Biomarker Of Cognitive Function Research Articles

Role of uric acid as a biomarker of cognitive function in schizophrenia during maintenance period.

Previous studies involving uric acid (UA) in some specialized disease populations have found that high UA is associated with enhanced patient function. The mechanism to explain this association may be that UA, an important antioxidant, exerts neuroprotective effects. Patients with schizophrenia (SCZ) have severe oxidative stress abnormalities, and cognitive impairment is a major obstacle to their rehabilitation. Only few studies have been conducted on UA and cognitive impairment in SCZ. This study aims to clarify the relationship between UA and cognitive impairment and explore whether UA could be used as a potential biological marker of cognition in SCZ during maintenance period. A total of 752 cases of SCZ during maintenance period from Baiyun Jingkang Hospital were included. Cognition was measured using the Mini-Mental State Examination scale. UA was measured using the Plus method. The participants were grouped on the basis of UA to evaluate the association of cognition with low-normal (3.50-5.07 mg/dL for men, 2.50-4.19 mg/dL for women), middle-normal (5.07-6.39 mg/dL for men, 4.19-5.18 mg/dL for women), high-normal (6.39-7.00 mg/dL for men, 5.18-6.00 mg/dL for women), and high (>7.00 mg/dL for men, >6.00 mg/dL for women) levels of UA. Multiple logistic regression and linear regression models and restricted cubic spline (RCS) were utilized to evaluate the relationship. Uric acid was positively associated with cognitive function. Subgroup analyses showed that high UA was associated with enhanced cognition in participants with low anticholinergic cognitive burden (ACB). Uric acid may be used as a simple objective biological indicator to assess cognition in SCZ during maintenance period.

Dynamic white matter changes in recovered COVID-19 patients: a two-year follow-up study.

Background and purpose: Long COVID with regard to the neurological system deserves more attention, as a surge of treated patients are being discharged from the hospital. As the dynamic changes in white matter after two years remain unknown, this characteristic was the focus of this study. Methods: We investigated 17 recovered COVID-19 patients at two years after discharge. Diffusion tensor imaging, neurite orientation dispersion and density imaging were performed to identify white matter integrity and changes from one to two years after discharge. Data for 13 revisited healthy controls were collected as a reference. Subscales of the Wechsler Intelligence scale were used to assess cognitive function. Repeated-measures ANOVA was used to detect longitudinal changes in 17 recovered COVID-19 patients and 13 healthy controls after one-year follow-up. Correlations between diffusion metrics, cognitive function, and other clinical characteristics (i.e., inflammatory factors) were also analyzed. Results: Longitudinal analysis showed the recovery trends of large-scale brain regions, with small-scale brain region deterioration from one year to two years after SARS-CoV-2 infection. However, persistent white matter abnormalities were noted at two years after discharge. Longitudinal changes of cognitive function showed no group difference. But cross-sectional cognitive difference between recovered COVID-19 patients and revisited HCs was detected. Inflammation levels in the acute stage correlated positively with white matter abnormalities and negatively with cognitive function. Moreover, the more abnormal the white matter was at two years, the greater was the cognitive deficit present. Conclusion: Recovered COVID-19 patients showed longitudinal recovery trends of white matter. But also had persistent white matter abnormalities at two years after discharge. Inflammation levels in the acute stage may be considered predictors of cognition and white matter integrity, and the white matter microstructure acts as a biomarker of cognitive function in recovered COVID-19 patients. These findings provide an objective basis for early clinical intervention.

Altered spontaneous brain activity in Down syndrome and its relation with cognitive outcome

Although Down syndrome (DS) is the most common genetic cause of neurodevelopmental delay, few neuroimaging studies have explored this population. This investigation aimed to study whole-brain resting-state spontaneous brain activity using fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) strategies to find differences in spontaneous brain activity among young people with DS and controls and to correlate these results with cognitive outcomes. The sample comprised 18 persons with DS (age mean = 28.67, standard deviation = 4.18) and 18 controls (age mean = 28.56, standard deviation = 4.26). fALFF and ReHo analyses were performed, and the results were correlated with other cognitive variables also collected (KBIT-2 and verbal fluency test). Increased activity was found in DS using fALFF in areas involving the frontal and temporal lobes and left cerebellum anterior lobe. Decreased activity in DS was found in the left parietal and occipital lobe, the left limbic lobe and the left cerebellum posterior lobe. ReHo analysis showed increased activity in certain DS areas of the left frontal lobe and left rectus, as well as the inferior temporal lobe. The areas with decreased activity in the DS participants were regions of the frontal lobe and the right limbic lobe. Altered fALFF and ReHo were found in the DS population, and this alteration could predict the cognitive abilities of the participants. To our knowledge, this is the first study to explore regional spontaneous brain activity in a population with DS. Moreover, this study suggests the possibility of using fALFF and ReHo as biomarkers of cognitive function, which is highly important given the difficulties in cognitively evaluating this population to assess dementia. More research is needed, however, to demonstrate its utility.

Associations Between Retinal Nerve Fiber Layer and Ganglion Cell Layer in Middle Age and Cognition From Childhood to Adulthood

The retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) have been proposed as potential biomarkers for Alzheimer disease (AD). Although a number of studies have shown that knowing the thickness of RNFL and GCL can help differentiate between patients with AD and healthy controls, it is unclear whether these associations are observable earlier in life. To examine whether RNFL and GCL thickness was associated with global cognitive performance in middle age and in childhood and with a decline in cognitive performance from childhood to adulthood and whether RNFL and GCL thickness was associated with decline in specific cognitive domains over the same period. This longitudinal cohort study involved members of the Dunedin Multidisciplinary Health and Development Study, a longitudinal representative birth cohort from New Zealand (n = 1037). Participants were born in 1972 to 1973 and followed up until age 45 years, with 94% of the living cohort still participating. Cognitive performance (Full Scale IQ, processing speed, perceptual reasoning, and verbal comprehension) measured at ages 7, 9, and 11 years (mean value) and age 45 years, and RNFL and GCL thickness measured via optical coherence tomography (OCT) at age 45 years. Data were analyzed between August 2020 and April 2021. Data from 865 participants were included in the present study (50.2% male, 49.8% female; 92.2% of the 938 study members seen at age 45 years). Of the 73 participants who were excluded, 63 were excluded because of issues with OCT scans and 10 were excluded because of diseases affecting the retina. Thinner RNFL and GCL were associated with lower Full Scale IQ in childhood and at age 45 years. Thinner RNFL was also associated with a greater decline in processing speed from childhood to adulthood. RNFL and GCL thickness in middle age was associated with cognitive performance in childhood and adulthood, and thinner RNFL with a decline in processing speed between childhood and adulthood. These data emphasize the potential utility of OCT measures as biomarkers of cognitive function; however, further longitudinal studies are needed to determine whether retinal thinning precedes cognitive decline and whether other confounding factors may account for this association.

Prostate-Specific Antigen and Testosterone Levels as Biochemical Indicators of Cognitive Function in Prostate Cancer Survivors and the Role of Diabetes.

Prostate cancer (PC) is one of the most common malignancies in men. The increase in the number of PC survivors is associated with many problems including cognitive impairment. Early detection of such problems facilitates timely protective intervention. This study examined the association between prostate-specific antigen (PSA) or testosterone (T) levels and cognitive function in patients undergoing radical prostatectomy. Such a correlation could help identify patient groups at risk of cognitive impairment. Participants underwent clinical (demographic data, medical history, physical examination, and blood analyses) and neuropsychological assessment (cognitive test battery). Preoperative PSA or T levels were not associated with cognitive function. However, long-term follow-up after prostatectomy showed a strong correlation between PSA levels and the results of verbal memory and executive function tests. A trend toward significance was also observed for visuospatial memory. The levels of free T and total T were not correlated with cognitive function. Only the levels of free T after hormonal treatment were significantly correlated with executive functions. Comorbid diabetes affected these correlations. In conclusion, PSA levels at a distant postoperative time and free T level after hormonal treatment may be biomarkers of cognitive function.

Diazepam induced sleep spindle increase correlates with cognitive recovery in a child with epileptic encephalopathy

BackgroundContinuous spike and wave of sleep with encephalopathy (CSWS) is a rare and severe developmental electroclinical epileptic encephalopathy characterized by seizures, abundant sleep activated interictal epileptiform discharges, and cognitive regression or deceleration of expected cognitive growth. The cause of the cognitive symptoms is unknown, and efforts to link epileptiform activity to cognitive function have been unrevealing. Converging lines of evidence implicate thalamocortical circuits in these disorders. Sleep spindles are generated and propagated by the same thalamocortical circuits that can generate spikes and, in healthy sleep, support memory consolidation. As such, sleep spindle deficits may provide a physiologically relevant mechanistic biomarker for cognitive dysfunction in epileptic encephalopathies.Case presentationWe describe the longitudinal course of a child with CSWS with initial cognitive regression followed by dramatic cognitive improvement after treatment. Using validated automated detection algorithms, we analyzed electroencephalograms for epileptiform discharges and sleep spindles alongside contemporaneous neuropsychological evaluations over the course of the patient’s disease. We found that sleep spindles increased dramatically with high-dose diazepam treatment, corresponding with marked improvements in cognitive performance. We also found that the sleep spindle rate was anticorrelated to spike rate, consistent with a competitively shared underlying thalamocortical circuitry.ConclusionsEpileptic encephalopathies are challenging electroclinical syndromes characterized by combined seizures and a deceleration or regression in cognitive skills over childhood. This report identifies thalamocortical circuit dysfunction in a case of epileptic encephalopathy and motivates future investigations of sleep spindles as a biomarker of cognitive function and a potential therapeutic target in this challenging disease.

BDNF as a Biomarker of Cognition in Schizophrenia/Psychosis: An Updated Review

Brain Derived Neurotrophic Factor (BDNF) has been linked to cognitive symptoms of schizophrenia, which has been documented in previous reviews by several authors. However, a trend has recently emerged in this field moving from studying schizophrenia as a disease to studying psychosis as a group. This review article focuses on recent BDNF studies in relation to cognition in human subjects during different stages of the psychotic process, including subjects at high risk of developing psychosis, patients at their first episode of psychosis, and patients with chronic schizophrenia. We aim to provide an update of BDNF as a biomarker of cognitive function on human subjects with schizophrenia or earlier stages of psychosis, covering new trends, controversies, current research gaps, and suggest potential future developments in the field. We found that most of current research regarding BDNF and cognitive symptoms in psychosis is done around schizophrenia as a disease. Therefore, it is necessary to expand the study of the relationship between BDNF and cognitive symptoms to psychotic illnesses of different stages and origins.

Investigating the role of blood metabolites as biomarkers of cognitive function and dementia in the MRC 1946 British Birth Cohort

AbstractBackgroundDecline in cognitive function in late midlife is indicative of dementia. Identifying early markers in this key phase is critical for identifying those at risk and guiding effective interventional strategies. As blood metabolites closely reflect the physiological status of an individual, they show promise as minimally invasive markers for population‐level implementation. Using the MRC 1946 British Birth Cohort, we aim to: 1) Identify blood metabolites associated with early cognitive changes relevant to dementia 2) Tease apart mediating life course factors to address key aetiological questions 3) Employ a network approach, weighted coexpression network analysis (WGCNA), to glean insights into underlying biology.MethodAt age 60‐64, levels of 1019 metabolites were quantified using liquid chromatography‐mass spectrometry (N=1740). At the same age and 5‐9 years later, four aspects of cognitive function were assessed: short‐term and delayed verbal memory, processing speed, and the Addenbrook’s Cognitive Examination‐IIII (ACE‐III). Using WGCNA, 14 modules of highly connected metabolites were identified. Linear regression models evaluated associations between metabolites/metabolite modules and cognitive outcomes, sequentially adjusting for sex, childhood cognitive ability, education, socioeconomic status (SES), lipid medication and lifestyle factors. To infer biological function, pathway analyses were conducted to identify enriched pathways within metabolite modulesResultAfter correcting for multiple testing, 154 metabolites were associated with cognitive outcomes. Many associations attenuated after adjusting for early life cognition and SES, with seven metabolites belonging to lipid, amino acid and xenobiotic families remaining. WGCNA revealed two modules, enriched in vitamin A and sphingolipid metabolism, to be positively associated with cognitive outcomes. However, after adjusting for education and childhood cognition, these associations were largely reduced. Two modules, enriched in amino acid and fatty acid metabolism, were negatively associated with cognitive outcomes, with associations of the fatty acid metabolism module remaining after adjusting for life course factors.ConclusionThese results provide support for a role for metabolites in reflecting early changes relevant to dementia, revealing insights into underlying biological mechanisms and lifelong interplay. It is hoped that these insights can be utilised to inform early diagnosis and the development of disease‐modifying treatments and interventions.

Early bedside biomarkers of cognitive function following neonatal brain injury - Wellcome Trust

Early bedside biomarkers of cognitive function following neonatal brain injury - Wellcome Trust

Peak alpha frequency is a neural marker of cognitive function across the autism spectrum.

Cognitive function varies substantially and serves as a key predictor of outcome and response to intervention in autism spectrum disorder (ASD), yet we know little about the neurobiological mechanisms that underlie cognitive function in children with ASD. The dynamics of neuronal oscillations in the alpha range (6-12Hz) are associated with cognition in typical development. Peak alpha frequency is also highly sensitive to developmental changes in neural networks, which underlie cognitive function, and therefore, it holds promise as a developmentally sensitive neural marker of cognitive function in ASD. Here, we measured peak alpha band frequency under a task-free condition in a heterogeneous sample of children with ASD (N=59) and age-matched typically developing (TD) children (N=38). At a group level, peak alpha frequency was decreased in ASD compared to TD children. Moreover, within the ASD group, peak alpha frequency correlated strongly with non-verbal cognition. As peak alpha frequency reflects the integrity of neural networks, our results suggest that deviations in network development may underlie cognitive function in individuals with ASD. By shedding light on the neurobiological correlates of cognitive function in ASD, our findings lay the groundwork for considering peak alpha frequency as a useful biomarker of cognitive function within this population which, in turn, will facilitate investigations of early markers of cognitive impairment and predictors of outcome in high risk infants.

Physical activity domains and cognitive function over three years in older adults with subjective memory complaints: Secondary analysis from the MAPT trial.

We aimed to examine the associations of physical activity (PA) domains (i.e., PA in leisure-time (LTPA), for housework (HPA), or for gardening (GPA)) with cognitive function in older adults with subjective memory complaints (no-dementia) and to investigate if those associations were dependent on the status of apolipoprotein E allele 4 (APOE4), omega-3 levels and mild cognitive impairment (MCI). Observational prospective secondary analysis using longitudinal data from a randomized controlled trial. Participants were 420 French community-dwelling people (aged 75.6±4.4; 66.4% women) randomized into the placebo group. They were assessed at baseline, 6-, 12-, 24- and 36-month using a battery of neuropsychological tests; a composite cognitive Z score was elaborated for all time points. Data on PA come from baseline and was obtained using a self-reported questionnaire. In time-adjusted analysis, LTPA significantly predicted cognitive function over three years for almost all tests and the composite Z score, with higher LTPA associated with better function; multivariate analysis showed a significant association only for verbal fluency. HPA was not associated to cognitive function, whereas GPA had mixed results. The magnitude of the PA-cognition associations was very weak, being the strongest for LTPA. Stratified analyses showed that the associations between PA and cognitive function were stronger for MCI, people with normal omega-3 index levels, and APOE4 non-carriers. PA domain is an important aspect to take into account when examining the associations between PA and cognitive function. Biomarkers of cognitive function may modulate the PA-cognition associations.

The effect of environmental temperature on exercise-dependent release of brain-derived neurotrophic factor

ABSTRACTBrain-derived neurotrophic factor (BDNF) is a biomarker of cognitive function that is released into the blood stream following exercise, and cognitive function is impaired by environmental temperatures that are hot and cold. Purpose: To evaluate the exercise-dependent release of BDNF in different environmental temperatures. Methods: Recreationally trained males each completed three trials consisting of cycling for 1 h at 60% Wmax at three different temperatures: 33°C (hot), 7°C (cold), and 20°C (moderate room temperature). Blood was taken from the antecubital vein pre-exercise, immediately post-exercise, and 3 h post-exercise. Respiratory gases were collected periodically throughout exercise and recovery. Results: BDNF was elevated immediately following an exercise bout (1711 ± 766 pg·ml−1) regardless of temperature from pre-exercise (1257 ± 653 pg·ml−1, p = 0.001) and returned to basal levels following 3 h of recovery (1289 ± 650 pg·ml−1, p = 0.786). There was no effect (p > 0.05) of temperature on BDNF following the exercise bout. Plasma glucose was elevated in hot (6.2 ± 0.9 mmol) over cold (5.3 ± 0.6 mmol, p = 0.035) and moderate room temperature (5.2 ± 0.5, p = 0.008). VO2 was elevated during exercise in hot (3.01 ± 0.45 L·min−1) over cold (2.67 ± 0.35 L·min−1, p = 0.005) and moderate room temperature (2.80 ± 0.38 L·min−1, p = 0.001). There was no relationship between BDNF and plasma glucose (p > 0.05) or VO2 across any time point or temperature (p > 0.05). Conclusion: With aerobic exercise, BDNF is elevated; however, the release of BDNF is not impacted by different environmental temperatures during exercise.

Reduced pCREB in Alzheimer's disease prefrontal cortex is reflected in peripheral blood mononuclear cells.

Cyclic-AMP response element-binding protein (CREB) signaling has a critical role in the formation of memories. CREB signaling is dysfunctional in the brains of mouse models of Alzheimer's disease (AD), and evidence suggests that CREB signaling may be disrupted in human AD brains as well. Here, we show that both CREB and its activated form pCREB-Ser133 (pCREB) are reduced in the prefrontal cortex of AD patients. Similarly, the transcription cofactors CREB-binding protein (CBP) and p300 are reduced in the prefrontal cortex of AD patients, indicating additional dysfunction of CREB signaling in AD. Importantly, we show that pCREB expression is reduced in peripheral blood mononuclear cells (PBMC) of AD subjects. In addition, pCREB levels in PBMC positively correlated with pCREB expression in the postmortem brain of persons with AD. These results suggest that pCREB expression in PBMC may be indicative of its expression in the brain, and thus offers the intriguing possibility of pCREB as a biomarker of cognitive function and disease progression in AD.

Biomolecule Detection Using a Resonant Capacitive Sensor

Biomarker detection is of paramount importance to the medical community for the assessment of health and human performance. Two biomarkers of interest are orexin A (a biomarker of cognitive function) and trimethylamine (a biomarker of the disease trimethylaminuria). For the purpose of orexin A and trimethylamine detection, resonant capacitive sensors with a peptide functionalized guanine dielectric layer are designed and fabricated, Figure 1. The molecular recognition peptides, Table 1, selectively capture the biomarkers. The binding of the biomarkers to the peptides changes the permittivity of the dielectric layer resulting in a significant shift in the resonant frequency, amplitude, and phase of the sensors thereby indicating the biomarkers’ presence. Due to the limited utilization of guanine in electronics, the first objective in designing these sensors has been guanine characterization. For characterization purposes, guanine was deposited as the dielectric layer in a capacitive test structure (CTS), and from these structures, the dielectric constant and loss tangent of guanine was determined by comparing the measured scattering-parameters (S-parameters) to an electrical model of the device. Subsequently, guanine was deposited as the dielectric for the resonant capacitive sensor to determine the resonance of the guanine-integrated structure and to serve as the sensor platform. After guanine characterization, the next objective is to investigate methods for peptide functionalization. The two methods of interest are spin-coating and chemical tethering (preferred). In order to be successful, the peptides must adhere to the guanine in a manner that does not interfere with the biomarker binding sites. The chemical tethering method offers a way to covalently cross-link the peptides to the guanine, but the spin-coating is less likely to interfere with the peptides’ binding sites. After determining a functionalization method, the guanine will be functionalized with peptides using this method. The final objective is to test the fabricated sensors. For testing, the S-parameters are measured to determine the resonance of the sensors pre-exposure (baseline) and following exposure to positive (orexin A in aqueous phase and trimethylamine in vapor phase) and negative controls. Acknowledgements: Support was provided through the Dayton Area Graduate Studies Institute Fellowship, and the Air Force Research Laboratory (Human Effectiveness and Materials and Manufacturing Directorates).

Relating Intrinsic Low-Frequency BOLD Cortical Oscillations to Cognition in Schizophrenia.

The amplitude of low-frequency fluctuations (ALFF) in the blood oxygenation level-dependent (BOLD) signal during resting-state fMRI reflects the magnitude of local low-frequency BOLD oscillations, rather than interregional connectivity. ALFF is of interest to studies of cognition because fluctuations in spontaneous intrinsic brain activity relate to, and possibly even constrain, task-evoked brain responses in healthy people. Lower ALFF has been reported in schizophrenia, but the cognitive correlates of these reductions remain unknown. Here, we assess relationships between ALFF and attention and working memory in order to establish the functional relevance of intrinsic BOLD oscillatory power alterations with respect to specific cognitive impairments in schizophrenia. As part of the multisite FBIRN study, resting-state fMRI data were collected from schizophrenia subjects (SZ; n=168) and healthy controls (HC; n=166). Voxelwise fractional ALFF (fALFF), a normalized ALFF measure, was regressed on neuropsychological measures of sustained attention and working memory in SZ and HC to identify regions showing either common slopes across groups or slope differences between groups (all findings p<0.01 height, p<0.05 family-wise error cluster corrected). Poorer sustained attention was associated with smaller fALFF in the left superior frontal cortex and bilateral temporoparietal junction in both groups, with additional relationships in bilateral posterior parietal, posterior cingulate, dorsal anterior cingulate (ACC), and right dorsolateral prefrontal cortex (DLPFC) evident only in SZ. Poorer working memory was associated with smaller fALFF in bilateral ACC/mPFC, DLPFC, and posterior parietal cortex in both groups. Our findings indicate that smaller amplitudes of low-frequency BOLD oscillations during rest, measured by fALFF, were significantly associated with poorer cognitive performance, sometimes similarly in both groups and sometimes only in SZ, in regions known to subserve sustained attention and working memory. Taken together, these data suggest that the magnitude of resting-state BOLD oscillations shows promise as a biomarker of cognitive function in health and disease.