Biomedical subjects

N Hirono

Publications and source records attributed to N Hirono.

At least 37 records · Page 2Linked to original sources

PubMed1999

Case-control study of presenilin-1 intronic polymorphism in sporadic early and late onset Alzheimer's disease.

OBJECTIVE: Presenilin-1 is a major causative gene for early onset familial Alzheimer's disease, and the apolipoprotein E epsilon4 allele is a major genetic risk factor known to influence late onset and sporadic early onset Alzheimer's disease. The presenilin-1 1/1 genotype has recently been reported to be associated with sporadic Alzheimer's disease. The purpose of this study is to determine whether Alzheimer's disease is associated with presenilin-1 gene polymorphism and the apolipoprotein E genotype in an extended case-control study. METHODS: An examination was conducted on 217 patients with Alzheimer's disease, along with an equal number of age and sex matched controls derived from the same community in a Japanese population, by using a chi2 test for homogeneity and a logistic regression analysis. A meta-analysis of data from the literature on allele frequencies in Alzheimer's disease and control populations was used for comparison with the Japanese allele frequencies obtained in this study. RESULTS: The presenilin-1 allele-1 frequencies were similar in patients with early onset Alzheimer's disease (0.61) and younger controls (0.61), and in those with late onset Alzheimer's disease (0.63) and elderly controls (0. 63). We found no evidence for a possible association between the presenilin-1 polymorphism and the apolipoprotein E epsilon4 allele. However, the meta-analysis showed that the association between the presenilin-1 1/1 genotype and Alzheimer's disease was significant (Peto odds ratio=1.16, 95% confidence interval=1.04-1.31). CONCLUSIONS: These results suggest a subtle but positive association of presenilin-1 gene polymorphism with Alzheimer's disease, although Japanese data in this study which failed to support such a relation would indicate an ethnic variation.

Adult↗

PubMed1999

Amygdalar volume and emotional memory in Alzheimer's disease.

OBJECTIVE: Everyday experience suggests that highly emotional events are often the most memorable. Experimental work in animals and humans has demonstrated that the amygdaloid complex plays a crucial role in emotional memory, i.e., memory of events arousing strong emotions. The aim of this study was to elucidate the relationship between medial temporal damage and impaired memory of real-life emotional events in patients with Alzheimer's disease. METHOD: In 36 patients with probable Alzheimer's disease who experienced the 1995 earthquake in Kobe, Japan, memories of events surrounding the earthquake were examined as an index of emotional memory with the use of a semistructured interview, and amygdalar and hippocampal volumes were quantified by magnetic resonance imaging. The effects of the atrophy of these structures on recall performance were determined by multiple regression analysis. RESULTS: Irrespective of generalized brain atrophy and cognitive impairments, emotional memory was correlated more with normalized amygdalar volume (right and left averaged) than with normalized hippocampal volume. General knowledge of the earthquake was correlated with neither amygdalar nor hippocampal volume. CONCLUSIONS: The results indicate that impairment of emotional event memory in patients with Alzheimer's disease is related to intensity of amygdalar damage and provide evidence of the amygdala's involvement in emotional memory in humans.

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PubMed1999

Lack of effect of apolipoprotein E E4 allele on neuropsychiatric manifestations in Alzheimer's disease.

The association between the apolipoprotein E epsilon 4 (APOE E4) allele and a wide spectrum of behavioral symptoms of Alzheimer's disease (AD) was investigated. Neither the severity nor the presence of any behavioral changes was associated with the number of APOE E4 alleles, even after controlling for the effects of age at onset, sex, education level, duration of illness, and severity of dementia. The findings do not support the hypothesis that neuropsychiatric manifestations of AD are different in patients with the APOE E4 allele.

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PubMed1999

Distinctive neurobehavioral features among neurodegenerative dementias.

The distinctive neuropsychiatric features of Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD) were investigated by using the Neuropsychiatric Inventory. The patients with FTD had significantly more euphoria, aberrant motor activity, and disinhibition and significantly fewer delusions compared with the patients with AD or DLB. The patients with DLB had significantly more hallucinations compared with the AD or FTD patients. The findings clearly demonstrate that AD, DLB, and FTD have distinctive neuropsychiatric features, which may correspond to different patterns of cerebral involvement characteristic of these three major degenerative dementias.

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PubMed1999

[Japanese version of the Short-Memory Questionnaire and Mini-Mental State Examination in relation to demographic variables: community survey of elderly healthy residents in Nakayama, Japan].

BACKGROUND AND PURPOSE: The Short-Memory Questionnaire (SMQ) developed by Koss et al. is a standardized, validated reliable informant-based scale to assess everyday memory problems. In the previous study, we prepared its Japanese version and validated the reliability in assessing patients with Alzheimer Disease. In the present study, we examined the relations between the performance evaluated by the Japanese version of the SMQ combined with the Mini-Mental State Examination (MMSE) and demographic variables (age, sex, and education). SUBJECTS AND METHODS: Subjects were a total of 613 elderly healthy individuals living in the rural residency of Nakayama, Japan. They consisted of 287 males and 326 females and ranged from 65 to 94 years in age and from 0 to 16 years in education. The MMSE was conducted by neuropsychiatrists to assess the severity of cognitive impairment, and the SMQ was conducted by public health nurses, who asked a family member of each subject. The effects of age, sex and education on the MMSE and SMQ scores were analyzed by analysis of variance (ANOVA) using post-hoc Scheffé test. RESULTS: The mean MMSE and SMQ scores (+/- SD) were 27.6 (+/- 2.5) and 44.5 (+/- 2.1), respectively. The post-hoc Scheffé test revealed significantly higher MMSE scores for individuals with 8 years or more in education than for those with less than 8 education years. Between males, no significant differences were observed in MMSE score; however, among females, significantly higher scores were noted in those aged 69 or younger than in those aged 70-74 or those aged 80 or older. Of individuals aged 80 or older, males showed significantly higher scores than females, whereas no significant differences were observed between sex in other age groups. As to the SMQ, higher scores were shown by persons with longer education years and by females than males. CONCLUSION: Low MMSE scores were related to low education level and older females. Low SMQ scores were not related to aging, but linked to low education level and males. Both the MMSE and SMQ, which can be easily administered, are affected by education years and sex. In addition, MMSE score depends on age. Therefore, careful consideration should be paid to age, education level and sex for future execution of the MMSE and SMQ.

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PubMed1998

Cognitive loss in dementia with Lewy bodies and Alzheimer disease.

BACKGROUND: Dementia with Lewy bodies (DLB) is emerging as a common cause of degenerative dementia. Some preliminary evidence exists that the pattern of cognitive impairment in DLB is different from that in Alzheimer disease (AD). OBJECTIVE: To delineate features of cognitive impairment of DLB on standardized neuropsychological tests. METHODS: We performed neuropsychological assessments of 26 patients with probable DLB (based on criteria of the consortium on DLB international workshop) and of 52 patients with probable AD (based on criteria of the National Institute of Neurological and Communicative Disorders and Stroke [now the National Institute of Neurological Disorders and Stroke])-Alzheimer's Disease and Related Disorders Association) who were matched to the patients with DLB 2:1 by age, sex, education, and Mini-Mental State Examination score. RESULTS: Compared with the group with probable AD, the group with probable DLB scored significantly lower on the picture arrangement, block design, object assembly, and digit symbol substitution subtests of the Wechsler Adult Intelligence Scale-Revised and on the Raven Colored Progressive Matrices test and significantly higher on the Mini-Mental State Examination locational orientation subtest and the Alzheimer's Disease Assessment Scale word recall subtest. A discriminant analysis revealed that the word recall score on the Alzheimer's Disease Assessment Scale and the block design score on the Wechsler Adult Intelligence Scale-Revised were the best discriminant factors. CONCLUSIONS: The disproportionately severe visuoperceptual, visuoconstructive, and visuospatial dysfunction and the disproportionately mild memory impairment in DLB compared with AD, which likely reflect the distribution of the pathologic changes in DLB, can help to differentiate DLB from AD.

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PubMed1998

Development of Wernicke-Korsakoff syndrome after long intervals following gastrectomy.

BACKGROUND: Surgical exclusion of portions of the gastrointestinal tract is a predisposing risk factor for the development of Wernicke-Korsakoff syndrome. When this disease occurs, it is usually within weeks after the gastrointestinal surgery. However, it is not well known that Wernicke-Korsakoff syndrome may occur after a long latent interval following gastrectomy. SETTING: A research-oriented hospital. PATIENTS: Three patients without a history of alcoholism or dietary deprivation developed Wernicke-Korsakoff syndrome 2 to 20 years after undergoing gastrectomy. In these patients, minor changes in dietary habit led to the development of Wernicke-Korsakoff syndrome. CONCLUSIONS: In addition to a long-standing latent deficiency in thiamin levels due to defective absorption following gastrectomy or gastrojejunostomy, other minor factors that may influence the intake of thiamin and the need for thiamin in subjects who have undergone gastrectomy may cause a state of thiamin deficiency resulting in Wernicke-Korsakoff syndrome. Results from our study indicate that the following measures are mandatory: educating patients about proper dietary habits, carefully monitoring their thiamin intake, recognizing Wernicke-Korsakoff syndrome early, and treating it immediately with appropriate measures.

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PubMed1998

Age at onset and language disturbances in Alzheimer's disease.

This study examined the effect of age at symptom onset of Alzheimer's disease (AD) on the pattern of language disturbance. We assessed 150 consecutive patients with a clinical diagnosis of mild-to-moderate AD using the Western Aphasia Battery and a 100-item picture-naming test. A multivariate linear regression analysis examined the effect of age at onset after controlling for gender, education, severity of dementia and duration of the disease. Patients with early onset performed significantly worse than did patients with late onset on the word comprehension and sequential commands subtests. On the other hand, late-onset patients performed more poorly than early-onset patients on the picture-naming test in a subgroup with mild language deficits. However, the trend disappeared in other subgroups with more degraded language function. We consider that the concomitant effects of normal aging worsened the picture-naming deficits in the late-onset patients, and the rapid decline of naming ability in the early-onset patients masked the aging effect with the progression of language deficits. The deterioration of word comprehension and the rapid decline of naming ability are the characteristics of early-onset patients. The different patterns of language deficits between early- and late-onset patients may correspond to the genetic heterogeneity of AD.

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PubMed1998

Age at onset and visuocognitive disturbances in Alzheimer disease.

We examined the relation of age at onset and visuocognitive disturbances in Alzheimer disease (AD) using a large sample of patients, quantitative neuropsychological measures, and multivariate statistics controlling for gender, education, stage of dementia, and disease duration. Significant positive coefficients were obtained with forward and backward digit and visual spans, visual counting, copying Rey complex figure, and block design task. The results indicated that patients with early-onset AD performed worse than late-onset AD patients on these tasks. There was no significant effect of age at onset on identification of overlapping figures, visual form discrimination, or Raven's colored progressive matrices. These findings confirm the greater attentional and visuospatial impairments in early onset patients when these confounding factors were controlled for, although no significant effect of age at onset in visuoperceptual function was observed.

Age Factors↗

PubMed1998

Lack of association of apolipoprotein E epsilon4 allele dose with cerebral glucose metabolism in Alzheimer disease.

Parietal cerebral glucose metabolism is reduced before substantial impairments appeared in subjects carrying the apolipoprotein E (APOE) epsilon4 allele, but the effect of the APOE epsilon4 allele on cerebral metabolism in Alzheimer disease (AD) is still undetermined. To investigate the effect of the APOE epsilon4 allele on cerebral metabolism in AD, we examined regional cerebral glucose metabolism in 83 patients with AD by using 18F-fluorodeoxyglucose and positron emission tomography. Cerebral glucose metabolism in the fronto-parieto-temporal association and limbic cortices was significantly decreased in the AD patients compared with 26 age- and sex-matched normal controls. Regional cerebral glucose metabolic rate was not correlated significantly with the number of APOE epsilon4 alleles in any region, which was consistent even after controlling the effects of age, sex, and severity of dementia, and in a subgroup analysis of those aged between 60 and 75. These results supported the view that the APOE epsilon4 allele is not associated with specific deficits in brain metabolism in AD despite evidence of preclinical alterations.

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PubMed1998

Hypofunction in the posterior cingulate gyrus correlates with disorientation for time and place in Alzheimer's disease.

The relation between orientation for time and place and regional cerebral glucose metabolism was examined in 86 patients with probable Alzheimer's disease of minimal to moderate severity. Regional glucose metabolic rates in the posterior cingulate gyri and in the right middle temporal gyrus were significantly correlated with temporal orientation, and the glucose metabolic rate in the right posterior cingulate gyrus was significantly correlated with locational orientation irrespective of age, sex, education, and memory impairment. The results suggest that dysfunction of these structures plays an important part in producing disorientation in patients with Alzheimer's disease.

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PubMed1998

Factors associated with psychotic symptoms in Alzheimer's disease.

OBJECTIVES: Many clinical and biological factors have been reported to be associated with the presence of psychosis in patients with Alzheimer's disease, although the associations were variable. The aim of this study was to clarify factors associated with the presence of psychosis in patients with Alzheimer's disease. METHODS: Psychiatric functioning was studied in 228 patients with Alzheimer's disease based on the results of the behavioural pathology in Alzheimer's disease rating scale or the neuropsychiatric inventory. The effects of sex, education level, age, duration of illness, cognitive function, and apolipoprotein E genotype were investigated for dichotomous psychotic status with a multiple logistic regression analysis. RESULTS: Of the 228 patients with Alzheimer's disease, 118 (51.8%) showed evidence of delusions or hallucinations. Of these, 94 had delusions only, three had hallucinations only, and 21 had both. Older age, female sex, longer duration of illness, and more severe cognitive impairment were the factors independently associated with the presence of psychosis. The presence of psychosis was not significantly related to either educational level or apolipoprotein E genotype. CONCLUSIONS: Age, sex, and severity of illness were independent factors associated with the presence of psychosis in patients with Alzheimer's disease. The reason why some patients with Alzheimer's disease develop psychosis remains unclear. There may be distinctive subtypes of Alzheimer's disease or the presence of individual factors which affect the development of psychosis.

Aged↗

PubMed1998

Regional metabolism: associations with dyscalculia in Alzheimer's disease.

OBJECTIVES: The ability to calculate, which is an important aspect of social daily living, is commonly impaired in patients with Alzheimer's disease even early in the course of the disease. Dyscalculia is often accompanied by focal brain damage, and has been argued to be an independent sign localised around the left temporoparietal region. However, the region most responsible for dyscalculia in Alzheimer's disease has not been determined. The relation between calculation ability and regional cerebral glucose metabolism in Alzheimer's disease was therefore examined. METHODS: The calculation ability, In 91 patients with probable Alzheimer's disease of minimal to moderate severity, was assessed using the arithmetic subtest of the Wechsler adult intelligence scale-revised and the performance correlated with regional cerebral glucose metabolism determined by "F-fluorodeoxyglucose and PET. RESULTS: Regional glucose metabolism in the left inferior parietal lobule and in the left inferior temporal gyrus was significantly correlated with the calculation performance irrespective of age, sex, education, and severity of disease. CONCLUSIONS: The results suggest that dysfunction of the left inferior parietal lobule and the left inferior temporal gyrus plays an important part in producing dyscalculia in patients with Alzheimer's disease.

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PubMed1998

Frontotemporal dementia and Alzheimer disease: evaluation of cortical atrophy with automated hemispheric surface display generated with MR images.

PURPOSE: To determine the features of cortical atrophy in frontotemporal dementia (FTD) and Alzheimer disease by using a hemispheric surface display generated with magnetic resonance (MR) images. MATERIALS AND METHODS: The extent of cortical atrophy was evaluated with automated MR hemispheric surface display and volumetry in 18 patients with FTD and in 18 matched patients with Alzheimer disease. Results were compared with those in 18 healthy, matched control subjects. RESULTS: Most cortical regions were significantly atrophic in FTD and Alzheimer disease. The frontal and anterior temporal lobes were significantly more atrophic in FTD than in Alzheimer disease. The mean hemispheric-to-intracranial volume ratio in patients with FTD (56.2%) and those with Alzheimer disease (58.4%) was significantly smaller than the ratio in the control subjects (66.0%). Asymmetry of hemispheric volume was significantly larger in the FTD group than in the Alzheimer disease and control groups. CONCLUSION: Cortical atrophy in FTD is more widespread than was previously thought. Asymmetric frontal and anterior temporal atrophy is a distinctive feature of FTD and distinguishes it from Alzheimer disease. Hemispheric surface display is a useful complement to tomographic images and is useful for the evaluation of focal cortical atrophy in degenerative dementias, especially FTD.

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PubMed1998

Apolipoprotein E epsilon 4 allele and whole brain atrophy in late-onset Alzheimer's disease.

OBJECTIVE: Diffuse brain atrophy is one of the gross pathological features of Alzheimer's disease and is a result of degenerative changes. The epsilon 4 allele of apolipoprotein E (APOE) is a risk factor or susceptibility gene in late-onset sporadic Alzheimer's disease and may influence the pathological changes associated with the disease. The aim of this study was to examine the relationship between the APOE epsilon 4 allele and whole brain atrophy. METHOD: Whole brain volume was quantified by using high-resolution magnetic resonance imaging and the computerized brain segmentation technique in 178 patients with late-onset sporadic Alzheimer's disease who carried no APOE epsilon 4 alleles (N = 62), one epsilon 4 allele (N = 93), or two (N = 23) and had comparable clinical severity of dementia. RESULTS: An apparent positive correlation was found between normalized whole brain volume (relative to total intracranial volume) and number of APOE epsilon 4 alleles; i.e., patients carrying two APOE epsilon 4 alleles had the least brain atrophy. This association between the APOE epsilon 4 allele and brain volume was similar in women and men and was independent of age, level of education, duration of illness since symptom onset, and severity of dementia. CONCLUSIONS: The results indicate that cognitive dysfunction progresses before severe brain atrophy develops in patients carrying the APOE epsilon 4 allele and suggest that an APOE epsilon 4-allele-related mechanism that affects neuronal function before a decrement in brain matter is involved in the development of dementia.

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PubMed1998

Alteration of regional cerebral glucose utilization with delusions in Alzheimer's disease.

The authors examined 65 patients with Alzheimer's disease for delusions and explored the relationship of delusions with regional cerebral glucose metabolism determined by [18F]fluorodeoxyglucose PET. In patients with delusions (n = 26), normalized glucose metabolism was significantly increased in the left inferior temporal gyrus and significantly decreased in the left medial occipital region as compared with those without delusions (n = 39). The two groups were similar in age, sex, and dementia severity. These results suggest that delusions in Alzheimer's disease are attributable to a dysfunction in specific brain areas rather than a simple reaction to intellectual deficits.

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PubMed1998

Amnestic people with Alzheimer's disease who remembered the Kobe earthquake.

BACKGROUND: Emotional memory is a special category of memory for events arousing strong emotions. To investigate the effects of emotional involvement on memory retention in individuals with Alzheimer's disease we studied peoples' memories of distressing experiences during a devastating earthquake. METHODS: Fifty-one subjects with probable Alzheimer's disease who experienced the Kobe earthquake at home in the greater Kobe area were studied. Memories of the earthquake were assessed 6 and 10 weeks after the disaster in semi-structured interviews, and were compared with memories of a magnetic resonance imaging (MRI) examination given after the earthquake. RESULTS: Forty-four (86.3%) of the subjects remembered the earthquake and 16 (31.4%) of subjects remembered the MRI experience. Factual content of the earthquake was lost in most of the subjects. CONCLUSIONS: Fear reinforces memory retention of an episode in subjects with Alzheimer's disease but does not enhance retention of its context, despite repeated exposure to the information.

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PubMed1998

Frontal lobe hypometabolism and depression in Alzheimer's disease.

Depression is common in Alzheimer's disease (AD). Clinicoanatomic studies in focal brain injuries and functional imaging studies both in primary depression and in depression secondary to neurologic diseases have demonstrated involvement of the frontal lobe. Frontal involvement has not been established in the depression of AD. We studied the correlation between focal brain metabolic abnormalities and depression in AD. In 53 patients with probable AD of minimal to moderate disability, we assessed the severity of depression using the Neuropsychiatric Inventory and correlated the depression score with regional cerebral glucose metabolism determined by 18F-fluorodeoxyglucose and PET. Depression was present in 19 patients (36%). The depression score correlated significantly with normalized glucose metabolic rates in the bilateral superior frontal and left anterior cingulate cortices. These results indicated an association between depression and decreased activity in the frontal lobe in AD and support frontal involvement, especially in the left side, in depression, irrespective of disease etiology.

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