Writing Impairments in Japanese Patients with Mild Cognitive Impairment and with Mild Alzheimer's Disease.

BACKGROUND/AIMS: We investigated writing abilities in patients with the amnestic type of mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD). To examine the earliest changes in writing function, we used writing tests for both words and sentences with different types of Japanese characters (Hiragana, Katakana, and Kanji). METHODS: A total of 25 aMCI patients, 38 AD patients, and 22 healthy controls performed writing to dictation for Kana and Kanji words, copied Kanji words, and wrote in response to a picture story task. Analysis of variance was used to test the subject group effects on the scores in the above writing tasks. RESULTS: For the written Kanji words, the mild AD group performed worse than the aMCI group and the controls, but there was no difference between the aMCI group and the controls. For the picture story writing task, the mild AD and aMCI groups performed worse than the controls, but the difference between the AD and the aMCI groups was not significant. CONCLUSIONS: The mild AD group showed defects in writing Kanji characters, and the aMCI group showed impairments in narrative writing. Our study suggests that narrative writing, which demands complex integration of multiple cognitive functions, can be used to detect the subtle writing deficits in aMCI patients.

Neural substrates for writing impairments in Japanese patients with mild Alzheimer's disease: a SPECT study.

Language is fairly well preserved in most patients with mild Alzheimer's disease, but writing ability seems to be impaired even in the early stages of the disease. To investigate the neural bases of writing impairments in Alzheimer's disease (AD), we examined the correlation between writing ability and regional cerebral blood flow (rCBF) in 52 Japanese patients with mild AD compared to 22 controls, using single photon emission computed tomography (SPECT). We found that, compared with control subjects, Kana writing to dictation and copying Kanji words were preserved in AD patients, but writing to dictating Kanji words was impaired. We classified the errors in the Kanji dictation task into four types to investigate the correlation between rCBF and the error type, as follows: non-response errors, phonologically plausible errors, non-phonologically plausible errors, and peripheral errors. Non-response errors, which indicated difficulty with retrieving Kanji graphic images, were the most frequent. When controlled for confounding factors, the number of non-response errors negatively correlated with rCBF in the left inferior parietal lobule, the posterior middle and inferior temporal gyri, and the posterior middle frontal gyrus. Thus, the impaired recall of Kanji in early Alzheimer's disease is related to dysfunctional cortical activity, which appears to be predominant in the left frontal, parietal, and temporal regions.

A point mutation in ribosomal protein L7/L12 reduces its ability to form a compact dimer structure and to assemble into the GTPase center.

An Escherichia coli mutant, LL103, harboring a mutation (Ser15 to Phe) in ribosomal protein L7/L12 was isolated among revertants of a streptomycin-dependent strain. In the crystal structure of the L7/L12 dimer, residue 15 within the N-terminal domain contacts the C-terminal domain of the partner monomer. We tested effects of the mutation on molecular assembly by biochemical approaches. Gel electrophoretic analysis showed that the Phe15-L7/L12 variant had reduced ability in binding to L10, an effect enhanced in the presence of 0.05% of nonionic detergent. Mobility of Phe15-L7/L12 on gel containing the detergent was very low compared to the wild-type proteins, presumably because of an extended structural state of the mutant L7/L12. Ribosomes isolated from LL103 cells contained a reduced amount of L7/L12 and showed low levels (15-30% of wild-type ribosomes) of activities dependent on elongation factors and in translation of natural mRNA. The ribosomal activity was completely recovered by addition of an excess amount of Phe15-L7/L12 to the ribosomes, suggesting that the mutant L7/L12 exerts normal functions when bound on the ribosome. The interaction of Ser15 with the C-terminal domain of the partner molecule seems to contribute to formation of the compact dimer structure and its efficient assembly into the ribosomal GTPase center. We propose a model relating compact and elongated forms of L7/L12 dimers. Phe15-L7/L12 provides a new tool for studying the functional structure of the homodimer.