[Disappearance of paroxysmal perceptual alteration by switching to aripiprazole in a schizophrenic patient].

We report a schizophrenic patient with paroxysmal perceptual alteration (PPA) which disappeared completely on switching from the previous antipsychotic to aripiprazole (APZ). PPA is an attack characterized by hypersensitivity of perception mainly involving in the modality of visual sensation. The prevalence of PPA is about 4% in schizophrenia. It is regarded as a psychopharmacological symptom associated with antipsychotics, and a hypothesis regarding the cause has been proposed: PPA is caused by noradrenergic activation which compensates for the sudden incompetence of dopaminergic neural transmission in the context of chronic hypofunction of the dopamine system caused by antipsychotics. Since APZ maintains the dopaminergic nervous system in a steady state by its partial agonism of the D2 receptor, it is suggested that APZ could correct the chronic dysfunction of the dopamine system associated with PPA, explaining its resolution in this patient. Because APZ is positioned as a drug which relatively preserves tonic neurotransmission from the perspective of the tonic/phasic model of dopaminergic neurotransmission, an alternative hypothesis whereby a decrease in the tonic component might cause PPA can be proposed. Additionally, this patient experienced 'general restlessness' like akathisia shortly after we added a low dose of APZ to his formula, and we think that the symptom demands closer consideration on switching to APZ. Especially in chronic schizophrenic patients, PPA can be the main cause of a reduced quality of life, and treatment is essential. Switching to APZ should be a significant treatment option for PPA.

Effect of linearization correction on statistical parametric mapping (SPM): a 99mTc-HMPAO brain perfusion SPECT study in mild Alzheimer's disease.

OBJECTIVE: Statistical parametric mapping (SPM) was employed to investigate the regional decline in cerebral blood flow (rCBF) as measured by 99mTc-hexamethyl propylene amine oxime (HMPAO) single photon emission computed tomography (SPECT) in mild Alzheimer's disease (AD). However, the role of the post reconstruction image processing on the interpretation of SPM, which detects rCBF pattern, has not been precisely studied. We performed 99mTc-HMPAO SPECT in mild AD patients and analyzed the effect of linearization correction for washout of the tracer on the detectability of abnormal perfusion. METHODS: Eleven mild AD (NINCDS-ADRDA, male/female, 5/6; mean+/-SD age, 70.6+/-6.2 years; mean+/-SD mini-mental state examination score, 23.9+/-3.41; clinical dementia rating score, 1) and eleven normal control subjects (male/female, 4/7; mean+/-SD age, 66.8+/-8.4 years) were enrolled in this study. 99mTc-HMPAO SPECT was performed with a four-head rotating gamma camera. We employed linearization uncorrected (LU) and linearization corrected (LC) images for the patients and controls. The pattern of hypoperfusion in mild AD on LU and LC images was detected by SPM99 applying the same image standardization and analytical parameters. A statistical inter image-group analysis (LU vs. LC) was also performed. RESULTS: Clear differences were observed between the interpretation of SPM with LU and LC images. Significant hypoperfusion in mild AD was found on the LU images in the left posterior cingulate gyrus, right precuneus, left hippocampus, left uncus, and left superior temporal gyrus (cluster level, corrected p < 0.005). With the LC images, significant hypoperfusion in AD was found only in the bilateral posterior cingulate gyrus and left precuneus (cluster level, corrected p < 0.005). A pattern of greater rCBF distribution at the high flow cortices and low flow cortices was observed on LC and LU images, respectively, in the case of both controls and mild AD patients. CONCLUSION: Hippocampal hypoperfusion could be detected by means of SPM in the LU images but not in the LC images. The results of SPM may vary in 99mTc-HMPAO SPECT with or without linearization correction, which should be carefully evaluated when interpreting the pattern of rCBF changes in mild Alzheimer's disease.

Symptoms underlying unawareness of memory impairment in patients with mild Alzheimer's disease.

Patients with Alzheimer's disease (AD) are often unaware of their cognitive impairment. This unawareness might have a multifactorial etiology, including impairment of cognitive domains and psychiatric symptoms. We conducted this study to determine the factors underlying unawareness of memory impairment (UMI) in patients with AD. In 103 patients with mild AD, the UMI was quantified as the difference between the patient's self-rating and the rating of the patient's caregiver on a standardized memory questionnaire system, the Everyday Memory Checklist. We then examined the relationships between UMI and memory, attention, language, visuospatial/constructive perception, frontal lobe function, and psychiatric symptoms. UMI was positively associated with memory impairment and delusions when effects of age, sex, and education were partialled out, suggesting that these symptoms are involved in the formation of UMI in the patients. Thus, existing treatments for memory impairment and delusions may be beneficial for increasing the awareness of mild AD patients of their cognitive impairment.

Cognitive impairment in patients with idiopathic normal pressure hydrocephalus.

Cognitive impairment in patients with idiopathic normal pressure hydrocephalous (iNPH) has not been clearly documented. We performed standardized neuropsychological assessments of 21 patients with iNPH and of 42 patients with Alzheimer's disease (AD) matched to the patients with iNPH 2:1 by age, sex, and Mini-Mental State Examination score. Compared with the AD group, the iNPH group scored significantly higher on the orientation subtest of the Alzheimer's Disease Assessment Scale and on the general memory and delayed recall subtests of the Wechsler Memory Scale-Revised (WMS-R), and significantly lower on the attention/concentration subtest of the WMS-R and on the digit span, arithmetic, block design and digit symbol substitution subtests of the Wechsler Adult Intelligence Scale-Revised. The impairment of frontal lobe functions is disproportionately severe and memory impairment is disproportionately mild in patients with iNPH compared with AD. Recognition of these features contributes to an early diagnosis, which can lead to a better prognosis.

Association between cognitive impairment and gait disturbance in patients with idiopathic normal pressure hydrocephalus.

We compared the scores of the Frontal Assessment Battery (FAB), initial fluency subtest, category fluency subtest and subtests of the Mini-Mental State Examination (MMSE) between patients with idiopathic normal pressure hydrocephalus (iNPH) and age-, sex- and MMSE-matched patients with Alzheimer's disease (AD). In patients with iNPH, the time and number of steps required to go and come back a 10-meter distance were measured (Walking test) and the associations between the scores of the cognitive tests and the performance of the Walking test were evaluated. The scores of the FAB and initial fluency subtest in patients with iNPH were significantly lower than those in patients with AD. The scores of the FAB, initial fluency subtest and serial 7 subtest of the MMSE significantly correlated with the two scores of the Walking test in patients with iNPH. The present results indicate that frontal lobe functions were impaired in patients with iNPH and that cognitive impairment was closely associated with gait disturbance in patients with iNPH.

Neural basis of fear conditioning induced by video clip: positron emission tomography study.

In patients with post-traumatic stress disorder (PTSD), re-experiencing the trauma is often induced by external cues in the environment. The cues, which were emotionally neutral for the patients before the traumatic event, become fearful ones after the event. This phenomenon is considered to be associated with fear conditioning. The paradigm was set up so that the emotionality changes in the patients with PTSD would be reproduced, and the regional cerebral blood flow (rCBF) measured with positron emission tomography (PET) was compared during exposure to the same stimuli before and after acquisition of fear conditioning. Ten healthy male subjects were asked to look at some emotionally neutral photos, then to watch a video with fearful content that also contained images similar to that presented in the photos, and afterwards to look at the photos again. Five of the 10 subjects felt that the object in the photos was more fearful after watching the video than before, and they were considered to have acquired fear conditioning. In those five subjects, the rCBF in the right amygdala and the left posterior cingulate gyrus after acquisition of fear conditioning significantly increased relative to the rCBF before conditioning. Thus, these regions seem to have a critical role in fear conditioning.

Everyday memory impairment of patients with mild cognitive impairment.

We evaluated everyday memory impairment in 24 patients with mild cognitive impairment (MCI) with the Rivermead Behavioral Memory Test (RBMT) and compared the scores with those of 48 age-, sex- and education-matched normal controls (NC) and 48 age-, sex- and education-matched Alzheimer disease (AD) patients. Overall everyday memory was impaired in MCI patients but the severity was milder than that in AD patients. The MCI patients showed impairment of everyday memory tasks requiring delayed recall. But they could normally perform tasks immediately after memorizing, except for recalling and retracing a simple new route. The total Profile score correctly classified 100% of the MCI patients and 91.7% of NC, thus demonstrating the usefulness of the RBMT for diagnosing MCI patients. Prospective memory tasks were not useful for detecting the patients with MCI.

Effectiveness of a clinical pathway for the diagnosis and treatment of dementia and for the education of families.

AIMS: Clinical pathways (CPs) are rarely used in the treatment of dementia. We established a CP for a series of medical practices (diagnosis, treatment, establishment of a care system, and caregiver education) for patients with dementia hospitalized for a three-week period, and evaluated its usefulness. METHODS: The length of hospital stay and hospital costs were compared between 23 consecutive patients with dementia hospitalized and treated using a CP and 20 controls treated by conventional medical practice without using a CP in a special ward for dementia patients. In the CP group, at the time of discharge, primary caregivers, physicians, and nurses were given a questionnaire to obtain their comments about the impression of treatment with the CP. RESULTS: The questionnaire survey indicated that the CP deepened the caregiver's understanding of the sequence of medical practices for the inpatient, the disorders of the inpatient, the treatment methods, and the methods for coping with the disorder. The CP was also useful for facilitating inpatient medical practice and promoting the establishment of a care system after discharge. The use of the CP significantly shortened the length of hospital stay and decreased hospital costs during hospitalization but increased the amount of work per day and made the medical staff feel that their freedom to choose medical procedures had been restricted. CONCLUSIONS: The CP was useful for execution of inpatient medical practices for patients with dementia.

Heterogeneity of cerebral blood flow in Alzheimer disease and vascular dementia.

BACKGROUND AND PURPOSE: Alzheimer disease (AD) and vascular dementia (VaD) are the two major diseases that cause dementia, and early diagnosis is important. Single photon emission CT (SPECT) of cerebral blood flow (CBF) is used for the early detection of dementia and as an auxiliary method for follow-up. AD shows reduced posterior blood flow and VaD manifests reduced anterior blood flow on CBF SPECT images. We examined the usefulness of 3D fractal analysis of CBF SPECT images to objectively quantify the heterogeneity of CBF in patients with AD and VaD. METHODS: Thirty-two patients with AD and 22 with VaD based on neuropsychologic tests and imaging findings, as well as 20 age-matched control subjects underwent technetium-99m hexamethyl propyleneamine oxime CBF SPECT. We then conducted statistical image processing by 3D fractal analysis on reconstructed data. Fractal dimension, an index of heterogeneity, was then calculated for the whole brain, as well as for the anterior and posterior regions of the brain. A higher fractal dimension indicates that the CBF SPECT image is uneven. The ratio of fractal dimension of the anterior region to fractal dimension of the posterior region (A/P ratio) was calculated. Heterogeneity of CBF was compared among the AD, VaD, and control groups. RESULTS: Fractal dimensions of the AD, VaD, and control groups were 1.072+/-0.179 (mean +/- SD), 1.005+/-0.156, and 0.806+/-0.06, respectively. A significant difference of fractal dimension was noted between the control group and the two types of dementia (P<.0001); however, no significant difference was noted between the AD and VaD groups. The A/P ratios of the AD and VaD groups were significantly different (0.952 and 1.163, respectively; P<.01). CONCLUSION: Analysis of CBF SPECT images quantitatively showed that the fractal dimension was significantly higher (indicating heterogeneity) in patients with AD and VaD when compared with age-matched control subjects. Comparison of the A/P ratio on CBF SPECT images between AD and VaD groups showed that the heterogeneity of CBF was posterior-dominant for AD and anterior-dominant for VaD. Thus, 3D fractal analysis enabled a simple and objective evaluation of the heterogeneity of CBF in patients with AD and VaD.