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Background A number of neuroimaging studies have addressed the specific effect of treatment with cholinesterase inhibitors on the frontal lobe in patients with Alzheimer's disease (AD). However, the neural effects of cholinesterase inhibitors on both apathy and executive dysfunction remain unclear. We examined whether baseline regional cerebral blood flow, as determined by using single-photon emission computed tomography, is capable of predicting changes in apathy and executive dysfunction in response to AD patients switching from donepezil to galantamine therapy. Methods We conducted a 24-week, prospective, open-label study of AD patients treated with galantamine who did not respond to previous treatment with donepezil. Single-photon emission computed tomography was performed at baseline, and behaviour and cognitive assessments including the Mini-Mental State Examination, the Japanese version of the Alzheimer's Disease Assessment Scale-cognitive subscale, the Frontal Assessment Battery, the Neuropsychiatry Inventory Brief Questionnaire Form, and the Dysexecutive Questionnaire were conducted at three time points (baseline and after 12 and 24 weeks of galantamine therapy). Results After galantamine therapy, the Neuropsychiatry Inventory Brief Questionnaire Form scores (apathy, irritability, and aberrant motor symptoms) and the Dysexecutive Questionnaire score improved significantly. The single-photon emission computed tomography findings showed that lower baseline regional cerebral blood flow values in several frontal areas, including the dorsolateral and ventrolateral prefrontal cortex, the anterior cingulate, and the orbitofrontal cortex, predicted greater reductions in the score for apathy (distress) on the Neuropsychiatry Inventory Brief Questionnaire Form and the Dysexecutive Questionnaire score after patients switched from donepezil to galantamine therapy. Conclusions Our study suggests that galantamine therapy, unlike donepezil, is characterized by a dual mechanism of action that may increase acetylcholine and the nicotinic receptor-modulation effect within the frontal lobe, both of which are associated with apathy and executive dysfunction in AD patients.

We described a patient with bilateral striatal infarcts, in whom stereotyped and disinhibited behaviors were insidiously emerged over 2 years mimicking frontotemporal dementia (FTD). A positron emission tomography with 18-fluorodeoxy glucose showed a hypometabolism in the frontal lobes, basal ganglia, and thalami. The peculiar behavioral alterations remained unchanged for the following 7 years, suggesting that the disease is not degenerative but of vascular origin. A disruption of the fronto-subcortical circuits at the level of the striatum or the anterior thalamic peduncle is attributable to the FTD-like behavioral and cognitive syndrome.

Although apolipoprotein E epsilon4 is an established risk factor for Alzheimer's disease, its effect on the rate of progression of Alzheimer's disease remains unknown. The purpose of this longitudinal study was to elucidate whether the rate of hippocampal atrophy is a function of the apolipoprotein E genotypes and severity of disease. Fifty-five patients with probable Alzheimer's disease were the subjects. The annual rate of hippocampal atrophy was determined by using magnetic resonance imaging repeated at a 1-year interval. On a two-way analysis of variance, the effect of the apolipoprotein E epsilon4 allele on hippocampal atrophy was significant, but neither the effect of severity nor the interaction term was significant. In further analysis with one-way analysis of variance, the mean annual rate of hippocampal atrophy was significantly different between the groups of patients with (9.76 +/- 4.27%) and without the apolipoprotein E epsilon4 allele (6.99 +/- 4.24%). Apolipoprotein E epsilon4 dose was significantly correlated with the rate of hippocampal atrophy (rs = 0.277, Spearman rank correlation coefficient), suggesting a gene dose effect. The involvement of the apolipoprotein E epsilon4 allele in the progression of hippocampal atrophy has implications for therapeutic approaches in Alzheimer's disease and should be taken into consideration in longitudinal studies including clinical drug trials.

Repeated falls are reported as one of the clinical characteristics in dementia with Lewy bodies (DLB). We examined the incidence of fall-related injuries in 561 dementia patients with various clinical diagnoses, including DLB and Alzheimer's disease (AD), in a ward established for dementia research. The incidence of fall-related injuries was significantly higher in DLB patients (10.7%) than in AD patients (1.1%) (P < 0.001). The high incidence in those patients with DLB cannot be attributed to Parkinsonism because none of the DLB patients with injuries showed extrapyramidal sign. Our observations suggest that patients with a clinical diagnosis of DLB have a high risk of fall-related injuries, even though they do not show Parkinsonism. An appropriate clinical discrimination between DLB and AD is recommended to manage and prevent fall-related injuries.

We studied two familial cases of human T-lymphotropic virus type I (HTLV-I)-associated myelopathy from the Kii Peninsula, an area of endemic adult T-cell leukemia-lymphoma (ATLL) in Japan. Incidence of familial clustering of HTLV-I-associated myelopathy was about 20%. Type C retrovirus was isolated from cultured cerebrospinal fluid and peripheral blood lymphocytes in both cases. Modes of transmission seem to be similar to those described in ATLL, although there are no reports of both HTLV-I-associated myelopathy and ATLL occurring in the same family. We suggest three possibilities: (1) that the virus associated with HTLV-I-associated myelopathy is different from the virus causing ATLL, although they seem to be morphologically and immunologically similar; (2) that HTLV-I-associated myelopathy may be determined by the ATLL-causing virus plus a specific genetic background; and (3) some combination of factors 1 and 2.