Phenotypic heterogeneity within a new family with the MAPT p301s mutation.

Mutations in the gene encoding the microtubule-associated protein tau (MAPT) cause frontotemporal dementia and parkinsonism linked to chromosome 17. Clinical variability is seen not only among families with different mutations, but also among family members with the same mutation. We investigated a newly identified familial frontotemporal dementia and parkinsonism family.

Functional brain imaging as a surrogate marker in vascular cognitive impairment.

Functional brain imaging represents cerebrovascular status, neuronal status, and neuronetwork status, and plays an increasingly important role in the evaluation of vascular cognitive impairment or vascular dementia. In this article, the roles of functional brain imaging are discussed in evaluation of subcortical lesions disrupting cortico-subcortical circuits and in the study of white-matter changes in dementia. Also mentioned is an ongoing clinical trial of extracranial-intracranial artery bypass surgery for hemispheric hemodynamic misery perfusion where single-photon emission tomography is used as a surrogate measure.

Does donepezil treatment slow the progression of hippocampal atrophy in patients with Alzheimer's disease?

Objective: The only approved pharmacological approach for the symptomatic treatment of Alzheimer's disease in Japan is the use of a cholinesterase inhibitor, donepezil hydrochloride. Recent in vivo and in vitro studies raise the possibility that cholinesterase inhibitors can slow the progression of Alzheimer's disease. The purpose of the present study was to determine whether donepezil has a neuroprotective effect in Alzheimer's disease by using the rate of hippocampal atrophy as a surrogate marker of disease progression.

Striatal infarcts mimicking frontotemporal dementia: a case report.

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.

[Validity of the Japanese version of Rivermead Behavioural Memory Test for evaluation of everyday memory function in patients with mild Alzheimer's disease].

Objective: To validate the Japanese version of Rivermead Behavioural Memory Test (RBMT) in evaluating everyday memory function in patients with mild Alzheimer's disease (AD).

Subjects And Methods: Subjects were 100 patients with probable AD of very mild or mild stages of dementia as measured by the Clinical Dementia Rating (CDR). Scores of the Japanese version of RBMT were correlated with scores of the Alzheimer's Disease Assessment Scale-Cognitive part (ADAS-J Cog) and of the Wechsler Memory Scale-Revised (WMS-R).

Differences in cerebral metabolic impairment between early and late onset types of Alzheimer's disease.

Unlabelled: The purpose of this study was to delineate the specific patterns of cerebral glucose metabolism with regard to the time of onset of Alzheimer's disease (AD).

Methods: Two groups of 20 AD patients with different ages of onset were examined. The early onset (EO) and late onset (LO) groups had mean ages of onset of 53.

Variation in FDG uptakes in different regions in normal human brain as a function of the time (30 and 60 minutes) after injection of FDG.

Objective: The authors' goal was to determine whether FDG uptakes in various regions of the brain are different for early and late scanning time in positron emission tomography (PET).

Method: F-18 fluorodeoxyglucose (FDG) PET was performed on 15 healthy normal subjects to obtain early and late acquisition glucose metabolic images (30 and 60 min after FDG injection), respectively. The two sets of images were compared in a voxel-by-voxel analysis.

Gender differences in cerebral glucose metabolism: a PET study.

Objective: Some studies have examined gender differences in brain function based on cerebral blood flow and cerebral metabolism by using positron emission tomography (PET). However, the findings of these studies are controversial and most of them were analyzed by the regions of interest (ROIs) method. Here, we evaluated gender differences of cerebral glucose metabolism under the resting state in a voxel-based analysis.

Voxel-based comparison of regional cerebral glucose metabolism between PSP and corticobasal degeneration.

Objectives: Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are neurodegenerative disorders that may be accompanied by dementia and parkinsonism as clinical symptoms. The purpose of this study was to elucidate cerebral metabolic differences of these two diseases with cognitive impairments by [18F] fluorodeoxyglucose (FDG) and positron emission tomography (PET).

Methods: A total of 12 patients with PSP (age: 62.

Transient global amnesia: increased signal intensity in the right hippocampus on diffusion-weighted magnetic resonance imaging.

We report on a patient with pure transient global amnesia (TGA) whose magnetic resonance imaging (MRI) demonstrated a small region of increased signal intensity in the right hippocampus on diffusion-weighted imaging (DWI). DWI was sensitive and useful for evaluating the early stage of TGA and might help to explain the pathophysiology of TGA.

Nanomolar amyloid beta protein activates a specific PKC isoform mediating phosphorylation of MARCKS in Neuro2A cells.

Myristoylated alanine-rich C kinase substrate (MARCKS), a protein associated with cell growth, neurosecretion and macrophage activation, is activated by protein kinase C (PKC) phosphorylation. We reported that amyloid beta protein (Abeta) activated MARCKS through a tyrosine kinase and PKC-delta in rat cultured microglia. Here we report that Abeta signaling pathway through a specific PKC isoform is involved in the phosphorylation of MARCKS in Neuro2A cells.

The effect of APOE epsilon4 allele on cerebral glucose metabolism in AD is a function of age at onset.

Background: Although the APOE epsilon4 allele is a well-known risk factor for developing AD, the impact of the epsilon4 allele on clinical manifestations in patients with AD is still controversial. One possible reason for this controversy is that previous studies did not consider the effect of patient age at symptom onset.

Objective: To investigate the possible impact of patient age at onset of AD on the effect of APOE genotype on regional cerebral glucose metabolism (rCMRglc).

Accelerated hippocampal atrophy in Alzheimer's disease with apolipoprotein E epsilon4 allele.

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.

Apolipoprotein E epsilon 4 and the pattern of regional brain atrophy in Alzheimer's disease.

Background: Although the APOE epsilon 4 allele increases the risk of developing AD, the effects of the epsilon 4 allele on brain atrophy in clinical AD patients are controversial.

Objective: To investigate a possible relationship between the genetic variants of APOE and brain atrophy in patients with AD.

Methods: Using MRI-based volumetry techniques, the authors compared the volumes of the hippocampal formation, amygdaloid complex, and whole brain in probable AD patients (based on criteria of the National Institute for Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association) with different APOE alleles.

Microglial signaling by amyloid beta protein through mitogen-activated protein kinase mediating phosphorylation of MARCKS.

Myristoylated alanine-rich C kinase substrate (MARCKS), an acidic protein associated with cell motility and phagocytosis, is activated upon phosphorylation by protein kinase C (PKC) and proline-directed protein kinases. In Alzheimer disease (AD), activated microglia expressing MARCKS migrates around senile plaques. We reported that amyloid beta protein (A beta), a major component of senile plaques, activated MARCKS through a tyrosine kinase and PKC-delta.

[Thrombolytic therapy for acute ischemic stroke].

In this paper, results of the recent clinical trials were reviewed, and problems in treating patients with thrombolysis were discussed. Data generated from randomized controlled trials over the past few years have shown that acute intervention can improve neurological outcome in patients with ischemic stroke. Intravenous recombinant tissue plasminogen activator has become established as an acute treatment for stroke.

Amyloid beta protein activates PKC-delta and induces translocation of myristoylated alanine-rich C kinase substrate (MARCKS) in microglia.

The increased accumulation of activated microglia containing amyloid beta protein (Abeta) around senile plaques is a common pathological feature in subjects with Alzheimer's disease (AD). Much less is known, however, of intracellular signal transduction pathways for microglial activation in response to Abeta. We investigated intracellular signaling in response to Abeta stimulation in primary cultured rat microglia.

Occipital glucose metabolism in dementia with lewy bodies with and without Parkinsonism: a study using positron emission tomography.

Reduction of glucose metabolism in the occipital lobe is reported in dementia with Lewy bodies (DLB) and Parkinson's disease. If dysfunction of the nigrostriatal system is responsible for occipital hypometabolism, (1) DLB patients with parkinsonism would show a lower occipital metabolism than do patients without parkinsonism, and (2) DLB patients without parkinsonism would show an occipital metabolism comparable to those of normal subjects and patients with Alzheimer's disease (AD). To examine these hypotheses, we studied the regional cerebral metabolic rate of glucose (rCMRglc) in patients with a clinical diagnosis of DLB or AD, using (18)F-fluorodeoxyglucose and positron emission tomography.

Neuronal substrates for semantic memory: a positron emission tomography study in Alzheimer's disease.

We examined 57 patients with mild Alzheimer's disease by using three kinds of verbal semantic memory tests (category fluency, confrontation naming and generation of verbal definition) and correlated each score with regional cerebral glucose metabolism determined by (18)F-fluorodeoxyglucose and positron emission tomography. The scores of all three verbal semantic memory tests correlated significantly with regional cerebral glucose metabolism in the left inferior temporal gyrus, even after controlling for the effects of age, sex and educational attainment. In contrast, the scores of the word recall test did not correlate significantly with regional cerebral glucose metaboliosm in the left inferior temporal gyrus, neither before nor after controlling for these confounders.

Neuropsychiatric aspects of dementia with Lewy bodies.

Neuropsychiatric symptoms are prominent clinical features of dementia with Lewy bodies (DLB). Visual hallucinations have been reported to be particularly common. Auditory hallucinations, delusions, and depression also may be characteristic to DLB.

Impact of emotion on memory. Controlled study of the influence of emotionally charged material on declarative memory in Alzheimer's disease.

Background: In an earlier study we showed that a powerful emotional experience (the Kobe earthquake) reinforced memory retention in patients with Alzheimer's disease, but we could not control factors other than the emotional impact of the earthquake.

Aims: To test our previous findings in a controlled experimental study.

Method: Recall tests consisting of two short stories were administered to 34 patients with Alzheimer's disease and 10 normal subjects.

Phosphorylation of tau is regulated by PKN.

For the phosphorylation state of microtubule-associated protein, tau plays a pivotal role in regulating microtubule networks in neurons. Tau promotes the assembly and stabilization of microtubules. The potential for tau to bind to microtubules is down-regulated after local phosphorylation.

Impact of white matter changes on clinical manifestation of Alzheimer's disease: A quantitative study.

Background And Purpose: There have been conflicting results involving the clinical significance of white matter changes in patients with Alzheimer's disease (AD). We studied the association between the volume of white matter hyperintensities (WMHs) on T2-weighted images and cognitive, neurological, and neuropsychiatric symptoms.

Methods: The subjects were 76 AD patients who had WMHs but no obvious cerebrovascular diseases.

Corticobasal degeneration: evaluation of cortical atrophy by means of hemispheric surface display generated with MR images.

Purpose: To determine the characteristics of cortical atrophy in corticobasal degeneration and Alzheimer disease by using a hemispheric surface display generated with magnetic resonance (MR) images.

Materials And Methods: The magnitude and extent of cortical atrophy were evaluated with MR hemispheric surface display and volumetric measurement in three groups: 17 patients with corticobasal degeneration, 17 matched patients with Alzheimer disease, and 17 matched healthy control subjects.

Results: The extent and magnitude of cortical atrophy were larger in the group with corticobasal degeneration than in the group with Alzheimer disease.

Rapamycin and FK506 induce long-term potentiation by pairing stimulation via an intracellular Ca(2+) signaling mechanism in rat hippocampal CA1 neurons.

Immunophilin-CsA and -FK506 complexes bind to calcineurin (CaN) and inhibit its phosphatase activity leading to enhancement of neuronal activities. However, inhibition of CaN activity is not the mediator of modulatory activity for IP3 and ryanodine receptors and does not mediate the neurotrophic actions of FK506. FK506 binding protein (FKBP)-12 also binds rapamycin, another immunosuppressant which does not affect CaN activity.