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Introduction: Recent advances in artificial intelligence (AI) have been substantial. We investigated the effectiveness of an online meeting in which normal older adults (otokai) used a music-generative AI that transforms text to music (Music Trinity Generative Algorithm-Human Refined [MusicTGA-HR])., Methods: One hundred eighteen community-dwelling, cognitively normal older adults were recruited through the internet (64 men, 54 women; mean age: 69.4 ± 4.4 years). Using MusicTGA-HR, the participants chose music that they thought was the most suitable to a given theme. We established 11 classes of 7-10 members and one instructor each. Each class held an online meeting once a week, and each participant presented the music they chose. The other participants and the instructor then commented on the music. Neuropsychological assessments were performed before and after the intervention for 6 months, and the results before and after the intervention were statistically analyzed., Results: The category and letter word fluencies (WFs) were significantly improved (category WF: p = .003; letter WF: p = .036), and the time of the Trail-Making Test-B was also significantly shortened (p = .039). The Brain Assessment, an online cognitive test we developed, showed significant improvement in the memory of numbers (p < .001)., Conclusion: The online meeting of the otokai, which used music-generative AI, improved the frontal lobe function and memory of independent normal older adults., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

Purpose: We have reported the relationship between low pulvinar nuclei (PN) intensity in susceptibility-weighted imaging and the appearance of visual hallucinations and cognitive function. The aim of the study was to examine the changes in the quantitative susceptibility mapping (QSM) in patients with Parkinson's disease (PD) who underwent deep brain stimulation (DBS) and verify whether the PN susceptibility value (SV) on QSM can predict visual hallucination and cognitive changes after DBS., Methods: This study examined 24 patients with PD who underwent DBS along with QSM imaging on magnetic resonance imaging (MRI). All MRIs were performed within 3 months before surgery. The PN SV was further assessed based on the QSM. Then, associations were examined among cognitive changes, hallucination, and PN SV. The cognitive function of the patient was compared immediately before surgery and at 1 year postoperatively., Results: Visual hallucinations were observed in seven patients during the follow-up period. The PN SV was ≥0.045 ppm in nine patients with PD, and six of them had visual hallucinations, whereas only one of 15 patients with PD with SV of <0.045 ppm had visual hallucinations (Fisher's exact test, p = .0037)., Conclusions: The SV of >0.045 ppm at the PN in QSM in patients with PD may provide useful information suggesting visual hallucination and cognitive deterioration after DBS treatment., (© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Background: Leisure activities are believed to contribute to healthy ageing. We compared the effects of choir singing and go playing on cortisol levels in Japanese older adults. We also examined its relevance to the older adults' emotional affect and cognitive performance., Methods: Thirty-six older adults participated either in choir or go playing, within a 2 (groups)×2 (time points) design. Dependent measures included levels of salivary cortisol, as well as key psychological, cognitive, and neuropsychological measures., Results: A significant two-way interaction was observed, showing that levels of salivary cortisol decreased for the choir but increased for the go groups. The decrease in salivary cortisol for the choir group correlated with the participant's negative affect and their degree of cognitive impairment., Conclusion: Choir singing has the potential to reduce Japanese older adults' physiological stress. The decreases can be seen more prominently for people with stronger negative affect and cognitive impairment. Further research is required to replicate these effects.

Objective: The severity of cerebral small vessel disease (SVD) on magnetic resonance imaging (MRI) has been assessed using hypertensive arteriopathy SVD and cerebral amyloid angiopathy (CAA)-SVD scores. In addition, we reported the modified CAA-SVD score including cortical microinfarcts and posterior dominant white matter hyperintensity. Each SVD score has been associated with cognitive function, but the longitudinal changes remain unclear. Therefore, this study prospectively examined the prognostic value of each SVD score, imaging findings of cerebral SVD, and neuropsychological assessment., Methods: This study included 29 patients diagnosed with mild cognitive impairment or mild dementia at memory clinic in our hospital, who underwent clinical dementia rating (CDR) and brain MRI (3D-fluid attenuated inversion recovery, 3D-double inversion recovery, and susceptibility-weighted imaging) at baseline and 1 year later. Each SVD score and neuropsychological tests including the Mini-Mental State Examination, Japanese Raven's Colored Progressive Matrices, Trail Making Test -A/-B, and the Rivermead Behavioral Memory Test were evaluated at baseline and 1 year later., Results: Twenty patients had unchanged CDR (group A), while nine patients had worsened CDR (group B) after 1 year. At baseline, there was no significant difference in each SVD score; after 1 year, group B had significantly increased CAA-SVD and modified CAA-SVD scores. Group B also showed a significantly higher number of lobar microbleeds than group A at baseline. Furthermore, group B had significantly longer Japanese Raven's Colored Progressive Matrices and Trail Making test-A times at baseline. After 1 year, group B had significantly lower Mini-Mental State Examination, Japanese Raven's Colored Progressive Matrices, and Rivermead Behavioral Memory Test scores and significantly fewer word fluency (letters)., Conclusion: Patients with worsened CDR 1 year after had a higher number of lobar microbleeds and prolonged psychomotor speed at baseline. These findings may become predictors of cognitive deterioration in patients who visit memory clinics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Matsuda, Shinohara, Ii, Tabei, Ueda, Nakamura, Hirata, Ishikawa, Matsuyama, Matsuura, Satoh, Maeda, Momosaki, Tomimoto and Shindo.)

Objective: The spread of coronavirus disease (COVID-19) has limited the implementation of face-to-face non-pharmacological treatment for the prevention of dementia. As a result, online non-pharmacological treatment has become increasingly important. In this study, we used an online conferencing system to implement an online version of a physical exercise program with music, and examined its effect on cognitive function., Methods: The participants were 114 healthy older adults [63 men and 51 women; mean age of 70.7 years (standard deviation = 4.6)]. Seventy-five participants were allocated to the physical exercise with music group (60 min, once a week, total 20 sessions), while the remaining 39 participants were assigned to the control group, and only underwent the examinations. In the physical exercise with music group, we performed neuropsychological examinations and brain tests both before and after the exercise program. Neuropsychological tests included the Mini-Mental State Examination, Raven's Colored Progressive Matrices (RCPM), the Rivermead Behavioral Memory Test, graphic imitation, word fluency (WF) (animal names and initial sounds), and the Trail Making Test-A/B. As an assessment of brain function, we developed an online examination of subtle cognitive decline, including tests of number and word memory, spatial grasp, the N-back task, and change inference., Results: In the N-back task, the physical exercise with music group improved significantly relative to the control group ( p = 0.008)., Discussion: The present findings suggest that the online version of the physical exercise with music program improved working memory, which mainly involves the frontal lobe., Competing Interests: The Department of Dementia and Neuropsychology, Advanced Institute of Industrial Technology, was established using donations provided by the Research Institute of Brain Activation., (Copyright © 2023 Tabei, Ogawa, Kamikawa, Abe, Ota and Satoh.)

Introduction: Due to the ongoing outbreak of the coronavirus disease 2019 (COVID-19), it is currently difficult to conduct in-person exercise classes. We thus started the program of an online physical exercise with musical accompaniment. Several interesting differences were found in the characteristics of the online participants compared with our previous in-person interventions., Participants and Methods: The total number of subjects was 88 (71.2 ± 4.9 years old; male 42, female 46). The questionnaire included the attributes of the participants, the perceived advantages of the exercise classes, and the presence or absence of noticeable changes in cognitive and physical function after participating in the classes., Results: The personal computers used to attend the online classes were operated by the participants themselves. About 42% of the participants felt that their sense of day of the week and volition were improved by attending the exercise classes for 3 months. The most frequent answer to the reason for participation was because it was free (81.8%). The second most frequent answer was because the classes were held online (75.0%). Almost half of the participants answered that they would not participate if it was held in person because of the risk of COVID-19 infection (75.0%) and the difficulty getting to the site where the exercise classes were held (59.1%)., Conclusion: Online physical exercise with musical accompaniment improved the perceived orientation, volition, activity, exercise habits, and health condition in 30-40% of the participants and also stimulated greater participation by males compared to classes held in person., Competing Interests: The Department of Dementia and Neuropsychology, Master Program of Innovation for Design and Engineering, Advanced Institute of Industrial Technology, was established using donations provided by the Research Institute of Brain Activation., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Objectives: Cerebral small vessel disease (SVD) is commonly observed among elderly individuals with cognitive impairment and has been recognized as a vascular contributor to dementia and behavioral and psychological symptoms (BPS), however, the relationship between BPS and SVD burden remains unclear., Methods: We prospectively recruited 42 patients with mild cognitive impairment (MCI) or mild dementia from the memory clinic in our hospital, who were assigned to either a clinical dementia rating (CDR) of 0.5 or 1.0, respectively. The presence of BPS was determined through interviews with caregivers. The patients underwent brain MRI and three types of SVD scores, total, cerebral amyloid angiopathy (CAA), and modified CAA, were assigned. Patients were also evaluated through various neuropsychological assessments., Results: The CDR was significantly higher in patients with BPS ( p  = 0.001). The use of antihypertensive agents was significantly higher in patients without BPS ( p  = 0.038). The time taken to complete trail making test set-A was also significantly longer in patients with BPS ( p  = 0.037). There was no significant difference in total SVD and CAA-SVD score ( p  = 0.745, and 0.096) and the modified CAA-SVD score was significantly higher in patients with BPS ( p  = 0.046). In addition, the number of total CMBs and lobar CMBs was significantly higher in patients with BPS ( p  = 0.001 and 0.001). Receiver operating characteristic curves for BPS showed that for modified CAA-SVD, a cutoff score of 3.5 showed 46.7% sensitivity and 81.5% specificity. Meanwhile, for the total number of cerebral microbleeds (CMBs), a cut-off score of 2.5 showed 80.0% sensitivity and 77.8% specificity and for the number of lobar CMBs, a cut-off score of 2.5 showed 73.3% sensitivity and 77.8% specificity., Conclusion: Overall, patients with BPS showed worse CDRs, reduced psychomotor speed, higher modified CAA-SVD scores, larger numbers of total and lobar CMBs. We propose that severe modified CAA scores and higher numbers of total and lobar CMBs are potential risk factors for BPS in patients with mild dementia or MCI. Therefore, by preventing these MRI lesions, the risk of BPS may be mitigated., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest., (Copyright © 2023 Shinohara, Matsuda, Ii, Tabei, Nakamura, Hirata, Ishikawa, Matsuyama, Matsuura, Maeda, Tomimoto and Shindo.)

Objective In the Japanese Community-Based Integrated Care System (CBICS), access to formal care services is based on voluntary consultations mainly from the families of people with dementia (PWD). The problem is that some people need services but do not consult their municipalities for various reasons. The purpose of this study is to examine the possibility of using health insurance claims data to identify and characterize these PWD. Methods Using health insurance claims data, we selected PWD prescribed with anti-dementia drugs. Of them, excluding those with a usage history of long-term care insurance services or other formal services, facility residents and deaths, we identified PWD not accessing the CBICS. We conducted a visit survey on their status, home care environment and reasons for not accessing services, a proposal for using services and a one-year follow-up. Result Based on the data of 1,809 late-stage elderly who resided in the Tamaki-cho, a town in Mie Prefecture, Japan, for a 2-month period, 16 PWD not accessing the CBICS were identified, and 15 PWD and their families participated in this study. Ten were men and 13 were physically and cognitively relatively independent. All lived with a family caregiver and refused services. Ten families needed but had not accessed the services due to refusal by PWD and other reasons. As a result, seven of these PWD started using long-term care insurance services or dementia prevention services. Conclusion PWD not accessing the CBICS can be identified using health insurance claims data. The results proved that the municipality has a cost-effective way of providing their services to PWD and their families, even if they have never consulted voluntarily.

Objective: White matter hyperintensity (WMH), defined as abnormal signals on magnetic resonance imaging (MRI), is an important clinical indicator of aging and dementia. Although MRI image analysis software can automatically detect WMH, the quantitative accuracy of periventricular hyperintensity (PVH) and deep white matter hyperintensity (DWMH) is unknown., Materials and Methods: This study was a sub-analysis of MRI data from an ongoing hospital-based prospective cohort study (the Gimlet study). Between March 2016 and March 2017, we enrolled patients who visited our memory clinic and agreed to undergo medical assessments of cognitive function and fecal examination to study the gut microbiome. Participants with a history of stroke were excluded. WMH was independently quantitatively analyzed using two MRI imaging analysis software modalities: SNIPER and FUSION. Intraclass correlation coefficients and the mean difference in volume were calculated and compared between modalities., Results: The data of 87 patients (49 women, mean age 74.8 ± 7.9 years) were analyzed. Both total WMH and DWMH volumes obtained using FUSION were greater (p < 0.001), and PVH volume was smaller (p < 0.001) than those obtained using SNIPER. Intraclass correlation coefficients for the lesion measurements of WMH, PVH, and DWMH between the different software were 0.726 (p < 0.001), 0.673 (p < 0.001), and 0.048 (p = 0.231), respectively., Conclusions: There were significant differences in the quantitative data of WMH between the two MRI imaging analysis software modalities. Thus, care should be taken for quantitative assessments of WMH., Competing Interests: Declaration of Competing Interest Dr. Saji received grants from the Grant-in-Aid for Scientific Research (C) and JSPS KAKENHI (Grant 20k07861), as well as research funds from the Comprehensive Research on Aging and Health program at the Japan Agency for Medical Research and Development (AMED). Dr. Saji received grants from the NARO Bio-oriented Technology Research Advancement Institution Project (for advanced integration research within agriculture and interdisciplinary fields), the Research Funding of Longevity Sciences from the NCGG, the Danone Institute of Japan Foundation, the Honjo International Scholarship Foundation, and the BMS/Pfizer Japan Thrombosis Investigator-initiated Research Program. These funders were not involved in the design, conduct, or publication of this work. All other authors have no actual or potential conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) show various clinical symptoms, including migraine, recurrent stroke, and cognitive impairment. We investigated the associations between magnetic resonance imaging (MRI) markers of small vessel disease and neuropsychological tests and identified the MRI characteristics for predicting cognitive impairment in patients with CADASIL., Methods: Subjects included 60 CADASIL patients diagnosed with genetic tests and registered in the Japanese CADASIL REDCap database between June 2016 and December 2020. Patient information including clinical data, modified Rankin Scale (mRS); MRI findings of small vessel disease including periventricular and deep white matter lesions (WML), lacunar infarcts, and cerebral microbleeds (CMBs); and neuropsychological tests, including the Japanese version of the Mini-Mental State Examination (MMSE), the Japanese version of the Montreal Cognitive Assessment (MoCA-J), and the Frontal Assessment Battery (FAB), were evaluated., Results: Data from 44 CADASIL patients were eligible for this study, compared between patients with and without dementia. Regarding the neuroimaging findings, the Fazekas score of periventricular and deep WML was higher in patients with dementia (periventricular, p = 0.003; deep, p = 0.009). The number of lacunar infarcts was higher in patients with dementia ( p = 0.001). The standardized partial regression coefficient (SPRC) in MoCA-J was 0.826 (95% CI, 0.723-0.942; p = 0.005) for the number of CMBs. The SPRC in MMSE was 0.826 (95% CI, 0.719-0.949; p = 0.007) for the number of CMBs. The SPRC for FAB decreased significantly to 0.728 (95% CI, 0.551-0.960; p = 0.024) for the number of lacunar infarcts. Receiver operating characteristic (ROC) curves for dementia showed that in the number of lacunar infarcts, a cut-off score of 5.5 showed 90.9% sensitivity and 61.1% specificity. For the number of CMBs, a cut-off score of 18.5 showed 45.5% sensitivity and 100% specificity., Conclusion: The characteristic MRI findings were that CADASIL patients with dementia had severe WML, both periventricular and deep, and a larger number of lacunar infarcts than those without dementia. The risk of dementia may be associated with ≥ 6 lacunar infarcts, ≥19 CMBs, or a Fazekas scale score of 3 in periventricular and deep WML., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Taniguchi, Shindo, Tabei, Onodera, Ando, Urabe, Kimura, Kitagawa, Miyamoto, Takegami, Ihara, Mizuta, Mizuno and Tomimoto.)

Background: The prevalence of cerebral microbleeds (CMBs) is significantly higher in patients with atrial fibrillation (AF) than in those without AF. CMBs in patients with AF have been reported to be primarily of the lobar type, but the exact cause of this remains unknown. We investigated the possibility that hemorrhagic transformation of embolic microinfarction can account for de novo lobar CMBs., Methods: A total of 101 patients who underwent ablation therapy for AF were prospectively registered, and 72 patients completed the assessment with MRI 6 months after catheter ablation. Brain MRI, including diffusion-weighted imaging (DWI) and susceptibility-weighted imaging (SWI), were examined at 1-3 days (baseline) and 6 months after catheter ablation. We quantitatively evaluated the spatial and temporal distribution of embolic microinfarctions and de novo CMBs., Results: Of the 101 patients, 68 were enrolled in this study. Fifty-nine patients (86.8%) showed embolic microinfarctions on baseline DWI immediately after catheter ablation. There were 137 CMBs in SWI, and 96 CMBs were of the lobar type. Six months later, there were 208 CMBs, including 71 de novo CMBs, and 60 of 71 (84.5%) were of the lobar type. Of the 71 de novo CMBs, 56 (78.9%) corresponded to the location of previous embolic microinfarctions found on baseline DWI. The platelet count was significantly lower and hematocrit/hemoglobin and Fazekas score were higher in the group with de novo CMBs than in the group without de novo CMBs., Conclusion: De novo CMBs frequently appeared after catheter ablation therapy. Our results suggest that embolic microinfarction can cause lobar CMBs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hirata, Kato, Muraga, Shindo, Nakamura, Matsuura, Ii, Shiga, Tabei, Satoh, Fukuma, Kagawa, Fujita, Kogue, Umino, Maeda, Sakuma, Dohi and Tomimoto.)

Background: Research on music therapy for dementia has taken a variety of measures and has been slow to consolidate evidence. Examining the outcomes that are currently being investigated and the measures that have been used can be useful for future research on music therapy for dementia., Objectives: This study used cited original papers from a review in the Cochrane Database of Systematic Reviews to determine if there are items that should be measured or scales that should be used in conducting research on music therapy for dementia. The rating scales used and the outcomes examined were extracted., Method: We used Dodd's criteria to identify (1) the outcome domains examined in music therapy for dementia, (2) the measures used, and (3) the measures capable of detecting significant intervention effects., Result: A search for reviews was conducted, and 7 systematic reviews (78 articles) were identified. Among them, 30 articles met the inclusion criteria. The 30 articles examined 18 of the 38 items in Dodd's outcome categories, while 20 items were not examined, and 78 different survey methods were used. The items most frequently surveyed in the studies were psychiatric outcomes, cognitive functioning, and global quality of life general outcomes., Conclusions: We found that many studies investigated cognitive function, behavioral and psychological symptoms of dementia (BPSD), and quality of life; compared to BPSD, various types of rating scales were used for cognitive function. By standardizing the rating scales, we can contribute to the accumulation of evidence for music therapy for dementia., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 by S. Karger AG, Basel.)

Introduction: We have developed an online cognitive test (Brain Assessment [BA]) which exhibits moderate correlations with established neuropsychological tests. We made a short version of the BA that requires only 10 min and investigated correlations with the original version., Participants and Methods: Three hundred and twenty-three subjects (26-82 years old, mean age 41.9 years) were recruited via the internet and performed the original version of the BA online, and, for the analyses of the original and short version, the results of the whole and of the first 2 min were utilized, respectively. Correlations were evaluated between both versions, and 144 subjects agreed to be interviewed about BA utilization., Results: Correlations between the short and original versions of the BA were strong (memory of numbers, r = 0.72: total, r = 0.73) or moderate (memory of words, r = 0.66; visuospatial, r = 0.42; working memory, r = 0.53; judgment, r = 0.54). We found a strong negative correlation between the "memory of words" subtest and age (short version, r = -0.85; original version, r = -0.88). Regarding the interview, most wanted to be assessed by the short version every year. In the case of a concerning score, they would then want to be examined by the original version of the BA and/or more specific neuropsychological tests., Discussion: We found that the short and the original versions of the BA exhibited strong correlations, and the correlation coefficients between age and subtest scores were almost the same between the two versions., Conclusion: The short version of the BA will be useful to perform cognitive assessments in the clinic., (© 2022 S. Karger AG, Basel.)

Catheter ablation is an important non-pharmacological intervention for atrial fibrillation (AF), but its effect on the incidence of asymptomatic cerebral emboli and long-term effects on cognitive function remain unknown. We prospectively enrolled 101 patients who underwent AF ablation. Brain magnetic resonance imaging (MRI) (72 patients) and neuropsychological assessments (66 patients) were performed 1-3 days (baseline) and 6 months after ablation. Immediately after ablation, diffusion-weighted MRI and 3-dimensional double inversion recovery (3D-DIR) detected embolic microinfarctions in 63 patients (87.5%) and 62 patients (86.1%), respectively. After 6 months, DIR lesions disappeared in 41 patients. Microbleeds (MBs) increased by 17%, and 65% of the de novo MBs were exactly at the same location as the microinfarctions. Average Mini-Mental State Examination scores improved from 27.9 ± 2.4 to 28.5 ± 1.7 (p = 0.037), and detailed neuropsychological assessment scores showed improvement in memory, constructional, and frontal lobe functions. Ejection fraction, left atrial volume index and brain natriuretic peptide level improved from baseline to 3-6 months after ablation. Despite incidental microemboli, cognitive function was preserved 6 months after ablation., (© 2021. The Author(s).)

Introduction: Several reports have shown that neuromelanin-sensitive magnetic resonance imaging (NMI) using 3T magnetic resonance imaging is useful for the differential diagnosis of Parkinson's disease (PD), progressive supranuclear palsy (PSP), and other neurological diseases. However, the number of cases in previous studies has been insufficient. We aimed to determine the relationship between NMI and severity of PD and related disorders, and thereby establish the diagnostic utility of NMI for diagnosing neurological diseases., Methods: We enrolled 591 patients (531 subjects after removal of duplicates) with parkinsonism who underwent NMI. The contrast ratio of the locus coeruleus (LC-CR) and the area of the substantia nigra pars compacta (SNc) were analyzed in each patient., Results: The patients' clinical diagnoses were as follows: 11 patients in the disease control group (DCG), 244 patients with PD, 49 patients with PSP, and 19 patients with multiple system atrophy with predominant parkinsonism. Additionally, some patients were diagnosed with dementia with Lewy bodies, vascular parkinsonism, and drug-induced parkinsonism. SNc in the patients with PD and PSP was significantly smaller than that in DCG. LC-CR in the patients with PD was lower than that in DCG; furthermore, LC-CR in the patients with PD was significantly lower than that in the patients with PSP. We found that an area under the receiver-operating characteristic curve, indicating diagnostic efficacy, of 0.85 for LC-CR is a promising biomarker for differentiating PD from PSP., Conclusion: NMI effectively contributes to differentiating neurodegenerative diseases, such as PD and PSP., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

White matter hyperintensities (WMHs) are risk factors for future cognitive impairment and are associated with an abnormal circadian blood pressure (BP) rhythm in patients with hypertension. However, whether this association exists in patients with heart failure (HF) is unclear. We performed a cross-sectional study of hospitalized patients with HF who underwent ambulatory BP monitoring and brain magnetic resonance imaging (MRI). A non-dipper BP pattern was defined as a < 10% nocturnal BP decline. WMHs on brain MRI scans were quantitated using a novel image analysis software (FUSION: FUsed Software for Imaging Of Nervous system). We enrolled 28 hospitalized patients with HF (age: 70.0 ± 9.8 years, 64.3% men). In the brain MRI analysis, the non-dipper group had higher WMH volume (18.9 ± 19.8 vs. 7.7 ± 8.3 mL, P = .047) and percentage of WMH/total brain volume (1.31 ± 1.28% vs. 0.55 ± 0.58%, P = .04) than the dipper group. In conclusion, using the newly developed MRI analysis software, we successfully quantitatively measured the volume of WMHs and found that the WMH volume increased 2.4 times in patients with a non-dipper pattern of nocturnal BP compared with those with a normal dipper pattern., (© 2021 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Introduction: It is well-known that cognitive function declines with age. In order to detect changes in cognitive function, cognitive tests should be performed repeatedly. Currently existing cognitive tests come in only a single version, so the subject is likely to remember the contents with repeated testing. And, under the outbreak of coronavirus disease 2019 (COVID-19), in-person assessment should be avoided. This study was performed to develop a new cognitive test (brain assessment, BA) that has 5 versions and can be performed on a personal computer (PC) through the Internet., Materials and Methods: Five thousand subjects performed the online BA, which consisted of 5 subtests: number memory, word memory, mental rotation test, N-back test, and judgment test. We standardized the raw scores (cognitive scores, CSs) using mean and standard deviation, which were 50 and 10, respectively. Then, we calculated the mean CS for each sex and age, plotted the relationships between ages and mean CSs on figures, and calculated the formula of cognitive changes during normal aging., Results: The CSs of all subtests decreased with aging. The regression coefficient was from -0.31 to -0.45. It is noteworthy that in most subtests, the CSs started to increase at 85 years of age., Discussion: Our BA has 5 versions and can be done on a PC using the Internet. We tested the BA in a large number of subjects, and the standard values of CSs were measured in individuals up to 89 years of age. By performing this test repeatedly, subjects can evaluate the degree of their cognitive decline. If the rate of cognitive decline is greater than that predicted using the normalized formula, the subjects can undertake strategies to improve their control of lifestyle-related diseases or other habits of daily living., Conclusion: The BA can be easily taken online using a PC, and its scores linearly declined with normal aging. The BA will be useful for detecting longitudinal cognitive changes and comparing them to the pattern seen in normal aging., (© 2021 S. Karger AG, Basel.)

Introduction: There are several problems with standard in-person neuropsychological assessments, such as habituation, necessity of human resources, and difficulty of in-person assessment under societal conditions during the outbreak of coronavirus disease 2019. Thus, we developed an online cognitive test (the Brain Assessment [BA]). In this study, we investigated the correlation between the results of the BA and those of established neuropsychological tests., Participants and Methods: Seventy-seven elderly persons (mean 71.3 ± 5.1 years old; range 65-86; male:female = 45:32) were recruited through the internet. Correlations were evaluated between the BA and the following widely used neuropsychological tests: the mini-mental state examination (MMSE), the Raven's colored progressive matrices (RCPM), the logical memory I and II of the Rivermead Behavioral Memory Test, the word fluency (WF) test, and the Trail-Making TestA/B., Results: We found moderate correlations between the total cognitive score of the BA and the total score of the MMSE (r = 0.433, p < 0.001), as well as between the total BA score and the total RCPM score (r = 0.582, p < 0.001) and time to complete the RCPM (r = 0.455, p < 0.001). Moderate correlations were also observed between the cognitive score of the memory of words BA subtest and the LM-I (r = 0.518, p < 0.001), the mental rotation subtest and figure drawing (r = 0.404, p < 0.001), the logical reasoning subtest and total RCPM score (r = 0.491, p < 0.001), and the memory of numbers and words subtests and WF (memory of numbers and total WF: r = 0.456, p < 0.001; memory of words and total WF: r = 0.571, p < 0.001)., Discussion: We found that the BA showed moderate correlations between established neuropsychological tests for intellect, memory, visuospatial function, and frontal function. The MMSE and the RCPM reflect Spearman's s-factor and g-factor, respectively, and thus the BA also covered both factors., Conclusion: The BA is a useful tool for assessing the cognitive function of generally healthy elderly persons., (© 2021 S. Karger AG, Basel.)

Objectives: Clinical characteristics of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) include migraine, recurrent stroke, white matter lesions, and vascular dementia. CADASIL is one of the most common hereditary cerebral small vessel diseases. Clinical presentation of CADASIL varies and a racial gap may exist between the Asian and Caucasian populations. This is the first nationwide epidemiological survey which aimed to elucidate the clinical features of CADASIL in Japan. Moreover, the registration database of CADASIL was constructed., Methods: Subjects included CADASIL patients who visited the hospitals (totally 1,448 hospitals) certified by the Japanese Society of Neurology and/or Japan Stroke Society in 2016. This study consisted of a two-step survey; patients with CADASIL were identified genetically by the first questionnaire, and their clinical features were assessed by the second questionnaire. Selected 6 hospitals registered the data of all CADASIL patients using a Research Electronic Data Capture (REDCap) system for the second questionnaire., Results: Based on the criteria, 88 patients (50 male and 38 female) with CADASIL were enrolled. The mean age of symptom onset was 49.5 years. Sixteen (18.2%) patients had an elderly onset (>60 years). Thirteen patients (13.6%) had history of migraine with aura and 33 patients (37.5%) had vascular risk factor(s). From among the 86 patients who were examined using magnetic resonance imaging, abnormal deep white matter lesions were detected in 85 patients (98.8%), WMLs extending to anterior temporal pole in 73 patients (84.9%), and cerebral microbleeds in 41 patients (47.7%). Anti-platelet therapy was received by 65 patients (73.9%). Thirty-eight patients (43.2%) underwent treatment with lomerizine hydrochloride. Thirty-four different mutations of NOTCH3 were found in exons 2, 3, 4, 5, 6, 8, 11, 14, and 19. Most of the mutations existed in exon 4 ( n = 44, 60.3%). The prevalence rate of CADASIL was 1.20 to 3.58 per 100,000 adults in Japan., Conclusion: This questionnaire-based study revealed clinical features and treatment status in Japanese CADASIL patient, although it may not be an exhaustive search. We have constructed the REDCap database for these CADASIL patients., (Copyright © 2020 Shindo, Tabei, Taniguchi, Nozaki, Onodera, Ueda, Ando, Urabe, Kimura, Kitagawa, Hanyu, Hirano, Wakita, Fukuyama, Kagimura, Miyamoto, Takegami, Saito, Watanabe-Hosomi, Mizuta, Ihara, Mizuno and Tomimoto.)

Corticobasal syndrome (CBS) is characterized by unilateral atrophy of the brain. New diagnostic criteria for CBS include intermediate somatosensory dysfunction. Here, we aimed to carefully examine intermediate somatosensory function to identify tests which can assess impairment in CBS patients. Using voxel-based morphometry (VBM), we also aimed to show the anatomical bases of these impairments. Subjects included 14 patients diagnosed with CBS and 14 patients with Parkinson's disease (PD). Patients were evaluated using intermediate somatosensory tests and neuropsychological assessments. VBM was used to analyze differences in gray matter volumes between CBS and PD patients. In the PD group, no tests showed a significant difference between the dominant-side onset and the non-dominant-side onset. In the CBS group, all tests showed worse scores on the affected side. For detecting intermediate somatosensory dysfunction in CBS, two tests are recommended: tactile object naming and 2-point discrimination. VBM analysis showed that the volume of the left post- and pre-central gyrus, and both sides of the supplementary motor area were significantly decreased in the CBS group compared to the PD group. Although CBS remains untreatable, early and correct diagnosis is possible by performing close examination of intermediate somatosensory function.

Background and Purpose- Cortical microinfarcts (CMIs) are small ischemic lesions found in cerebral amyloid angiopathy (CAA) and embolic stroke. This study aimed to differentiate CMIs caused by CAA from those caused by microembolisms, using 3-Tesla magnetic resonance imaging. Methods- We retrospectively investigated 70 patients with at least 1 cortical infarct <10 mm on 3-dimensional double inversion recovery imaging. Of the 70 patients, 43 had an embolic stroke history (Emboli-G) while 27 had CAA-group. We compared the size, number, location, and distribution of CMIs between groups and designed a radiological score for differentiation based on the comparisons. Results- CAA-group showed significantly more lesions <5 mm, which were restricted to the cortex ( P <0.01). Cortical lesion number was significantly higher in Emboli-G than in CAA-group (4 versus 2; P <0.01). Lesions in CAA-group and Emboli-G were disproportionately located in the occipital lobe ( P <0.01) and frontal or parietal lobe ( P =0.04), respectively. In radiological scoring, ≥3 points strongly predicted microembolism (sensitivity, 63%; specificity, 92%) or CAA (sensitivity, 63%; specificity, 91%). The areas under the receiver operating characteristic curve were 0.85 and 0.87 for microembolism and CAA, respectively. Conclusions- Characteristics of CMIs on 3T-magnetic resonance imaging may differentiate CMIs due to CAA from those due to microembolisms.

Background: We previously reported the enhanced effects of physical exercise when combined with music (ExM) on cognitive function in community-dwelling normal elderly people compared to exercise alone. Following that study, participants voluntarily continued the ExM classes for 5 years., Objective: To identify the effects of a 5-year ExM intervention on cognitive function in normal elderly people., Methods: Fifty-four subjects continued the ExM classes once a week for 5 years (ExM group). Thirty-three subjects retired from the ExM class during the 5 years (Retired group). Twenty-one subjects never participated in any intervention over the 5 years (No-exercise group). Cognitive function and ADLs were assessed using neuropsychological batteries and the functional independence measure (FIM), respectively. The voxel-based specific regional analysis system for Alzheimer's disease (VSRAD) was used to investigate medial temporal lobe atrophy., Results: Analyses of the raw scores after the 5-year intervention showed significant differences between the ExM and No-exercise groups in their MMSE scores, Raven's colored progressive matrices (RCPM) time, logical memory (LM)-I, as well as the total and physical exercise sub-scores of the FIM. Analysis of subjects aged 70- 79 years at the beginning of this project showed significantly quicker performance on the RCPM in the ExM compared to No-exercise groups. The correlation coefficients between the total number of ExM sessions attended and the degree of changes in physical, neuropsychological, and VSRAD scores were significant for RCPM performance time and LM-I scores., Conclusion: Long-term ExM intervention reinforces multifaceted cognitive function in normal elderly people, and is especially beneficial for psychomotor speed.

Purpose: Deep brain stimulation (DBS) is an established therapy for Parkinson's disease (PD). However, deteriorating cognitive function after DBS is a considerable problem for affected patients. This study was undertaken to assess whether pulvinar findings in susceptibility-weighted imaging (SWI) can suggest cognitive worsening. Methods: We examined 21 patients with PD who underwent DBS along with SWI and neuromelanin-sensitive MR imaging (NMI). We further assessed pulvinar hypointensity based on the SWI findings and also the area of the substantia nigra (SN) pars compacta in NMI. We then examined associations among cognitive changes, pulvinar hypointensity, and SN area. The cognitive function of the patient immediately before surgery was compared with function at 1 year postoperatively. Results: Pulvinar hypointensity in SWI was found in 11 of 21 patients with PD at baseline. One year postoperatively, six of the 21 patients demonstrated a Mini-Mental State Examination score that was ≥3 points lower than the baseline score. We observed pulvinar hypointensity in SWI before DBS surgery in five of these six patients ( p = 0.072). During the first postoperative year, six of 21 patients reported both transient or permanent hallucinations; we observed pulvinar hypointensity in these six patients, while 10 patients without pulvinar hypointensity had no hallucinations. Conclusion: Pulvinar hypointensity in SWI in patients with PD may provide information that is useful for suggesting cognitive deterioration after DBS treatment., (Copyright © 2019 Matsuura, Maeda, Satoh, Tabei, Araki, Umino, Kajikawa, Nakamura and Tomimoto.)

Background: Since the advent of magnetic resonance imaging technology, cerebral microbleeds can be diagnosed in vivo. However, the underlying mechanism of cerebral microbleed formation is not fully understood., Objectives: This study aimed to identify the factors associated with cerebral microbleeds after carotid artery stenting (CAS)., Method: We retrospectively examined 125 patients who underwent CAS for carotid stenosis. Cerebral microbleeds were investigated using T2*-weighted gradient-echo (GRE) imaging before and after CAS. We analyzed the possible association of new microbleeds with the following risk factors: the number of baseline microbleeds and ischemic cerebral lesions, the occurrence of cerebral hyperperfusion syndrome, and new ischemic cerebral lesions after CAS., Results: Baseline cerebral microbleeds were detected in 53 patients (42.4%). New cerebral microbleeds after CAS were observed in 13 of 125 patients (10.4%) and were exclusively associated with new ischemic lesions but not with other risk factors. No patient showed a merged image of a new cerebral microbleed on GRE imaging or a new ischemic lesion on diffusion-weighted imaging. Lobar and deep microbleeds were noted in 12/13 (92.3%) and 1 patient (7.7%), respectively. Of 12 patients with new microbleeds, 10 (76.9%) and 2 (15.4%) had a new microbleed in the ipsilateral and contralateral hemispheres, respectively., Conclusions: We found that new cerebral microbleeds developed after CAS and that these might be associated with new ischemic lesions, mostly in the territory of the treated carotid artery. We speculate that these microbleeds result from the deoxygenation of hemoglobin in the embolus or, alternatively, small hemorrhagic transformation of ischemic lesions., (© 2019 The Author(s) Published by S. Karger AG, Basel.)

We aimed to determine whether neuropsychological deficits and brain atrophy could predict the efficacy of non-pharmacological interventions. Forty-six participants with mild-to-moderate dementia were monitored for 6 months; 25 underwent an intervention involving physical exercise with music, and 21 performed cognitive stimulation tasks. Participants were categorized into improvement (IMP) and no-IMP subgroups. In the exercise-with-music group, the no-IMP subgroup performed worse than the IMP subgroup on the Rivermead Behavioural Memory Test at baseline. In the cognitive-stimulation group, the no-IMP subgroup performed worse than the IMP subgroup on Raven's Colored Progressive Matrices and the cognitive functional independence measure at baseline. In the no-IMP subgroup, voxel-based morphometric analysis at baseline revealed more extensive gray matter loss in the anterior cingulate gyrus and left middle frontal gyrus in the exercise-with-music and cognitive-stimulation groups, respectively. Participants with mild-to-moderate dementia with cognitive decline and extensive cortical atrophy are less likely to show improved cognitive function after non-pharmaceutical therapy.

Aim: To build a dementia screening system in the community to facilitate collaboration among patients/caregiver(s), family clinic physicians and memory clinic specialists., Methods: We placed a Dementia Network Promoter (DNP) in four cities in Mie prefecture, Japan. Based on requests from patients/caregiver(s), family clinic physicians ordered dementia screening from the DNP. The DNP carried out screenings at the clinic using an IT device (iPad), and sent the results to a dementia specialist at the Mie University Hospital Dementia Center. The dementia specialist assessed the results of the screening tests, and made a treatment recommendation for a follow-up consultation with a memory clinic or continuing observation by the family clinic. The DNP reported the recommendation of the dementia specialist to the family clinic physician, who provided this information to the patients/caregiver(s). We investigated the characteristics of the patients referred for consultation with the memory clinic., Results: A total of 158 patients participated in the screening. The majority of patients were in vulnerable living situations characterized by minimal social and family support. The mean score on the Mini-Mental State Examination was 24.1 ± 5.2. Of patients screened, 62% were referred for consultation at the memory clinic, and 57% of those referred completed a consultation at the memory clinic. Patients referred to the memory clinic showed significantly worse cognitive function and ability to complete activities of daily living., Conclusions: A dementia screening system might facilitate early consultation and intervention for patients with dementia, and build a more effective network to connect families and memory clinics. Geriatr Gerontol Int 2018; 18: 599-606., (© 2018 Japan Geriatrics Society.)

Introduction: This study aims to investigate the association between the presence and frequency of cortical lesions (CLs), and the clinical and psychological features of multiple sclerosis (MS)., Methods: A total of 19 patients with MS were examined using double inversion recovery (DIR) sequences with 3T magnetic resonance imaging (MRI) and classified into two groups: CL and non-CL. In-house software was used to quantitatively determine the atrophy of each brain region. Activities of daily living (ADL) were estimated using the Kurtzke Expanded Disability Status Scale (EDSS). Cognitive function was assessed using the following tests: Mini-Mental State Examination (MMSE), Trail Making Test (TMT), and Paced Auditory Serial Addition Task (PASAT). Z -scores were used to assess significant differences in the neuropsychological test outcomes between the groups., Results: Six of 19 patients had subcortical and deep WM lesions (non-CL group; diagnosed with relapsing-remitting MS). Thirteen of 19 patients had both subcortical and cortical lesions (CL group; 9-relapsing-remitting MS; 4-primary/secondary progressive MS). There were no significant differences in age, education, and disease duration, but EDSS scores were significantly higher in the CL group compared to the non-CL group. There were no significant differences in gray and white matter volume between the CL and the non-CL groups, but the white matter lesion volume was significantly higher in the CL group compared to the non-CL group. Neuropsychological tests showed significant performance worsening in the CL group as compared to the standard values for healthy individuals in their age group, especially in the TMT data., Conclusions: Progressive MS, which was associated with decreased physical functioning, ADL, and cognitive impairment, was found in patients in the CL group.

Background/aims: The missing fundamental phenomenon (MFP) is a universal pitch perception illusion that occurs in animals and humans. In this study, we aimed to determine whether the MFP is impaired in patients with Alzheimer's disease (AD) using an auditory pitch perception experiment. We further examined anatomical correlates of the MFP in patients with AD by measuring gray matter volume (GMV) on magnetic resonance images via voxel-based morphometric analysis., Methods: We prospectively enrolled 29 patients with AD and 20 healthy older adults. Auditory stimuli included 12 melodies of Japanese nursery songs that were expected to be familiar to participants. We constructed the melodies using pure and missing fundamental tones (MFTs)., Results: Patients with AD exhibited significantly poorer performance on the MFT task than healthy controls. MFT scores were positively correlated with GMV in the bilateral insula and temporal poles, left inferior frontal gyrus, right entorhinal cortex, and right cerebellum., Conclusions: These results suggest that impairments in the MFP represent a manifestation of the degeneration of auditory-related brain regions in AD. Further studies are required to more fully elucidate the neural mechanisms underlying auditory impairments in patients with AD and related dementia disorders.

Purpose: Istradefylline is useful in treating the wearing-off state in Parkinson's disease (PD). We investigated the effectiveness of istradefylline (ISD) in improving arousal, sleep, and gait deficits in patients with PD., Methods: We examined 14 patients with PD treated with ISD. We assessed the patients using the Unified Parkinson's Disease Rating Scale, Parkinson's Disease Questionnaire, Timed Up-and-Go test (TUG), Freezing of Gait Questionnaire (FOG-Q), Epworth Sleepiness Scale (ESS), and Parkinson's Disease Sleep Scale (PDSS) before and 1 month after ISD use., Results: ESS scores were significantly lower 1 month after the start of ISD treatment (6.79±6.50) than before the intervention (8.14±6.15, Wilcoxon signed-rank test, p=0.0033). PDSS scores were not significantly different 1 month after beginning the treatment (112±23mm) when compared to those before the intervention (110±27mm, Wilcoxon signed-rank test, p=0.40). TUG scores were not changed after 1 month of ISD use (14.9±8.3s) when compared to those before the intervention (21.3±30.0s, Wilcoxon signed-rank test, p=0.59). Although these measures were not significantly affected by ISD treatment, some patients remarkably improved after the treatment. FOG-Q scores were significantly lower 1 month after the beginning of treatment (9.79±7.16) than those before the intervention (12.14±5.82, Wilcoxon signed-rank test, p=0.030)., Conclusions: ISD may improve daytime sleepiness and FOG in patients with PD., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Aims: The aims of this study were (1) to investigate the influence of physical movement on near-infrared spectroscopy (NIRS) data, (2) to establish a video-NIRS system which simultaneously records NIRS data and the subject's movement, and (3) to measure the oxygenated hemoglobin (oxy-Hb) concentration change (Δoxy-Hb) during a word fluency (WF) task., Experiment 1: In 5 healthy volunteers, we measured the oxy-Hb and deoxygenated hemoglobin (deoxy-Hb) concentrations during 11 kinds of facial, head, and extremity movements. The probes were set in the bilateral frontal regions. The deoxy-Hb concentration was increased in 85% of the measurements., Experiment 2: Using a pillow on the backrest of the chair, we established the video-NIRS system with data acquisition and video capture software. One hundred and seventy-six elderly people performed the WF task. The deoxy-Hb concentration was decreased in 167 subjects (95%)., Experiment 3: Using the video-NIRS system, we measured the Δoxy-Hb, and compared it with the results of the WF task. Δoxy-Hb was significantly correlated with the number of words., Conclusion: Like the blood oxygen level-dependent imaging effect in functional MRI, the deoxy-Hb concentration will decrease if the data correctly reflect the change in neural activity. The video-NIRS system might be useful to collect NIRS data by recording the waveforms and the subject's appearance simultaneously.

Objectives: Cerebral microbleeds (CMBs) are often observed in memory clinic patients. It has been generally accepted that deep CMBs (D-CMBs) result from hypertensive vasculopathy (HV), whereas strictly lobar CMBs (SL-CMBs) result from cerebral amyloid angiopathy (CAA) which frequently coexists with Alzheimer's disease (AD). Mixed CMBs (M-CMBs) have been partially attributed to HV and also partially attributed to CAA. The aim of this study was to elucidate the differences between SL-CMBs and M-CMBs in terms of clinical features and regional distribution., Materials: We examined 176 sequential patients in our memory clinic for clinical features and CMB location using susceptibility-weighted images obtained on a 3T-MRI. The number of lobar CMBs in SL-CMBs and M-CMBs was counted in each cerebral lobe and their regional density was adjusted according to the volume of each lobe., Results: Of the total 176 patients, 111 patients (63.1%) had CMBs. Within the patients who had CMBs, M-CMBs were found in 54 patients (48.6%), followed by SL-CMBs in 35 (31.5%) and D-CMBs in 19 (17.1%). The SL-CMB group showed a significantly higher prevalence of family history of dementia, whereas the M-CMB group showed an increasing trend toward hypertension and smoking. The prevalence of AD was significantly higher in the SL-CMBs group, whereas the prevalence of AD with cerebrovascular disease was higher in the M-CMBs group. The regional density of lobar CMBs was significantly higher in the occipital lobe in the M-CMB group, whereas the SL-CMB group showed higher regional density between regions an increasing tendency in the parietal and occipital lobe., Conclusion: The between-group differences in clinical features and regional distribution indicate there to be an etiological relationship of SL-CMBs to AD and CAA, and M-CMBs to both HV and CAA.

Background: While several studies support an association of white matter hyperintensity (WMH) volume and regional cerebral blood flow (rCBF) with cognitive decline in Alzheimer's disease (AD), no reports have simultaneously considered the effects of both factors on cognitive decline., Objective: The purpose of the present study was to compare WMH volume and rCBF in relation to cognitive function by developing a new software program to fuse magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) data., Method: We used MRI, SPECT, and neuropsychological data from 182 serial outpatients treated at the memory clinic of our hospital., Results: Twenty-nine AD patients fulfilled the inclusion criteria (18 females, mean age: 73.1 ± 7.9 years, mean Mini-Mental State Examination: 23.1 ± 3.0). Analysis of variance revealed that posterior deep WMH (DWMH) volume was significantly larger than both anterior periventricular hyperintensity (PVH) and DWMH, and posterior PVH volumes. Multivariate regression analysis showed that increased volumes of the anterior PVH and the posterior DWMH and decreased rCBF of the parietal cortex negatively affected cognitive function. The other areas had no significant negative effects on cognitive function., Conclusion: Our findings show that the volume of the posterior WMH was significantly larger than that of other areas, and the increased posterior WMH volume and decreased rCBF of the parietal cortex negatively affected cognitive function. Therefore, the posterior WMH volume and the parietal rCBF are key parameters of cognitive decline in AD patients.

Findings from previous studies suggest that physical exercise combined with cognitive training produces more positive effects on cognitive function in elderly people than physical exercise alone. However, the brain plasticity associated with these proposed benefits of combined therapy has not yet been investigated in elderly subjects. We hypothesized that the dual task group would experience greater benefits than the physical exercise alone and non-exercise control groups with regard to both cognitive function and brain plasticity. This study investigated the effect of physical exercise with musical accompaniment on structural brain changes in healthy elderly people. Fifty-one participants performed physical exercise (once a week for an hour with professional trainers) with musical accompaniment (ExM), 61 participants performed the same exercise without music (Ex), and 32 participants made up the non-exercise group (Cont). After the 1-year intervention, visuospatial functioning of the ExM but not the Ex group was significantly better than that of the Cont group. Voxel-based morphometry analyses revealed that the ExM group showed greater right superior frontal gyrus volume and preserved volumes of the right anterior cingulate gyrus, left superior temporal gyrus, and insula. These results indicate that compared with exercise alone, physical exercise with music induces greater positive effects on cognitive function and leads to subtle neuroanatomical changes in the brains of elderly people. Therefore, physical exercise with music may be a beneficial intervention to delay age-related cognitive decline.

Background: Cerebral amyloid angiopathy (CAA) is classified as type 1 with capillary amyloid β (Aβ) or type 2 without capillary Aβ. While it is known that CAA activates complement, an inflammatory mediator, there is no information on the relationship between capillary Aβ and complement activation., Methods: We evaluated 34 autopsy brains, including 22 with CAA and 12 with other neurodegenerative diseases. We assessed the vascular density of CAA by analyzing the expression of complement (C1q, C3d, C6, C5b-9), macrophage scavenger receptor (MSR), and apolipoprotein E (ApoE)., Results: Capillary immunostaining for C1q, C3d, MSR, and ApoE was identified almost exclusively in CAA-type1 brains. There was intense expression of C1q, C3d, MSR, and ApoE, as well as weaker expression of C5b-9 and C6 in the arteries/ arterioles of both CAA subtypes, but not in control brains. C5b-9 and C6 were preferentially expressed in arteries/arterioles with subcortical hemorrhage or cortical superficial siderosis. Triple immunofluorescence revealed that C1q, C3d, and ApoE were colocalized with Aβ in CAA brain capillaries., Conclusion: Complement, MSR, and ApoE were only coexpressed in the presence of Aβ accumulation in capillaries, suggesting a role for complement activation in the propagation of Aβ. Additionally, C5b-9 expression may be associated with hemorrhagic brain injury in CAA., (© 2018 S. Karger AG, Basel.)

A 63-year-old, right-handed professional chorus conductor developed right putaminal hemorrhage, and became unable to experience emotion while listening to music. Two years later, neurological examination revealed slight left hemiparesis. Neuromusicological assessments revealed impaired judgment of "musical sense," and the inability to discriminate the sound of chords in pure intervals from those in equal temperament. Brain MRI and tractography identified the old hemorrhagic lesion in the right putamen and impaired fiber connectivity between the right insula and superior temporal lobe. These findings suggest that musical anhedonia might be caused by a disconnection between the insula and auditory cortex.

Purpose: Neuromelanin-sensitive MR imaging (NMI) is an increasingly powerful tool for the diagnosis of Parkinson's disease (PD). This study was undertaken to evaluate longitudinal changes on NMI in PD patients., Methods: We examined longitudinal changes on NMI in 14 PD patients. The area and contrast ratio (CR) of the substantia nigra pars compacta (SNc) were comparatively analyzed., Results: The total area and CR of the SNc upon follow-up NMI were significantly smaller than those on initial NMI (from 33.5±18.9 pixels and 6.35±2.86% to 21.5±16.7 pixels and 4.19±2.11%; Wilcoxon signed-rank test, p<0.001 and p=0.022, respectively). The area and CR of the dominant side SNc upon initial NMI were significantly greater than those on follow-up NMI (from 15.3±9.1 pixels and 6.5±2.7% to 7.9±8.5 pixels and 3.7±2.9%; Wilcoxon signed-rank test, p=0.002 and p=0.007, respectively). On a case-by-case basis, the area of the SNc invariably decreased upon follow-up NMI in all patients. We further demonstrated that the total area and CR of the SNc negatively correlated with disease duration (Pearson correlation coefficient, r=-0.63, p<0.001 and r=-0.41, p=0.031, respectively). In area analyses, our results demonstrated very high intraclass correlation coefficients for both intra- and inter-rater reliability., Conclusion: NMI is a useful and reliable tool for detecting neuropathological changes over time in PD patients., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Little research has been conducted regarding the role of pulvinar nuclei in the pathogenesis of visual hallucinations due to the difficulty of assessing abnormalities in this region using conventional magnetic resonance imaging (MRI). The present study aimed to retrospectively investigate the relative abilities of diffusion-weighted imaging (DWI), fluid-attenuated inversion recovery (FLAIR), and susceptibility-weighted imaging (SWI) to visualize the pulvinar and to ascertain the relationship between pulvinar visualization and visual hallucinations., Methods: A retrospective analysis of 3T MRIs from 73 patients (31 males, 42 females; mean age 73.5 ± 12.7 years) of the Memory Clinic of Mie University Hospital was conducted. Correlations between pulvinar visualization and the following were analyzed: age, sex, education, hypertension, hyperlipidemia, diabetes mellitus, Mini-Mental State Examination score, Evans index, and visual hallucinations., Results: DWI detected low-signal pulvinar areas in approximately half of the patients (52.1%). Participants with pulvinar visualization were significantly older, and the pulvinar was more frequently visualized in patients who had experienced visual hallucinations compared to those who had not. No significant association was observed between whole brain atrophy and pulvinar visualization., Conclusions: The results of the present study indicate that diffusion-weighted 3T MRI is the most suitable method for the detection of pulvinar nuclei in patients with dementia experiencing visual hallucinations.

Background/aims: Constructional apraxia (CA) is usually diagnosed by having patients draw figures; however, the reported assessments only evaluate the drawn figure. We designed a new assessment battery for CA (the Mie Constructional Apraxia Scale, MCAS) which includes both the shape and drawing process, and investigated its utility against other assessment methods., Methods: We designed the MCAS, and evaluated inter- and intrarater reliability. We also investigated the sensitivity, specificity, and positive and negative predictive values in dementia patients, and compared MCAS assessment with other reported batteries in the same subjects., Results: Moderate interrater reliability was shown for speech therapists with limited experience. Moderate to substantial intrarater reliability was shown several weeks after initial assessment. When cutoff scores and times were set at 2/3 points and 39/40 s, sensitivity and specificity were 77.1 and 70.4%, respectively, with positive and negative predictive values of 80.0 and 66.7%, respectively. Dementia patients had significantly worse scores and times for Necker cube drawing than an elderly control group on the MCAS, and on other assessments., Conclusions: We conclude that the MCAS, which includes both the assessment of the drawn Necker cube shape and the drawing process, is useful for detecting even mild CA.