[Show abstract][Hide abstract] ABSTRACT: To clarify which aspects of word meaning are primarily affected in the early stage of semantic dementia (SD), we investigated a SD patient with materials comprising 80 line drawings and corresponding one or two character kanji words. Semantic tasks were comprised of picture naming, reading aloud kanji words, written or spoken word-to-picture matching, picture association and phonological lexical decision.
His performances were deteriorated in almost tasks at least some extent, except for phonological lexical decision task. Naming and reading were profoundly impaired, while deterioration in picture association was relatively mild.
His performance for low familiarity words was worse than in that for high familiarity words. Comprehension tasks were performed better than naming or reading tasks. However, there were 5% words which couldn’t be comprehended in any tasks.
We compared his blood perfusion with normal elderly’s one using SPM2. Hypoperfusion area was restricted in the left temporal pole.
Even in early stage of SD hypoperfusion area was restricted only in the left anterior temporal lobe and phonological representation of words (lexical judgment) were still preserved, semantic memory loss of the patient might have extended to the meaning conception itself represented by the word.
[Show abstract][Hide abstract] ABSTRACT: Recent researches have suggested that brain-derived neurotrophic factor (BDNF) may be implicated in the pathophysiology of mood disorder. This study examined the association between the BDNF Val66Met polymorphism and major depressive disorder (MDD) in a Japanese population. We genotyped the BDNF Val66Met polymorphism in 154 major depressive patients and 154 age- and sex-matched control subjects. The genotypic distributions and allele frequencies were similar among the patients and control subjects. When the relationships of the polymorphism with several clinical variables (i.e., age, sex, age of onset, number of episode, presence of psychotic features, suicidal behavior, and family history) were examined, the dose of Met allele had significant effects on psychotic feature and suicidal behavior and family history. These results suggest that the BDNF Val66Met polymorphism is not related to the development of MDD but related to clinical features of MDD in a Japanese population.
American Journal of Medical Genetics Part B Neuropsychiatric Genetics 12/2007; 144B(8):1003-6. DOI:10.1002/ajmg.b.30520 · 3.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Prosaposin is the precursor of four sphingolipid activator proteins (saposins A, B, C, and D) for lysosomal hydrolases and is abundant in the nervous system and muscle. In addition to its role as a precursor of saposins in lysosomes, intact prosaposin has neurotrophic effects in vivo or in vitro when supplied exogenously. We examined the distribution of prosaposin in the central and peripheral nervous systems and its intracellular distribution. Using a monospecific antisaposin D antibody that crossreacts with prosaposin but not with saposins A, B, or C, immunoblot experiments showed that both the central and peripheral nervous systems express unprocessed prosaposin and little saposin D. Using the antisaposin D antibodies, we demonstrated that prosaposin is abundant in almost all neurons of both the central and peripheral nervous systems, including autonomic nerves, as well as motor and sensory nerves. Immunoelectron microscopy using double staining with antisaposin D and anticathepsin D antibodies showed strong prosaposin immunoreactivity mainly in the lysosomal granules in the neurons in both the central and peripheral nervous systems. The expression of prosaposin mRNA, examined using in situ hybridization, was observed in these same neurons. Our results suggest that prosaposin is synthesized ubiquitously in neurons of both the central and peripheral nervous systems.
Cell and Tissue Research 12/2007; 330(2):197-207. DOI:10.1007/s00441-007-0464-9 · 3.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This report concerns longitudin's investigations with comprehensive neuropsychologic's assessments and precise morphologic's, CT and MRI scan-based, and function's, SPECT scan-based brain imaging examinations of seven patients who had selective progressive amnesia on their initi's visit. Progressive loss of recent memory remained for sever's years the single most s'sient feature in six of them. The atrophy of the hippocamp's region was observed morphologic'sly, and dysfunction confined to the bilater's medi's tempor's lobe involving the hippocamp's area was demonstrated function'sly. These findings are consistent with recently reported atypic's cases of 'Szheimer's disease with unique neur-opathologic's changes, namely the presence of numerous neurofibrillary tangles and few plaques in the hippocamp's region only.
[Show abstract][Hide abstract] ABSTRACT: When comparing with early-onset Alzheimer's disease (EO-AD) and late-onset Alzheimer's disease (LO-AD), some symptomatological differences in clinical features can be seen between them. Rapid progression, more severe language problems or visuospatial dysfunction occur more often in EO-AD patients. However, there have been very few reports about the differences in behavioral and psychological symptoms between these two groups.
The aim of this study was to demonstrate the differences in behavioral symptoms between EO-AD and LO-AD groups.
Three hundred and seven consecutive outpatients with AD were put into an EO-AD group (46 patients) or a LO-AD group (261 patients). Comprehensive assessment batteries, including the Neuropsychiatric Inventory (NPI), were administered at the first medical assessment.
Significant differences were found between the EO-AD and LO-AD groups in terms of NPI total score (EO-AD: 10.3 +/- 10.9, LO-AD: 17.8 +/- 17.0, p = 0.004) and number of patients who experienced each NPI subscale score (delusion; EO-AD: 13.0%, LO-AD: 50.6%, p < 0.001). There were no differences in cognitive functions or dementia severity between two groups.
In EO-AD, behavioral and psychological symptoms are relatively fewer than LO-AD at the first medical assessment.
International Journal of Geriatric Psychiatry 09/2007; 22(9):896-901. DOI:10.1002/gps.1760 · 2.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Vascular endothelial growth factor (VEGF) has been implicated in neuronal survival, neuroprotection, regeneration, growth, differentiation, and axonal outgrowth, which are known to be involved in the pathophysiology of major depressive disorder (MDD). Recently, the VEGF mRNA expression in the peripheral leukocytes from Alzheimer's disease or cardiovascular disease was reported to be changed. We hypothesized that the expression of the VEGF mRNA in the peripheral leukocytes may be a good candidate for the biological marker for MDD. Thirty two patients with MDD and age- and sex-matched control subjects were included in this expression study. The VEGF mRNA levels in the peripheral leukocytes from drug-naive MDD patients were significantly higher than those from the control subjects and the magnitude of the decrease of VEGF mRNA after 8-week treatment significantly correlated with clinical improvement. Then, we genotyped two single nucleotide polymorphic markers of VEGF gene, which were reported to be associated with amyotrophic lateral sclerosis and Alzheimer's disease, in patients with MDD and control subjects (n=154, each). We did not find any significant association between these markers and MDD or its clinical subtypes. Our investigation indicates that the higher expression levels of VEGF mRNA in the peripheral leukocytes are associated with the depressive state and their recovery after treatment may be associated with the clinical improvement.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 05/2007; 31(3):658-63. DOI:10.1016/j.pnpbp.2006.12.011 · 3.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Despite many studies about the association between caregiver burden and behavioral and psychological symptoms of dementia (BPSD), there have been no population-based studies to evaluate caregiver burden associated with each BPSD.
To evaluate caregiver burden associated with the individual BPSD in elderly people living in the community.
The subjects were 67 participants with dementia living with their caregivers (diagnosed in the third Nakayama study): 51 Alzheimer's disease, 5 vascular dementia and 11 other. The Neuropsychiatric Inventory (NPI) and NPI Caregiver Distress Scale (NPI-D) were used to assess subjects' BPSD and related caregiver distress, respectively.
In the subjects exhibiting BPSD, aberrant motor behavior had the highest mean NPI score, and depression/dysphoria had the lowest. Agitation/aggression had the highest mean NPI-D score, and euphoria/elation had the lowest. Delusion, agitation/aggression, apathy/indifference, irritability/lability and aberrant motor behavior showed a correlation between the NPI and NPI-D scores.
The burden associated with BPSD is different for each symptom and does not always depend on frequency and severity of BPSD. These findings suggest that some symptoms, such as agitation/aggression and irritability/lability, may affect the caregivers significantly, although their frequency and severity are low.
[Show abstract][Hide abstract] ABSTRACT: To investigate the frequency, rate of causes of dementia, and clinical characteristics of early-onset dementia in consecutive patients of a memory clinic.
A total of 668 consecutive demented patients were involved in this study. We examined the distribution of patients' diagnosis, differences in sex, education, dementia severity and cognitive function at the first visit, and the duration from onset to consultation. We also examined the changes in the proportion of subjects during the research period.
There were 185 early-onset patients, 28% of all demented patients. No significant differences were observed between the early-onset and late-onset dementia groups in Clinical Dementia Rating and Mini-Mental State Examination score at the first consultation, but the duration from onset to consultation was significantly longer in the early-onset group. In the early-onset group, the rates of patients with Alzheimer's disease and dementia with Lewy bodies were relatively low and the rate of patients with frontotemporal lobar degeneration was relatively high. There were no significant differences in the proportion between either demented subjects and nondemented subjects or early-onset dementia patients and late-onset dementia patients during the research period.
We conclude that early-onset dementia is not rare and its clinical characteristics and causes are different from late-onset dementia.
[Show abstract][Hide abstract] ABSTRACT: To determine the usefulness of brain perfusion SPECT for evaluating the severity and progression of Alzheimer's disease (AD).
Eighty-four AD patients were included. At entry, 99mTc-HMPAO-SPECT, the Mini Mental State Examination (MMSE), Mental Function Impairment Scale (MENFIS), and the Raven Colored Progression Matrix (RCPM) were performed for all 84 patients. During the follow-up periods, two individual MMSE evaluations in 34 patients, two MENFIS evaluations in 30 patients, and two RCPM evaluations in 20 patients were performed. Based on the regions of decreased cerebral blood flow demonstrated on 3D-SSP images of SPECT, the cases were classified as type A (no decrease), type B (decreased blood flow in the parietal or temporal lobe), type C (decreased blood flow in the frontal lobe and parietal or temporal lobe), type Pc (decreased blood flow in posterior cingulate gyrus only), and "other types". The types of decreased blood flow, scores on neuropsychological evaluations, and symptom progression were analyzed.
The MENFIS, MMSE, and RCPM scores were poorest in type C patients at entry. The degree of decrease of these scores during the follow-up periods was also greatest in type C. The greatest difference between patients with and without rapid progression in SPECT data of the mild AD patients (MMSE score > or = 24) was in the frontal lobe.
Decreased blood flow in the frontal lobe of AD patients is correlated not only with reduced cognitive function at the time of the evaluation but with rapid progression in the subsequent clinical course.
Annals of Nuclear Medicine 02/2007; 21(1):15-23. DOI:10.1007/BF03033995 · 1.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Neuropsychiatric disturbances are common and burdensome symptoms of dementia. Assessment and measurement of neuropsychiatric disturbances are indispensable to the management of patients with dementia. Neuropsychiatric Inventory (NPI) is a comprehensive assessment tool that evaluates psychiatric symptoms in dementia. We translated the NPI-Caregiver Distress Scale part of NPI (NPI-D) and NPI-Brief Questionnaire Form (NPI-Q) into Japanese and examined their validity and reliability.
The subjects were 152 demented patients and the caregivers who lived with them. These patients consisted of 76 women and 76 men; their mean age was 73.9 +/- 7.8 (S.D.; range: 49 to 93) years. Their caregivers consisted of 46 men and 106 women; their mean age was 65.0 +/- 11.4 (S.D.; range: 35 to 90) years. The Mini-Mental State Examination (MMSE) was conducted with all patients and NPI-Q, NPI, NPI-D, and the Zarit caregiver burden interview (ZBI) were conducted with all caregivers. We examined validity of NPI-D by comparing its score with the MMSE and ZBI scores, and the validity of NPI-Q by comparing its score with the NPI and NPI-D scores. In order to evaluate test-retest reliability, NPI-D was re-adopted to 30 randomly selected caregivers by a different examiner one month later and NPI-Q was re-executed by 27 randomly selected caregivers one day later.
Total NPI-D score was significantly correlated with ZBI (rs = 0.59, p < 0.01). Test-retest reliability of NPI-D was adequate (ri = 0.47, p < 0.01). Total NPI-Q severity score and distress score were strongly correlated with NPI (r = 0.77, p < 0.01) and NPI-D (r = 0.80, p < 0.01) scores, respectively. Test-retest reliability of the scores of NPI-Q was acceptably high (the severity score; ri = 0.81, p < 0.01, the distress score; ri = 0.80, p < 0.01).
The Japanese version of NPI-D and NPI-Q demonstrated sufficient validity and reliability as well as the original version of them. These are useful tools for evaluating psychiatric symptoms in demented patients and their caregivers' distress attributable to these symptoms.
Nō to shinkei = Brain and nerve 10/2006; 58(9):785-90.
[Show abstract][Hide abstract] ABSTRACT: We examined alteration of regional cerebral blood flow (rCBF) in a case of Alzheimer's disease (AD) patient with musical hallucination. To detect regions related to musical hallucination, single-photon emission computed tomography (SPECT) imaging of the patient and nine sex, age, and cognitive function-matched AD patients without delusions and hallucinations were compared using statistical parametric mapping 99 (SPM99). In comparison with controls, the patient had increased rCBF in left temporal regions and left angular gyrus. This profile could be relevant to the neuroanatomical basis of musical hallucinations.
European Archives of Psychiatry and Clinical Neuroscience 07/2006; 256(4):236-9. DOI:10.1007/s00406-005-0631-5 · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: LIM (PDLIM5) is a small protein that interacts with protein kinase C-epsilon and the N-type calcium channel alpha-1B subunit and modulates neuronal calcium signaling. Recently, the LIM mRNA expression in postmortem brains and immortalized lymphoblastoid cells from mood disorder patients was reported to be changed and seems to be involved in its pathophysiology. We hypothesized that the expression of the LIM mRNA in the native peripheral leukocytes may be a good candidate for the biological marker for mood disorders. Twenty patients with major depression and age- and sex-matched control subjects were included in this expression study. The LIM mRNA levels in the peripheral leukocytes from drug-naive depressive patients were significantly lower than those from control subjects and increased significantly after 4-week paroxetine treatments, to almost the same level as controls'. Hamilton depressive scores (HAM-D) were improved about 50% after 4-week treatment but neither paroxetine concentrations nor the changes of HAM-D scores showed significant correlation with the change of the mRNA levels. Then, we genotyped three single nucleotide polymorphic markers of LIM gene, which were reported to be associated with bipolar disorder in patients with major depression and control subjects (n=130, each), but there were no associations between these SNPs and major depression. Our investigation indicates that the lower expression levels of LIM mRNA in the peripheral leukocytes are associated with the depressive state and that its recovery after treatment may be an adaptive change induced by the antidepressant.
[Show abstract][Hide abstract] ABSTRACT: The authors explored the neural substrate of visual hallucinations in dementia with Lewy bodies (DLB) by investigating changes in regional cerebral blood flow (rCBF) and psychiatric symptoms, before and after cholinesterase inhibitor treatment. Twenty subjects with DLB were treated with donepezil for a 12-week period. Hallucinations attenuated while receiving therapy, whereas occipital rCBF focally increased, suggesting that functional visual association cortex deficits may cause visual hallucinations in patients with DLB.
[Show abstract][Hide abstract] ABSTRACT: To estimate the rate that subjects with Mild Memory Impairment /Not Dementia (MMI/ND) shifted to dementia in a population-based cohort and to establish simple diagnostic methods for identification of high-risk persons for dementia.
Subjects in a community-based elderly cohort of MMI/ND were followed longitudinally. Subjects were selected from the participants in the first Nakayama study. MMI/ND was defined as memory deficit with objective memory assessment, without dementia, impairment of general cognitive function, or disability in activities of daily living. The conversion rate was calculated using the person-year method.
At baseline, the sample consisted of 104 subjects (59 female; 45 male) selected from 1,162 community dwellers aged over 65 year. During the five-year follow-up, 14 subjects died, 13 moved to other communities, and six refused to participate further. Eleven (10.6%) subjects were diagnosed with Alzheimer's disease (AD), five (4.8%) were diagnosed with vascular dementia (VaD), and six (5.8%) were diagnosed with dementia of other etiology. The annual conversion rate that MMI/ND shifted to AD is calculated on 8.5% per 100 person-year, and shifted to dementia on 16.1% per 100 person-year in this survey.
The rate at which subjects with MMI/ND whose conditions shifted to dementia was the same as the rate that subjects with mild cognitive impairment (MCI) shifted to dementia in a previous report. It would be useful to identify groups of high-risk individuals for dementia by simple diagnostic methods.
International Journal of Geriatric Psychiatry 02/2006; 21(2):134-9. DOI:10.1002/gps.1437 · 2.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Despite many reports about cognitive decline and behavioral changes in patients with frontotemporal lobar degeneration (FTLD), there have been very few systematic studies of initial symptoms of frontotemporal dementia (FTD) and semantic dementia (SD).
It was the aim of this study to investigate FTD and SD and to establish whether they are characterized by different initial symptoms.
Three groups of patients were studied: FTD (n = 36), SD (n = 17) and age-matched Alzheimer's disease (AD) patients (n = 52). Information on initial symptoms was obtained from caregivers. Symptoms were classified into 22 distinct categories from the following domains, based on previous studies of symptoms of FTLD: (1) change in social behavior, affection, and daily activities, (2) cognitive decline, (3) language impairments, and (4) other abnormal symptoms.
Change in social behavior, affection, and daily activities was significantly more common in patients with FTD; on the other hand, language impairments were significantly more common in patients with SD as initial symptoms. Apathy and stereotypic behaviors were the most common initial symptoms among patients with FTD, while anomia, paraphasia, and impairment in word comprehension were the most common initial symptoms among patients with SD. Memory disturbance was the most common initial symptom among patients with AD.
Behavioral and psychiatric symptoms are predominant initial symptoms in FTD, while language symptoms are predominant initial symptoms in SD. In addition to the assessment of current symptoms, the assessment of initial symptoms is useful for differential diagnosis in patients with FTD, SD and AD..
[Show abstract][Hide abstract] ABSTRACT: Chorea-acanthocytosis (ChAc) is a hereditary neurodegenerative disease showing Huntington disease-like neuropsychiatric symptoms
and peripheral blood red cell acanthocytosis. Recently, we have identified the gene, CHAC, encoding a newly discovered protein, chorein, in which a deletion mutation was found in three Japanese ChAc families. Although
four patients possessed the same mutation homozygously, their clinical characteristics varied, which means that multifactorial
effects on the pathogenesis are present. Even some of the heterozygous carriers in the families showed a slight degree of
acanthocytosis and psychiatric features including emotional lability or cognitive disturbance. We found heterozygous carriers
of the deletion-mutation allele in the group of patients with mood disorder. The CHAC gene product, chorein, may function as an important protein in the brain not only for motor but also for mental function.
[Show abstract][Hide abstract] ABSTRACT: 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.