Masashi Kasuya

Prevalence and Cognitive Performances of Clinical Dementia Rating 0.5 and Mild Cognitive Impairment in Japan. The Tajiri Project

The borderline zone condition between normal aging and dementia is a major issue of concern. Although the term mild cognitive impairment (MCI) is popular, its prevalence and neuropsychological features have not been fully investigated. We investigated the prevalence and neuropsychological features for Clinical Dementia Rating (CDR) 0.5 and MCI. For normal aging, the effects of age and educational level on cognitive performance were examined. We examined 1501 older residents (46.8%) in Tajiri 65 years of age and older. They performed the Cognitive Abilities Screening Instrument (CASI). Depressive scores and subjective memory complaints were also evaluated. There was no age effect but an educational effect on cognitive performance in healthy adults. We found the overall prevalence of CDR 0.5 to be 30.2%, whereas that of MCI was only 4.9%. All CASI domains were deteriorated except for long-term memory and visual construction in the CDR 0.5 participants compared with healthy adults, suggesting that CDR 0.5 is similar to very mild Alzheimer disease. Memory complaints’ data suggested that it would be better to exclude memory complaints from the MCI criteria. We considered that the concept of CDR 0.5 would be more applicable to community residents rather than that of the MCI.

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.

Combined Memory and Executive Function Tests Can Screen Mild Cognitive Impairment and Converters to Dementia in a Community: The Osaki-Tajiri Project

Background: The borderline condition between health and dementia, defined as Clinical Dementia Rating (CDR) 0.5, should be detected for the possible prediction of dementia. Since the CDR requires information from collateral sources, it is difficult to rate people living alone. The aim is to develop a set of tests without collateral information for detecting CDR 0.5 and converters to dementia. Methods: 625 participants were selected from the community; 412 were CDR 0 (healthy), 168 were CDR 0.5 (defined here as mild cognitive impairment; MCI), and were 45 CDR 1+ (dementia). Neuropsychological tests were administered to assess memory, orientation, attention and executive function. We analyzed various combinations of tests by receiver operating characteristic curve and area under the curve (AUC). Among the participants, 497 were randomly selected to be re-examined after 5 years to predict further decline towards dementia. Results: We found that a combination of tests for orientation, memory, attention, executive function, and abstraction and judgment could discriminate subjects with MCI from healthy participants with high accuracy (AUC = 0.83). The predictive accuracy was better than that of the Mini Mental State Examination (AUC = 0.77). The same tests, except orientation, could also predict converters to dementia (AUC = 0.88). Conclusions: We consider that a combination of tests can be helpful for the early detection of individuals with MCI and converters to dementia in the community.

Behavioral and psychological symptoms assessed with the BEHAVE-AD-FW are differentially associated with cognitive dysfunction in Alzheimer’s disease

To assess the possible neurological basis of behavioral and psychological symptoms of dementia (BPSD), the relationships between BPSD and cognitive function were evaluated in 40 patients with Alzheimers disease (AD). BPSD was assessed using the Behavioral Pathology in Alzheimers Disease Frequency Weighted Severity Scale (BEHAVE-AD-FW) for behavioral symptoms and psychological symptoms separately, and cognitive function was also assessed using the Cognitive Abilities Screening Instrument (CASI). We found that only behavioral symptoms were associated with cognitive function based on the CASI total score and the score for the CASI attention domain. Administration of risperidone, an atypical anti-psychotic drug, for one month, improved the behavioral symptoms and the scores for the CASI attention and orientation domains. Our data suggest that BPSD in AD may reflect two largely independent pathophysiological processes: one associated with behavioral symptoms partly overlapping with attention, and the other associated with psychological symptoms predominantly unrelated to cognitive function.

Health economic effect of donepezil treatment for CDR 0.5 converters to Alzheimer's disease as shown by the Markov model

The previous health economic simulation of donepezil based on the Markov model revealed the treatment for mild to moderate stage of Alzheimer disease (AD) to be cost-effective. Our aim was to examine the economic effect of donepezil treatment for mild cognitive impairment, from which about 15% convert to dementia per year. We constructed a new Markov model using three simulations. Namely, Simulation A hypothesized that mild AD patients, i.e., Clinical Dementia Rating (CDR) 1, received donepezil as in the previous study. Simulation B hypothesized that all CDR 0.5 subjects received donepezil, and Simulation C considered that only the CDR 0.5 converters to dementia received donepezil. We calculated the models as follows: Simulation B, supposes that the annual transition probabilities were reduced even from 15% to 10% by donepezil, however, the drug had a negative economic effect. By contrast, in Simulation C, the annual transition probability was reduced from only 15% to 12% by donepezil, there was a positive economic effect. Since it is necessary to reduce the annual transition probability from 15% to 12% in order to manifest a concomitant economic benefit, we consider that early detection of CDR 0.5 converters in the community is important for health policy planning.

Greater responsiveness to donepezil in Alzheimer patients with higher levels of acetylcholinesterase based on attention task scores and a donepezil PET study.

The aim of the study was to predict donepezil responders among patients with Alzheimer disease (AD) based on cognitive tests and positron emission tomography. The Mini-Mental State Examination, Digit Symbol subtest (DigSm) of Wechsler Adult Intelligence Scale Revised, and Trail-Making Test A were administered for 80 patients with AD to assess global function, attention, and executive function, respectively. The same tests and the Clinical Global Impression (CGI) scale were conducted after treatment with oral donepezil (5 mg/d) for 6 months (study 1). [11C]-Donepezil positron emission tomography examinations were conducted before and after treatment for 30 randomly selected patients. The distribution volume (DV), which indicates the density of donepezil-binding sites, was calculated using Logan graphical analysis (study 2). In study 1, 35 patients were identified as responders based on the CGI and Mini-Mental State Examination changes. These patients had higher baseline DigSm scores compared with nonresponders. In study 2, 15 patients were responders. DigSm correlated with DV at baseline. DV at baseline and %DV change in responders were higher than in nonresponders, and these variables correlated with &Dgr;DigSm and CGI scores. Higher baseline attention may predict responsiveness to donepezil in patients with AD, and higher acetylcholinesterase levels result in a greater clinical effect.

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

of comprehensive assessments independent of ARCS performance. We performed correlational and stepwise linear regression analyses to explore the association between subtests of the ARCS and tests of corresponding cognitive domains from the formal neuropsychological battery, before and after the addition of either apathy or depression scale scores. Results: The sample comprised 73 individuals including 18 with dementia, 27 with cognitive impairment and 28 without cognitive impairment. Mean patient AES score was 33.4 (SD 8.8) and mean DASS-21 depression score was 11.7 (SD 10.8). Correlations between tests of comparable cognitive domains from ARCS and neuropsychological test battery were: category fluency r1⁄40.58, visuospatial tests r1⁄40.62, delayed verbal recall r1⁄40.71, object naming r1⁄4 0.76, attention r1⁄40.84. Increasing symptoms of apathy or depression had no effect on these associations with only one exception. There were small reductions of performance on ARCS category fluency test relative to category fluency in the neuropsychological test battery. Conclusions: Symptoms of depression or apathy do not appear to be major threats to the validity of unsupervised cognitive testing using the ARCS.

P1-200: Decreased instrumental ADL level predicts conversion of mild cognitive impairment to dementia in a community: The Osaki-tajiri project (6)

Yoshitaka Ouchi, Mari Kasai, Masashi Kasuya, Kyoko Akanuma, Mitsue Meguro, Hiroshi Ishii, Satoshi Yamaguchi, Hiroyasu Ishikawa, Naofumi Tanaka, Kenichi Meguro, Tohoku University Graduate School of Medicine, Sendai, Japan; Tohoku Medical Service Welfare Group, Hachinohe, Japan; The Osaki-Tajiri SKIP Center, Osaki, Japan; Kawasaki Kokoro Hospital, Kawasaki, Japan. Contact e-mail: y-ohuchi@mail.tains.tohoku.ac.jp

IC-P3-189: Decreased binding of [11C] donepezil as shown by PET correlated with clinical effect of donepezil administration in Alzheimer's disease: The Osaki-Tajiri project (4)

Masashi Kasuya, Hiroyasu Ishikawa , Nobuyuki Okamura , Motohisa Kato, Yumi Sasaki , Eriko Nakata , Yoichi Ishikawa , Yoshihito Funaki, Naofumi Tanaka , Ren Iwata , Kazuhiko Yanai , Kenichi Meguro, Department of Geriatric Behavioral Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan; Miyagi University, Miyagi, Japan; Department of Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Japan; Cyclotron RI Center, Tohoku University, Sendai, Japan. Contact e-mail: kasuya-mi@umin.ac.jp