Kazutaka Nukariya

Association between BDNF Polymorphism (Val66Met) and Executive Function in Patients with Amnestic Mild Cognitive Impairment or Mild Alzheimer Disease

Background: In the present study, we examined whether brain-derived neurotrophic factor (BDNF) polymorphism (Val66Met) influenced the changeable executive dysfunction of patients with two separate disease stages: amnestic mild cognitive impairment (A-MCI) or mild Alzheimer disease (AD), which are comparatively similar demented conditions. Methods: Among 200 outpatients with dementia and MCI, 146 outpatients with mild AD or A-MCI were recruited and divided into two genotypic groups, valine homozygosity (Val/Val) and methionine (Met) carriers, based on the representative BDNF functional polymorphism Val66Met. Next, we compared the Frontal Assessment Battery (FAB) total and subtest scores between the two genotypic groups according to each of two different disease stages: A-MCI (n = 42) and mild AD (n = 104). Results: Among patients with only a mild stage of AD, the FAB total and go/no-go scores were significantly lower (p < 0.05) among the subjects with the Val/Val genotype than among the Met carriers. However, no significant differences in any other demographic variables were observed between the genotypes according to each of different disease stages. A significant interaction between Val66Met and age was not observed for the FAB scores. Conclusion: These results suggested that the BDNF gene may significantly influence executive dysfunction, including inhibition tasks, among patients with mild-stage AD.

Association between executive dysfunction and hippocampal volume in Alzheimer's disease

BACKGROUND Some previous research has hypothesized that executive dysfunction in patients with early Alzheimers disease (AD) occurs as a result of a disconnection between different cerebral areas. The aim of the present study was to evaluate how the hippocampal volume influences executive function as a non-memory cognitive function. METHODS From 157 consecutive patients with AD or amnestic mild cognitive impairment (A-MCI), we recruited 107 subjects who had a global Clinical Dementia Rating (CDR) of 0.5 or 1.0 and whose degree of hippocampal atrophy had been measured using magnetic resonance imaging (MRI); the severity of atrophy was assessed using the voxel-based specific regional analysis for Alzheimers disease (VSRAD) system. We divided the subjects into three groups: mild atrophy, 0 < Z-score < 1.0 (N = 21); moderate atrophy, 1.0 ≤ Z-score < 2.0 (N = 46); or severe atrophy, 2.0 ≤ Z-score < 4.0 (N = 40) according to the Z-score and compared the Frontal Assessment Battery (FAB) and its subtest scores between each atrophy group. RESULTS The results demonstrated that age, sex ratio, duration of illness, education years, MMSE score, Behave-AD score, and proportion of atrophy area in total brain (%) were not significantly different among the three groups. Only the go/no-go score among the six subtests was significantly lower for increasing atrophy severity (P < 0.05). Furthermore, hippocampal atrophy significantly influenced the go/no-go score independently of interactions from whether the diagnosis was early AD or A-MCI (P < 0.05). CONCLUSION These results support a significant association between hippocampal atrophy and executive dysfunction as a non-memory cognitive impairment in patients with early AD and A-MCI.

Association between brain-derived neurotrophic factor (BDNF) gene polymorphisms and executive function in Japanese patients with Alzheimer's disease

Background:  To address the functional roles of genetic polymorphisms of brain‐derived neurotrophic factor (BDNF) in Alzheimers disease (AD) from a neuropsychological aspect, we used a cross‐sectional study design to investigate the association between novel single nucleotide polymorphisms (SNPs) of the BDNF gene (Val66Met (G196A) and C270T) and the Frontal Assessment Battery (FAB) score, which reflects executive function as a non‐memory cognitive impairment.

Differentiation between amnestic-mild cognitive impairment and early-stage Alzheimer's disease using the Frontal Assessment Battery test

Background:  Previous research has described the executive dysfunction that occurs in patients with amnestic‐mild cognitive impairments (A‐MCI) and early‐stage Alzheimers disease (EAD), which are comparatively similar stages of dementia. The aim of the present cross‐sectional study is to evaluate executive dysfunction using the Frontal Assessment Battery (FAB) screening test in two groups and to investigate the interaction with other cognitive impairments.

Association between nerve growth factor gene polymorphism and executive dysfunction in Japanese patients with early-stage Alzheimer's disease and amnestic mild cognitive impairment.

Background/Aims: To address the clinical neurocognitive roles of nerve growth factor (NGF) genetic polymorphism in early-stage Alzheimer’s disease (AD) and amnestic mild cognitive impairment (A-MCI), we investigated the association between this single-nucleotide polymorphism (SNP) and executive dysfunction as a nonmemory cognitive impairment. Methods: Among 200 outpatients with dementia and MCI whose NGF SNP rs6330 genotype was identified, those with A-MCI (n = 35) and early-stage AD (n = 67) were recruited and divided into three groups according to genotype (C/C: n = 58, C/T: n = 39, T/T: n = 5). Then, the Frontal Assessment Battery (FAB) scores were compared among the three (C/C, C/T, T/T) or two (C/C, T carrier) genotype groups. Results: Among the subtests, a significant difference was only noted for the go/no-go scores (p < 0.01) between C/C and T carriers. However, no significant differences in the demographic variables and other neuropsychological subtest scores reflecting attentional and memory function were observed among the genotypes. Conclusion: Regarding the functional roles of neurotrophin polymorphisms as they relate to executive dysfunction, the NGF gene rs6330 might influence the inhibition task in Japanese patients with early-stage AD or A-MCI.

Hemodialysis for lithium intoxication: preliminary guidelines for emergency

Abstract: In Japan, 9 cases of severe lithium intoxication have been treated by hemodialysis so far, and the usefulness and indications of this procedure are not yet understood fully. We have recently experienced a case of lithium intoxication treated by hemodialysis. Considering this case together with those reported previously, we have prepared some preliminary guidelines for the application of hemodialysis to patients with lithium intoxication. The blood concentration of lithium, renal function, the severity of consciousness disturbance and clinical symptoms such as somatic complications are, of course, important indices for the application of this therapy. We think that the signs of intoxication and the time interval between the onset and the beginning of treatment also serve as useful indices for application of hemodialysis.

Cognitive Dysfunction in Patients With Late-Life Somatic Symptom Disorder: A Comparison According to Disease Severity

BACKGROUND Late-life somatic symptom disorder (SSD) is characterized by various aging-associated factors, such as a functional decline, psychosocial problems, and cognitive dysfunction. However, the details of the cognitive dysfunction that occur in late-life SSD are still unknown. OBJECTIVE The aims of this study were to reveal the cognitive profile of patients with late-life SSD and to evaluate how cognitive dysfunction affects disease severity. METHODS We compared the cognitive profiles of patients with late-life SSD (n = 40) with those of normal control subjects (n = 21). In addition, we divided the patients with late-life SSD into mild-to-moderate (n = 24) and severe (n = 16) groups and compared the cognitive profiles of the 3 groups. RESULTS Patients with late-life SSD exhibited a lower Mini-Mental State Examination total score and attention decline. In the 3-group comparison, the severe group had a lower Mini-Mental State Examination score and Frontal Assessment Battery score than the normal control group, whereas no significant difference was seen between the mild-to-moderate and the normal control groups. CONCLUSIONS Our data suggest that different cognitive patterns may exist depending on disease severity, possibly indicating differences in pathogenesis.

Psychological distress of family members with cancer patients in Japan.

BACKGROUND: There were no previous studies in Japan on the psychological distress of members of families with cancer patients which focussed on the disclosure of the diagnosis of cancer. This study was designed to investigate factors that may have an effect on the psychological distress of family members. METHODS: The subjects were 95 members of families of cancer patients in the surgical ward; one member was recruited from each patients family. The psychiatrist investigated the demographic factors of both the patient and the family member: for the patient - gender, age, occupation, cancer site, disclosure (or not) of cancer diagnosis, cancer stage and performance status (PS); for the family member - gender, age, occupation, relationship to the patient, physical illness, frequency of visiting the ward, the period from when the family member was informed of the diagnosis, and any past experience of the loss of close relatives due to cancer. Furthermore, we conducted a survey on the family members anxiety and depression by using the Spielberger State - Trait Anxiety Inventory (STAI) and the Center for Epidemiological Studies Depression Scale (CES-D). RESULTS: A multiple regression analysis indicated that the factors which were associated with the STAI scores independently were the lack of disclosure of the diagnosis to the patient (P=0.01), and advanced or recurrent cancer (P=0.01). The factors which were associated with the CES-D scores independently were the lack of disclosure of the diagnosis to the patient (P=0.03), advanced or recurrent cancer (P=0.01), and the family members past history of psychiatric disorders (P=0.01). CONCLUSIONS: The results suggested that the psychological distress of a family member increases when the patient is not informed of the cancer diagnosis, when the cancer is advanced or recurrent, and when the family member has a past history of psychiatric disorders. (Int J Psych Clin Pract 2002; 6: 205-210 )

Executive Dysfunction Correlated With 2-Year Treatment Response in Patients With Late-Life Undifferentiated Somatoform Disorders.

BACKGROUND Late-life somatoform disorders (SDs) are characterized by various aging-associated factors. Recently, cognitive decline, including executive dysfunction, has been reported as an etiological factor of late-life SDs. The response to treatment for late-life SDs varies from one patient to another. Treatment strategies for late-life SDs require these etiological factors to be considered. We hypothesized that the treatment response in patients with late-life SDs was associated with executive dysfunction. OBJECTIVE The aim of the present study was to confirm the changes in disease severity over a 2-year follow-up period and to determine which etiological factors are related to the treatment response in patients with late-life SDs. METHODS We examined 55 patients with late-life SDs who were treated with pharmacotherapy and supportive psychotherapy at baseline. The changes in the disease severity and cognitive profiles over a 2-year follow-up period were evaluated. Additionally, we investigated which etiological factors at baseline were related to treatment resistance. RESULTS Of the 55 patients who were enrolled in the present study, 31 completed the 2-year follow-up period. Overall, the disease severity improved significantly in patients with late-life SDs. On the contrary, executive function decreased throughout the research period. Moreover, we found that executive dysfunction and the presence of hyperlipidemia at baseline were related to treatment resistance. CONCLUSIONS These results suggest that aging-associated etiological factors be considered for the treatment of late-life SDs.

White matter hyperintensities are associated with the severity of late-life somatoform disorders and executive functions.

BACKGROUND Medically unexplained symptoms are often seen in the elderly. Recently, correlations between medically unexplained symptoms and somatoform disorders (SDs) have been reported. The existence of many interactive psychiatric aetiologies is known among SDs. Late-life SDs might be influenced by some aetiological factors caused by ageing processes, such as structural changes in the brain and cognitive dysfunctions. AIMS Under such circumstances, we investigated the presence of subcortical white matter hyperintensities (WMHs), which increase with ageing, and hypothesized that subcortical WMHs are related to the disease severity of late-life SDs. Furthermore, we confirmed whether cognitive dysfunction influences this process. METHODS To evaluate these hypotheses, we examined patients with medically unexplained symptoms who met the criteria for undifferentiated somatoform disorder and divided the patients into three groups according to the degree of subcortical WMHs: grade 0, grade 1, and grade 2. The subcortical WMHs were rated using Fazekas grading. Differences in symptom severity and cognitive functions were compared among the three groups. RESULTS The grade 2 group had the severest symptoms. Furthermore, the grade 2 group had lower cognitive function scores than the other groups. CONCLUSIONS The present study showed that the presence of subcortical WMHs in patients with late-life SDs was a predictor of disease severity. Moreover, cognitive dysfunction appeared to play a role in the advancement of disease severity.