Osaki-Tajiri Project Research Articles

Decreased Behavioral Abnormalities After Treatment with Combined Donepezil and Yokukansankachimpihange in Alzheimer Disease: An Observational Study. The Osaki-Tajiri Project.

IntroductionYokukansan is one of the traditional herbal medicines (Kampo medicine in Japan) commonly used in the treatment of the Behavioral and Psychological Symptoms of Dementia (BPSD). We performed an observational study using yokukansankachimpihange, which contains a nobiletin-rich Citrus reticulata, to determine whether it could improve BPSD as well as cognitive impairment in patients with Alzheimer disease (NINCDS-ADRDA).MethodsForty-six (23 vs. 23) patients were enrolled in the study sample (donepezil group vs. donepezil + yokukansankachimpihange group). The BPSD were assessed using the Frequency-Weighted Behavioral Pathology in Alzheimer Disease Rating Scale (BEHAVE-AD-FW). The Mini-Mental State Examination and the Digit Symbol test of WAIS-R were used to evaluate impairment of global cognitive function and executive function, respectively.ResultsNo significant changes in the cognitive functions or the total BPSD scores were noted for either treatment group. Regarding the subscales of the BPSD, the subscale of Diurnal Rhythm showed a significant decrease after the treatment, and those of Affective Disturbance and Anxiety and Phobias tended to be decreased. The donepezil + yokukansankachimpihange group had a lower rate of use of anti-psychotics compared with the donepezil group, although this was not statistically significant.ConclusionThese results suggest that combined treatment of yokukansankachimpihange with donepezil has a positive clinical effect on improving the behavioral abnormalities, despite the lack of any effect on cognitive functions. Improvements in the diurnal rhythm may improve affective disturbance and anxiety. Thus, yokukansankachimpihange is considered to have a mild stabilizing effect on emotion.

Long-Term Effect of Cholinesterase Inhibitors and Special Nursing Home Replacement on Lifetime Expectancy for Alzheimer Disease and Dementia with Lewy Bodies: The Osaki-Tajiri Project

Long-Term Effect of Cholinesterase Inhibitors and Special Nursing Home Replacement on Lifetime Expectancy for Alzheimer Disease and Dementia with Lewy Bodies: The Osaki-Tajiri Project

Monitoring of drug treatment and psychosocial intervention with SPECT in Alzheimer patients Implications for neurologically appropriate psychosocial interventions. An observational study. The Osaki-Tajiri Project.

ABSTRACTWe previously examined cerebral blood flow (CBF) with single-photon emission computed tomography (SPECT) in Alzheimer’s disease (AD) with reference to drug treatment (donepezil) and psychosocial intervention.Objective:The aim is to provide “brain-based” evidence for psychosocial interventions using SPECT.Methods:The participants were 27 consecutive outpatients with AD who received the drug and psychosocial intervention, and SPECT three times (baseline, pre-/post-intervention) at 6 month-intervals. The significance level of changes in CBF (Z score) and the extent of significantly changed areas, calculated with the eZIS system, were used as monitoring parameters. The participants were classified into three groups: improve (post-intervention CBF increased), worsening (progressive decline), and no change.Results:Six, 8, and 13 patients were classified as improve, worsening, and no change, respectively. All subjects in the improve group showed improvement in cognitive test scores for the MMSE and/or the CGI scores associated with the brain area with a CBF increase (right parietal lobe), suggesting appropriate psychosocial intervention (visuospatial intervention).Conclusion:These results suggest that monitoring of CBF with the eZIS system may be clinically applicable for monitoring of drug treatment and psychosocial intervention in AD patients.

IT IS DIFFICULT FOR OTHERS TO UNDERSTAND CAREGIVER BURDEN FOR PATIENTS WITH RIGHT FRONTAL LOBE DAMAGE MANIFESTING IN LIFE DYSFUNCTIONS THAT CANNOT SIMPLY BE ATTRIBUTED TO IMPAIRED GENERAL COGNITIVE FUNCTION: THE OSAKI-TAJIRI PROJECT

IT IS DIFFICULT FOR OTHERS TO UNDERSTAND CAREGIVER BURDEN FOR PATIENTS WITH RIGHT FRONTAL LOBE DAMAGE MANIFESTING IN LIFE DYSFUNCTIONS THAT CANNOT SIMPLY BE ATTRIBUTED TO IMPAIRED GENERAL COGNITIVE FUNCTION: THE OSAKI-TAJIRI PROJECT

Impaired Picture Arrangement subscores (WAIS-III) associated with decreased place orientation and frontal/occipital blood flow in Alzheimer's disease: Implications for social judgment dysfunction. The Osaki-Tajiri Project

Alzheimer's disease (AD) patients manifest not only memory impairment but also deficit of social judgment. However, contrary to frequently recognized deficit, only two neuropsychological tests have been established for assessing “judgment” : the Cognitive Abilities Screening Instrument domain Abstraction & judgment and the Picture Arrangement subscale of WAIS-III. For the former, we previously reported an association with decreased regional cerebral blood flow (rCBF) in the left parietal lobe. Herein, we analyzed the scores of the Picture Arrangement test. Forty-nine AD patients were classified into two groups, i.e., the high and low PA score groups. The 99mTc-ECD SPECT investigation was performed with the voxel-based analysis using SPM5. The Mini-Mental State Examination subscores of “place orientation” showed a correlation with the PA scores. The low PA score group exhibited significantly decreased rCBFs in the Left Inferior Frontal Gyrus (LIFG), Left Superior Frontal Gyrus (LSFG) and Right Occipital Lobe (ROL), compared with the high PA score group. The ability of PA may be associated with the place orientation, which may be necessary to re-arrange the pictures. The ROL was related to visual recognition. The LSFG may be involved in executive function or “frontal reasoning.”

Impaired attention function based on the Montréal Cognitive Assessment in vascular dementia patients with frontal hypoperfusion: The Osaki-Tajiri project

We previously reported that the Montréal Cognitive Assessment (MoCA) was effective in the evaluation of cerebrovascular diseases. We also demonstrated that the test was effective for screening for very mild vascular dementia (VaD) in the community. Herein, we examined the effectiveness of MoCA in the assessment of patients with VaD in an outpatient clinic. Forty-four patients with VaD (National Institute of Neurological Disorders and Stroke–Association Internationale pour la Recherche et l’Enseignement en Neurosciences [NINDS-AIREN] criteria) and 58 patients with Alzheimer’s disease (AD) (National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer’s Disease and Related Disorders Association [NINCDS-ADRDA] criteria) were compared with 67 non-demented control subjects. All were outpatients at the Tajiri Memory Clinic, Osaki-Tajiri, northern Japan. All underwent 1.5 Tesla MRI and ethyl cysteinate dimer (ECD) single photon emission computed tomography (SPECT) examinations. The SPECT images were used to classify the VaD patients into two subgroups, those with frontal hypoperfusion (F-VaD) and those without frontal hypoperfusion. The frontal hypoperfusion pattern was defined as the “P2” pattern of the Sliverman classification, with or without focal hypometabolism in other areas, based on the agreement of three neurologists who were blinded to the results of the neuropsychological examinations. Total scores and attention subscores on the MoCA were lower in the F-VaD group compared with other groups. Our results suggest that the MoCA attention subscale can detect VaD participants, particularly those with frontal hypoperfusion.

Impaired ‘logical judgment’ associated with ‘behavioral and emotional judgment’ in Alzheimer’s patients: Implication for right temporal function—the osaki-tajiri project

Impaired ‘logical judgment’ associated with ‘behavioral and emotional judgment’ in Alzheimer’s patients: Implication for right temporal function—the osaki-tajiri project

Effect of memantine on improving bpsd in Alzheimer's patients may be due to a cognitive effect as assessed with behave-ad-fw: The osaki-tajiri project

Effect of memantine on improving bpsd in Alzheimer's patients may be due to a cognitive effect as assessed with behave-ad-fw: The osaki-tajiri project

Words are processed faster than pictures in Alzheimer’s brain: The osaki-tajiri project

Words are processed faster than pictures in Alzheimer’s brain: The osaki-tajiri project

Effectiveness of the Montreal Cognitive Assessment (MoCA) for assessing frontal hypoperfusion in people with vascular dementia: The Osaki-Tajiri Project

Effectiveness of the Montreal Cognitive Assessment (MoCA) for assessing frontal hypoperfusion in people with vascular dementia: The Osaki-Tajiri Project

A momentary visual presentation task can discriminate semantic dementia from Alzheimer's disease as demonstrating semantic memory access disorders: The Osaki-Tajiri Project

A momentary visual presentation task can discriminate semantic dementia from Alzheimer's disease as demonstrating semantic memory access disorders: The Osaki-Tajiri Project

Vascular dementia with left thalamic infarction: Neuropsychological and behavioral implications suggested by involvement of the thalamic nucleus and the remote effect on cerebral cortex. The Osaki–Tajiri project

Vascular dementia (VaD) is a condition whereby decreased cerebral perfusion causes cognitive deterioration. We hypothesized that lesions of the anterior nucleus (AN) including the mammillo-thalamic tract cause a decline in the recollection of past episodes/events, and that the left thalamic infarction can cause frontal dysfunction through the “diaschisis.” We investigated 18 VaD cases with only left thalamic infarction. 99mTc-ECD single photon emission computed tomography (SPECT) was used to assess regional cerebral blood flow (CBF). To test the first hypothesis, the scores on the Cognitive Abilities Screening Instrument (CASI) domain Recent memory or the rating on the Clinical Dementia Rating (CDR) domain Memory were analyzed. To test the second hypothesis, we selected the six regions of interest that correlated with the two measures, i.e., word fluency and/or depressive state, as assessed with the Geriatric Depression Scale (GDS). We found that all patients had amnesia, especially in the AN group, six of the eight patients had scores of 1+ on the CDR Memory scale, and all but one disclosed the CASI domain Recent memory impairment. There were significant correlations between the left anterior cingulate CBF and word fluency scores, and between the right rectal gyrus CBF and GDS scores. We suggest that these observations are due to a remote effect of the thalamic lesion.

Activated thalamic glucose metabolism after combined donepezil and psychosocial intervention in Alzheimer's disease: The Osaki-Tajiri project

Activated thalamic glucose metabolism after combined donepezil and psychosocial intervention in Alzheimer's disease: The Osaki-Tajiri project

Brain regions underlying distinct groups of “delusional ideas” (BEHAVE-AD-FW) in Alzheimer's Dementia: The osaki-tajiri project

Brain regions underlying distinct groups of “delusional ideas” (BEHAVE-AD-FW) in Alzheimer's Dementia: The osaki-tajiri project

Chronic Kidney Disease: A Risk Factor for Dementia Onset: A Population‐Based Study. The Osaki‐Tajiri Project

To examine the relationship between the incidence of dementia and chronic kidney disease (CKD). Longitudinal data analyses. Baseline data and follow-up data from the Osaki-Tajiri Project. The Tajiri Project dementia prevalence study in 1998 involved 497 community-dwelling, older men and women (346 with Clinical Dementia Rating score (CDR) of 0 (healthy), 119 with a CDR of 0.5 (questionable dementia), and 32 with a CDR of 1 or greater (dementia)). Two hundred fifty-four participants with CDR of 0 and 0.5 who were reclassified as converters (n=28) or nonconverters (n=230) to dementia in the incidence study in 2003 were followed. The prevalence of CKD and the onset of dementia were retrospectively analyzed, and the effects of other vascular risk factors on converters and CKD were analyzed. Weighted logistic regression showed CKD to be significantly associated with incident dementia after adjustment for age, sex, education, hypertension, diabetes mellitus, dyslipidemia, ischemic heart disease, and anemia. The odds ratio for conversion to dementia for those with CKD compared to those without was 5.3 (95% confidence interval=1.7, 16.2). Apart from dyslipidemia, there were no associations between dementia and the other vascular risk factors. CKD was strongly associated with the incidence of dementia independent of age, sex, education, and other vascular risk factors.

Prognosis of Vascular Mild Cognitive Impairment Includes Vascular Dementia Onset and Death by Cardiovascular Disease: Reanalysis From the Osaki-Tajiri Project

The relationship of predementia stage with cerebrovascular disease (CVD) has not been fully clarified. Following our Prevalence Study 1998 in Tajiri, Japan, Incidence Study 2003 disclosed that 17.9% of subjects developed vascular dementia (VaD). Some cases developed after stroke (type I), whereas others already met the criteria for subcortical VaD (SVD) despite very mild stage (Clinical Dementia Rating [CDR] 0.5) and progressed to mild stage (CDR 1) (type II). We hypothesized that prognosis of vascular mild cognitive impairment (MCI) included type II VaD or death due to causes associated with vascular risk factors. Prevalence Study 1998 included 497 randomly selected participants, including 346 with a CDR of 0, 119 with a CDR of 0.5, and 32 with a CDR of 1+. The first 2 groups were targeted for Incidence Study 2003. Based on the database, we reanalyzed the ratio of SVD in the subjects with CDR 0.5 and VaD, prognosis with or without CVD, and 2 types of VaD onset. The criteria for SVD were achieved by 67% of those with VaD and by 7% of those with vascular MCI (ie, CDR 0.5). In the CDR 0 group, CVD had no affect on prognosis; however, in the CDR 0.5 group, CVD had an affect on death by cardiovascular disease. The majority of subjects in the CDR 0 and CDR 0.5-CVD (-) groups were classified as type I, whereas all subjects in the CDR 0.5-CVD (+) group were type II. Although vascular MCI is treatable, it may progress to death as well as apparent dementia. Individuals with this "buried under the community" phenomenon of SVD should be targeted for secondary prevention interventions.

Improved Visual Hallucination by Donepezil and Occipital Glucose Metabolism in Dementia with Lewy Bodies: The Osaki-Tajiri Project

Deficits in the cholinergic system are pronounced in dementia with Lewy bodies (DLB) and are more severe in patients with visual hallucinations (VHs). The aim is to identify the occipital glucose metabolism patterns by positron emission tomography (PET) and the changes following donepezil treatment. 13 DLB patients with VHs were enrolled in the study. After the first FDG-PET study, 5 mg/day donepezil was administered orally, and a second PET study was performed 3 months later. After donepezil administration, VHs disappeared completely in 6 patients, and the PET studies revealed significantly decreased glucose metabolism in the medial occipital cortex. These results suggest that VHs in DLB were associated with impaired glucose metabolism in the medial occipital cortex. Donepezil treatment may modify regional glucose metabolism.

Silent Infarction or White Matter Hyperintensity and Impaired Attention Task Scores in a Nondemented Population: The Osaki-Tajiri Project

Whether silent infarction can be completely asymptomatic remains unclear. Although the central cholinergic system affects cognition, little attention has been given to infarction. We hypothesized that specific damage to the cholinergic pathways due to infarction or white matter hyperintensity (WMH) would deteriorate cognition, especially attention. A total of 502 representative elderly participants enrolled in the Osaki-Tajiri Project in 1998 were studied. Participants with focal neurologic signs or previous history of stroke or transient ischemic attack were excluded from the analysis. MRIs were available for all participants, and the Cholinergic Pathways Hyperintensities scale (CHIPS) was used to assess vascular damage in the cholinergic pathways. The Mini-Mental State Examination (MMSE), word fluency test, Digit Symbol test, and digit span test were used to assess global cognitive function and several aspects of attention. Participants were divided into 3 groups according to the comorbidity of cerebrovascular disease (CVD) and cholinergic involvement: non-CVD, CVD with cholinergic involvement [CVD-Ch(+)], and CVD without cholinergic involvement [CVD-Ch(-)]. Cognitive scores were compared among the 3 groups. In the non-CVD group, the correlations between cognitive function and the CHIPS score were examined. The CVD-Ch(+) group exhibited significantly lower scores for the Digit Symbol test compared with the other two groups, regardless of the MMSE score. In the non-CVD group, the CHIPS score of white matter changes was irreversibly correlated (ie, biologically meaningful) with the Digit Symbol score in participants age >80 years. Our findings suggest that silent infarction or WMH may deteriorate attention regardless of global cognitive function by interrupting the central cholinergic pathway.

Assessment of mental deterioration with the Cognitive Abilities Screening Instrument (CASI) and glucose hypometabolism in Alzheimer’s disease: The Osaki-Tajiri Project

The Cognitive Abilities Screening Instrument (CASI) is a screening test for dementia consisting of 9 domains. We investigated the relationships between CASI domain scores and cerebral glucose metabolism (CMRglc) as shown by positron emission tomography. Fifteen patients with very mild Alzheimer’s disease (AD) and 15 with mild AD were studied using the [ 18F]fluoro-deoxyglucose method. The 9 CASI domains were classified into four clusters (recent memory, frontal cortex cluster, posterior cortex cluster, and orientation). Using the region of interest method, the recent memory cluster was correlated with the bilateral hippocampal CMRglc, the frontal cortex cluster was correlated with the bilateral anterior and right inferior frontal CMRglc, the posterior cortex cluster was correlated with the bilateral temporo-parieto-occipital and occipital CMRglc, and the orientation cluster was correlated with the left anterior frontal CMRglc (Spearman’s correlations). The use of statistical parametric mapping showed that most CASI domains were correlated with CMRglc of the left frontal lobe, the temporal lobe, and the angular gyrus. These findings show that the mental dysfunction assessed using CASI in AD patients has a neurobiological basis.

Healthy brain aging process demonstrated stable cognitive performances: The osaki-tajiri project

Healthy brain aging process demonstrated stable cognitive performances: The osaki-tajiri project