Disease duration: the key to accurate CSF tap test in iNPH.

OBJECTIVES: The cerebrospinal fluid tap test for idiopathic normal pressure hydrocephalus (iNPH) is one of the good predictors of the shunt treatment, although this test has a low sensitivity. We aimed to identify key parameters that could be used to improve this sensitivity. MATERIALS & METHODS: During 2010-2011, we recruited and then followed 93 patients with possible iNPH for 12 months after shunt. Among them, 82 patients were finally enrolled in this study. The modified Rankin Scale, iNPH grading scale, and several quantitative measurements were evaluated at entry, after the tap test, before and after shunt. Area under the receiver-operating characteristic curves (AUCs), sensitivities, and specificities of the tap test for predicting shunt effectiveness were calculated for each measurement. They were additionally assessed after stratification by disease duration since the initial presentation of iNPH symptoms. RESULTS: The gait disturbance on the iNPH grading scale had the highest accurate scale at the tap test for predicting effectiveness 12 months after shunt: AUC 0.74, sensitivity 56.5%, specificity 91.7%. This AUC increased to 0.76, 0.91 and 0.94 in the subgroup of disease duration <24, <12, and <6 months, respectively. The sensitivity and specificity of the gait disturbance on the iNPH grading scale in the subgroup of <12 months' duration were 92.3% and 90.0%. CONCLUSIONS: The shorter period of clinical symptoms, for example, <12 months, made the tap test sufficiently accurate examination for predicting improvement 12 months after shunt surgery. The findings imply that the tap test should be applied to patients being considered for shunt surgery as soon as possible.

Distribution of cortical benzodiazepine receptor binding in right-handed healthy humans: a voxel-based statistical analysis of iodine 123 iomazenil SPECT with partial volume correction.

BACKGROUND AND PURPOSE: CBR imaging is highly susceptible to a PVE produced by morphologic changes in the brain related to aging and brain laterality. We assessed the influence of PVE produced by regional age-related changes in gray matter volume on I-123 iomazenil SPECT and elucidated the age-related changes in human CBR binding by using PVE-corrected SPECT images. MATERIALS AND METHODS: Nineteen right-handed healthy volunteers (range, 25-82 years; mean, 55 ± 21 years) underwent MR imaging and quantitative I-123 iomazenil SPECT imaging. The influence of age-related changes in rGMC on SPECT images before PVE correction was assessed. PVE correction of the SPECT images was performed by using an MR imaging-based method. Voxel-based linear regression analyses of the PVE-corrected SPECT images were performed by using SPM5. RESULTS: The age-related reductions in rGMC and BP without PVE correction revealed a significant direct proportional correlation. Voxel-based statistical analysis with PVE correction showed no significant age-related changes in BP. CONCLUSIONS: PVE correction was indispensable for the analysis of I-123 iomazenil SPECT images. PVE-corrected quantitative I-123 iomazenil SPECT images revealed no age-related changes in CBR binding in right-handed healthy humans.

TATA box-binding protein gene is associated with risk for schizophrenia, age at onset and prefrontal function.

Schizophrenia is a common polygenic disease in distinct populations, while spinocerebellar ataxia type 17 (SCA17) is a rare autosomal dominant neurodegenerative disorder. Both diseases involve psychotic symptoms. SCA17 is caused by an expanded polyglutamine tract in the TATA box-binding protein (TBP) gene. In the present study, we investigated the association between schizophrenia and CAG repeat length in common TBP alleles with fewer than 42 CAG repeats in a Japanese population (326 patients with schizophrenia and 116 healthy controls). We found that higher frequency of alleles with greater than 35 CAG repeats in patients with schizophrenia compared with that in controls (p = 0.042). We also examined the correlation between CAG repeats length and age at onset of schizophrenia. We observed a negative correlation between the number of CAG repeats in the chromosome with longer CAG repeats out of two chromosomes and age at onset of schizophrenia (p = 0.020). We further provided evidence that TBP genotypes with greater than 35 CAG repeats, which were enriched in patients with schizophrenia, were significantly associated with hypoactivation of the prefrontal cortex measured by near-infrared spectroscopy during the tower of Hanoi, a task of executive function (right PFC; p = 0.015, left PFC; p = 0.010). These findings suggest possible associations of the genetic variations of the TBP gene with risk for schizophrenia, age at onset and prefrontal function.

Actions anchored by concepts: defective action comprehension in semantic dementia.

OBJECTIVE: To study the ability of patients with semantic dementia to understand actions, in order to examine the contribution of semantic memory to action comprehension. METHODS: The ability to comprehend symbolic and instrumental actions was assessed in 6 patients with semantic dementia and 10 healthy controls. The patients were also given the imitation test of meaningful and meaningless actions. RESULTS: In all patients with semantic dementia, comprehension of both symbolic and instrumental actions was defective. The comprehension of symbolic actions was more impaired than that of instrumental actions. Their ability to imitate other's actions was well preserved. CONCLUSION: This study showed that comprehension of action was impaired in semantic dementia, suggesting that semantic memory has an important role in comprehension of human action.

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. 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.

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.

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). METHODS: The authors compared rCMRglc between probable AD patients (based on criteria of the National Institute of Neurologic Disease and Stroke/AD and Related Disorders Association) with APOE epsilon4/4 and APOE epsilon3/3 alleles in early-onset (< or =65 years old) and late-onset (>65 years old) groups. In each group, the patients with APOE epsilon4/4 and APOE epsilon3/3 alleles were comparable for age at onset, age at examination, sex, disease duration, education level, and severity of dementia. RESULTS: In the early-onset group, the patients with the APOE epsilon4/4 genotype showed a significant decrease of rCMRglc in the medial temporal lobe and a significant increase of rCMRglc in the inferior parietal and posterior temporal cortices as compared with those patients with the APOE epsilon3/3 genotype. In the late-onset group, there were no significant differences in the rCMRglc pattern between the patients with APOE epsilon4/4 and APOE epsilon3/3 alleles. CONCLUSIONS: The current findings indicate that the impact of the APOE epsilon4 genotype on cerebral glucose metabolism of patients with AD may be a function of age at symptom onset.

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. One group (n = 46) had the epsilon 3/3 allele, one group (n = 46) had the epsilon 3/4 allele, and one group (n = 46) had the epsilon 4/4 allele. The three groups were matched for age, sex, disease duration, education level, and severity of dementia represented by their score of the Mini-Mental State Examination. A possible difference in pattern of cognitive deficits with dose of the APOE epsilon 4 allele was also examined. RESULTS: The normalized hippocampal volume was correlated with the number of APOE epsilon 4 alleles (r = -0.285, p = 0.0007). The amygdalar volume was also correlated with the number of APOE epsilon 4 alleles (r = -0.178, p = 0.037). The number of APOE epsilon 4 alleles was positively correlated with the whole-brain volume (r = 0.185, p = 0.030). It was also correlated with Wechsler Adult Intelligence Scale-Revised performance IQ (r = 0.203, p = 0.017) and with Wechsler Memory Scale-Revised attention/concentration score (r = 0.191, p = 0.025). CONCLUSIONS: Different patterns of regional brain atrophy were found among patients of different APOE genotypes. The effect of APOE epsilon 4 allele on the brains of AD patients may have regional specificity.

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. The subjects consisted of 15 DLB patients with parkinsonism, 7 DLB patients without parkinsonism and 7 AD patients without parkinsonism. The medial and lateral occipital rCMRglc was significantly lower in the DLB patients without parkinsonism than in the AD patients. There were no significant differences in occipital metabolic rates between the DLB groups with and without parkinsonism. DLB patients without parkinsonism showed a significant reduction of occipital glucose metabolism which is comparable with that of DLB patients with parkinsonism. The neurobiological bases of occipital hypometabolism in DLB may be pathological processes in the brainstem or basal forebrain structures other than the nigrostriatal system.

Treatment for aortic graft infection.

Nine patients with an aortic graft infection presented after undergoing aortic grafting. Seven of 9 patients underwent an initial aortic reconstruction in our hospital. The incidence of aortic graft infection was 1.5% (7/456). There were 6 cases of paraprosthetic infection and 3 cases of aortointestinal fistulas. The treatments consisted of a complete graft excision and an axillofemoral bypass in 6 patients, a complete graft excision alone, a partial graft excision and a femorofemoral bypass, and the preservation of the graft with omental wrapping and irrigation in 1 each. Broad-spectrum antibiotics were intravenously administered to all patients and were then replaced by selective antibiotics for the responsible organisms. All surviving patients received antibiotics orally for 3-6 months. The early postoperative mortality rate was 11.1%. Aortoduodenal fistula occurred in 1 patient with graft excision alone. Graft thrombosis occurred in 2 patients with an axillofemoral bypass. No late graft infection or stump blowout occurred in any patient. We believe that a complete excision of the infected graft as well as the maintenance of distal tissue perfusion is necessary. However, based on the condition of the patient, the appearance of the operating field, and the difficulty of a repeat operation, we would like to stress the importance of selecting the best and safest treatment plan for each case.

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. Our results suggested that the left inferior temporal lobe contributes to verbal semantic memory.

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. The two stories were identical except for one passage in each story: one was emotionally charged (arousing story) and the other (neutral story) was not. RESULTS: In both groups, the emotionally charged passage in the arousing story was remembered better than the counterpart in the neutral story. In addition, the extent of the memory improvement was similar in the subjects and in the controls. CONCLUSIONS: The results provide further evidence that emotional arousal enhances declarative memory in patients with Alzheimer's disease, and give a clue to the management of people with dementia.

Cortical activation during retrieval of arithmetical facts and actual calculation: a functional magnetic resonance imaging study.

By using functional magnetic resonance imaging (fMRI), the neural substrates involved in mental recitation of the single-digit multiplication table and serial subtraction were studied. The former depends mostly on well-learned arithmetical facts, while the latter requires arithmetic processing. Activation during each task was compared with that in a number counting control. During the recitation of single-digit multiplication, the activated regions included the area lying along the left intraparietal sulcus, the premotor and supplementary motor areas, and the posterior portion of the left inferior frontal gyrus. The areas activated during serial subtraction included these areas as well as the bilateral prefrontal and right parietal areas. From the results obtained during retrieval of the multiplication table in this study and previous studies, it was concluded that semantic memory of the multiplication table is stored in the area lying along the intraparietal sulcus and that the frontal areas play an executive role in utilizing the semantic memory of arithmetical facts. It was assumed that the arithmetical facts requiring actual calculation are also stored in the same region. The additional activation during serial subtraction compared with the activation during retrieval of the multiplication table is probably due to the processes of actual calculation. These processes include proper alignment of digits, which may have caused the right parietal activation, and maintaining digits needed for the mental serial subtractions, which may have caused the bilateral prefrontal activation.

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. We quantified the volume of WMHs by using fast-fluid-attenuated inversion recovery images and whole brain atrophy by using 3D spoiled gradient-echo images. Effects of WMHs and brain atrophy on dementia severity, cognitive function, neuropsychiatric disturbances, and neurological findings were examined. RESULTS: Whole brain atrophy was significantly associated with dementia severity and cognitive disturbances, as well as with grasp reflex and some kinds of neuropsychiatric disturbances. After we controlled for the effects of brain atrophy, duration of symptoms, and demographic factors, we found that WMH volume was not associated with global cognitive disturbances or dementia severity but was significantly associated with urinary incontinence, grasp reflex, and aberrant motor behaviors. Brain atrophy and WMH volume were not significantly correlated either before or after controlling for age, sex, education, and duration of symptoms. WMH volume was associated with hypertension, but brain atrophy was not positively correlated with any vascular risk factors. CONCLUSIONS: Our results support the hypothesis that WMHs in AD patients are superimposed phenomena of vascular origin. WMHs contribute to specific neurological and neuropsychiatric manifestations but not to global cognitive impairment, which is more closely associated with brain atrophy.

Regional differences in cerebral blood flow during recitation of the multiplication table and actual calculation: a positron emission tomography study.

UNLABELLED: Regional cerebral differences in activation by two types of calculation, quantitative number processing and use of rote verbal arithmetic memory, were investigated. METHODS: The two types of processing were induced by serial number subtraction (the Subtra-task) and recitation of the multiplication table (the Multi-task), respectively. Regional cerebral blood flow (rCBF) under the two tasks was measured in ten healthy right-handed Japanese men using (15)O-labeled water and positron emission tomography (PET). Statistical parametric mapping (SPM) was used for estimating rCBF differences during these tasks. RESULTS: The activated areas during the Subtra-task were consistent with those reported to be involved in quantitative number processing. Although most of the regions activated during the Multi-task were in common with the regions activated during the Subtra-task, the spatial extent of the activation during the Multi-task was smaller. Moreover, the left lenticular nucleus was activated during the Multi-task, but not in the Subtra-task, while the prefrontal cortex was activated in the Subtra-task but not in the Multi-task. CONCLUSION: The difference in the regions activated by the two tasks, and the difference in the spatial extent of each region by the two tasks indicated that the anatomical networks of the two processes were segregated.

Urinary incontinence: an unrecognised adverse effect with donepezil.

Donepezil has been licensed for use in Japan to improve cognitive function since 1999. Among 94 patients with probable Alzheimer's disease who we treated with donepezil, seven patients developed urinary incontinence, although this event was transient in most patients.

Fall-related injuries in dementia with Lewy bodies (DLB) and Alzheimer's disease.

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.

Visuoperceptual impairment in dementia with Lewy bodies.

BACKGROUND: In dementia with Lewy bodies (DLB), vision-related cognitive and behavioral symptoms are common, and involvement of the occipital visual cortices has been demonstrated in functional neuroimaging studies. OBJECTIVES: To delineate visuoperceptual disturbance in patients with DLB in comparison with that in patients with Alzheimer disease and to explore the relationship between visuoperceptual disturbance and the vision-related cognitive and behavioral symptoms. DESIGN: Case-control study. SETTING: Research-oriented hospital. PATIENTS: Twenty-four patients with probable DLB (based on criteria of the Consortium on DLB International Workshop) and 48 patients with probable Alzheimer disease (based on criteria of the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association) who were matched to those with DLB 2:1 by age, sex, education, and Mini-Mental State Examination score. MAIN OUTCOME MEASURES: Four test items to examine visuoperceptual functions, including the object size discrimination, form discrimination, overlapping figure identification, and visual counting tasks. RESULTS: Compared with patients with probable Alzheimer disease, patients with probable DLB scored significantly lower on all the visuoperceptive tasks (P<.04 to P<.001). In the DLB group, patients with visual hallucinations (n = 18) scored significantly lower on the overlapping figure identification (P = .01) than those without them (n = 6), and patients with television misidentifications (n = 5) scored significantly lower on the size discrimination (P<.001), form discrimination (P = .01), and visual counting (P = .007) than those without them (n = 19). CONCLUSIONS: Visual perception is defective in probable DLB. The defective visual perception plays a role in development of visual hallucinations, delusional misidentifications, visual agnosias, and visuoconstructive disability charcteristic of DLB.

Features of regional cerebral glucose metabolism abnormality in corticobasal degeneration.

We studied regional cerebral glucose metabolism in 15 patients with a clinical diagnosis of corticobasal degeneration (CBD), 15 patients with probable Alzheimer's disease (AD), and 15 healthy controls for 19 brain regions. Asymmetry in regional glucose metabolism was found in the central and frontal cortices in patients with CBD as compared with either the normal controls or the patients with AD. Regional glucose metabolism in CBD patients was significantly lower in the paracentral and superior parietal areas and thalamus than in patients with AD. Relative glucose metabolism in patients with CBD was significantly higher in the posterior cingulate, medial temporal and basal frontal areas, and significantly lower in the paracentral and superior parietal areas than in those with AD. These features of regional glucose metabolic abnormality in CBD may correspond to neurological and cognitive disturbances peculiar to CBD.