Corticobasal degeneration initially developing motor versus non-motor symptoms: a comparative clinicopathological study.

BACKGROUND: Clinical presentations of pathologically confirmed corticobasal degeneration (CBD) vary, and the heterogeneity makes its clinical diagnosis difficult, especially when a patient lacks any motor disturbance in the early stage. METHODS: We compared clinical and pathological features of four pathologically confirmed CBD cases that initially developed non-motor symptoms, including behavioural and psychiatric symptoms but without motor disturbance (CBD-NM), and five CBD cases that initially developed parkinsonism and/or falls (CBD-M). The age range at death for the CBD-NM and CBD-M subjects (58-85 years vs 45-67 years) and the range of disease duration (2-18 years vs 2-6 years) did not significantly differ between the groups. RESULTS: Prominent symptoms in the early stage of CBD-NM cases included self-centred behaviours such as frontotemporal dementia (n = 1), apathy with and without auditory hallucination (n = 2), and aggressive behaviours with delusion and visual hallucination (n = 1). Among the four CBD-NM cases, only one developed asymmetric motor disturbance, and two could walk without support throughout the course. Final clinical diagnoses of the CBD-NM cases were frontotemporal dementia (n = 2), senile psychosis with delirium (n = 1), and schizophrenia (n = 1). Neuronal loss was significantly less severe in the subthalamic nucleus and substantia nigra in the CBD-NM cases than in the CBD-M cases. The severity of tau pathology in all regions examined was comparable in the two groups. CONCLUSION: CBD cases that initially develop psychiatric and behavioural changes without motor symptoms may have less severe degenerative changes in the subthalamic nucleus and substantia nigra, and some CBD cases can lack motor disturbance not only in the early stage but also in the last stage of the course.

Medial profrontal cortex and anterior cingulate cortex in the generation of alpha activity induced by transcendental meditation: a magnetoencephalographic study.

Previous EEG studies have shown that transcendental meditation (TM) increases frontal and central alpha activity. The present study was aimed at identifying the source of this alpha activity using magnetoencephalography (MEG) and electroencephalography (EEG) simultaneously on eight TM practitioners before, during, and after TM. The magnetic field potentials corresponding to TM-induced alpha activities on EEG recordings were extracted, and we attempted to localize the dipole sources using the multiple signal classification (MUSIC) algorithm, equivalent current dipole source analysis, and the multiple spatio-temporal dipole model. Since the dipoles were mapped to both the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC), it is suggested that the mPFC and ACC play an important role in brain activity induced by TM.

Delusion of theft and phantom intruder delusion in demented elderly patients in Japan.

Delusion of theft and phantom intruder delusion are among the most frequent delusions in dementia. The purpose of this study was to clarify the clinical characteristics of patients with these symptoms. The authors conducted a questionnaire survey; items included age, gender, dementia diagnosis, cognitive function, and activities of daily living. Other clinical characteristics were evaluated using the quality of life questionnaire for dementia. A total of 217 patients with dementia were rated. Frequencies of delusion of theft were as follows: frequent, 7%; sometimes, 11%; rare, 16%; and none, 66%. Frequencies of phantom intruder delusion were as follows: frequent, 4%; sometimes, 10%; rare, 9%; and none, 77%. Comparison between positive and negative groups with these symptoms revealed that positive groups had higher scores in 2 of 6 domains of the quality of life questionnaire for dementia, namely, negative affect and actions, and restlessness. The positive group with delusion of theft had higher scores in cognitive function and activities of daily living than did the negative group. These results suggest that negative affect and action and restlessness might be related to delusion of theft or phantom intruder delusion and that delusion of theft frequently occurs in the early stage of dementia.

An autopsy case of hereditary diffuse leukoencephalopathy with spheroids, clinically suspected of Alzheimer's disease.

We report here a case of orthochromatic leukodystrophy with spheroids. A 40-year-old woman developed forgetfulness. About 1 year after the onset, clinical examination confirmed global intellectual deterioration with amnesia, spatiotemporal disorientation, and impairment of judgment. At age 43, she experienced tonic-clonic convulsions several times, and died of pneumonia at the age of 44. Alzheimer's disease was suspected clinically. Pathologically, there was severe diffuse demyelination of the deep white matter of the frontal, parietal and occipital lobes with relative preservation of the subcortical U fibers. In the central demyelinated areas, myelin loss was severe with diffuse gliosis, moderate loss of axons, and many axonal spheroids. At the periphery of the severely degenerated regions, there were a lot of macrophages and most had non-metachromatic lipid granules. The cerebral cortex was intact. The neuropathological findings of this case are consistent with hereditary diffuse leukoencephalopathy with spheroids (HDLS). Ten cases of HDLS were reviewed and presented many findings in common. The gray matter was intact and U fibers were well preserved in most cases. In white matter lesions, severe loss of myelin, moderate to severe axonal loss, much axonal swelling, and the presence of macrophages and hypertrophic astrocytes were common findings. In some cases with HDLS, dementia appeared without obvious neurological manifestations in the early stage. We should remember that some cases with HDLS show clinical symptoms similar to Alzheimer's disease, especially in the early stage.

Cyclooxygenase-2 in the hippocampus is up-regulated in Alzheimer's disease but not in variant Alzheimer's disease with cotton wool plaques in humans.

We examined neuronal expression of cyclooxygenase-2, a pro-inflammatory protein, and neuron densities in the CA1-4 of the hippocampus in three cases of Alzheimer's disease with cotton wool plaques (CWP-AD), 17 cases of typical Alzheimer's disease without CWPs (tAD), and 26 normal controls. Cyclooxygenase-2 expression was significantly increased in all of the CA1-4 in tAD, but not in any subdivision in CWP-AD, compared with controls. Cyclooxygenase-2 expression in tAD was also significantly up-regulated compared with that in CWP-AD in all subdivisions. Furthermore, neuron density in the hippocampus was not significantly reduced in CWP-AD cases compared with controls despite remarkable intra- and extraneuronal Abeta deposition. These findings suggest that unknown factors besides Abeta deposition are necessary for the cyclooxygenase-2 up-regulation and neurodegeneration in Alzheimer's disease.

Development and evaluation of a health-related quality of life questionnaire for the elderly with dementia in Japan.

OBJECTIVES: The purpose of this study was the development of the quality of life (QOL) questionnaire for dementia (QOL-D) in Japan. METHODS: We performed a questionnaire survey of QOL assessment in elderly patients with dementia in Japan, and developed QOL-D. RESULTS: The final version consists of only 31 items grouped into six response sets, each with its own scale. Reliability is good to excellent, and validity is, to some extent, established. The six domains of health-related QOL are divided into two groups. One is the positive and the other is the negative aspects of health-related QOL. The positive aspects have been shown to correlate positively with cognitive function and activities of daily living (ADL) score, whereas the negative aspects have not. The concept of QOL for elderly patients with dementia in Japan is similar to that in Western countries. CONCLUSION: We demonstrated that QOL-D is a reliable and valid instrument for QOL assessment in elderly patients with dementia in Japan.