Kimie Yonemura

Living-related liver transplantation for type II citrullinemia using a graft from heterozygote donor.

BACKGROUND Type II citrullinemia (CTLN2) characterized by a liver-specific argininosuccinate synthetase deficiency is an adult onset genetical disorder caused by the mutation of SLC25A13 gene, which results in fulminant hyperammonemia often with poor prognosis. METHODS A 16-year-old Japanese boy presented fulminant hyperammonemia and encephalopathy and recovered after aggressive medical treatment. The patient was diagnosed as CTLN2 by plasma amino acid pattern and detection of the mutated SLC25A13 gene. We performed living-related liver transplantation (LRLT) using a graft from the genetically proven heterozygote father. RESULTS Serum amino acid concentration was normalized within a day after transplantation without protein restriction and medication. The patients postoperative course was natural. The patient is back in school 6 months after surgery. CONCLUSIONS Living-related liver transplantation using a graft from genetically proven heterozygote donors might be a permissible treatment modality for CTLN2. Long-term observation may be necessary to make a definite conclusion possible.

Declining of memory functions of normal elderly persons

Two studies examined the declining of memory functions in normal elderly persons using the Yokota memory test (YMT), which includes 15 items concerning verbal and non‐verbal memory functions. In the first study, 552 subjects over 40 years of age in five age groups were examined. Factor analysis revealed that YMT consisted of two factors pertaining to short‐term/working memory, and two factors pertaining to long‐term memory. It is suggested that the former was more affected than the latter, with aging. In the second study, YMT was examined in relation to the revised version of Hasegawa dementia scale (HDS‐R), which was the most popular intelligence scale for the elderly in Japan. As a result, memory functions differentially declined with the decreasing score of HDS‐R, which suggests that memory functions differentially declined with progressive risk of dementia.

Cerebrospinal fluid levels of phosphorylated tau and Aβ1-38/Aβ1-40/Aβ1-42 in Alzheimer’s disease with PS1 mutations

Abstract We studied seven cases of Alzheimer’s disease (AD). Six of the patients had presenilin 1 (PS1) mutations (PS1AD). Three novel PS1 mutations (T99A, H131R and L219R) and three other missense mutations (M233L, H163R and V272A) were found in the PS1AD group. We measured the levels of phosphorylated tau (ptau-181, ptau-199) and Aβ (Aβ1-42, Aβ1-40 and Aβ1-38) in the cerebrospinal fluid (CSF) of PS1AD patients, early-onset sporadic AD (EOSAD), late-onset sporadic AD (LOSAD) and non-demented subjects (ND). The CSF levels of Aβ1-42 in the three AD groups were significantly lower than those of the ND group (p < 0.0001). CSF levels of Aβ1-42 in the PS1AD group were significantly lower than those in the two sporadic AD groups. The Aβ1-40 and Aβ1-38 levels in the CSF of the PS1AD group were significantly lower than those of the three other groups (p < 0.0001, respectively). The levels of Aβ1-40, Aβ1-38 and Aβ1-42 in the CSF of the PS1AD group remained lower than those of the ND group for 4 years. Not only CSF Aβ1-42, but also Aβ1-40 and Aβ1-38 decreased in the advanced stages of PS1AD.

Multicenter population-based study on the prevalence of early onset dementia in Japan: Vascular dementia as its prominent cause

In Japan, the government and media have become aware of the issues of early onset dementia (EOD), but policies for EOD have not yet been established and support systems are inadequate. To provide practical data about EOD, a two‐step postal survey was performed.

New evidence of temporal kinetics of CSF Aβ1-38/1-40/1-42 and phosphorylated tau in seven FAD cases with novel PSEN1 mutations

MCI were classified as AD-like rather than control-like using this classifier. There was strong evidence for mitochondrial dysfunction in MCI and AD blood. Expression inmany complex I-V genes, mitochondrial ribosome subunits and other genes associated with oxidative phosphorylation were decreased. These mirror changes observed in AD brain. Increased expression of genes encoding adhesionmolecules and other immune-related genes was also found along with an small elevation in monocyte number in AD and basophil number in MCI and AD.Conclusions:We report an accurate blood expression biomarker of AD which identifies people displaying structural changes in their brain consistent with an AD diagnosis. The majority of MCI were classified as AD rather than control, using the AD biomarker. This suggests the classifier detects either early prodromal AD or related disease with common aetiology. This study identifies targets such as mitochondrial activity which could be monitored in blood in future therapeutic interventions.

Prevalence and illnesses causing early-onset dementia in Japan: A multi-center study

aim of this study is to evaluate the frequency of cognitive deficit and depressive symptoms in patients stratified according to the risk of developing cardiovascular events, as well as to compare the cognitive performance between low and high risk groups. Methods: The Framingham Score was used to stratify 110 patients in low, medium or high risk for cardiovascular disease. The Mini Mental State Examination (MMSE) and the Geriatric Depression Scale (GDS-15) were used to evaluate the cognitive performance and the presence of depressive symptoms. The cutoff for the presence of depressive symptoms was considered 6 on GDS. Results: The high risk group showed significant lower scores on MMSE (p<0.001) regardless of education when compared to the other groups. The GDS-15 results did not differ significantly among the groups of cardiovascular risk (p1⁄40.161) however, they showed that the prevalence of depressive symptoms was higher (37%) in the group with cardiovascular risk than in the general population (5-17%). Conclusions: The present findings corroborate the differential cognitive performance of patients with high cardiovascular risk. It was also noted the high prevalence of depressive symptoms in patients with cardiovascular risk, although it was not significantly different among the groups, it was higher than in the general population.

P3-019: Diverse neurological symptoms presenting severe dementia, psychiatric Symptoms and motor deficits in early-onset familial Alzheimer's disease

brain imaging was performed in 3 cases of CBS-AD and 7 cases of CBS-CBD. All cases of CBS-AD demonstrated decreased activity in the parietal lobes, and all CBS-CBD cases showed decreased activity in the temporal or frontal lobes. Conclusions: Alzheimer disease like CBD can present as clinical CBS. Clinical features and structural imaging are insufficient to distinguish between the two pathologic substrates. However, age at onset after 65, the presence of tremor and decreased frontotemporal activity on functional imaging are more suggestive of CBD as underlying pathology for clinical CBS.