Authors: Shiraishi, Hideki | Yamakawa, Yuriko | Itou, Ayaka | Muraki, Toshiaki | Asada, Takashi
Article Type: Research Article
Abstract: Previous studies have discussed the effectiveness or ineffectiveness of prism adaptation for neglect patients. Purpose: The aim of present study was to determine the long-term effect of prism adaptation with activity performance instead of pointing performance on chronic neglect patients. Subjects: Seven patients with chronic unilateral spatial neglect were recruited. Methods: We performed an 8-week intervention using prismatic glasses. Changes in eye movement before and after intervention were measured using an eye mark recorder system. We also assessed intentional spatial bias in terms of center of gravity in the standing position using a tactile sensor scan system. Additionally, regional cerebral …blood flow was measured using SPECT (IMP) before and after intervention. Results: Eye movements significantly improved on the neglected side (p < 0.01), and the effects were sustained for up to 6 weeks after the removal of the prism. The center of gravity significantly moved to the left and forward. Furthermore, rCBF showed a significant increase at the parietal cortex, pericalleosal area of the left hemisphere (P < 0.05). Conclusion: These results suggest that intervention using prismatic glasses could improve eye movement on the neglected side and correct intentional spatial bias. Prism intervention might be one valuable method for the activation of the important areas of the brain in neglect patients. Show more
Keywords: Prism intervention, long-term intervention, unilateral spatial neglect, chronic patient, eye movement, center of gravity, regional cerebral blood flow
DOI: 10.3233/NRE-2008-23203
Citation: NeuroRehabilitation, vol. 23, no. 2, pp. 137-151, 2008
Authors: Ochiai, Ryuji | Saitou, Katsuyoshi | Suzukamo, Chika | Osaki, Noriko | Asada, Takashi
Article Type: Research Article
Abstract: Background: Mild cognitive impairment (MCI) is a global-scale issue, due in large part to the rapidly growing elderly population. The main polyphenol contained in coffee beans, chlorogenic acid (CGA), improves attention in healthy individuals. The utility of CGAs for treating MCI, however, has not been evaluated. Objective: To determine the effects of continuous CGA intake on cognitive function, especially attention, in patients diagnosed with MCI. Methods: The study was a randomized controlled crossover trial including 34 patients with MCI. Participants were randomly divided into two groups: Those who first ingested a placebo beverage and those who first ingested an active …beverage containing CGAs (553.6 mg/bottle) twice daily for 12 weeks. After a 4-week washout period, the subjects ingested the other beverage (i.e., placebo or active beverage) in the same manner. Endpoint measures included scores on the Japanese version of the Mini-Mental State Examination (MMSE), the Japanese version of the Alzheimer’s Disease Assessment Scale-cognitive component (ADAS-cog) testing overall cognitive function, and the Japanese version of the Trail Making Test (TMT-A, TMT-B) testing attention, along with the results of blood tests to evaluate safety. Results: In the TMT-B test, participants had a significantly reduced number of errors while ingesting the CGA beverage as compared with the placebo beverage (p < 0.05), although there was no difference in test completion time. Scores in the MMSE, ADAS-cog, and TMT-A did not differ significantly between conditions. Conclusion: Continuous intake of CGAs appears to improve attention and executive function among cognitive functions in MCI. Show more
Keywords: Attention, chlorogenic acid, coffee, crossover studies, mild cognitive impairment, polyphenol, trail making test
DOI: 10.3233/JAD-190757
Citation: Journal of Alzheimer's Disease, vol. 72, no. 4, pp. 1209-1216, 2019
Authors: Ito, Naoki | Saito, Hitomi | Seki, Shinobu | Ueda, Fumitaka | Asada, Takashi
Article Type: Research Article
Abstract: Background: Dementia and its first or transitional stage, mild cognitive impairment (MCI), is a major concern for the aging Japanese society. Thus, the use of dietary supplements to improve or maintain cognitive function has become a topic of public interest. Objective: In this study, we evaluated the effects of a composite supplement containing food-derived antioxidants, specifically astaxanthin and sesamin (AS), on cognitive function in people with MCI. Method: Twenty-one healthy participants with MCI were recruited in our double-blind placebo-controlled pilot study. They were assigned to either an AS group, who received ingestible capsules containing AS, or a placebo group, who …received identical placebo capsules. To assess cognitive functions, we performed the Japanese version of the Central Nervous System Vital Signs (CNSVS) test and the Alzheimer’s Disease Assessment Scale-Cog test at baseline, after 6 weeks, and after 12 weeks of dietary supplementation. Results: The CNSVS test revealed significant improvements in psychomotor speed and processing speed in the AS group compared with the placebo group, suggesting that the daily supplementation of AS improved cognitive functions related to the ability to comprehend, and perform complex tasks quickly and accurately. Conclusion: Our results provide support for the use of AS as a dietary supplementation for improving cognitive functions. Show more
Keywords: Astaxanthin, CNSVS, cognitive functions, mild cognitive impairment, sesame extract, sesamin
DOI: 10.3233/JAD-170969
Citation: Journal of Alzheimer's Disease, vol. 62, no. 4, pp. 1767-1775, 2018
Authors: Bun, Shogyoku | Ikejima, Chiaki | Kida, Jiro | Yoshimura, Atsuko | Lebowitz, Adam Jon | Kakuma, Tatsuyuki | Asada, Takashi
Article Type: Research Article
Abstract: A number of studies have examined the effect of a single supplement against Alzheimer's disease (AD) with conflicting results. Taking into account the complex and multifactorial nature of AD pathogenesis, multiple supplements may be more effective. Physical activity is another prospect against AD. An open-label intervention study was conducted to explore a potential protective effect of multiple supplements and physical activity. Their interaction was also examined. Participants were community-dwelling volunteers aged 65 or older as of May 2001 in a rural area of Japan. Among 918 cognitively normal participants included in the analyses, 171 took capsules daily for three years …that contained n-3 polyunsaturated fatty acid, Ginkgo biloba leaf dry extracts, and lycopene. Two hundred and forty one participants joined the two-year exercise intervention that included a community center-based and a home-based exercise program. One-hundred and forty eight participated in both interventions. A standardized neuropsychological battery was administered at baseline in 2001, the first follow-up in 2004-2005, and the second in 2008-2009. The primary outcome was AD diagnosis at follow-ups. A complementary log-log model was used for survival analysis. A total of 76 participants were diagnosed with AD during follow-up periods. Higher adherence to supplementation intervention was associated with lower AD incidence in both unadjusted and adjusted models. Exercise intervention was also associated with lower AD incidence in the unadjusted model, but not in the adjusted model. We hypothesized that the combination of supplements acted in a complementary and synergistic fashion to bring significant effects against AD occurrence. Show more
Keywords: Alzheimer's disease, dietary supplements, exercise, Gingko biloba, intervention study, lycopene, n-3 PUFA
DOI: 10.3233/JAD-142232
Citation: Journal of Alzheimer's Disease, vol. 45, no. 1, pp. 15-25, 2015
Authors: Yasuno, Fumihiko | Tanimukai, Satoshi | Sasaki, Megumi | Ikejima, Chiaki | Yamashita, Fumio | Kodama, Chiine | Mizukami, Katsuyoshi | Asada, Takashi
Article Type: Research Article
Abstract: Although nutrients or agents with antioxidant properties were reported to show a preventive effect on cognitive decline in animal studies, epidemiologic data on select antioxidants have shown conflicting results. We investigated whether a combination of antioxidants from supplements is effective for the improvement of cognitive function of elderly. Forty-one subjects from a community dwelling aged 65 years and older took supplements containing n-3 polyunsaturated fatty acids (n-3 PUFA), lycopene, and Ginkgo biloba extracts (GE) daily for 3 years. The data of 622 subjects without supplement intake were used as control. We investigated the changes in cognitive function during a 3-year …follow-up. We also investigated the influence of apolipoprotein E (APOE) genotype on the effect of antioxidants. We found that a combination of antioxidants improved cognitive function of aged persons after 3 years. Our present study also indicated this improvement in cognitive function with supplement intake in both APOE4 non-carrier (E4−) and APOE4 carrier (E4+) groups. Especially, in E4+, we found a large effect size of the improvement of cognition. When multiple antioxidants are used in combination, they protect against vulnerability to other agents and synergistically potentiate their antioxidant properties. These synergistically potentiated antioxidant effects of agents contribute to the improvement of cognitive function. Show more
Keywords: Antioxidant, apolipoprotein E4 allele (APOE4), cognitive function, Ginkgo biloba extracts (GE), lycopene, n-3 polyunsaturated fatty acid (n-3 PUFA)
DOI: 10.3233/JAD-2012-121225
Citation: Journal of Alzheimer's Disease, vol. 32, no. 4, pp. 895-903, 2012
Authors: Takahashi, Sho | Mizukami, Katsuyoshi | Arai, Tetsuaki | Ogawa, Ryoko | Kikuchi, Norihiro | Hattori, Satoshi | Darby, David | Asada, Takashi
Article Type: Research Article
Abstract: Background: Studies have shown that developing major depressive disorder (MDD) at 50 years of age or older can predict dementia. Depression is particularly common in dementia with Lewy bodies (DLB), and occasionally occurs before the onset of extrapyramidal symptoms. Moreover, systemic autonomic dysfunction, including an abnormal ventilatory response to hypercapnia (VRH), is common in patients with DLB. Objective: Here, we aimed to determine whether the VRH is useful for distinguishing depression that is predictive of DLB from other types of MDD. Methods: Participants were 35 consecutive patients with first onset MDD at 50 years or older with bradykinesia. After diagnosing …the clinical subtype of MDD according to DSM-IV criteria, each subject underwent a battery of psychological tests, autonomic examinations including VRH, brain magnetic resonance imaging, and 123 I-meta-iodobenzylguanidine scintigraphy. Results: Longitudinal follow-up showed that all 18 patients with abnormal VRH results developed DLB, whereas none of the 17 patients with normal VRH results converted to DLB within the study period (sensitivity: 100% , specificity: 100%). Additionally, over half of the DLB converters showed abnormalities on other autonomic examinations. For converters, the most common MDD subtype had psychotic and melancholic features simultaneously. The frequency of hypersensitivity to psychotropics was higher in converters than it was in non-converters. Conclusion: In the present study, patients with abnormal VRH results were very likely to develop DLB. Thus, for patients with late-onset MDD accompanied by bradykinesia, the VRH in combination with the clinical subtype of MDD or hypersensitivity to psychotropics may be useful for diagnosing prodromal DLB. Show more
Keywords: Autonomic failure, conversion, dementia with Lewy bodies, depression, ventilatory response to hypercapnia
DOI: 10.3233/JAD-150507
Citation: Journal of Alzheimer's Disease, vol. 50, no. 3, pp. 751-758, 2016
Authors: Kida, Jiro | Nemoto, Kiyotaka | Ikejima, Chiaki | Bun, Shogyoku | Kakuma, Tatsuyuki | Mizukami, Katsuyoshi | Asada, Takashi
Article Type: Research Article
Abstract: Background: While longitudinal studies have investigated the relationships between mild cognitive impairment (MCI) subtypes and dementia subtypes, the results have been contradictory. In addition, some research shows that depression accompanied by MCI might increase the risk of Alzheimer’s disease (AD). Objective: The aim of this study is to longitudinally investigate the relationships between MCI subtypes and dementia subtypes, with special attention to the effect of comorbid depressive symptoms in a Japanese rural community. Methods: Non-demented participants (n = 802) completed a baseline and follow-up study. Outcomes were conversion to dementia especially AD, MCI, or no conversion. A complementary log-log analysis was …conducted to investigate the risk of dementia and AD in amnestic MCI (aMCI) compared to nonamnestic MCI (naMCI) groups. The impact of depressive symptoms on the transition from MCI to AD and from cognitively normal to MCI or AD was also analyzed. Results: The risk of developing dementia, in particular AD, for the aMCI group was significantly higher than that for the naMCI group. In the aMCI group, the presence of depressive symptoms increased the risk of developing AD, but depressive symptoms in the naMCI group did not. In the cognitively normal group, the presence of depressive symptoms increased the risk of aMCI but not naMCI or AD. Conclusion: MCI subtyping could be useful in finding a prodrome for dementia and in particular for AD. The differing impacts of depressive symptoms on the development of AD suggest that the relationship between depressive symptoms and cognitive impairment could differ in aMCI and naMCI patients. Show more
Keywords: Alzheimer’s disease, community, conversion, depressive symptoms, mild cognitive impairment
DOI: 10.3233/JAD-150603
Citation: Journal of Alzheimer's Disease, vol. 51, no. 2, pp. 405-415, 2016
Authors: Asada, Takashi | Tanaka, Mieko | Araki, Wataru | Jon Lebowitz, Adam | Kakuma, Tatsuyuki
Article Type: Research Article
Abstract: Background: Interventions to prevent or attenuate cognitive decline and dementia in older adults are becoming increasingly important. Recently, cognitive training exercise can be via computer or mobile technology for independent or home use. Recent meta-analysis has reported that Computerized Cognitive Training (CCT) is effective at enhancing cognitive function in healthy older and Alzheimer’s disease adults, although little is known about individual characteristics of each computerized program. Objective: We developed a new CCT named Brain Training Based on Everyday Living (BTEL) to enhance cognitive capacity for Instrumental Activities of Daily Living (IADL). We aim to evaluate the efficacy of the BTEL …among cognitively healthy old individuals and to explore its concurrent validity and construct concept. Methods: We conducted a double-blind study where 106 individuals aged 65 years and older (intervened = 53, control = 53) worked on the active and placebo tasks three times a week over three months (clinical trial: UMIN000048730). The main results were examined using ANCOVA and calculating correlation coefficients. Results: We found no effect on total score of the three tests; however, there was significant effect for the BTEL on: recognition in MMSE, and immediate recall in HDSR. The tasks are associated with prefrontal cortex. In addition, correlations indicated that each BTEL domain had some validity as a cognitive assessment tool. Different from previous CCT, we determined the neuropsychological characteristics of specific cognitive tasks of the BTEL to a certain degree. Conclusions: We found modest efficacy of the BTEL in cognitively healthy old individuals and confirmed its concurrent validity and the conceptual construct. Show more
Keywords: Activities of daily living, Alzheimer’s disease, brain training, mild cognitive impairment, neuropsychology
DOI: 10.3233/JAD-231165
Citation: Journal of Alzheimer's Disease, vol. 99, no. 2, pp. 549-558, 2024
Authors: Nakamura, Shin | Yomota, Satoshi | Ito, Hitomi | Akinaga, Nobuyuki | Hori, Ayaka | Chinomi, Kenta | Suzuki, Hideaki | Uchida, Kazuhiko | Asada, Takashi
Article Type: Research Article
Abstract: Background: Maintaining cognitive function is integral to a healthy social life in the aged. Although neuropsychological tests and brain imaging methods can assess cognitive dysfunction, these techniques are subjective, psychologically burdensome, and cannot be conducted easily. Objective: We sought to develop an objective, low-burden novel cognitive function scale based on functional near-infrared spectroscopy (fNIRS) of hemodynamic changes in the cerebral cortex during daily task performance. Methods: A total of 63 participants (aged 60–80 years) identified as non-dementia controls (NDC) or with mild cognitive impairment (MCI) were recruited and randomly assigned to training and test data sets. Explanatory variables were hemodynamic …responses during low-burden sensory and simple tasks without higher-order brain functioning. Results: A logistic regression analysis of the fNIRS index in NDCs and MCI patients revealed area under the curve, sensitivity, specificity, and holdout results of 0.98, 94%, 88%, and 62% respectively. Correlation between fNIRS index and MCI odds showed positive linearity (R2 = 0.96). Conclusion: Positive correlation between the fNIRS index and MCI odds indicated effectiveness of this fNIRS measurement. Although additional experiments are necessary, the fNIRS index representing degree of cognitive decline can be an onsite monitoring tool to assess cognitive status. Show more
Keywords: Cognitive dysfunction, functional neuroimaging, mental status and dementia tests, neuropsychological tests, neurovascular coupling, spectroscopy near-infrared
DOI: 10.3233/JAD-210072
Citation: Journal of Alzheimer's Disease, vol. 81, no. 4, pp. 1579-1588, 2021
Authors: Omori, Chiori | Kaneko, Madoka | Nakajima, Etsuko | Akatsu, Hiroyasu | Waragai, Masaaki | Maeda, Masahiro | Morishima-Kawashima, Maho | Saito, Yuhki | Nakaya, Tadashi | Taru, Hidenori | Yamamoto, Tohru | Asada, Takashi | Hata, Saori | Suzuki, Toshiharu | for the Japanese Alzheimer's Disease Neuroimaging Initiative
Article Type: Research Article
Abstract: p3-Alcα is a metabolic fragment of Alcadeinα (Alcα). Similar to the generation of the p3 fragment from amyloid-β protein precursor (AβPP) processing, Alcα is cleaved by α- and γ-secretases, leading to the secretion of p3-Alcα peptides into cerebrospinal fluid (CSF). p3-Alcα is also detected in the plasma, similar to amyloid-β (Aβ), which is a metabolic fragment of AβPP cleaved by amyloidogenic β- and γ-secretases. Because p3-Alcα is a non-aggregatable and stable peptide, unlike aggregatable Aβ and metabolically labile p3 of AβPP, the changes of p3-Alcα in quality and/or quantity in CSF and plasma are expected to be a marker for …assessing alteration of substrate cleavage by γ-secretase, such as Aβ generation from AβPP. The present study describes a sandwich enzyme-linked immunosorbent assay for quantifying levels of p3-Alcα35, the major form of the p3-Alcα species, and examines levels of p3-Alcα35 in the plasma of three independent Japanese cohorts. In two of the three cohorts, the p3-Alcα35 levels were significantly increased with a concomitant decrease in the Mini-Mental State Examination score, or in clinically diagnosed Alzheimer's disease (AD) patients, when compared with age-matched non-demented subjects. The values were significantly lower in AD subjects who were administered donepezil, when compared to AD subjects without donepezil treatment. The increase in plasma p3-Alcα35 levels may indicate an endophenotype in subjects in whom AD is due to a progressing cognitive impairment in subjects with a γ-secretase malfunction, or a disorder of the clearance of peptides. Show more
Keywords: Alzheimer's disease, alcadein, diagnosis, donepezil, γ-secretase, p3-Alc, plasma biomarker
DOI: 10.3233/JAD-131610
Citation: Journal of Alzheimer's Disease, vol. 39, no. 4, pp. 861-870, 2014