Actual Clinical Practice Assessment: A Rapid and Easy-to-Use Tool for Evaluating Cognitive Decline Equivalent to Dementia.

Background Screening tests reveal the early signs of cognitive decline, enabling better self-care and preparation for the future. We developed and evaluated the accuracy of a rapid (20 s) and easy-to-use tool called ONSEI, assessing the cognitive decline equivalent to dementia in actual clinical practice by correlating clinical diagnoses with the ONSEI classification. Methods In this retrospective observational study, data were collected from individuals who visited three neurosurgical clinics in neighboring prefectures of Tokyo, Japan. ONSEI analysis was performed using a smartphone or tablet. The tool adopts a machine-learning algorithm using the speaker's age, time-orientation task score, and acoustic features of spoken responses to that task. Significant differences in accuracy, sensitivity, and specificity were evaluated by Fisher's exact test. Results The overall classification accuracy of ONSEI was 98.1% (p<0.001). The sensitivity and specificity were 97.3% (p<0.001) and 98.5% (p<0.001), respectively. The proportion of correct classifications was consistent across different age groups. Conclusion ONSEI showed high classification accuracy for dementia in cognitively normal individuals in actual clinical practice, regardless of the facility at which the tests were conducted or the age of the participants. Thus, ONSEI can be useful for dementia screening and self-care.

Brain activity predicts future learning success in intensive second language listening training.

This study explores neural mechanisms underlying how prior knowledge gained from pre-listening transcript reading helps comprehend fast-rate speech in a second language (L2) and applies to L2 learning. Top-down predictive processing by prior knowledge may play an important role in L2 speech comprehension and improving listening skill. By manipulating the pre-listening transcript effect (pre-listening transcript reading [TR] vs. no transcript reading [NTR]) and type of languages (first language (L1) vs. L2), we measured brain activity in L2 learners, who performed fast-rate listening comprehension tasks during functional magnetic resonance imaging. Thereafter, we examined whether TR_L2-specific brain activity can predict individual learning success after an intensive listening training. The left angular and superior temporal gyri were key areas responsible for integrating prior knowledge to sensory input. Activity in these areas correlated significantly with gain scores on subsequent training, indicating that brain activity related to prior knowledge-sensory input integration predicts future learning success.

Severity of Depressive Symptoms and Volume of Superior Temporal Gyrus in People Who Visit a Memory Clinic Unaccompanied.

BACKGROUND/AIMS: Depression and cognitive decline are reported to be interrelated. Depression of older adults with memory complaints who seek medical help have not been well documented. This study was carried out to test the hypothesis that a relatively high level of depressive symptoms associated with brain structure is characteristic of people who visited a memory clinic unaccompanied (UA). METHOD: We retrospectively compared Center for Epidemiologic Studies Depression Scale (CES-D, for evaluation of depressive symptoms) scores of UA subjects (n = 21) with those of people who were accompanied (n = 75). Within each groups, we further examined the association between brain morphology and the CES-D scores using FreeSurfer software. RESULTS: We found that the relatively high CES-D scores of UA subjects were inversely associated with the normalized volumes of bilateral superior temporal gyrus (STG). CONCLUSION: Our results suggest that depressive symptoms of UA subjects demonstrated by the relatively high levels of CES-D scores were primary, because of the inverse association with the normalized volume of bilateral STG. Thus, focusing on the depressive symptoms may be a suitable approach to satisfy potential medical needs of UA subjects with or without memory impairment.

Electrical determination of current injection and internal quantum efficiencies in AlGaN-based deep-ultraviolet light-emitting diodes.

We propose a method to determine the current injection efficiency (CIE) and internal quantum efficiency (IQE) of light-emitting diodes (LEDs) during current injection. The method is based on fourth-order polynomial fitting of a modified rate equation to electroluminescence data. Our method can extract the CIE at low injection current densities, unlike conventional methods that generally assume the CIE to be unity. We apply the method to AlGaN-based deep-ultraviolet LEDs. Results show that the CIE was only approximately 51% at low injection current densities and was almost independent of injection current density up to 100 A/cm2. The peak IQE was 77%.

Prevalence of depression and depressive symptoms among older Japanese people: comorbidity of mild cognitive impairment and depression.

BACKGROUND: The aim of the study was to estimate the prevalence of DSM-III-R major depressive episodes (MDEs), depressive symptoms cases (DSCs) (defined as a score of ≥6 on the Geriatric Depression Scale but falling short of MDE), and coexisting mild cognitive impairment (MCI) among Japanese community-dwelling older people. METHODS: Prevalence was estimated based on screening evaluation, individual interviews, and door-to-door visits. MDE and DSC were diagnosed, and the cognitive status of the participants was determined to be dementia, MCI, or normal. RESULTS: A total of 1888 subjects of 2698 candidates (70.0%) participated. The prevalence of MDE and DSC were estimated to be 4.5% (95% CI, 3.4-6.0) and 11.5% (95% CI, 4.2-28.0), respectively. MCI was more prevalent in subjects with depression (26.2%) than those with normal mood (17.9%). Although no prototypical profile of cognitive dysfunction was revealed, multiple MCI was more prevalent in subjects with depression (12.2%) than subjects with normal mood (3.8%). Conversely, subjects with MCI (26.3%) were more likely to develop depression compared with those with normal cognitive function (18.0%). CONCLUSIONS: The prevalence of depression in our subjects seems to be similar with that of previous studies. MCI was more prevalent in subjects with depression than those with normal mood. Individuals with depression showed no particular association with any of the four MCIs. Given that depression and MCI are often associated with each other and that MCI is a predictor for development of dementia, the risk of developing dementia in the depressed older people with coexisting MCI should be acknowledged.

Improvement in delusions and hallucinations in patients with dementia with Lewy bodies upon administration of yokukansan, a traditional Japanese medicine.

BACKGROUND: This multicentre open-label trial examined the efficacy and safety of the traditional Japanese medicine, or Kampo medicine, yokukansan (YKS), for behavioural and psychological symptoms of dementia (BPSD) in patients with dementia with Lewy bodies. METHODS: Sixty-three dementia with Lewy bodies patients with probable BPSD (M:W, 30:33; mean age, 78.2±5.8 years) were enrolled and treated with YKS for 4 weeks. RESULTS: Significant improvements in Neuropsychiatric Inventory scores (mean decrease, 12.5 points; P<0.001) and Zarit Burden Interview-Japanese edition tests (mean decrease, 3.6 points; P=0.024) were observed. In patients who consented to an assessment after 2 weeks of treatment, a time-dependent significant improvement was observed in the Neuropsychiatric Inventory score (n=23; mean decrease, 14.4; P<0.001), each subscale, including delusions and hallucinations, the Zarit Burden Interview-Japanese edition (n=22; mean decrease, 8.2; P<0.01) and the behavioural pathology in Alzheimer's disease insomnia subscale. The Mini-Mental State Examination and the Disability Assessment for Dementia (DAD) showed no significant change. Adverse events were observed in 11 (18%) patients. Three patients (5%) discontinued YKS due to adverse reactions, namely, spasticity and exacerbation of BPSD, edema, and nausea. Hypokalaemia (<3.5 mEq/L) was present in four patients (6%) at the study endpoint. Worsening of extrapyramidal symptoms was not observed. CONCLUSION: YKS improved BPSD in dementia with Lewy bodies patients and caregiver burden scores without deterioration in cognitive function. YKS is useful for the treatment of delusions and hallucinations in BPSD.

Issues facing home-based medical support services.

The first part of the present review describes the current status of elderly people with behavioral and psychological symptoms of dementia (BPSD) in the community and basic viewpoints for differentiating between different forms of dementia. Specifically, it focuses on four points among the data and research related to determining the current status of elderly people with BPSD. We also propose basic concepts for differentiating between the core symptoms of dementia and BPSD, BPSD and delirium, and agitation and delirium. In the second part of the present review, various aspects of the symptom 'agitation' are discussed based on the experience of our home visit medical service for people with dementia by describing two cases. In cases such as Case 1, where the subject was given high doses of antipsychotics, we believe the problem was that the physicians immediately abstracted all of the abnormal behavior in the subject's life as 'agitation', and provided treatment to the subject accordingly. In Case 2, where the subject had dementia with Lewy bodies (DLB), we propose that it is crucial to differentiate clearly between agitation and delirium. Both of these cases show the risks of focusing treatment simply on agitation. When BPSD occurs in a person with dementia, the burden on caregivers increases. At such times, physicians tend to side with the family rather than with the patient. However, medical care is intended to be for the afflicted person, and physicians should base their plans for medical intervention on this principle.

Mitochondrial DNA variants in a Japanese population of patients with Alzheimer's disease.

The evidence for the role of mitochondria in Alzheimer's disease (AD) has been well investigated, based on the amyloid hypothesis and its relation to the mitochondrial dysfunction due to oxidative stress. However, contrasting reports describe an unclear picture on the relationship between AD and mitochondrial DNA (mtDNA) variations. Therefore, we analyzed complete mtDNA sequences from 153 AD patients and 129 normal control subjects to determine if inherited mtDNA polymorphisms or rare variants, or both contribute to the etiology of late-onset AD. The results reported herein indicate that inherited mtDNA common polymorphisms could not be the single major causes of AD but that some rare variants in the protein-coding-region may have protective effects for high-risk populations with the APOE e4 allele. Furthermore, our results support the idea that the np956-965 poly-c insertion and 856A>G variant might be a riskfactor for AD.

Decreased ventilatory response to hypercapnia in dementia with Lewy bodies.

A systematic autonomic dysfunction observed among patients with dementia with Lewy bodies (DLB) has recently attracted close attention. Here, we compare cardiovascular and pulmonary autonomic functions among patients with DLB, patients with Alzheimer's disease, and healthy control subjects. All 15 DLB patients demonstrated severely low ventilatory response to hypercapnia, whereas none of the other subjects demonstrated abnormal results. The majority of the DLB patients showed impaired heart rate variability, low uptake on (123)I-metaiodobenzylguanidine myocardial scintigraphy, and orthostatic hypotension. Ventilatory response to hypercapnia as a marker of respiratory autonomic function is a promising diagnostic tool for DLB.

Prevalence of four subtypes of mild cognitive impairment and APOE in a Japanese community.

BACKGROUND: The results of previous reports estimating the prevalence of mild cognitive impairment (MCI) have varied widely according to the criteria used to define MCI. METHODS: We assessed the cognitive function of Japanese community-dwelling individuals >or=65 years old and attempted to estimate the prevalence of four MCI subtypes (amnestic single, amnestic multiple, nonamnestic single, and nonamnestic multiple) using two cutoffs (1 and 1.5 SD) below normative standard. Presence of apolipoprotein E4 allele (APOE4), which is known as a strong risk factor for AD, is reportedly associated with high risk of conversion from MCI to AD. We therefore calculated the frequency of APOE4 carriers for each MCI subtype. RESULTS: Initially 1888 (70%) of 2698 baseline samples participated, and 1433 (53%) subjects who had complete clinical data including APOE typing remained for the final analysis. The prevalence of MCI subtypes varied within the range of 1.7-16.6%, depending on the criteria applied. Prevalence of MCI was higher using a cutoff at -1.0 SD than at -1.5 SD, and prevalence of amnestic MCI single at -1.5 SD was lowest among all subtypes of MCI. Frequency of APOE4 was higher for amnestic MCI than for non-amnestic MCI or the cognitively normal group. CONCLUSION: The prevalence of MCI was highly dependent on the diagnostic criteria applied. A higher frequency of APOE4 in participants with amnestic MCI subtype suggested a greater risk of future AD. For future interventions to delay the onset of dementia, targeting individuals with amnestic MCI multiple at -1 SD might be desirable.

Dementia and mild cognitive impairment among non-responders to a community survey.

We aimed to estimate the prevalence of mild cognitive impairment (MCI) among elderly non-responders to a community-based survey. We conducted a two-phase, population-based cross-sectional study of community-dwelling individuals aged 65 years or older in Tone, located in central Japan. The first phase of the study consisted of physical and cognitive examinations of individuals who responded to the first recruitment (quick-responders), whereas the second phase included individuals who did not respond in the first phase (delayed-responders). We compared the prevalence of MCI and dementia between delayed-responders and quick-responders. Of the 2,698 potential candidates, 1,888 (1,619 quick-responders, 225 delayed-responders, and 44 nursing home residents) were enrolled (70.0%). The prevalence of MCI was 2.3-fold increased in delayed-responders compared to the quick-responders (OR=2.27, 95% CI: 1.37-3.77, p=0.002, aged< or =74). In order to develop a method for the early detection of dementia, we must pay more attention to delayed-or non-responders.

A randomized cross-over study of a traditional Japanese medicine (kampo), yokukansan, in the treatment of the behavioural and psychological symptoms of dementia.

The effectiveness and safety of yokukansan (TJ-54), a traditional Japanese medicine (kampo) for the treatment of the behavioural and psychological symptoms of dementia (BPSD), were evaluated in 106 patients diagnosed as having Alzheimer's disease (AD) (including mixed-type dementia) or dementia with Lewy bodies. Patients were randomly assigned to group A (TJ-54 treatment in period I and no treatment in period II; each period lasting 4 wk) or group B (no treatment in period I and TJ-54 treatment in period II). BPSD and cognitive functions were evaluated using the Neuropsychiatric Inventory (NPI) and the Mini-Mental State Examination (MMSE), respectively. Activities of daily living (ADL) were evaluated using Instrumental Activities of Daily Living (IADL) in outpatients and the Barthel Index in in-patients. For the safety evaluation, adverse events were investigated. Significant improvements in mean total NPI score associated with TJ-54 treatment were observed in both periods (Wilcoxon test, p=0.040 in period I and p=0.048 in period II). The mean NPI scores significantly improved during TJ-54 treatment in groups A and B (p=0.002 and p=0.007, respectively) but not during periods of no treatment. Among the NPI subscales, significant improvements were observed in delusions, hallucinations, agitation/aggression, depression, anxiety, and irritability/lability. The effects of TJ-54 persisted for 1 month without any psychological withdrawal symptoms in group A. TJ-54 did not show any effect on either cognitive function or ADL. No serious adverse reactions were observed. The present study suggests that TJ-54 is an effective and well-tolerated treatment for patients with BPSD.

Lack of association between TrkA single nucleotide polymorphisms and sporadic Alzheimer's disease in a Japanese population.

Nerve growth factor and its receptor with tyrosine kinase activity (TrkA) have been implicated in the development of Alzheimer's disease (AD). Entire coding regions of TrkA gene harboring exons 1 through 17 were sequenced in 114 patients with sporadic AD and 112 control subjects in a Japanese population, and six known and two novel single nucleotide polymorphisms were identified, but no mutation associated with sporadic AD was identified. Concurrently, case-control analysis of TrkA gene A1674G polymorphism in 534 patients with sporadic AD and 454 control subjects has revealed no significant differences in TrkA genotype or allele frequencies even after stratification for Apolipoprotein E epsilon4 carrier statuses. Thus, the TrkA genotype does not appear to influence the risk of developing sporadic AD in a Japanese population.

Log-linear models for assessing gene-age interaction and their application to case-control studies of the apolipoprotein E (apoE) gene in Alzheimer's disease.

Case-control studies provide a powerful approach for detecting disease-susceptibility genes or assessing gene-environment interactions. We investigated the situation in which the gene being studied plays a role in several diseases, and the allele frequency among subjects free of the disease of interest consequently decreases with age as subjects die from other diseases. The logistic model is one approach frequently used for analyzing case-control data, but it cannot accommodate this dependence of genotype and age. Using a log-linear model, we therefore proposed a hierarchical procedure that could be used as a valid method for assessing interactions in such situations. We then applied this procedure to observed data on Alzheimer's disease and the apolipoprotein E gene in Japan. We were able to derive an appropriate inference on whether the interaction was a gene-age interaction or merely a bias due to death from other diseases.

A new EEG method for estimating cortical neuronal impairment that is sensitive to early stage Alzheimer's disease.

OBJECTIVES: To test the hypothesis that elecetroencephalographic (EEG) analysis is sensitive to cortical neuronal impairment in early stage Alzheimer's disease (AD), and that this analysis correlates with corresponding changes in cerebral blood flow. METHODS: We examined an EEG measure of neuronal impairment in the cerebral cortex in terms of its ability to detect very mild AD. This measure, the mean value of the resting state EEG alpha dipolarity (D(alpha)), approaches unity without cortical sulcal lesions, whereas brains with randomly distributed cortical sulcal lesions lower D(alpha) values well below unity. D(alpha) was evaluated in 25 patients with very mild AD, 33 patients with moderately severe AD, and 56 normal age-matched subjects. These subjects also received SPECT, and strong correlation between D(alpha) and regional cerebral blood flow (rCBF) was observed. RESULTS: D(alpha) values greater than 0.977 correctly classified normal subjects, but also included 10% of very mild AD. D(alpha) values less than 0.952 correctly classified very mild AD as well as moderately severe AD, but also included 10% of normal subjects. D(alpha) values also correlated positively with bilateral temporal-parietal rCBF (a characteristic finding in AD patients); both declined with increasing dementia severity. CONCLUSIONS: Analysis of D(alpha) in this sample supports the hypothesis that early stages of AD can be discriminated from normal aging using measures of cortical neuronal impairment. Furthermore, dementia severity, as reflected by the degree of impairment, is reflected in declining D(alpha) values and increasing variance (greater spread of the D(alpha) values).