Naruhiko Maki

Increased prevalence of vascular dementia in Japan A community-based epidemiological study

Background and Objective: It has been suggested that there is a major difference in the ratio of AD to vascular dementia (VaD) between Japan and Western countries. To determine the type-specific prevalence of dementia in community-dwelling elderly from the Japanese community of Nakayama, all patients with dementing illness underwent a CT scan. Methods: A door-to-door three-phase population survey was carried out on all persons aged 65 years and older residing at home on the prevalence day (January 1, 1997). The ascertainment of cases was made between January 1997 and March 1998. The study included a psychiatric interview; physical, neurologic, and neuropsychologic examinations; comprehensive laboratory tests; and cranial CT. A public health nurse also interviewed a person close to each subject. Dementia was defined according to the Diagnostic and Statistical Manual of Mental Disorders, third edition–revised, criteria, AD according to the National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer’s Disease and Related Disorders Association, and VaD according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition, combined with information from the patient’s neurologic history and CT scanning. Results: Of 1438 inhabitants, 1162 (81.0%) completed the protocol. The prevalence of dementia was 4.8%. Of the 60 subjects with dementia, 35% had AD, 47% had VaD, and 17% had dementia resulting from other causes. Conclusions: The prevalence of dementia was similar to previous reports, but, contrary to results of virtually all studies conducted in developed countries and those recently conducted in Japan, almost half of the cases in the present study appeared to have VaD with neuroradiologic confirmation.

The Stereotypy Rating Inventory for frontotemporal lobar degeneration

A many behavioral disturbances, Stereotypic behaviors are among the best discriminators of Frontotemporal Lobar Degeneration (FTLD). A recent preliminary report suggests many of the behavioral symptoms, including stereotypic behaviors in FTLD patients, respond to medication with selective serotonin re-uptake inhibitors. However, there is no scale that evaluates stereotypic behaviors comprehensively. To assess the wide range of stereotypic behaviors encountered in FTLD, we developed a new instrument, the Stereotypy Rating Inventory (SRI). The SRI assesses five distinctive stereotypic behavioral disturbances often seen in patients with FTLD: eating and cooking behaviors, roaming, speaking, movements, and daily rhythm. The SRI uses the same technique as the Neuropsychiatric Inventory (NPI) in that both the frequency and the severity of each behavior are determined. The studies reported here demonstrate the content and concurrent validity, as well as inter-rater and test-retest reliability, of the instrument. Scores of FTLD patients (n=26) on the SRI were much higher than those of patients with Alzheimers disease (n=46), patients with vascular dementia (n=26), and normal control subjects (n=40). The SRI appears to be a useful instrument for detecting stereotypic behaviors and monitoring of therapies in FTLD patients.

Efficacy of fluvoxamine as a treatment for behavioral symptoms in frontotemporal lobar degeneration patients

Patients with frontotemporal lobar degeneration (FTLD) present a profound personality change, social misconduct, overeating, and stereotyped behavior. We examined the hypothesis that many of the behavioral symptoms of FTLD will respond to selective serotonin reuptake inhibitors (SSRIs). Sixteen FTLD patients were treated with an SSRI (fluvoxamine maleate) in an open 12-week trial. Treatment responses for stereotyped behavior and other neurobehavioral symptoms were evaluated by the Stereotypy Rating Inventory and the Neuropsychiatric Inventory. The behavioral symptoms, especially stereotyped behaviors of FTLD, significantly improved after treatment. Randomized, placebo- and other SSRI-controlled trials may improve available treatments.

Interrater reliability of the Physical Self-Maintenance Scale and the Instrumental Activities of Daily Living Scale in a variety of health professional representatives

This study was performed to assess interrater reliability of the Japanese version of the Physical Self-Maintenance Scale (PSMS) and the Instrumental Activities of Daily Living Scale (IADL), which are simple and efficient assessment instruments of functional abilities in elderly patients. The subjects were 25 consecutive patients with Alzheimers disease who were outpatients of the Department of Neuropsychiatry in Ehime University School of Medicine and their principal caregivers. One neuropsychiatrist administered the PSMS and IADL, and all sessions were videotaped. Then one clinical psychologist, one public health nurse and one neurologist, and one occupational therapist from another institution, viewed the videotape and performed reassessments. All interrater reliabilities between the neuropsychiatrist and the neurologist, the public health nurse, the clinical psychologist and the occupational therapist were extremely good. Interrater reliability between the public health nurse and the clinical psychologist, between the clinical psychologist and the neurologist and between the public health nurse and the neurologist was also extremely good. The PSMS and IADL showed good interrater reliability between personnel from different disciplines. They are likely to be useful tests for everyday medical consultations and for field research.

The Validity of the MMSE and SMQ as Screening Tests for Dementia in the Elderly General Population – A Study of One Rural Community in Japan

Objective: To compare the validity of the Mini Mental State Examination (MMSE) and the Short-Memory Questionnaire (SMQ) as screening tests to detect dementia in the elderly general population. Subjects: Six hundred and sixty-two subjects and their informants from the elderly general population sample who had completed these tests. Setting: One rural community survey in Japan. Method: We used receiver-operating characteristic analysis to compare the performance of the MMSE and the SMQ with the clinical diagnosis of dementia according to DSM-III-R. Results: The areas under the receiver-operating characteristic curve of the MMSE and the SMQ were 0.980 (SE = 0.006) and 0.982 (SE = 0.008), respectively. This differed from chance to a highly significant degree for both the MMSE and the SMQ, but the difference between the two scales was not statistically significant. Conclusion: As screening tests to detect dementia in the elderly general population, the SMQ which is assessed by informants demonstrates a statistically significant discriminating ability as well as the MMSE.

Alteration of rCBF in Alzheimer's disease patients with delusions of theft

We investigated the neural substrate of the delusion of theft in patients with Alzheimers disease (AD). Nine AD patients with only one type of delusion (delusions of theft) and nine age, cognitive function-matched AD patients without any type of delusions were selected from 334 consecutive outpatients of Ehime University Hospital. All subjects underwent 99mTc-HMPAO SPECT scanning, and SPECT images were analyzed by Statistical Parametric Mapping (SPM). AD patients with delusions of theft showed significant hypoperfusion in the right medial posterior parietal region compared to patients without delusions. Our data suggest that attention impairment or lack of awareness of illness caused by right parietal dysfunction might play a role in producing the delusion of theft.

Frontotemporal Lobar Degeneration: A Study in Japan

Frontotemporal lobar degeneration is the most common form of cortical dementia occurring in the presenium after Alzheimer’s disease. We analyzed two types of frontotemporal dementia (FTD) and semantic dementia (SD) selected from a consecutive series of outpatients based on neuropsychological symptoms, psychiatric symptoms and abnormal behavior. In our series of 134 patients with primary degenerative dementia, there were 16 cases of FTD and 6 cases of SD. Patients with subgroups of FTD and patients with SD were distinguishable only by the presence of aphasia in the latter group. They were not distinguishable from one another by other neuropsychological examinations, behavioral abnormalities or psychiatric symptoms assessed with the Neuropsychiatric Inventory.

Utility of 99mTc-HM-PAO SPECT hippocampal image to diagnose early stages of Alzheimer's disease using semiquantitative analysis

Objective: Examination of the utility of 99mTc-hexamethylpropylene amine oxide (99mTc-HM-PAO) SPECT hippocampal image to diagnose early stages of Alzheimer’s disease (AD) using semiquantitative analysis. Subjects: 10 early-stage AD patients and 8 normal sex-matched elderly controls. Setting: Outpatient division of the Ehime University Hospital. Method: We performed 99mTc-HM-PAO SPECT perfusion imaging in each subject. A semiquantitative method of assessing regional variation was used. The regions of interest for temporal regions were set at images parallel to the long axis of the hippocampal formation which were reconstructed at 30Results: The regional cerebral blood flow ratio of the bilateral medial temporal lobe at the hippocampal image was significantly lower in the AD subjects than in the normally aged controls without any other differences in ordinary transaxial images. Conclusion: This study suggests that 99mTc-HM-PAO SPECT hippocampal images might be a helpful tool for the diagnosis of very-early-stage AD.

Relationship between Blood Flow Kinetics and Severity of Alzheimer’s Disease: Assessment of Severity Using a Questionnaire-Type Examination, Alzheimer’s Disease Assessment Scale, Cognitive Sub-Scale (ADAScog)

We assessed hemokinetics associated with changes in Alzheimer’s disease (AD) severity in 90 AD patients by researching the relationship between AD Assessment Scale, cognitive sub-scale (ADAScog) scores and regional cerebral blood flow (rCBF). In the present study, we employed the questionnaire-type ADAScog examination to accurately assess the severity of AD. Between five groups classified on the basis of ADAScog score, significant differences were observed in parietal, lateral temporal and superior frontal rCBF. In addition, in parietal and lateral temporal regions, significant correlations were also observed between ADAScog score and rCBF. In superior frontal rCBF, significant differences were noted only between group 5 (≥40 ADAScog points) and each of the other groups; there was no significant correlation between rCBF and ADAScog score. Thus, we propose the following mechanism for blood flow kinetics associated with changed severity: In an early stage of AD, blood flow in the medial temporal cortex is impaired, and gradually involves the temporoparietal regions. While the medial temporal impairment of blood flow reaches a plateau, temporoparietal blood flow continues to be impaired well into a severe stage, at which point blood flow impairment in the frontal region is initiated.

APOE Genotype and Alzheimer´s Disease

Rubinsztein and Easton [1] have recently reported a meta-analysis of the variation in the apolipoprotein E (APOE) genotype with Alzheimer’s disease (AD). Unfortunately, in their study, they have misrepresented our data [2] in figures 1 and 3. In figure 1, the risk for those patients possessing an Â4 allele is shown for 27 separate studies of late-onset cases. In all but our study, the odds ratio exceeds a value of 1.0. In other words, there is an increased risk for AD in those with an Â4 allele. In reporting the data from our study, however, both the odds ratio and the confidence intervals have been recorded as being significantly below the value of 1.0. This infers that our study demonstrated a decreased risk for AD for patients possessing an Â4 allele. These values, and those for the Â2 allele in figure 3, are simply incorrect. Furthermore, the inclusion of such data would underestimate the risk for AD associated with the Â4 allele in the meta-analysis (table 3 and 4). The Â4 allele frequency for controls in our study was 0.147 as compared with 0.134 in other studies (n = 5,008), and the Â4 allele frequency in AD was 0.328 in our study and 0.38 (range 0.236–0.52) in the other studies (n = 2,896) [2]. Unfortunately, our data in the recent analysis [1] have been made conspicuous by the erroneous values shown in figures 1 and 3.