Prefrontal intra-individual ERP variability and its asymmetry: exploring its biomarker potential in mild cognitive impairment.

BACKGROUND: The worldwide trend of demographic aging highlights the progress made in healthcare, albeit with health challenges like Alzheimer's Disease (AD), prevalent in individuals aged 65 and above. Its early detection at the mild cognitive impairment (MCI) stage is crucial. Event-related potentials (ERPs) obtained by averaging EEG segments responded to repeated events are vital for cognitive impairment research. Consequently, examining intra-trial ERP variability is vital for comprehending fluctuations within psychophysiological processes of interest. This study aimed to investigate cognitive deficiencies and instability in MCI using ERP variability and its asymmetry from a prefrontal two-channel EEG device. METHODS: In this study, ERP variability for both target and non-target responses was examined using the response variance curve (RVC) in a sample comprising 481 participants with MCI and 1,043 age-matched healthy individuals. The participants engaged in auditory selective attention tasks. Cognitive decline was assessed using the Seoul Neuropsychological Screening Battery (SNSB) and the Mini-Mental State Examination (MMSE). The research employed various statistical methods, including independent t-tests, and univariate and multiple logistic regression analyses. These analyses were conducted to investigate group differences and explore the relationships between neuropsychological test results, ERP variability and its asymmetry measures, and the prevalence of MCI. RESULTS: Our results showed that patients with MCI exhibited unstable cognitive processing, characterized by increased ERP variability compared to cognitively normal (CN) adults. Multiple logistic regression analyses confirmed the association between ERP variability in the target and non-target responses with MCI prevalence, independent of demographic and neuropsychological factors. DISCUSSION: The unstable cognitive processing in the MCI group compared to the CN individuals implies abnormal neurological changes and reduced and (or) unstable attentional maintenance during cognitive processing. Consequently, utilizing ERP variability measures from a portable EEG device could serve as a valuable addition to the conventional ERP measures of latency and amplitude. This approach holds significant promise for identifying mild cognitive deficits and neural alterations in individuals with MCI.

A screening method for mild cognitive impairment in elderly individuals combining bioimpedance and MMSE.

We investigated a screening method for mild cognitive impairment (MCI) that combined bioimpedance features and the Korean Mini-Mental State Examination (K-MMSE) score. Data were collected from 539 subjects aged 60 years or older at the Gwangju Alzheimer's & Related Dementias (GARD) Cohort Research Center, A total of 470 participants were used for the analysis, including 318 normal controls and 152 MCI participants. We measured bioimpedance, K-MMSE, and the Seoul Neuropsychological Screening Battery (SNSB-II). We developed a multiple linear regression model to predict MCI by combining bioimpedance variables and K-MMSE total score and compared the model's accuracy with SNSB-II domain scores by the area under the receiver operating characteristic curve (AUROC). We additionally compared the model performance with several machine learning models such as extreme gradient boosting, random forest, support vector machine, and elastic net. To test the model performances, the dataset was divided into a training set (70%) and a test set (30%). The AUROC values of SNSB-II scores were 0.803 in both sexes, 0.840 for males, and 0.770 for females. In the combined model, the AUROC values were 0.790 (0.773) for males (and females), which were significantly higher than those from the model including MMSE scores alone (0.723 for males and 0.622 for females) or bioimpedance variables alone (0.640 for males and 0.615 for females). Furthermore, the accuracies of the combined model were comparable to those of machine learning models. The bioimpedance-MMSE combined model effectively distinguished the MCI participants and suggests a technique for rapid and improved screening of the elderly population at risk of cognitive impairment.

Corrigendum: Prefrontal event-related potential markers in association with mild cognitive impairment.

[This corrects the article DOI: 10.3389/fnagi.2023.1273008.].

Saccadic eye movement variables as biomarkers for cognitive decline in elderly individuals.

Alzheimer's disease (AD) is the leading cause of Dementia, and mild cognitive impairment (MCI) is often considered a precursor to the development of AD dementia and other types of Dementia. Biomarkers such as amyloid beta are specific and sensitive in identifying AD and can identify individuals who have biological evidence of the disease but have no symptoms, but clinicians and researchers may not easily use them on a large scale. Ocular biomarkers, such as those obtained through eye tracking (ET) technology, have the potential as a diagnostic tool due to their accuracy, affordability, and ease of use. In this study, we show that eye movement (EM) metrics from an interleaved Pro/Anti-saccade (PS/AS) ET task can differentiate between cognitively normal (CN) and MCI subjects and that the presence of Aß brain deposits, a biomarker of AD, significantly affects performance on these tasks. Individuals with Aß deposits (Aß+) performed worse than those without (Aß-). Our findings suggest that eye-tracking measurements may be a valuable tool for detecting amyloid brain pathology and monitoring changes in cognitive function in CN and MCI individuals over time.Clinical Relevance- The PS/AS paradigm, which measures saccadic eye movements, can accurately detect subtle cognitive impairments and changes in the brain associated with Alzheimer's disease in CN and MCI individuals. This makes it a valuable tool for identifying individuals at risk for cognitive decline and tracking changes in cognitive function over time.

Prefrontal event-related potential markers in association with mild cognitive impairment.

Background: Alzheimer's disease (AD) is among the leading contributors of dementia globally with approximately 60-70% of its cases. Current research is focused on the mild cognitive impairment (MCI), which is associated with cognitive decline but does not disrupt routine activities. Event-related potential (ERP) research is essential in screening patients with MCI. Low-density channel electroencephalography (EEG) is frequently used due to its convenience, portability, and affordability, making it suitable for resource-constrained environments. Despite extensive research on neural biomarkers for cognitive impairment, there is a considerable gap in understanding the effects on early stages of cognitive processes, particularly when combining physiological and cognitive markers using portable devices. The present study aimed to examine cognitive shortfalls and behavioral changes in patients with MCI using prefrontal selective attention ERP recorded from a prefrontal two-channel EEG device. Methods: We assessed cognitive decline using the Mini-Mental State Examination (MMSE) and the Seoul Neuropsychological Screening Battery (SNSB). We administered auditory selective attention tasks to 598 elderly participants, including those with MCI (160) and cognitively normal (CN) individuals (407). We conducted statistical analyses such as independent t-tests, Pearson's correlations, and univariate and multiple logistic regression analyses to assess group differences and associations between neuropsychological tests, ERP measures, behavioral measures, and MCI prevalence. Results: Our findings revealed that patients with MCI demonstrated slower information-processing abilities, and exhibited poorer task execution, characterized by reduced accuracy, increased errors, and higher variability in response time, compared to CN adults. Multiple logistic regression analyses confirmed the association between some ERP and behavioral measures with MCI prevalence, independent of demographic and neuropsychological factors. A relationship was observed between neuropsychological scores, ERP, and behavioral measures. Discussion: The slower information processing abilities, and poor task execution in the MCI group compared to the CN individuals suggests flawed neurological changes and reduced attentional maintenance during cognitive processing, respectively. Hence, the utilization of portable EEG devices to capture prefrontal selective attention ERPs, in combination with behavioral assessments, holds promise for the identification of mild cognitive deficits and neural alterations in individuals with MCI. This approach could potentially augment the traditional neuropsychological tests during clinical screening for MCI.

Reduced body cell mass and functions in lower extremities are associated with mild cognitive impairment and Alzheimer's dementia.

This study examined the alterations of segmental body composition in individuals with Alzheimer's pathology (AD), including mild cognitive impairment (MCI) and dementia. A multifrequency bioimpedance analysis (BIA) was used to provide segmental water and impedance variables from 365 cognitively normal (CN), 123 MCI due to AD, and 30 AD dementia participants. We compared the BIA variables between the three groups, examined their correlations with neuropsychological screening test scores, and illustrate their 95% confidence RXc graphs. AD dementia participants were older, more depressive, and had worse cognitive abilities than MCI due to AD and CN participants. Although the BIA variables showed weak partial correlations with the cognitive test scores, we found patterns of an increasing water content in lean mass, increasing extra to intracellular water ratio, and decreasing reactance and phase angle in the lower extremities with effect sizes ranging from 0.26 to 0.51 in the groups of MCI and dementia due to AD compared with CN individuals. The RXc graphs upheld the findings with a significant displacement downward and toward the right, dominantly in the lower extremities. Individuals with AD pathology exhibit a reduced body cell mass or cell strength, an abnormal cellular water distribution, and an overhydration status in lean mass, especially in the lower extremities.

Segmental bioelectrical impedance analysis for Korean older population with cold pattern.

Objective: This study examined the association of whole-body composition and segmental bioimpedance variables with cold pattern (CP) in different sexes. Methods: We assigned 667 older individuals to a CP group (n = 488) and a non-CP group (n = 179) by using an eight-item self-administered questionnaire. Seven body composition variables and three pairs of segmental bioimpedance variables for the upper and lower extremities, which were obtained from a segmental multifrequency bioimpedance analyzer, were employed to investigate their association with CP. Participants' characteristics were first described. Then we compared the selected body composition and bioimpedance variables between the CP and non-CP groups. Finally, their association with CP was investigated using univariate and multivariate regression analyses. All analyses were performed separately for women and men. Results: Both women and men exhibited a comparable mean age in the CP and non-CP groups; however, women with CP had significantly lower blood pressures, whereas men with CP showed a higher proportion of osteoarthritis than those without CP. Compared with the non-CP group, individuals with CP exhibited significantly smaller body sizes indicated by shorter height and smaller weight, lower body mass index, and smaller volume-to-body surface area ratio in both sexes. After controlling for age, height, weight, and other covariates, we found significant reductions in body lean mass such as fat-free mass and body cell mass, basal metabolic rate per unit mass, total body water, and intra-to-extracellular water ratio in the CP group. With regard to segmental bioimpedance analysis, the resistance ratios and phase angles in the upper and lower extremities yield significant associations with CP incidence, as demonstrated by the odds ratio (95% confidence interval) of 1.72 (1.16-2.57), 1.69 (1.18-2.48), 0.60 (0.40-0.89), and 0.57 (0.39-0.82), respectively. However, these results did not emerge in men. Conclusion: Abnormal cellular water distribution and deterioration in body cell mass and/or cell strength are associated with CP prevalence, regardless of age, height, weight. These findings are similar in the upper and lower extremities and are more pronounced in women. The abovementioned patterns may be considered effective indicators for identifying CP in the older adult population.

Corrigendum: Segmental bioimpedance variables in association with mild cognitive impairment.

[This corrects the article DOI: 10.3389/fnut.2022.873623.].

Segmental Bioimpedance Variables in Association With Mild Cognitive Impairment.

Objective: To examine the changes in body composition, water compartment, and bioimpedance in mild cognitive impairment (MCI) individuals. Methods: We obtained seven whole-body composition variables and seven pairs of segmental body composition, water compartment, and impedance variables for the upper and lower extremities from the segmental multi-frequency bioelectrical impedance analysis (BIA) of 939 elderly participants, including 673 cognitively normal (CN) people and 266 individuals with MCI. Participants' characteristics, anthropometric information, and the selected BIA variables were described and statistically compared between the CN participants and those with MCI. The correlations between the selected BIA variables and neuropsychological tests such as the Korean version of the Mini-Mental State Examination and Seoul Neuropsychological Screening Battery - Second Edition were also examined before and after controlling for age and sex. Univariate and multivariate logistic regression analyses with estimated odds ratios (ORs) were conducted to investigate the associations between these BIA variables and MCI prevalence for different sexes. Results: Participants with MCI were slightly older, more depressive, and had significantly poorer cognitive abilities when compared with the CN individuals. The partial correlations between the selected BIA variables and neuropsychological tests upon controlling for age and sex were not greatly significant. However, after accounting for age, sex, and the significant comorbidities, segmental lean mass, water volume, resistance, and reactance in the lower extremities were positively associated with MCI, with ORs [95% confidence interval (CI)] of 1.33 (1.02-1.71), 1.33 (1.03-1.72), 0.76 (0.62-0.92), and 0.79 (0.67-0.93), respectively; with presumably a shift of water from the intracellular area to extracellular space. After stratifying by sex, resistance and reactance in lower extremities remained significant only in the women group. Conclusion: An increase in segmental water along with segmental lean mass and a decrease in body cell strength due to an abnormal cellular water distribution demonstrated by reductions in resistance and reactance are associated with MCI prevalence, which are more pronounced in the lower extremities and in women. These characteristic changes in BIA variables may be considered as an early sign of cognitive impairment in the elderly population.

Psycho-Electrophysiological Benefits of Forest Therapies Focused on Qigong and Walking with Elderly Individuals.

We developed two distinct forest therapy programs (FTPs) and compared their effects on dementia prevention and related health problems for older adults. One was focused on Qigong practice in the forest (QP) and the other involved active walking in the forest (WP). Both FTPs consisted of twelve 2-h sessions over six weeks and were conducted in an urban forest. We obtained data from 25, 18, and 26 participants aged 65 years or above for the QP, WP, and control groups, respectively. Neuropsychological scores via cognition (MoCA), geriatric depression (GDS) and quality of life (EQ-5D), and electrophysiological variables (electroencephalography, bioimpedance, and heart rate variability) were measured. We analyzed the intervention effects with a generalized linear model. Compared to the control group, the WP group showed benefits in terms of neurocognition (increases in the MoCA score, and alpha and beta band power values in the electroencephalogram), sympathetic nervous activity, and bioimpedance in the lower body. On the other hand, the QP group showed alleviated depression and an increased bioimpedance phase angle in the upper body. In conclusion, both active walking and Qigong in the forest were shown to have distinctive neuropsychological and electrophysiological benefits, and both had beneficial effects in terms of preventing dementia and relieving related health problems for elderly individuals.

Predicting Dementia With Prefrontal Electroencephalography and Event-Related Potential.

Objective: To examine whether prefrontal electroencephalography (EEG) can be used for screening dementia. Methods: We estimated the global cognitive decline using the results of Mini-Mental Status Examination (MMSE), measurements of brain activity from resting-state EEG, responses elicited by auditory stimulation [sensory event-related potential (ERP)], and selective attention tasks (selective-attention ERP) from 122 elderly participants (dementia, 35; control, 87). We investigated that the association between MMSE and each EEG/ERP variable by using Pearson's correlation coefficient and performing univariate linear regression analysis. Kernel density estimation was used to examine the distribution of each EEG/ERP variable in the dementia and non-dementia groups. Both Univariate and multiple logistic regression analyses with the estimated odds ratios were conducted to assess the associations between the EEG/ERP variables and dementia prevalence. To develop the predictive models, five-fold cross-validation was applied to multiple classification algorithms. Results: Most prefrontal EEG/ERP variables, previously known to be associated with cognitive decline, show correlations with the MMSE score (strongest correlation has |r| = 0.68). Although variables such as the frontal asymmetry of the resting-state EEG are not well correlated with the MMSE score, they indicate risk factors for dementia. The selective-attention ERP and resting-state EEG variables outperform the MMSE scores in dementia prediction (areas under the receiver operating characteristic curve of 0.891, 0.824, and 0.803, respectively). In addition, combining EEG/ERP variables and MMSE scores improves the model predictive performance, whereas adding demographic risk factors do not improve the prediction accuracy. Conclusion: Prefrontal EEG markers outperform MMSE scores in predicting dementia, and additional prediction accuracy is expected when combining them with MMSE scores. Significance: Prefrontal EEG is effective for screening dementia when used independently or in combination with MMSE.

Principal Characteristics of Affected and Unaffected Side Trunk Movement and Gait Event Parameters during Hemiplegic Stroke Gait with IMU Sensor.

This study describe the characteristics of hemiplegic stroke gait with principal component analysis (PCA) of trunk movement (TM) and gait event (GE) parameters by the inertial measurement unit (IMU) sensors: (1) Background: This process can determine dominant variables through multivariate examination to identify the affected, unaffected, and healthy lower-limb sides; (2) Methods: The study monitored forty patients with stroke and twenty-eight healthy individuals comprising the control group for comparison. The IMU sensors were attached to each subject while performing a 6 m walking test. Sixteen variables extracted from the measured data were divided into 7 GE and 9 TM variables explaining pelvis tilt, oblique, and rotation. (3) Results: The tilt range variables of the trunk movement on the affected and unaffected sides were lower than those of the healthy side; this showed between-group differences in various GE variables. For the healthy and affected sides, 80% of variances were explained with 2 or 3 PCs involving only a few dominant variables; and (4) Conclusions: The difference between each side leg should be considered during the development of a diagnosis method. This research can be utilized to develop functional assessment tools for personalized treatment and to design appropriate training protocols.

Traditional Korean Medicine-Based Forest Therapy Programs Providing Electrophysiological Benefits for Elderly Individuals.

We aimed to develop forest therapy programs (FTPs) to prevent dementia and related health problems in the elderly population, with the assumption that health benefits are FTP-type specific and depend on the participant's psychophysiological traits. For this purpose, we developed two distinct FTPs, namely, a guided-breathing meditation program (BP) and a walking program (WP); we adopted the approach of Sasang constitutional (SC) medicine, which categorizes individuals into one of three SC types (SC1, SC2, or SC3) for medical care. The FTPs ran 11 sessions over 11 weeks. We recruited 29/31/28 participants who were 65 years of age or older for the BP/WP/control groups, respectively; obtained electrophysiological measurements via electroencephalogram (EEG), heart rate variability (HRV), and bioimpedance; and analyzed the intervention effects with analysis of covariance. Compared with the control, the BP and WP resulted in benefits for neural activity and parasympathetic nervous activity (PNA), respectively, and both FTPs yielded distinct beneficial effects on bioimpedance. Constitution-specific effects were also present. The SC1- and SC2-type participants gained positive effects in neural activity from the BP and WP, respectively. The SC3-type participants showed improvements in PNA from the WP. In conclusion, for older individuals, both programs conferred health benefits that would help prevent dementia, and the benefits were program-specific and constitution-specific.

Short-Term Efficacy of Pulsed Radiofrequency Thermal Stimulation on Acupoints for Chronic Low Back Pain: A Preliminary Study of a Randomized, Single-Blinded, Placebo-Controlled Trial.

BACKGROUND: The objective of this study was to evaluate the pain-relief efficacy of thermal stimulation induced by a pulsed radiofrequency (PRF) thermal stimulation applied to acupoints (APs) in patients with low back pain (LBP). The study was designed as a randomized, single-blinded, placebo-controlled trial. Methods. Fifty-six LBP patients whose minimum pain intensity score on a visual analogue scale (VAS, 0-100 mm) was more than 30 mm were randomly allocated to either the placebo-controlled or the treatment group at a 1:1 ratio. The treatment and placebo-controlled groups received PRF thermal stimulation plus cupping therapy and cupping therapy only, respectively. Each patient was scheduled to receive a total of three treatment sessions over one week with allowing a window up to 4 days. Six of the 13 predefined APs were selected differently for each session depending on the change in patient's symptoms and intensity of pain. The primary outcome was the mean difference between the placebo-controlled and treatment group of VAS changes from the baseline to the end of the follow-up period. RESULTS: The patients' reported VAS scores from baseline to the end of follow-up (average: 9.8 days) were significantly decreased by 8.036 points (two-sided 95% CI, -11.841 to -4.231) and 13.393 points (two-sided 95% CI: 17.198 to -9.588) in the treatment and the placebo-controlled groups, respectively. However, the change in VAS scores between the treatment group and the placebo-controlled group was not significantly different (2.015 mm, two-sided 95% CI: -5.288 to 9.317). CONCLUSION: The trial results indicated that treatment with either PRF thermal stimulation with cupping therapy or cupping therapy alone effectively relieved LBP. The efficacy of PRF thermal stimulation combined with cupping therapy was not superior to that of cupping therapy alone. Trial registration number: Clinical Research Information Service (KCT0002137). The trial was registered retrospectively on 10 November, 2016.

Glucose-independent segmental phase angles from multi-frequency bioimpedance analysis to discriminate diabetes mellitus.

We investigated segmental phase angles (PAs) in the four limbs using a multi-frequency bioimpedance analysis (MF-BIA) technique for noninvasively diagnosing diabetes mellitus. We conducted a meal tolerance test (MTT) for 45 diabetic and 45 control subjects stratified by age, sex and body mass index (BMI). HbA1c and the waist-to-hip-circumference ratio (WHR) were measured before meal intake, and we measured the glucose levels and MF-BIA PAs 5 times for 2 hours after meal intake. We employed a t-test to examine the statistical significance and the area under the curve (AUC) of the receiver operating characteristics (ROC) to test the classification accuracy using segmental PAs at 5, 50, and 250 kHz. Segmental PAs were independent of the HbA1c or glucose levels, or their changes caused by the MTT. However, the segmental PAs were good indicators for noninvasively screening diabetes In particular, leg PAs in females and arm PAs in males showed best classification accuracy (AUC = 0.827 for males, AUC = 0.845 for females). Lastly, we introduced the PA at maximum reactance (PAmax), which is independent of measurement frequencies and can be obtained from any MF-BIA device using a Cole-Cole model, thus showing potential as a useful biomarker for diabetes.