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Background and ObjectivesPrevious studies have evaluated the diagnostic effect of amyloid PET in selected research cohorts. However, these studies did not assess the clinical impact of the combination of amyloid and tau PETs. Our objective was to evaluate the association of the combination of 2 PETs with changes in diagnosis, treatment, and management in a memory clinic cohort.MethodsAll participants underwent amyloid [18F]florbetaben PET and tau PET using [18F]PI-2620 or [18F]Florzolotau, which are potentially useful for the diagnosis of non-Alzheimer disease (AD) tauopathies. Dementia specialists determined a pre- and post-PET diagnosis that existed in both a clinical syndrome (cognitive normal [CN], mild cognitive impairment [MCI], and dementia) and suspected etiology, with a confidence level. In addition, the dementia specialists determined patient treatment in terms of ancillary investigations and management.ResultsAmong 126 registered participants, 84.9% completed the study procedures and were included in the analysis (CN [n = 40], MCI [n = 25], AD [n = 20], and non-AD dementia [n = 22]). The etiologic diagnosis changed in 25.0% in the CN, 68.0% in the MCI, and 23.8% with dementia. Overall changes in management between pre- and post-PET occurred in 5.0% of CN, 52.0% of MCI, and 38.1% of dementia. Logistic regression analysis revealed that tau PET has stronger associations with change management than amyloid PET in all participants and dementia groups.DiscussionThe combination of amyloid and tau PETs was associated with changes in management and diagnosis of MCI and dementia, and the second-generation tau PET has a strong impact on the changes in diagnosis and management in memory clinics.Classification of EvidenceThis study provides Class I evidence that the combination of amyloid and tau PETs was associated with changes in management and diagnosis of MCI and dementia.

We propose a non-invasive and cost-effective method to automatically detect dementia by utilizing solely speech audio data. We extract paralinguistic features for a short speech segment and use Gated Convolutional Neural Networks (GCNN) to classify it into dementia or healthy. We evaluate our method on the Pitt Corpus and on our own dataset, the PROMPT Database. Our method yields the accuracy of 73.1% on the Pitt Corpus using an average of 114 seconds of speech data. In the PROMPT Database, our method yields the accuracy of 74.7% using 4 seconds of speech data and it improves to 80.8% when we use all the patient's speech data. Furthermore, we evaluate our method on a three-class classification problem in which we included the Mild Cognitive Impairment (MCI) class and achieved the accuracy of 60.6% with 40 seconds of speech data.

Background Although the effects of various types of cognitive interventions have been evaluated, effectiveness and cost-saving effect of the combination of the different cognitive interventions is unknown. Objective This study aimed to evaluate the feasibility of conducting a definitive trial to assess the effectiveness of combined cognitive intervention. Methods A matched controlled trial of learning therapy (LT), a combination of cognitive training and stimulation, was conducted. The samples were recruited from the nursing homes. Inclusion criteria were as follows: age 65 years or older, clinical diagnosis of dementia, level of activities of daily living at II or above, Mini-Mental State Examination score between 10 and 26, receiving long-term-care services without history of LT, and provision of written consent. The primary outcomes were safety, validity of eligibility, retention rate, and effect on the functions of daily living represented by Criterion Time for Certification of Needed Long-Term-Care (CT for CNLTC) at 12 months. Cost-benefit analysis was also conducted to assess the cost saving effect of LT. Results No serious adverse events were detected. The exclusion rate at the screening phase was 5% and the retention rate was 77% at 12 months. LT demonstrated statistically significant improvement in CT for CNLTC at 12 months (Δ=18.8, almost equivalent to "one" degree of the care needed level) and saved the long-term-care cost by JPY 200,000 (USD 1,618). Conclusions LT is effective for improving care recipients' level of care needed and has a cost saving effect. A randomized controlled trial is required to verify these findings. Clinical trial registration This study was approved by the ethics committee at Keio University School of Medicine (ID: 20150061). This trial was registered at University hospital Medical Information Network Clinical Trial Registry (UMIN-CTR ID: UMIN000018223).

Tau aggregates represent a key pathologic feature of Alzheimer’s disease and other neurodegenerative diseases. Recently, PET probes have been developed for in vivo detection of tau accumulation; however, they are limited because of off-target binding and a reduced ability to detect tau in non-Alzheimer’s disease tauopathies. The novel tau PET tracer, [18F]PI-2620, has a high binding affinity and specificity for aggregated tau; therefore, it was hypothesized to have desirable properties for the visualization of tau accumulation in Alzheimer’s disease and non-Alzheimer’s disease tauopathies. To assess the ability of [18F]PI-2620 to detect regional tau burden in non-Alzheimer’s disease tauopathies compared with Alzheimer’s disease, patients with progressive supranuclear palsy (n = 3), corticobasal syndrome (n = 2), corticobasal degeneration (n = 1) or Alzheimer’s disease (n = 8), and healthy controls (n = 7) were recruited. All participants underwent MRI, amyloid β assessment and [18F]PI-2620 PET (Image acquisition at 60–90 min post-injection). Cortical and subcortical tau accumulations were assessed by calculating standardized uptake value ratios using [18F]PI-2620 PET. For pathologic validation, tau pathology was assessed using tau immunohistochemistry and compared with [18F]PI-2620 retention in an autopsied case of corticobasal degeneration. In Alzheimer’s disease, focal retention of [18F]PI-2620 was evident in the temporal and parietal lobes, precuneus, and cingulate cortex. Standardized uptake value ratio analyses revealed that patients with non-Alzheimer’s disease tauopathies had elevated [18F]PI-2620 uptake only in the globus pallidus, as compared to patients with Alzheimer’s disease, but not healthy controls. A head-to-head comparison of [18F]PI-2620 and [18F]PM-PBB3, another tau PET probe for possibly visualizing the four-repeat tau pathogenesis in non-Alzheimer’s disease, revealed different retention patterns in one subject with progressive supranuclear palsy. Imaging-pathology correlation analysis of the autopsied patient with corticobasal degeneration revealed no significant correlation between [18F]PI-2620 retention in vivo. High [18F]PI-2620 uptake at 60–90 min post-injection in the globus pallidus may be a sign of neurodegeneration in four-repeat tauopathy, but not necessarily practical for diagnosis of non-Alzheimer’s disease tauopathies. Collectively, this tracer is a promising tool to detect Alzheimer’s disease-tau aggregation. However, late acquisition PET images of [18F]PI-2620 may have limited utility for reliable detection of four-repeat tauopathy because of lack of correlation between post-mortem tau pathology and different retention pattern than the non-Alzheimer’s disease-detectable tau radiotracer, [18F]PM-PBB3. A recent study reported that [18F]PI-2620 tracer kinetics curves in four-repeat tauopathies peak earlier (within 30 min) than Alzheimer’s disease; therefore, further studies are needed to determine appropriate PET acquisition times that depend on the respective interest regions and diseases., This study reports that the novel tau-tracer, [18F]PI-2620 (late time frame), is a promising tool for detecting Alzheimer’s disease-tau deposits. However, this may have limited utility for the detection of four-repeat tau-pathology due to the lack of correlation with post-mortem pathology and different distribution with the non-Alzheimer’s disease tau-tracer, [18F]PM-PBB3., Graphical Abstract Graphical Abstract

Background Subjective cognitive decline (SCD) may herald the first symptoms of Alzheimer's disease (AD) whereas individuals with beta-amyloid (Aβ) deposition are regarded as a high-risk group for AD. Recently, amyloid positron emission tomography (PET) studies have demonstrated clinical and cognitive feature differences between Aβ-positive and negative SCD, but details of their differences remain unclear. We aimed to investigate the relationships among Aβ deposition, clinical, and cognitive features in patients with SCD. Methods Forty-two patients with SCD (22 women, 74.5 ± 4.7 years) were examined using fluorine-18 florbetaben PET and were divided into Aβ-positive (n = 10) and negative (n = 32) groups. We compared cognitive and psychological outcomes, and single photon emission computed tomography (SPECT) imaging data between the two groups. In addition, a linear regression analysis was performed to assess relationships between the severity of SCD and neuropsychological tests, affective scores, and demographic factors. Results The rate of score changes from the immediate recall to delayed recall in the logical memory subtest of the Wechsler's Memory Scale Revised were different between the groups (P = 0.04). However, the binary logistic regression analysis showed no significant differences between the two. In addition, the severity of SCD was significantly strong in women (P = 0.002). Furthermore, within the Aβ-negative group, subjective memory loss correlated with word fluency category score (P = 0.023) and apathy scale (P = 0.037). Conclusions No significant differences were observed between Aβ-positive and -negative SCD on any of the neuropsychological measures, clinical measures, or SPECT imaging. Further, the severity of SCD was not predicted by the symptoms of anxiety, depression, or neuropsychological examination.

BackgroundDepressive and neurocognitive disorders are debilitating conditions that account for the leading causes of years lived with disability worldwide. Overcoming these disorders is an extremely important public health problem today. However, there are no biomarkers that are objective or easy-to-obtain in daily clinical practice, which leads to difficulties in assessing treatment response and developing new drugs. Due to advances in technology, it has become possible to quantify important features that clinicians perceive as reflective of disorder severity. Such features include facial expressions, phonic/speech information, body motion, daily activity, and sleep. The overall goal of this proposed study, the Project for Objective Measures Using Computational Psychiatry Technology (PROMPT), is to develop objective, noninvasive, and easy-to-use biomarkers for assessing the severity of depressive and neurocognitive disorders.MethodsThis is a multi-center prospective study. DSM-5 criteria for major depressive disorder, bipolar disorder, and major and minor neurocognitive disorders are inclusion criteria for the depressive and neurocognitive disorder samples. Healthy samples are confirmed to have no history of psychiatric disorders by Mini-International Neuropsychiatric Interview, and have no current cognitive decline based on the Mini Mental State Examination. Participants go through approximately 10-minute interviews with a psychiatrist/psychologist, where participants talk about non-specific topics such as everyday living, symptoms of disease, hobbies, etc. Interviews are recorded using RGB and infrared cameras, and an array microphone. As an option, participants are asked to wear wrist-band type devices during the observational period. The interviews take place ≤10 times within up to five years of follow-up. Various software is used to process the raw video, voice, infrared, and wearable device data. A machine learning approach is used to predict the presence of symptoms, severity, and the improvement/deterioration of symptoms.DiscussionThe PROMPT goal is to develop objective digital biomarkers for assessing the severity of depressive and neurocognitive disorders in the hopes of guiding decision-making in clinical settings as well as reducing the risk of clinical trial failure. Challenges may include the large variability of samples, which makes it difficult to extract the features that commonly reflect disorder severity.Trial RegistrationUMIN000021396, University Hospital Medical Information Network (UMIN)

This study aimed to investigate the long-term impacts of disclosing amyloid status for a risk of Alzheimer disease (AD) to cognitively normal research participants with subjective cognitive decline (SCD), which represents an initial manifestation of AD. Forty-two participants were classified as the amyloid-positive ( n = 10) or amyloid-negative ( n = 32) groups. We assessed symptoms of anxiety, depression, and test-related distress at 6, 24, and 52 weeks after results disclosure. No difference was found over time in anxiety, depression, and test-related distress in either group. Although no significant differences were observed between groups in anxiety or depression, the amyloid-negative group had a significantly higher level of test-related distress than the amyloid-positive group at 52 weeks. Disclosing amyloid status to cognitively healthy research participants with SCD did not cause significant long-term psychological risks. However, a theoretical spectrum of subjective concern may exist about cognitive decline in amyloid-negative individuals.

Previous clinical trials have demonstrated the efficacy of yokukansan, a traditional Japanese medicine, for the treatment of behavioral and psychological symptoms of dementia (BPSD). However, less evidence is available for the treatment of BPSD with yokukansankachimpihange (YKSCH), which consists of yokukansan and two additional herbal ingredients. The present study was conducted to investigate the efficacy and safety of YKSCH for treating BPSD in patients with Alzheimer’s disease (AD). We enrolled outpatients with mild-to-moderate AD who exhibited BPSD and obtained a Neuropsychiatric Inventory (NPI) score of >3 including subscale scores for “agitation”, “anxiety”, “irritability”, and “sleep and night-time behavior change”. A daily YKSCH dose of 7.5 g was administered for 12 weeks with concomitant administration of anti-dementia medication. BPSD was evaluated using the NPI at baseline and every 4 weeks during the intervention. We also examined apathy using the Japanese translation of the Apathy Scale, the short version of the Japanese version of the Zarit Caregiver Burden Interview, and the Modified Crichton Rating Scale for Predicting Activities of Daily Living. Cognitive dysfunction was evaluated using the Mini Mental State Examination and the AD Assessment Scale-Cognitive (Japanese version). Five participants were enrolled. The NPI total score tended to decrease between the baseline and 8-week evaluations during the YKSCH intervention (Wilcoxon signed rank test, P = 0.063). In terms of the NPI subscale scores, “apathy”, “agitation”, “delusions”, and “sleep and night-time behavior change” decreased after the intervention in those who exhibited each symptom at baseline. There were no significant differences in the other scores examined. No serious adverse events were observed. YKSCH could ameliorate BPSD in patients with mild-to-moderate AD with agitation, anxiety, irritability, and sleep and night-time behavior change, and it was well-tolerated.

In Japan, 4.6 million people are living with dementia and the number is expected to rise to 7 million by 2025. Amyloid-β (Aβ) positron emission tomography (PET) is used for cognitively normal Japanese people with or without subjective cognitive decline (SCD) for the purpose of clinical trials or diagnosis. Nevertheless, no empirical studies have been conducted on the safety of disclosing amyloid status to such populations. We conducted amyloid PET imaging on 42 participants (Aβ positive (n = 10) and negative (n = 32)). State anxiety and depression were measured at pre- and post-disclosure, and test-related distress at post-disclosure. Mean state anxiety and depression scores were below the cut-off through pre- and post-disclosure in the Aβ positive and negative groups. State anxiety and depression did not change over time and were not different between groups. Mean test-related distress scores were within normal limits at post-disclosure in both groups. No significant difference was found between groups. Disclosing Aβ positive results did not cause greater mood disturbance than negative results in a short period of time. The short-term psychological safety of disclosing Aβ PET results to asymptomatic Japanese adults with SCD was indicated.

Background: In an aging society, neuropsychological testing using video teleconferencing (VTC) is increasingly important. Despite the potential benefit of a VTC-administered Montreal Cognitive Asse...

Few studies, to our knowledge, have examined whether early improvements in individual, instead of overall, depressive symptoms predict remission in major depressive disorder (MDD). This post hoc analysis used data from 194 patients with MDD enrolled in a 6-week double-blind, placebo-controlled, randomized trial of mirtazapine, to identify improvements in specific individual depressive symptoms in the early phase that are associated with subsequent remission. Trajectories of individual depressive symptoms over 6 weeks were compared between remitters and nonremitters. Early improvement was defined as a ≥20% decrease in the Hamilton Rating Scale for Depression 17 items (HAM-D17) total score in weeks 1 and 2, and remission was defined as a HAM-D17 final score of ≤7. Reliability parameters were calculated for early improvements in predicting later remission. Whether improvement in each of the HAM-D17 symptoms in weeks 1 or 2 predicted remission was examined, using binary logistic regression analyses. As a result, improvements in weeks 1 and 2 were associated with sensitivity of 0.82 and 0.99 and specificity of 0.54 and 0.44, respectively, in predicting remission in week 6. Improvements in insomnia late (P = .04) and insight (P = .007) in week 1 and somatic symptoms general (P = .002) and insight (P = .04) in week 2 were associated with remission in week 6. In conclusion, early improvements in insight, insomnia late, and somatic symptoms general, as well as overall depressive symptoms, may serve as specific clinical indicators of subsequent remission in patients with MDD receiving mirtazapine.

Subjective cognitive decline (SCD) may herald the first symptoms of Alzheimer's disease (AD) whereas individuals with beta-amyloid (Aβ) deposition are regarded as a high-risk group for AD. Recently, amyloid positron emission tomography (PET) studies have demonstrated clinical and cognitive feature differences between Aβ-positive and negative SCD, but details of their differences remain unclear. We aimed to investigate the relationships among Aβ deposition, clinical, and cognitive features in patients with SCD.Forty-two patients with SCD (22 women, 74.5 ± 4.7 years) were examined using fluorine-18 florbetaben PET and were divided into Aβ-positive (n = 10) and negative (n = 32) groups. We compared cognitive and psychological outcomes, and single photon emission computed tomography (SPECT) imaging data between the two groups. In addition, a linear regression analysis was performed to assess relationships between the severity of SCD and neuropsychological tests, affective scores, and demographic factors.The rate of score changes from the immediate recall to delayed recall in the logical memory subtest of the Wechsler's Memory Scale Revised were different between the groups (P = 0.04). However, the binary logistic regression analysis showed no significant differences between the two. In addition, the severity of SCD was significantly strong in women (P = 0.002). Furthermore, within the Aβ-negative group, subjective memory loss correlated with word fluency category score (P = 0.023) and apathy scale (P = 0.037).No significant differences were observed between Aβ-positive and -negative SCD on any of the neuropsychological measures, clinical measures, or SPECT imaging. Further, the severity of SCD was not predicted by the symptoms of anxiety, depression, or neuropsychological examination.

Background Psychiatrists in clinical practice face a number of stressors related to patient care, such as overwork. On the other hand, they gain satisfaction from their work. We quantified and assessed the potential relationship between levels of occupational stress, satisfaction, and depressive symptoms among Japanese clinical psychiatrists. We surveyed 206 psychiatrists with up to 15 years of clinical experience who primarily worked in patient care. Levels of occupational stress and occupational satisfaction were measured using the Visual Analogue Scale and the level of depressive symptoms was measured by the Center for Epidemiologic Studies Depression Scale. Workplace stressors and satisfiers were also evaluated. Results Out of 206 psychiatrists, 154 (74.8%) responded to the survey. The respondents’ mean (SD) age was 34.3 (5.2) years. The estimated prevalence of significant depressive symptoms was 34.4% (n = 53), and the experienced frequent violence was 14.9% (n = 23). The level of depressive symptoms was inversely correlated with the level of occupational satisfaction. In respondents who reported a moderate level of occupational stress, having fewer depressive symptoms was associated with higher occupational satisfaction, but this association was not significant in those who reported a high level of stress. In addition, high occupational satisfaction was associated with interest towards work content, ability to work at one’s discretion, opportunities for growth and career development, and ease of communication with supervisors and colleagues. Conclusions Nearly one-third of the psychiatrists screened positive for significant depressive symptoms. Having fewer depressive symptoms was associated with higher occupational satisfaction in those who reported a moderate level of stress. Implications from the present findings may be to enhance occupational satisfaction by discussing work interests with a supervisor, as well as increased opportunities for career development, which may prevent depression among psychiatrists. Electronic supplementary material The online version of this article (doi:10.1186/s13104-015-1054-7) contains supplementary material, which is available to authorized users.