Yoshitaka Ikejiri

Factors associated with psychotic symptoms in Alzheimer’s disease

OBJECTIVES Many clinical and biological factors have been reported to be associated with the presence of psychosis in patients with Alzheimer’s disease, although the associations were variable. The aim of this study was to clarify factors associated with the presence of psychosis in patients with Alzheimer’s disease. METHODS Psychiatric functioning was studied in 228 patients with Alzheimer’s disease based on the results of the behavioural pathology in Alzheimer’s disease rating scale or the neuropsychiatric inventory. The effects of sex, education level, age, duration of illness, cognitive function, and apolipoprotein E genotype were investigated for dichotomous psychotic status with a multiple logistic regression analysis. RESULTS Of the 228 patients with Alzheimer’s disease, 118 (51.8%) showed evidence of delusions or hallucinations. Of these, 94 had delusions only, three had hallucinations only, and 21 had both. Older age, female sex, longer duration of illness, and more severe cognitive impairment were the factors independently associated with the presence of psychosis. The presence of psychosis was not significantly related to either educational level or apolipoprotein E genotype. CONCLUSIONS Age, sex, and severity of illness were independent factors associated with the presence of psychosis in patients with Alzheimer’s disease. The reason why some patients with Alzheimer’s disease develop psychosis remains unclear. There may be distinctive subtypes of Alzheimer’s disease or the presence of individual factors which affect the development of psychosis.

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.

Age at onset and regional cerebral glucose metabolism in Alzheimer's disease

This study assessed 46 patients with Alzheimer’s disease and 21 aged controls using positron emission tomography. Repeated analyses using a general linear model examined the effect of age at onset on the pattern of the regional cerebral metabolic rate of glucose (rCMRglc). The results showed significant age effects on the rCMRglc in the fronto-temporo-parietal association cortices and retrosplenial areas. Disease duration, overall cognitive severity or normal aging could not account for the effects. The age effects were delineated as a double dissociation, that is, early-onset patients have a more severe reduction of regional glucose metabolism in the association cortices, while late-onset patients show a more prominent metabolic deficit in the paralimbic area.

Hypofunction in the posterior cingulate gyrus correlates with disorientation for time and place in Alzheimer’s disease

The relation between orientation for time and place and regional cerebral glucose metabolism was examined in 86 patients with probable Alzheimer’s disease of minimal to moderate severity. Regional glucose metabolic rates in the posterior cingulate gyri and in the right middle temporal gyrus were significantly correlated with temporal orientation, and the glucose metabolic rate in the right posterior cingulate gyrus was significantly correlated with locational orientation irrespective of age, sex, education, and memory impairment. The results suggest that dysfunction of these structures plays an important part in producing disorientation in patients with Alzheimer’s disease.

Theta rhythm increases in left superior temporal cortex during auditory hallucinations in schizophrenia : a case report

Auditory hallucinations (AH), the perception of sounds and voices in the absence of external stimuli, remain a serious problem for a large subgroup of patients with schizophrenia. Functional imaging of brain activity associated with AH is difficult, since the target event is involuntary and its timing cannot be predicted. Prior efforts to image the patterns of cortical activity during AH have yielded conflicting results. In this study, MEG was used to directly image the brain electrophysiological events associated with AH in schizophrenia. We observed an increase in theta rhythm, as sporadic bursts, in the left superior temporal area during the AH states, whereas there was steady theta band activity in the resting state. The present finding suggests strong association of the left superior temporal cortex with the experience of AH in this patient. This is consistent with the hypothesis that AH arises from areas of auditory cortex subserving receptive language processing.

Age at onset and visuocognitive disturbances in Alzheimer disease

We examined the relation of age at onset and visuocognitive disturbances in Alzheimer disease (AD) using a large sample of patients, quantitative neuropsychological measures, and multivariate statistics controlling for gender, education, stage of dementia, and disease duration. Significant positive coefficients were obtained with forward and backward digit and visual spans, visual counting, copying Rey complex figure, and block design task. The results indicated that patients with early-onset AD performed worse than late-onset AD patients on these tasks. There was no significant effect of age at onset on identification of overlapping figures, visual form discrimination, or Ravens colored progressive matrices. These findings confirm the greater attentional and visuospatial impairments in early onset patients when these confounding factors were controlled for, although no significant effect of age at onset in visuoperceptual function was observed.

Procedural memory in patients with mild Alzheimer's disease.

Motor, perceptual, and cognitive skill learning abilities of mild Alzheimers disease (AD) patients were compared to sex-, age-, and education-matched controls. We excluded patients who were unable to perform each skill learning task with a predetermined criterion. In those who completed the task, skill learning was as good as in normal controls. On the cognitive and perceptual skill learnings, some of the AD patients, whose cognitive but not declarative memory functions were more severely impaired than in those who completed the whole session, failed to complete the task, while all patients could complete the motor task. These results support that view that patients with mild AD can acquire motor, perceptual, and cognitive skills and that the neural system subserving procedural skill is not related to the neural systems for declarative memory.

Different neural substrates for Kanji and Kana writing: a PET study.

To investigate the neural substrate underlying the mechanisms of Kanji and Kana writing, we conducted a PET activation study during mental writing task in eight right-handed normal Japanese subjects. During scans subjects were required to mentally write a Kanji or three Kana letters with their right hand, for each stimulant word presented auditorily. The direct comparisons between Kanji writing and Kana writing revealed that the left posterior inferior temporal gyrus was activated in Kanji writing while the left angular gyrus was activated in Kana writing. In addition, more extensive areas were activated in Kanji writing compared with Kana writing. These results suggest that different respective neural substrates are involved in Kanji and Kana writing respectively.

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.