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Authors: Chung, Jun Ku | Plitman, Eric | Nakajima, Shinichiro | Chakravarty, M. Mallar | Caravaggio, Fernando | Takeuchi, Hiroyoshi | Gerretsen, Philip | Iwata, Yusuke | Patel, Raihaan | Mulsant, Benoit H. | Graff-Guerrero, Ariel

Article Type: Research Article

Abstract: Previous studies have highlighted that decreased hippocampal volume, an early neural correlate of dementia, is commonly observed in patients with mild cognitive impairment (MCI). However, it is unclear whether neurodegenerative and resultant clinical trajectories are accelerated in MCI patients with concomitant depressive symptoms, leading to a faster conversion to dementia stages than those who are not depressed. No longitudinal study has investigated whether depressed amnestic MCI (DEP+aMCI) patients show an earlier onset of progression to dementia than non-depressed amnestic MCI (DEP-aMCI) patients and whether progressive hippocampal volume reductions are related in the conversion process. Using data from Alzheimer’s Disease Neuroimaging …Initiative, we examined 2-year follow-up data from 38 DEP+aMCI patients and 38 matched DEP-aMCI patients and compared their ages of conversion from aMCI to AD and trajectories of progressive hippocampal volume changes. DEP+ and DEP- patients were defined as having baseline Geriatric Depression Scale scores of 5 or above and 0, respectively. DEP+ converters showed earlier ages of conversion to dementia (p  = 0.009) and greater left hippocampal volume loss than both DEP- converters and DEP+ non-converters over the 2-year period (p  = 0.003, p  = 0.001, respectively). These findings could not be explained by changes in total brain volume, differences in their clinical symptoms of dementia, daily functioning, or apolipoprotein E4 genotypes. No difference in conversion rate to dementia or progressive hippocampal volume change was found between DEP+ patients and DEP-patients, which suggested depressive symptoms themselves may not lead to progression of dementia from MCI. In conclusion, there is a synergistic effect of depressive symptoms and smaller left hippocampal volume in MCI patients that accelerates conversion to dementia. Show more

Keywords: Dementia, depression, hippocampus, mild cognitive impairment

DOI: 10.3233/JAD-150679

Citation: Journal of Alzheimer's Disease, vol. 49, no. 3, pp. 743-754, 2016

Authors: Chung, Jun Ku | Plitman, Eric | Nakajima, Shinichiro | Caravaggio, Fernando | Iwata, Yusuke | Gerretsen, Philip | Kim, Julia | Takeuchi, Hiroyoshi | Shinagawa, Shunichiro | Patel, Raihaan | Chakravarty, M. Mallar | Graff-Guerrero, Ariel | for the Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Suspected non-Alzheimer’s disease pathology (SNAP) characterizes individuals showing neurodegeneration (e.g., hypometabolism) without amyloid-β (Aβ). Findings from previous studies regarding clinical and structural trajectories of SNAP are inconsistent. Using data from the Alzheimer’s Disease Neuroimaging Initiative, patients with amnestic mild cognitive impairment (MCI) were categorized into four groups: amyloid positive with hypometabolism (Aβ+ND+), amyloid only (Aβ+ND–), neither amyloid nor hypometabolism (Aβ–ND–), and SNAP (Aβ–ND+). Aβ+ND+(n  = 33), Aβ+ND–(n  = 32), and Aβ–ND–(n  = 36) were matched to SNAP for age, gender, apolipoprotein E4 (apoE4) genotype, and scores on the Montreal Cognitive Assessment. Elderly controls (n  = 40) were also matched to SNAP for age, gender, …and apoE4 genotype. Longitudinal changes were compared across groups in terms of hippocampal volume, clinical symptoms, daily functioning, and cognitive functioning over a 2-year period. At baseline, no difference in cognition and functioning was observed between SNAP and Aβ+groups. SNAP showed worse clinical symptoms and impaired functioning at baseline compared to Aβ–ND–and controls. Two years of follow-up showed no differences in hippocampal volume changes between SNAP and any of the comparison groups. SNAP showed worse functional deterioration in comparison to Aβ–ND–and controls. However, Aβ+ND+ showed more severe changes in clinical symptoms in comparison to SNAP. Thus, patients with MCI and SNAP showed 1) more severe functional deterioration compared to Aβ–ND–and controls, 2) no differences with Aβ+ND–, and 3) less cognitive deterioration than Aβ+ND+. Future studies should investigate what causes SNAP, which is different from typical AD pathology and biomarker cascades. Show more

Keywords: Functional decline, hippocampus, mild cognitive impairment, suspected non-Alzheimer’s pathology

DOI: 10.3233/JAD-170201

Citation: Journal of Alzheimer's Disease, vol. 58, no. 3, pp. 747-762, 2017

Authors: Chung, Jun Ku | Plitman, Eric | Nakajima, Shinichiro | Caravaggio, Fernando | Shinagawa, Shunichiro | Iwata, Yusuke | Gerretsen, Philip | Kim, Julia | Takeuchi, Hiroyoshi | Patel, Raihaan | Chakravarty, M. Mallar | Strafella, Antonio | Graff-Guerrero, Ariel | for the Alzheimer’s Disease Neuroimaging Initiative

Article Type: Short Communication

Abstract: The clinical and structural trajectories of suspected non-Alzheimer’ pathology (SNAP) remain elusive due to its heterogeneous etiology. Baseline and longitudinal clinical (global cognition, daily functioning, symptoms of dementia, and learning memory) and hippocampal volume trajectories over two years were compared between patients with amnestic mild cognitive impairment (aMCI) with SNAP with reduced hippocampal volumes (SNAP+HIPPO) and aMCI patients with SNAP without reduced hippocampal volumes. SNAP+HIPPO showed overall worse baseline cognitive functions. Longitudinally, SNAP+HIPPO showed faster deterioration of clinical symptoms of dementia. Having both hippocampal atrophy and cortical hypometabolism without amyloid pathology may exacerbate symptoms of dementia in aMCI.

Keywords: Functional decline, hippocampus, mild cognitive impairment, suspected non-Alzheimer’s pathology

DOI: 10.3233/JAD-170098

Citation: Journal of Alzheimer's Disease, vol. 60, no. 2, pp. 341-347, 2017