Logistic regression model was used to determine the association of circulating cholesterol level with the risk of Mild Cognitive Impairment (MCI). Results: Mild increase of serum LDL-c level correlated with better visual and executive, language, memory and delayed recall abilities. Higher circulating TC and HDL-c levels were found to be associated with poorer cognitive function, especially in aging female subjects. Higher circulating TC, HDL-c and HDL/LDL ratio indicated an increased risk of MCI, especially in female subjects. Conclusion: Slight increase in circulating LDL-c level might benefit cognitive function in aging adults. However, higher circulating TC and HDL-c levels might indicate a decline of cognitive function, especially in aging female subjects.


2020 ◽  
Vol 16 (14) ◽  
pp. 1309-1315
Author(s):  
Peilin An ◽  
Xuan Zhou ◽  
Yue Du ◽  
Jiangang Zhao ◽  
Aili Song ◽  
...  

Background: Inflammation plays a significant role in the pathophysiology of cognitive impairment in previous studies. Neutrophil-lymphocyte ratio (NLR) is a reliable measure of systemic inflammation. Objective: The aim of this study was to investigate the association between NLR and mild cognitive impairment (MCI), and further to explore the diagnostic potential of the inflammatory markers NLR for the diagnosis of MCI in elderly Chinese individuals. Methods: 186 MCI subjects and 153 subjects with normal cognitive function were evaluated consecutively in this study. Neutrophil (NEUT) count and Lymphocyte (LYM) count were measured in fasting blood samples. The NLR was calculated by dividing the absolute NEUT count by the absolute LYM count. Multivariable logistic regression was used to evaluate the potential association between NLR and MCI. NLR for predicting MCI was analyzed using Receiver Operating Characteristic (ROC) curve analysis. Results: The NLR of MCI group was significantly higher than that of subjects with normal cognitive function (2.39 ± 0.55 vs. 1.94 ± 0.51, P < 0.001). Logistic regression analysis showed that higher NLR was an independent risk factor for MCI (OR: 4.549, 95% CI: 2.623-7.889, P < 0.001). ROC analysis suggested that the optimum NLR cut-off point for MCI was 2.07 with 73.66% sensitivity, 69.28% specificity, 74.48% Positive Predictive Values (PPV) and 68.36% negative predictive values (NPV). Subjects with NLR ≥ 2.07 showed higher risk relative to NLR < 2.07 (OR: 5.933, 95% CI: 3.467-10.155, P < 0.001). Conclusion: The elevated NLR is significantly associated with increased risk of MCI. In particular, NLR level higher than the threshold of 2.07 was significantly associated with the probability of MCI.


The prevalence of cognitive impairment caused by neurodegenerative diseases and other neurologic disorders associated with aging is expected to rise dramatically between now and year 2050, when the population of Americans aged 65 or older will nearly double. Cognitive impairment also commonly occurs in other neurologic conditions, as well as in non-neurologic medical disorders (and their treatments), idiopathic psychiatric illnesses, and adult neurodevelopmental disorders. Cognitive impairment can thus infiltrate all aspects of healthcare, making it necessary for clinicians and clinical researchers to have an integrated knowledge of the spectrum of adult cognitive disorders. The Oxford Handbook of Adult Cognitive Disorders is meant to serve as an up-to-date, scholarly, and comprehensive volume covering most diseases, conditions, and injuries resulting in impairments in cognitive function in adults. Topics covered include normal cognitive and brain aging, the impact of medical disorders (e.g., cardiovascular, liver, pulmonary) and psychiatric illnesses (e.g., depression and bipolar disorder) on cognitive function, adult neurodevelopmental disorders (e.g., Down Syndrome, Attention Deficit/Hyperactivity Disorder), as well as the various neurological conditions (e.g., Alzheimer’s disease, chronic traumatic encephalopathy, concussion). A section of the Handbook is also dedicated to unique perspectives and special considerations for the clinicians and clinical researchers, covering topics such as cognitive reserve, genetics, diversity, and neuroethics. The target audience of this Handbook includes: (1) clinicians, particularly psychologists, neuropsychologists, neurologists (including behavioral and cognitive neurologists), geriatricians, and psychiatrists (including neuropsychiatrists), who provide clinical care and management for adults with a diverse range of cognitive disorders; (2) clinical researchers who investigate cognitive outcomes and functioning in adult populations; and (3) graduate level students and post-doctoral trainees studying psychology, clinical neuroscience, and various medical specialties.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Alexandre Chan ◽  
Angie Yeo ◽  
Maung Shwe ◽  
Chia Jie Tan ◽  
Koon Mian Foo ◽  
...  

Abstract Strong evidence suggests that genetic variations in DNA methyltransferases (DNMTs) may alter the downstream expression and DNA methylation patterns of neuronal genes and influence cognition. This study investigates the association between a DNMT1 polymorphism, rs2162560, and chemotherapy-associated cognitive impairment (CACI) in a cohort of breast cancer patients. This is a prospective, longitudinal cohort study. From 2011 to 2017, 351 early-stage breast cancer patients receiving chemotherapy were assessed at baseline, the midpoint, and the end of chemotherapy. DNA was extracted from whole blood, and genotyping was performed using Sanger sequencing. Patients’ self-perceived cognitive function and cognitive performance were assessed at three different time points using FACT-Cog (v.3) and a neuropsychological battery, respectively. The association between DNMT1 rs2162560 and cognitive function was evaluated using logistic regression analyses. Overall, 33.3% of the patients reported impairment relative to baseline in one or more cognitive domains. Cognitive impairment was observed in various objective cognitive domains, with incidences ranging from 7.2% to 36.9%. The DNMT1 rs2162560 A allele was observed in 21.8% of patients and this was associated with lower odds of self-reported cognitive decline in the concentration (OR = 0.45, 95% CI: 0.25–0.82, P = 0.01) and functional interference (OR = 0.48, 95% CI: 0.24–0.95, P = 0.03) domains. No significant association was observed between DNMT1 rs2162560 and objective cognitive impairment. This is the first study to show a significant association between the DNMT1 rs2162560 polymorphism and CACI. Our data suggest that epigenetic processes could contribute to CACI, and further studies are needed to validate these findings.


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