Efficacy and Concurrent Validity of Computerized Brain Training Based on Everyday Living (BTEL) Based on Instrumental Activities of Living for Cognitively Healthy Old Individuals: A Preliminary Study.

Background: Interventions to prevent or attenuate cognitive decline and dementia in older adults are becoming increasingly important. Recently, cognitive training exercise can be via computer or mobile technology for independent or home use. Recent meta-analysis has reported that Computerized Cognitive Training (CCT) is effective at enhancing cognitive function in healthy older and Alzheimer's disease adults, although little is known about individual characteristics of each computerized program. Objective: We developed a new CCT named Brain Training Based on Everyday Living (BTEL) to enhance cognitive capacity for Instrumental Activities of Daily Living (IADL). We aim to evaluate the efficacy of the BTEL among cognitively healthy old individuals and to explore its concurrent validity and construct concept. Methods: We conducted a double-blind study where 106 individuals aged 65 years and older (intervened = 53, control = 53) worked on the active and placebo tasks three times a week over three months (clinical trial: UMIN000048730). The main results were examined using ANCOVA and calculating correlation coefficients. Results: We found no effect on total score of the three tests; however, there was significant effect for the BTEL on: recognition in MMSE, and immediate recall in HDSR. The tasks are associated with prefrontal cortex. In addition, correlations indicated that each BTEL domain had some validity as a cognitive assessment tool. Different from previous CCT, we determined the neuropsychological characteristics of specific cognitive tasks of the BTEL to a certain degree. Conclusions: We found modest efficacy of the BTEL in cognitively healthy old individuals and confirmed its concurrent validity and the conceptual construct.

Utility of paced breathing tablet guidance apparatus with real-time feedback on autonomic function for individuals with mild cognitive impairment: a pilot study.

BACKGROUND: Mild cognitive impairment (MCI) individuals also show significant parasympathetic deficits, while autonomic nervous system (ANS) flexibility can strengthen cognitive and brain function. Paced (or slow) breathing has significant effects on the ANS and is associated with relaxation and well-being. However, paced breathing requires considerable time and practice, a significant barrier to its widespread adoption. Feedback systems appear promising to make practice more time-efficient. A tablet guidance system providing real-time feedback on autonomic function was developed for MCI individuals and tested for efficacy. METHODS: In this single-blind study, 14 outpatients with MCI practised with the device for 5 min twice a day for 2 weeks. The active group received feedback (FB+), whereas the placebo group (FB-) did not. Coefficient of variation of R-R intervals as the outcome indicator was measured immediately after the first intervention (T1 ), the end of the 2-week intervention (T2 ), and 2 weeks later (T3 ). RESULTS: The mean outcome of the FB- group remained unchanged during the study period, whereas the outcome value of the FB+ group increased and retained the intervention effect for an additional 2 weeks. CONCLUSIONS: Results indicate this FB system-integrated apparatus may be useful for MCI patients for effectively learning paced breathing.

Development of informant-reported or self-reported MCI-J questionnaire.

Several studies have reported a high prevalence of missed and delayed mild cognitive impairment (MCI) or mild dementia diagnosis, which could lead to delayed treatment and increased patient and caregiver burden. OBJECTIVES: This study aimed to develop a new questionnaire for nonprofessionals to help detect early signs of MCI and dementia. Respondents included patients, family caregivers, or health professionals. Scores are calculated based on the respondent type and age of subject. METHODS: This study consisted of four steps and included 461 respondents. Steps 1-3 were conducted by a working group, and step 4, by 67 specialist members of the Japanese Society of Geriatric Psychiatry. A scoring algorithm was created and predictive diagnostic probability was analyzed using misdiscrimination rate and cross-validation after item selection to establish a cut-off value for MCI or dementia symptoms. Alzheimer's disease, Lewy body dementia, and frontotemporal dementia were diagnosed. RESULTS: The prediction error rate for patient or informant respondents was confirmed from the evaluation results of 13 items. Sensitivity and specificity were 90.6% and 56.6%, respectively, with a cut-off score of 2. Overall, 82% (61 pairs) of respondents received a definitive diagnosis following a diagnosis from the questionnaire. CONCLUSIONS: This questionnaire could promote earlier presentation to clinical settings for treatment. The high sensitivity indicates the utility of this instrument, but it is not meant as a definitive diagnostic tool and should be followed with a professional assessment.

Sick Students: Presenteeism Among Nursing Students in 3 Countries.

BACKGROUND: Presenteeism, the act of going to work while sick, is associated with increases in medication errors, patient falls, diminished quality of care, and higher costs. To date, presenteeism has not been described among nursing students. PURPOSE: This study described presenteeism in nursing students from 3 different international nursing programs. METHOD: A self-administered survey with open-ended responses was used. RESULTS: While nearly all student respondents believed going to class and clinical experiences put their classmates and patients at risk, the overall presenteeism rate was 85.5% for class and 69.5% for clinical experiences. Although there were significant differences between universities for reasons for presenteeism, a lack of opportunity for making up missed lecture or clinical time predominated. CONCLUSION: Nursing students in 3 culturally different cities reported going to class and clinical experiences while sick despite recognizing the safety risk.

Effects of Anserine/Carnosine Supplementation on Mild Cognitive Impairment with APOE4.

BACKGROUND: Oral supplementation of anserine/carnosine helps preserve cognitive functions in healthy older adults. Mild cognitive impairment (MCI) is a transition between cognitive-normal and dementia. Therefore, it needs to investigate whether anserine/carnosine supplementation (ACS) has effects on subjects with MCI. METHODS: A randomized, double-blind, placebo-controlled 12-week trial was performed. Fifty-four subjects with MCI were randomized to an active group ingesting 750 mg of anserine and 250 mg of carnosine per day or a placebo (1:1). Evaluation of cognitive change was conducted utilizing a psychometric test battery. RESULTS: The score improvement in the global Clinical Dementia Rating (gloCDR) was superior in the active group than placebo (p = 0.023). No beneficial effect in the active group was detected in the other psychometric tests including the Mini-Mental State Examination (MMSE), the Wechsler Memory Scale, and the Alzheimer's Disease Assessment Scale (ADAS). When APOE4 positive (APOE4 (+)) or negative (APOE4 (-)) subjects were separately analyzed, beneficial change in the APOE4 (+) subjects was observed in MMSE (p = 0.025) as well as in gloCDR (p = 0.026). CONCLUSIONS: The present study might suggest that protective effects against cognitive decline in APOE4 (+) MCI subjects exist.

Post-fracture Rehabilitation Effects on Brain Function in Older People.

BACKGROUND: Deterioration of cognitive function is an underlying cause of older people's fractures. The purpose of this study was to evaluate electroencephalogram and cognitive function in patients hospitalized with fractures, both at admission (before intervention) and at the time of discharge (after intervention), to investigate the effects of rehabilitation on brain function. METHODS: A total of 24 patients hospitalized with fracture due to a fall were enrolled in this study. All the subjects received 140 minutes of rehabilitation every day during hospitalization. Touch Panel-type Dementia Assessment Scale (TDAS) was used to test their cognitive function. In electroencephalography (EEG), the Neuronal Activity Topography (NAT) system was used to calculate the "Alzheimer's disease (AD) - normal controls (NLc) differential similarity" in sNAT, ie, a numerical index to show the proximity to AD or normal NLc. RESULTS: There was no significant difference in the total TDAS score among subjects who were examined before and after intervention, but 12 subjects who were observed with deterioration of cognitive functionat at before intervention had a significant improvement in "word-recognition," a sub-item in TDAS (P < 0.05). In addition, the NAT analysis findings showed that the differential similarity in sNAT significantly approached the NLc pattern (P < 0.05). CONCLUSION: EEGs in patients with fractures resulting from a fall became more similar to NL patterns at the time of discharge. In addition, recent-memory function of patients who had decline in cognitive function improved.

Boundary EEG Asymmetry Is Associated to Linguistic Competence in Vascular Cognitive Impairments.

Background and Purpose: We recently noted a gradual change in the boundary electroencephalography (EEG) oscillation of 7.8 Hz between theta (θ) and alpha (α) bands in response to increased atherosclerosis levels in the elderly. The aim of this study was to investigate the role of boundary EEG oscillations of θ-α bands on cognitive functions in vascular cognitive impairments (VCI) patients. Materials and Methods: We examined 55 patients with VCI in carotid stenosis, and underwent EEG in a resting state with closed eyes for 5 min. The asymmetry index (AI) along homologous channel pairs (e.g., F7-8) was assessed using neuronal activity topography (NAT). AI referring to 10 frequency components ranging from 4 to 20 Hz and neuropsychological assessments including linguistic competence were analyzed. Results: The main findings was that the language score had a positive association with AI in 7.8 Hz at F7-8 and a negative association with AI in 6.3 Hz at C3-4 and 14.1 Hz at F3-4. Conclusion: EEG asymmetry in a boundary range might have a special role in linguistic competence, suggesting the application of neural oscillation on the cognitive function evaluation and neurorehabilition induced by a frequency-specific transcranial alternating current stimulation.

Altered Neuronal Activity Topography Markers in the Elderly with Increased Atherosclerosis.

Background: Previously, we reported on vascular cognitive impairment (VCI) templates, consisting of patients with VCI associated with carotid stenosis (>60%) using a quantitative electroencephalographic (EEG) technique called neuronal activity topography (NAT). Here using the VCI templates, we investigated the hypothesis that internal carotid artery-intima-media thickness (ICA-IMT) is associated with EEG spectrum intensity (sNAT) and spectrum steepness (vNAT). Methods: A total of 221 community-dwelling elderly subjects were recruited. Four groups were classified according to quartiles of ICA-IMT as assessed by ultrasonography: control group A, normal (≤0.9 mm); group B, mild atherosclerosis (1-1.1 mm); group C, moderate atherosclerosis (1.2-1.8 mm); and group D, severe atherosclerosis (≥1.9 mm). EEG markers of power ratio index (PRI), and the binary likelihood of being in the VCI group vs. the that of being in control group A (sL x:VCI-A , vL x:VCI-A ) were assessed, respectively. Differences in mean total scores for PRI, sL x:VCI-A , vL x:VCI-A , between control group A and the other groups were compared using Dunnett's test, respectively. Results: The mean total scores of the PRI were 3.25, 3.00, 2.77, and 2.26 for groups A, B, C, and D, respectively. There was a significant decrease in the PRI in group D compared with group A (P = 0.0066). The mean total scores of the sL x:VCI-A were -0.14, -0.11, -0.1, and -0.03 for groups A, B, C, and D, respectively. The sL x:VCI-A in group D was significantly higher compared to that in group A (P < 0.0001). The mean total scores of the vL x:VCI-A were -0.04,-0.01, 0.01, and 0.06 for group A, B, C, and D, respectively. The vL x:VCI-A in group D and group C was significantly higher compared to that in group A, respectively (P < 0.0001, P = 0.02). Conclusion: Community-dwelling elderly subjects in the increased carotid atherosclerosis of ICA-IMT (≥1.9 mm) were at greatest risk of an EEG change as assessed by NAT.

Neuronal activity topography parameters as a marker for differentiating vascular cognitive impairment in carotid stenosis.

Previously, we reported on the differentiation between patients with Alzheimer disease and normal controls using a quantitative electroencephalographic technique called neuronal activity topography (NAT). In this technique, cerebral neuronal activities are characterized by the signal intensity and coherence (sNAT and vNAT, respectively). In the present study, we examined 47 patients with vascular cognitive impairment in carotid stenosis and 52 normal controls. All subjects underwent electroencephalography in a resting state with closed eyes for 5 minutes. Electroencephalographic markers of the differential likelihood, that is, the sensitivity-versus-specificity characteristics, sL(x:VCI-NLc) and vL(x:VCI-NLc), were assessed with neuronal activity topography and were compared between the 2 groups. sL(x:VCI-NLc) and vL(x:VCI-NLc) crossed each other at a cutoff value of the differential likelihood. Separation of the patients and controls was made with a sensitivity of 92% and 88%, as well as a false-positive rate of 8% and 12% for sL(x:VCI-NLc) and vL(x:VCI-NLc), respectively. Using sNAT, we accurately differentiated 92% patients with vascular cognitive impairment. We recommend that sNAT, rather than vNAT, should be used in detecting vascular cognitive impaired patients.

Normalized power variance change between pre-ictal and ictal phase of an epilepsy patient using NAT analysis: a case study.

Variance of state variables shifts due to phase-instability and may serve as an early-warning signal of phase transition of complex systems such as an epileptic seizure of brain cortical activity. Neuronal Activity Topology (NAT) analysis calculates a normalized-power-variance (NPV) of electroencephalogram (EEG) data in each frequency band to obtain relative values comparable among different power states.

EEG markers for characterizing anomalous activities of cerebral neurons in NAT (neuronal activity topography) method.

A pair of markers, sNAT and vNAT, is derived from the electroencephalogram (EEG) power spectra (PS) recorded for 5 min with 21 electrodes (4-20 Hz) arranged according to the 10-20 standard. These markers form a new diagnosis tool "NAT" aiming at characterizing various brain disorders. Each signal sequence is divided into segments of 0.64 s and its discrete PS consists of eleven frequency components from 4.68 (3 × 1.56) Hz through 20.34 (13 × 1.56) Hz. PS is normalized to its mean and the bias of PS components on each frequency component across the 21 signal channels is reset to zero. The marker sNAT consists of ten frequency components on 21 channels, characterizing neuronal hyperactivity or hypoactivity as compared with NLc (normal controls). The marker vNAT consists of ten ratios between adjacent PS components denoting the over- or undersynchrony of collective neuronal activities as compared with NLc. The likelihood of a test subject to a specified brain disease is defined in terms of the normalized distance to the template NAT state of the disease in the NAT space. Separation of MCI-AD patients (developing AD in 12-18 months) from NLc is made with a false alarm rate of 15%. Locations with neuronal hypoactivity and undersynchrony of AD patients agree with locations of rCBF reduction measured by SPECT. The 2-D diagram composed of the binary likelihoods between ADc and NLc in the two representations of sNAT and vNAT enables tracing the NAT state of a test subject approaching the AD area, and the follow-up of the treatment effects.

Complete amino acid sequence and characterization of the reaction mechanism of a glucosamine-induced novel alcohol dehydrogenase from Agrobacterium radiobacter (tumefaciens).

A glucosamine-induced novel alcohol dehydrogenase has been isolated from Agrobacterium radiobacter (tumefaciens) and its fundamental properties have been characterized. The enzyme catalyzes NAD-dependent dehydrogenation of aliphatic alcohols and amino alcohols. In this work, the complete amino acid sequence of the alcohol dehydrogenase was determined by PCR method using genomic DNA of A. radiobacter as template. The enzyme comprises 336 amino acids and has a molecular mass of 36 kDa. The primary structure of the enzyme demonstrates a high homology to structures of alcohol dehydrogenases from Shinorhizobium meliloti (83% identity, 90% positive) and Pseudomonas aeruginosa (65% identity, 76% positive). The two Zn(2+) ion binding sites, both the active site and another site that contributed to stabilization of the enzyme, are conserved in those enzymes. Sequences analysis of the NAD-dependent dehydrogenase family using a hypothetical phylogenetic tree indicates that these three enzymes form a new group distinct from other members of the Zn-containing long-chain alcohol dehydrogenase family. The physicochemical properties of alcohol dehydrogenase from A. radiobacter were characterized as follows. (1) Stereospecificity of the hydride transfer from ethanol to NADH was categorized as pro-R type by NMR spectra of NADH formed in the enzymatic reaction using ethanol-D(6) was used as substrate. (2) Optimal pH for all alcohols with no amino group examined was pH 8.5 (of the C(2)-C(6) alcohols, n-amyl alcohol demonstrated the highest activity). Conversely, glucosaminitol was optimally dehydrogenated at pH 10.0. (3) The rate-determining step of the dehydrogenase for ethanol is deprotonation of the enzyme-NAD-Zn-OHCH(2)CH(3) complex to enzyme-NAD-Zn-O(-)CH(2)CH(3) complex and that for glucosaminitol is H(2)O addition to enzyme-Zn-NADH complex.