Japan Phychogeriatric Society

The Long and Winding Road: Can Psychogeriatrics Point a Way to the Door of Psychiatric Services in Japan?

Heii Arai(Department of Psychiatry, Juntendo University School of Medicine) and Maki Takano

The average life expectancy in Japan in 1947 was 54.0 yrs for females and 50.1 yrs for males. This increased greatly over the second half of the 20th century and currently stands at an average of 77.6 yrs for males and 84.6 yrs for females, according to a recent Government announcement in 2001. The proportion of the population of elderly people has been consequently growing rapidly due to this phenomenon as well as the concomitant decline in the birth-rate. Over 1.5 million elderly people are supposed to suffer from dementing illness in Japan, about half of whom probably have Alzheimer's disease (AD), which is one of the most common causes of dementia in the elderly. There are currently estimated to be about 11 million people worldwide with AD, and this number is forecast to double by the year 2025.
Under these circumstances, clinicians should be aware of the value of early and accurate diagnosis and treatment for dementia from the following two viewpoints. Firstly, early diagnosis of AD certainly gives patients a better chance to benefit from existing treatments of acetylchollinesterase inhibitors that can improve their quality of life. Secondly and more importantly from the clinical viewpoint, treatable dementia has to be ruled out at the first step of differential diagnosis for dementing illnesses. In particular, confusional state caused by consciousness disturbance (ex. amentia and delirium) and pseudo-dementia caused by depression should be differentiated from true dementia and treated adequately, so as to possibly induce full-recovery. General practitioners are unlikely to take the second point into consideration and seem to prescribe acetylcholinesterase soon after they see demented patients. Some of them might not be so skilled at differential diagnosis of dementia because of relatively poor understanding and knowledge of the psychiatric concepts for mental diseases or conditions. In other words, differential diagnosis is one of the strongest fields for psychiatrists and where the role of the psychiatrist is crucial.

Psychogeriatrics in China

Xin Yu
(Institute of Mental Health, Peking University)

Ageing is a global problem. China, which is the most populated nation in the world, became an elderly country in the beginning of this century. The unpredicted aging process brings about challenges to the Chinese society and health care system as well. Chinese psychiatrists are facing even greater challenges, since geriatric psychiatry is still at its infancy. To obtain reliable epidemiological data on mental disorders of the elderly in such a huge country like China, seems an impossible mission. However, quite a few of the epidemiological studies that were conducted with reliable diagnostic criteria and instruments may depict a broad picture only of current situations on mental health of Chinese elderly. Data about dementia are inconsistent. Prevalence rates of Alzheimer's disease (AD) and vascular dementia (VD) vary in studies. Besides the differences in methodology, the differences in residential location (north vs. south, rural vs. urban) may contribute to the etiology of dementia. Contrary to the inconsistent results of dementia, prevalence of depression is consistently low, no matter in which age group. Cultural aspects may play a role in the development of depression in elderly. We need more studies in order to understand this issue better.

Rapid Eye Movement Sleep Behavior Disorder

Takayuki Kumano-go,*1 Akira Mikami,*2 Nakamori Suganuma,*2 Hiroyoshi Adachi,*2
Yoshihisa Shigedo,*1 Yoshiro Sugita,*2 and Masatoshi Takeda*1
(*1Department of Clinical Neuroscience, Osaka University Graduate School of Medicine
*2Department of Medical Science III, Osaka University School of Health Sport Sciences)

Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by loss of normal voluntary muscle atonia during REM sleep, and is associated with excessive motor activity related to dreaming. The movements are often potentially harmful and may lead to repeated injuries to the patients and/or their bedpartners.
RBD is more common in the elderly and affects predominantly males. A recent survey reported an estimated prevalence of RBD of 0.38% in the elderly and 0.5% in the general population. Because the treatment of RBD is effective and safe in most cases, awareness and diagnosis of RBD is critical.
Overnight polysomnography is required to differentiate accurately between RBD and other sleep disorders, even though the patients have been clinically diagnosed as RBD according to the minimal criteria of the International Classification of Sleep Disorders. Muscle tone persists during REM sleep in RBD patients, and may be frequently augmented for prolonged periods of time. The density of REMs or phasic muscle activity occurring during REM sleep significantly increases in these patients, although their overall sleep architecture is usually normal, with the expected cycles of non-REM and REM sleep.
RBD occurs in both acute and chronic form. Acute cases are associated with intoxication and withdrawal. Chronic cases are most often either idiopathic or associated with neurological disordersA|especially neurodegenerative diseases. The etiology of idiopathic RBD is still unknown, but a recent study has shown an association between some cases of idiopathic RBD and neurodegenerative disorders with parkinsonism such as Parkinson's disease, multiple system atrophy, and diffuse Lewy body disease. RBD patients thus need to be carefully followed up in terms of neurological evaluation.

Alzheimer Amyloid α-Secretase: A Special Target for Drug Development

Shoichi Ishiura(Department of Life Sciences, Graduate School of Arts and Sciences, University of Tokyo) and Nika Hotoda, Beata Szabo, Masashi Asai, Chinatsu Hattori, Eiichiro Tanaka, Hisashi Koike, and Noboru Sasagawa

Multiple lines of evidence suggest that increased production and deposition of amyloid b peptide (Ab) contribute to Alzheimer's disease (amyloid hypothesis). Several factors regulate processing of amyloid precursor protein. Mechanisms of Ab production and clearance from the brain have been the subject of considerable interest. Here we summarize recent advances in the identification of amyloid secretases and rational drug design.

Hippocampal Role in Cognitive Functions and Memory, and Effects of a Novel Cognitive Enhancer on Learning Deficits Due to Hippocampal Lesions

Taketoshi Ono (Department of Physiology, Faculty of Medicine, Toyama Medical and Pharmaceutical University) and Hisao Nishijo

In the 21st century, advances in basic research on higher brain functions in both system and molecular levels will proceed therapeutics to alleviate senile dementia, including Alzheimer's disease. In this review, we present our recent experimental results in the hippocampal formation (HF) in reference to human amnesia and a role of the HF in episodic memory and learning. First, we analyzed the activity of the HF neurons in both monkeys and rats. Neural activity in the monkey HF was analyzed during a spatial moving task in which the monkey could control a motorized, movable device (cab) and its route to a target location by pressing the bars. Some HF neurons responded to the occurrence of significant events (or episodes) in the place field where neuronal activity increased. This indicates that HF gating of incoming information may depend on where the monkey is located. These responses suggest representation related to episodic memory, and linkage among diverse information including both spatial and non-spatial cues. Rats were also trained to explore a circular open-field to obtain rewards [intracranial self-stimulation (ICSS)]. When ICSS delivery place was changed, about 20% of the place neurons shifted place fields to locations newly associated with ICSS rewards. These neurophysiological results suggest that the HF is crucial to represent associative relations among multiple cues or factors and to learn such relations. Second, we investigated effects of the newly developed compound (T-588), on learning and memory in rats. Treatment with the compound ameliorated deficits in learning the spatial tasks due to selective lesions of the CA1 subfield.

Auditory Event-Related Potentials (P300) and Regional Cerebral Blood Flow in Elderly Depressed Patients

Kazuyoshi Harada,*1 Noriaki Sumi,*2 Osamu Fujimoto,*3 Kunitoshi Tada,*4 Hisashige Nan-no,*5 Tsuyoshi Nishimura,*6 and Masatoshi Takeda*1(*1Department of Clinical Neuroscience, Psychiatry, Osaka University Graduate School of Medicine
*2Department of Neuropsychiatry, Osaka Medical Center for Cancer and Cardiovascular Diseases
*3Department of Psychiatry, Osaka Prefectural Hospital*4Department of Psychiatry, Sumitomo Hospital
*5Minoh Sanatorium for Psychiatric Diseases*6Koshien University)

In order to evaluate the degree of impairment of cerebral function and the organic factors involved in elderly depressed patients, auditory event-related potentials (ERP; P300) and N-isopropyl-p [123I] iodoamphetamine (123I-IMP) single photon emission computed tomography (SPECT) were examined.
Methods: Three groups of patients, the depression (D) group, consisting of 23 cases where the magnetic resonance imaging (MRI) showed no abnormalities, the depression with silent cerebral infarction (D/SCI) group, consisting of 28 cases with silent cerebral infarction, and the post-stroke depression (D/PS) group, consisting of 19 cases at over six months after onset of cerebral infarction where no abnormalities in intellectual function were seen, but neurological symptoms such as hemiplegia were present, and 27 healthy individuals were investigated. All of the patients fulfilled the ICD-10 diagnostic criteria for depressive episode, and disease onset occurred when the patients were over 55 years. The ERP (P300) was recorded using a tone discrimination task. Regional cerebral blood flow (rCBF) was measured by 123I-IMP SPECT, and the relative rCBF of each region of interest was evaluated by comparison with the mean cerebellar rCBF. In addition, the mean cerebral blood flow (MCBF) in the cerebral cortex was assessed.
Results: The D group included many cases in which the P300 peak latency was relatively short and the MCBF was stable, relative to the other two groups. In the D/PS group, there were many cases where the P300 peak latency was prolonged and the MCBF was reduced. In the D/SCI group, many differences in the results from both indicators existed among individual cases, and no fixed trend was identified.
Conclusion: From the perspective of determining therapeutic tactics for elderly depressed patients and forecasting prognosis, it is important to review in detail, on an individual basis, components such as higher brain functions including cognitive functions, cerebral circulatory dynamics, and psychological/environmental factors. We believe that it is useful to evaluate a combination of factors when making such a review, including diagnostic imaging such as MRI, ERP (P300), and rCBF.

An Environmental Change Does Not Affect Dementia Prevalence but Affects Depressive State and Physical Activity: A Trans-Cultural Study of Japanese Elderly Subjects and Japanese Elderly Immigrants in Brazil

Kenichi Meguro,*1 Mitsue Meguro,*2 Paulo Caramelli,*3 Junichi Ishizaki,*1 Hideo Ambo,*4 Rosa Y. S. Chubaci,*5 Hiroshi Ishii,*1 Satoshi Yamaguchi,*1 Masumi Shimada,*1 Gerson S. Hamada,*6 Ricardo Nitrini,*2 and Atsushi Yamadori*1

Dementia, depressive state, and physical inactivity, are some of the main topics of geriatric medicine. We previously showed the prevalence of dementia in Tajiri, Miyagi Prefecture, Japan. To investigate the environmental effects, first-generation immigrants are one of the best samples. Brazil is the country with the largest number of Japanese immigrants.
Objective: To evaluate the effects of environment on dementia, depressive state, and physical activity, the Tajiri subjects and the elderly Japanese emigrants from Miyagi Prefecture to Brazil were compared.
Methods: The total elderly population in Tajiri and that the elderly members of the Miyagi Association in the Sao Paulo metropolitan area in Brazil were compared. All data were gathered using a standardized interview covering physical status, cognitive function (Mini-Mental State Examination, MMSE), and depressive state (Self-reported Depressive Scale, SDS). Dementia and depression were diagnosed based on the DSM-IV.
Results: Seventy-six percent of the immigrants perceived their health as being excellent or relatively good, whereas only 56% of Tajiri subjects did so. The percentage of subjects with a history of diabetes mellitus, a lifestyle related disease, was 8.4% in Tajiri and 24.2% in Brazil. In spite of similar prevalences of dementia with slightly different MMSE distributions, the two groups had a different SDS distribution; the immigrants showed lower depressive scores.
Conclusion: In spite of environmental changes influencing physical activity and diabetes, cognitive function was not apparently affected. Although the immigrants lives were marked with hardship, their depressive scores were unexpectedly lower than Japanese, probably due to their stronger mental activity.

Early Onset Alzheimer Type Dementia More Rapidly Deteriorates than Late Onset Type: A Follow-up Study on MMSE Scores in Japanese Patients

Heii Arai,*1 Hiroe Tsubaki,*2 Yoshio Mitsuyama,*3 Naoki Fujimoto,*4 Yasuo Urata,*5 and Akira Homma*6
(*1Department of Psychiatry, Juntendo University School of Medicine
*2Graduate School of Systems Management, University of Tsukuba
(currently, Graduate School of Business Sciences, University of Tsukuba)
*3Department of Psychiatry, Miyazaki Medical College Hospital
*4Internal Medicine the third division, Siga Medical Center (currently, Fujimoto Clinic)
*5Central Pharmaceutical Research Institute, Japan Tobacco Inc.
*6Department of Psychiatry, Tokyo Metropolitan Institute of Gerontology)

Cognitive function in patients with Alzheimer type dementia (ATD) changes over time, and the rate of progression varies according to reports. An aim of the study is to examine the rate of progression in patients with ATD by the onset of the disease.
Methods: Forty patients with early onset dementia at the age of 65 or less and 99 patients with late onset dementia at the age of more than 65 years in whom Mini-Mental State Examination (MMSE) scores could be followed up for at least 12 months were enrolled and examined retrospectively for changes in MMSE scores over time.
Results: It was demonstrated that the rate of decrease in MMSE scores was significantly higher in Alzheimer disease (AD) than in senile dementia of Alzheimer type (SDAT) and that the decrease in MMSE scores was significantly slower in patients with higher initial scores.
Conclusion: ATD patients are likely to be classified into AD or SDAT for evaluation of decreased cognitive function. Initial MMSE score and the subtype according to age at onset are important predictors for the progression of intellectual impairment in ATD patients.

Global Increase in Cortical Opioid Binding Potential with Aging: In Vivo Quantification with [11C]diprenorphine PET

Takeshi Uema,*1,*4 James S. Rakshi,*1 Kengo Ito,*3 Takashi Nishikawa,*4Masatoshi Takeda,*4 and David J. Brooks*1,*2(*1MRC Cyclotron Unit, Hammersmith Hospital
*2Institute of Neurology*3National Institute for Longevity Sciences, National Chubu Hospital
*4Department of Psychiatry and Behavioural Sciences, Osaka University Graduate School of Medicine)

Recent studies using positron emission tomography (PET) have shown an increase of m-opioid receptors with aging in the human brain. However, its physiological role and relationship between the other subtypes of opioid receptors is still obscure. We used a non-selective radiotracer [11C]diprenorphine and PET to estimate the effects of aging on brain opioid binding.
Methods: Seventeen normal male subjects were studied. Their ages ranged from 27 to 65 years (mean; 46 years). The data was analysed with global and regional opioid activities on images reflecting binding potential (Bmax/Kd) using statistical parametric mapping (SPM).
Results: The main effect of age was shown in the global opioid binding potential (p=0.046). A post-hoc test revealed that the binding potentials began to increase abruptly in those aged 40 and above. SPM found that the binding activity of brain opioid receptors significantly increased with age throughout the cerebral cortex except in the primary visual and sensory-motor cortices where little specific binding occurs. There were no age-related changes in subcortical structures except for a part of the putamen.
Conclusion: The increase of opioid binding activities with aging probably depends on the density of m-opioid receptors, not k- nor d-opioid receptors in association cortices. The detailed distribution shown by SPM suggests that this phenomenon may not be due to compensatory up-regulation by the decrease in the endogenous opioid. The Increase of cortical opioid binding may contribute to the pathophysiology of depression and high risk of suicide attempts with advancing age.

Prevalence of Dementia Among the Elderly in a Japanese Community PopulationA|Comparative Study on the 1983 and 1996 Survey: The Aichi Study

Hiroto Shibayama,*1 Hiroshi Kobayashi,*3 Makoto Nakagawa,*3 Yasuo Marui,*3 Tatsuo Miyachi,*3
Yuhei Kayukawa,*3 Kenichi Yamada,*3 Hiromu Iwata,*2 Tohru Takeuchi,*3 Kiyoshi Iwai,*3 Susumu Kogawa,*2 Naoki Kagawa,*3 Makoto Imai,*3 Yutaka Mizuno,*1 Naoki Hashimoto,*3 Yasuo Ibuki,*3 Shunichiro Ogasawara,*3 Fumiyasu Tadano,*3 Takeo Nakagawa,*4 and Tatsuro Ohta*3
(*1Obu Dementia Care Research and Training Center
*2Department of Psychiatry, Aichi Prefectural Shiroyama Hospital
*3Department of Psychiatry, Nagoya University Graduate School of Medicine
*4School of Physical Education, Chukyo University)

An epidemiological survey of dementia among community residents over 65 years of age in Aichi Prefecture (Japan) was conducted in 1983 and 1996. We compared the prevalence rates of dementia in 1996, with the previously published rates of 1983.
Methods: The study employed a two-stage design. First stage: A test based on the DSM-III-R criteria for dementia was administered to all participating residents, who were randomly drawn from the resident register (856,879) of Aichi Prefecture in 1995 (495,923 in 1983). Second stage: A detailed clinical and cognitive evaluation (including MMSE and neurological examination) of the subjects identified in the first stage was carried out by trained psychiatrists.
Results: The prevalence rate for dementia in 1996 was 4.8% (moderate and severe 2.1%) compared with 5.8% (2.2%) in 1983; for senile dementia of Alzheimer type (SDAT) it was 2.8% in 1996 and 2.4% in 1983; for cerebrovascular dementia (CVD), 1.8% in 1996 and 2.8% in 1983.
Conclusion: Up to this time, the cases of CVD have been more frequent than those of SDAT in Japan, especially in the urban areas. However, the relationship between CVD and SDAT has now reversed. These data suggest that SDAT is a common condition and that its public health impact will continue to increase with the increasing longevity of the population in Japan.

An Autopsy Case of Traumatic Brain Injury (TBI) Presenting as Frontotemporal Dementia with Kluver-Bucy Syndrome

Osamu Yokota,*1 Seishi Terada,*1 Hideki Ishizu,*1,*3 Hanae Nakashima,*1 Yoshikatsu Fujisawa,*2 Ken Sasaki,*2 and Shigetoshi Kuroda*1
(*1Department of Neuropsychiatry, Okayama University Graduate School of Medicine and Dentistry*2Kinoko Espoir Hospital*3Department of Laboratory Medicine, Zikei Institute of Psychiatry

We report an autopsy case of traumatic brain injury (TBI) that presented clinically as frontotemporal dementia (FTD) with Kluver-Bucy syndrome after a one-year latency period. The head injury was relatively slight, and clouding of consciousness was not noted at the time. Repeated CT scans demonstrated no obvious cerebral contusions. The case presented with four of six core symptoms of the Kluver-Bucy syndrome, including hyperorality, changes in emotional behavior (aggression and impulsiveness), hypersexuality, and bulimia. Histopathological examination revealed small cerebral contusions in the bilateral temporal lobe. Loss of myelin and axons was also revealed, especially in the base of the frontotemporal lobe. The laminar structure in the frontotemporal cortex was well preserved. No Pick bodies or Pick's inflated cells were demonstrated by Bodian staining in any region. In the contusions, a small amount of hemosiderin was deposited. In the Lund and Manchester group's research criteria for frontotemporal dementia, head trauma related to the onset of dementia is one of the diagnostic exclusion features. However, 1) assessment of whether a past minor head injury is related to the onset of dementia after a long latency is controversial, and 2) a subset of the TBI cases might be difficult to distinguish from FTD. Further analysis of autopsy cases presenting as FTD following a minor head injury might provide important clues to differentiate clinically FTD from TBI.

Subcortical Haemorrhage in the Right Temporal Lobe Exhibiting
only Transient Agitated Delirium

Jiro Ohnishi(Neurology Service, Hyogo Prefectural Rehabilitation Center)

A 55-year-old man with cerebral haemorrhage localized in the rostral subcortical region of the right temporal lobe exhibited a transient agitated delirium (AgD) consisting of the global disorder of attention, irritation, excitation, hallucination, delusion, and excessive movement, and recovered from that without any remaining neurologically defective symptoms. As local lesions that could cause AgD, the right temporal lobe and the right parietal lobe are mainly suggested, but other neurological symptoms such as hemiplegia and hemianopsia are usually present. There has been no report on patients with local injury of the white matter in the right temporal lobe who solely exhibited AgD. Therefore, the present case appeared to be important in distinguishing the disease state exhibiting attentional disorder.

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