Characterization of spheroids in hereditary diffuse leukoencephalopathy with axonal spheroids.

Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is a neurodegenerative disease clinically characterized by slowly progressive cognitive decline and motor dysfunction. Neuropathology shows diffuse degeneration in the white matter, with prominent presence of widespread axonal spheroids. To investigate the mechanism underlying HDLS neurodegeneration, we characterized spheroids and examined their development in the degenerated white matter. Analysis revealed that the spheroids are an early neuropathological manifestation in the white matter degeneration and involve axonal component proteins and α-synuclein. The development of spheroids facilitates in initiating neurodegeneration in HDLS.

Characteristics of cognitive function in early and late stages of amnestic mild cognitive impairment.

AIM: The detection of the early stages in amnesic mild cognitive impairment (aMCI) is considered important in diagnosing progression to Alzheimer's disease. The current study sought to investigate differences in cognitive function between control subjects with no memory loss (control), and subjects in the early stage of aMCI (EMCI) and late stage of aMCI (LMCI). METHODS: A total of 100 community-dwelling older adults aged 65 years and over were recruited from 1543 potential subjects. Subjects were classified into three groups based on the degree of objective memory impairment; control (n=29), EMCI (n=34) and LMCI (n=37). Multiple neuropsychological tests were carried out to examine cognitive function. RESULTS: The EMCI individuals showed lower cognitive function relative to controls; not only in logical memory, but also in letter fluency (P<0.05). There were no significant differences in neuropsychological scores between the EMCI and LMCI groups, except for category fluency and logical memory. In addition, the EMCI subjects' logical memory score showed a significant relationship with letter fluency, category fluency and digit span backward test performance (P<0.05). CONCLUSIONS: These results suggest that the application of multiple neuropsychological tests might be useful in diagnosing older adults with EMCI and LMCI.

Validation of the Telephone Interview for Cognitive Status (TICS) in Japanese.

BACKGROUND: In recent years, the population of elderly people in Japan with dementia has increased. Detection of cognitive impairment in the early stages is important for adequate treatment, care, and prevention. AIM: To investigate whether the reliability and validity of the instrument would carry over to a different population and language before using it for population-based epidemiological studies. METHODS: We studied 135 subjects, 49 patients with Alzheimer's disease (AD) and 86 healthy controls (CTL) using the Telephone Interview for Cognitive Status (TICS) and developed the Japanese version of the TICS (TICS-J). We also evaluated combination of another telephone battery, the Category Fluency Test (CF). RESULTS: The sensitivity and specificity of the TICS-J to differentiate AD patients from CTL was 98.0% and 90.7%, respectively. Pearson's correlation coefficient for the TICS-J and Mini-Mental State Examination (MMSE) was 0.858 (p < 0.001). On the Receiver Operating Characteristic (ROC), the area under the curve for the TICS-J was 98.7%. The combination of the TICS-J with the CF did not change the validity of the discrimination. CONCLUSION: These results indicated that TICS-J was a sensitive and specific instrument for differentiating AD patients from healthy controls.

Biochemical characteristics of variant transthyretins causing hereditary leptomeningeal amyloidosis.

Transthyretin (TTR) is a tetrameric protein that can dissociate into amyloidogenic monomers and cause TTR-related amyloidosis. A rare phenotype, called hereditary leptomeningeal TTR amyloidosis, in which TTR amyloid deposition occurs mainly in leptomeninges and subarachnoid vessels, has been reported in patients with several different TTR variants. In the present study, we examined TTR variants immunoprecipitated from the serum and cerebrospinal fluid (CSF) of patients with hereditary leptomeningeal TTR amyloidosis using matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (IP-Mass method). The leptomeningeal-type TTR variants were not detected in the serum but were found at low levels in the CSF. The undetectable levels of the leptomeningeal-type TTR variants in serum could explain the minute amounts of systemic deposition of these variants. The relatively high level of unstable TTR variants in CSF, probably due to increased secretion from the choroid plexus, is considered to be the pathogenesis of the leptomeningeal-type of TTR amyloidosis.