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We report results of our investigation of the case of a 34-year-old woman (YJ) who showed persistent left unilateral spatial neglect (USN) in daily living, frequently hitting obstacles or bumping into the wall, although her visuospatial ability was mostly preserved in paper and pencil neuropsychological tests. In order to clarify this apparent discrepancy, her eye fixation pattern was monitored in testing situations and in natural daily activities using an eye camera. The results showed that when taking the standard tests YJ tended to shift her fixation point to the left edge of the testing frame to overcome over-searching tendency to the right as left hemianopics without left USN would do. However in natural situations, this compensatory leftward fixation was not found. This may be due to the lack of adequate frames of reference in the natural environment. Our findings suggest limitation of laboratory neuropsychologicial testing to fully appreciate the scope of a patient's disability in natural settings.

Background/Aims: Patients with idiopathic normal pressure hydrocephalus (iNPH) are often given shunt operations to reduce the triad symptoms (cognitive impairment, gait disturbance and urinary disturbance). We examined whether they also reduce caregiver burden. Methods: The personal strain (PS) and role strain (RS) factors, which are related to the stress and constraints, respectively, on the caregivers of 81 iNPH patients were evaluated with the Zarit burden interview (ZBI) and each of the triad symptoms was evaluated with the iNPH grading scale (iNPHGS) before and 1 year after the shunt operation. Results: Each of the iNPHGS scores, the total ZBI score and PS factor significantly improved after the shunt operation, but the RS factor did not. The improvement of cognitive impairment was the major factor in reducing caregiver burden. Conclusion: Shunt operations reduced the caregiver burden of iNPH patients.

Background: The influence of depressive symptoms on awareness of memory disturbances in patients with Alzheimer disease (AD) and metamemory is unknown. Objective: We compared the level of awareness of memory disturbances in AD patients with and without depression using 2 measures: a questionnaire comparing discrepancies in patients/ caregivers' assessments and the patients' predictions of their own performances on a memory task. Methods: AD patients with depression (n = 21) or without depression (n = 21) were asked to complete an assessment of self-reported memory dysfunction (Short Memory Questionnaire; SMQ) and memory task performance prediction (10-words-recall Questionnaire). In addition, the caregivers' evaluations of the memory deficits in the study patients were assessed using the SMQ. Results: We observed a greater discrepancy in the SMQ scores given by the caregivers' and the patients' among AD patients without depression, compared with those with depression. A greater discrepancy was also observed in the ratio score (patient's predicted performance/actual performance) for the 10-words-recall Questionnaire in AD patients without depression than in those with depression. Conclusions: AD patients with depression may estimate their memory ability either more accurately or more negatively than AD patients without depression, as shown using the above 2 methods.

Background: Recent studies have emphasized specific deficits of attention and executive functions, such as those of cognitive flexibility, divided attention, in geriatric patients with depression. In Alzheimer’s disease (AD), depressive symptoms are known to occur even from an early stage of the disease. However, the nature of the impairment of executive functions in depression associated with AD remains unclear, because of the frequent occurrence of the apathy syndrome as a major confounding factor. Method: In this study, we conducted a comprehensive comparative neuropsychological assessment in AD patients with (n = 21) and without (n = 21) depression. The diagnosis of depression was based on provisional criteria proposed by Olin’s group. Results: In terms of apathy symptoms, both groups had a similar degree of deficits, which were mild as assessed according to Neuropsychiatric Inventory criteria. While no significant differences were observed in regard to the scores in general intellectual functioning, episodic memory and some attention and executive tasks between the two groups, AD patients with depression showed significantly lower scores in several attention and executive function tasks, such as the dual-task performance task administered to assess the capacity for divided attention, and the cognitive flexibility (Trail Making Test; Part B), than AD patients without depression. Conclusions: Our results suggest that depressive symptoms in AD patients increase the deficits of cognitive flexibility and divided attention. This is the first study to report a correlation between depressions, diagnosed based on the provisional criteria for depression in AD by Olin’s group, and an impaired capacity for divided attention in AD patients.

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.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).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.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.

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.

Objective : To investigate the cerebral glucose metabolism of subjects who had a Clinical Dementia Rating (CDR) of 0.5, we studied 40 subjects whose CDR was 0.5 and 40 age-matched healthy subjects. Methods : Cerebral glucose image of each subject was obtained by [ 18 F]-2-fluoro-deoxy- d -glucose (FDG) positron emission tomography (PET). The anatomically standardized images were produced with NEUROSTAT. Then, the two groups were compared with the Statistical Parametric Mappings (SPM) 99. Results : A comparison with the SPM 99 revealed that relative cerebral glucose metabolism was lower in the posterior cingulate gyri and parietal lobules in the CDR 0.5 group than in the healthy subjects group. Conclusion : These findings are very similar to those in patients with probable Alzheimer's disease (AD) and suggest that the majority of subjects with CDR 0.5 are suffering from very mild AD or at least a prodromal state of AD.

To investigate a possible effect of the apolipoprotein (APOE) epsilon4 allele on memory decline in Alzheimer's disease (AD), we examined 64 AD patients with the APOE epsilon3/3, epsilon3/4, or epsilon4/4 allele using the Alzheimer Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and its subtests at the initial examination and at the 1-year follow-up visit. One-year changes in the scores of the Word Recall subtest, Word Recognition subtest, and total ADAS-Cog were significantly correlated with the number of APOE epsilon4 alleles after controlling for the effects of age, sex, education, test interval, and baseline scores. Findings revealed that APOE epsilon4 allele is related to an accelerated memory decline in AD.

The specific effects of visual and verbal memory on the ability of emotional arousal to enhance declarative memory were examined by using multiple linear regression analysis on data from a sample of 56 patients with probable Alzheimer's disease (AD). The enhancing effect of emotion on memory was evaluated by an illustrated story paradigm, and the visual and verbal memory by a standard memory test. In AD, memory enhancement by emotion was significantly correlated with visual memory but not with verbal memory, regardless of age, sex, educational attainment, and severity of dementia, suggesting a close association between memory enhancement by emotion and visual memory.

Personal semantic memory is factual knowledge about a person's own past. Although personal semantic memory is assumed to have features of both semantic memory and episodic memory, the relationship to episodic memory and to semantic memory have not been well documented. In patients with Alzheimer's disease, episodic memory, semantic memory, and personal semantic memory are all defective. In this study, the hypothesis that defective personal semantic memory is related to both semantic and episodic memory dysfunction was tested in patients with Alzheimer's disease. Functions of episodic, semantic, and personal semantic memory were examined by using the Wechsler Memory Scale-Revised (WMS-R), subtests of the WAIS-R (Information, Vocabulary, Comprehension and Similarities), and the Family Line Test (FLT) in 62 patients who met the NINCDS/ADRDA criteria for probable Alzheimer's disease. Specific effects of episodic and semantic memory on personal semantic memory were examined by using multiple linear regression analysis with the total score of the FLT as the dependent variable and the WMS-R Delayed Recall weighted sum score and the WAIS-R Semantic Memory score (a composite of standardized scores of the four subtests) as the independent variables. Personal semantic memory function was significantly correlated with both the episodic and semantic memory functions, after controlling age, sex, educational attainment, and severity of dementia. This result supports the hypotheses that personal semantic memory has features of both episodic and semantic memory, and that semantic memory is transformed from episodic memory.

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).A total of 12 patients with PSP (age: 62.8+/-6.0 years old, m: 7, f: 5, Mini-Mental State Examination (MMSE): 23.4+/-2.6), 12 patients with CBD (age: 64.8+/-6.3 years old, m: 6, f: 6, MMSE: 22.9+/-4.5), and age-matched healthy subjects (normal control (NC)) (age: 63.8+/-7.7 years old, m: 7, f: 5) were subjected to FDG-PET to obtain glucose metabolic images. We compared regional cerebral metabolic images by a voxel-by-voxel analysis with statistical parametric mapping (SPM) among PSP, CBD, and NC subjects, and evaluated differences of hypometabolic regions.The patients with PSP showed reduced cerebral glucose metabolism in the medial and lateral frontal gyri, basal ganglia, and midbrain compared with NC, whereas the patients with CBD showed significant reduction in the parietal lobes (p0.001). SPM also revealed parietal hypometabolism in CBD patients compared with PSP patients (p0.001).The predominant parietal glucose metabolic reduction in CBD patients was different from previously reported findings. This finding would be the characteristic substance of patients with CBD accompanying cognitive impairments. Our findings suggest that measurement of glucose metabolism by PET and a voxel-based analysis is useful to understand the pathophysiology of these two diseases with cognitive impairments.

Background: Although the APOE e4 allele is a well-known risk factor for developing AD, the impact of the e4 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 e4/4 and APOE e3/3 alleles in early-onset (≤65 years old) and late-onset (>65 years old) groups. In each group, the patients with APOE e4/4 and APOE e3/3 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 e4/4 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 e3/3 genotype. In the late-onset group, there were no significant differences in the rCMRglc pattern between the patients with APOE e4/4 and APOE e3/3 alleles. Conclusions: The current findings indicate that the impact of the APOE e4 genotype on cerebral glucose metabolism of patients with AD may be a function of age at symptom onset.

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.

The Cognitive Fluctuation Inventory (CFI) was developed to evaluate cognitive fluctuation in patients with dementia with Lewy bodies (DLB). The objective of this study was to assess the content validity and inter-rater reliability of the CFI.Nine specialists in DLB treatment were invited to participate in the survey to assess the content validity of the CFI. They were asked to assess the relevance and comprehensibility of the question items. In the validation study, inter-rater reliability was assessed using the intraclass correlation coefficient (ICC).Regarding content validity, all nine specialists considered the main question and sub-questions to be relevant to cognitive fluctuation in patients with DLB. Eight out of nine specialists considered the CFI to be a comprehensive measure for detecting cognitive fluctuation in patients with DLB. In the analysis, which used data from 29 patients and their caregivers, the ICC of the CFI was 0.746, which suggests good inter-rater reliability.We found that the CFI showed good content validity and inter-rater reliability for evaluating cognitive fluctuation in patients with DLB.

BackgroundIn 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.AimsTo test our previous findings in a controlled experimental study.MethodRecall 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.ResultsIn 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.ConclusionsThe 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.

There is evidence of two neuronal systems for visual cognition which are referred to as spatial vision and object vision. We subjected 49 patients with mild-to-moderate probable Alzheimer's disease (AD) to tasks associated with these two types of visual cognition. Visual counting was employed as a task to assess visuospatial recognition. Identification of overlapping figures and discrimination of visual forms were used as visuoperceptual tasks that require an ability to recognize objects. Regional cerebral glucose metabolism (rCMRglc) of the subjects was also determined by positron emission tomography. Multivariate statistics controlling for the confounding factors assessed the correlation between the task performances and the rCMRglc. The visual counting score significantly correlated with the metabolic rate of the bilateral inferior parietal lobules. On the other hand, the scores of the visuoperceptual tasks significantly correlated with the metabolic rate of the right middle temporal gyrus and the right inferior parietal lobule. The present study showed that visuospatial disturbance was related to bilateral parietal metabolism, and that visuoperceptual disturbance was related to right temporo-parietal metabolism in patients with mild-to-moderate AD.

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.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.The extent and magnitude of cortical atrophy were larger in the group with corticobasal degeneration than in the group with Alzheimer disease. The parasagittal and paracentral regions were significantly more atrophic in patients with corticobasal degeneration than in patients with Alzheimer disease (P.05). The mean hemispheric-to-total intracranial volume ratios were significantly smaller in the patients with corticobasal degeneration (61%) and those with Alzheimer disease (64%) than in control subjects (69%). Asymmetry of hemispheric volume was significantly larger in the group with corticobasal degeneration than in the control group.The extent of cortical atrophy in corticobasal degeneration is more widespread than was previously thought. Parasagittal and paracentral atrophy is a distinctive feature of corticobasal degeneration and distinguishes it from Alzheimer disease.

Objective: To compare the validity of the Mini Mental State Examination (MMSE) and the Short-Memory Questionnaire (SMQ) as screening tests to detect dementia in the elderly general population. Subjects: Six hundred and sixty-two subjects and their informants from the elderly general population sample who had completed these tests. Setting: One rural community survey in Japan. Method: We used receiver-operating characteristic analysis to compare the performance of the MMSE and the SMQ with the clinical diagnosis of dementia according to DSM-III-R. Results: The areas under the receiver-operating characteristic curve of the MMSE and the SMQ were 0.980 (SE = 0.006) and 0.982 (SE = 0.008), respectively. This differed from chance to a highly significant degree for both the MMSE and the SMQ, but the difference between the two scales was not statistically significant. Conclusion: As screening tests to detect dementia in the elderly general population, the SMQ which is assessed by informants demonstrates a statistically significant discriminating ability as well as the MMSE.

We evaluated remote autobiographical memory impairment in 25 patients with probable Alzheimer’s disease (AD) and 25 sex-, age- and education-matched healthy subjects by using a newly developed, highly effective assessment tool for remote memory, the Family Line Test (FLT). The FLT yields a total score, scores for 3 lifetime periods and the duration of remote memory impairment. In the patients with AD, the total score was significantly lower and the duration of remote memory impairment was significantly longer than in the healthy controls. A prominent temporal gradient in remote memory impairment was documented in the patients with AD. The total FLT score and duration of remote memory impairment correlated with recent memory and general cognitive dysfunctions.

OBJECTIVE—Presenilin-1 is a major causative gene for early onset familial Alzheimer's disease, and the apolipoprotein E e4 allele is a major genetic risk factor known to influence late onset and sporadic early onset Alzheimer's disease. The presenilin-1 1/1 genotype has recently been reported to be associated with sporadic Alzheimer's disease. The purpose of this study is to determine whether Alzheimer's disease is associated with presenilin-1 gene polymorphism and the apolipoprotein E genotype in an extended case-control study. METHODS—An examination was conducted on 217 patients with Alzheimer's disease, along with an equal number of age and sex matched controls derived from the same community in a Japanese population, by using a χ2 test for homogeneity and a logistic regression analysis. A meta-analysis of data from the literature on allele frequencies in Alzheimer's disease and control populations was used for comparison with the Japanese allele frequencies obtained in this study. RESULTS—The presenilin-1 allele-1 frequencies were similar in patients with early onset Alzheimer's disease (0.61) and younger controls (0.61), and in those with late onset Alzheimer's disease (0.63) and elderly controls (0.63). We found no evidence for a possible association between the presenilin-1 polymorphism and the apolipoprotein E e4 allele. However, the meta-analysis showed that the association between the presenilin-1 1/1 genotype and Alzheimer's disease was significant (Peto odds ratio=1.16, 95% confidence interval=1.04-1.31). CONCLUSIONS—These results suggest a subtle but positive association of presenilin-1 gene polymorphism with Alzheimer's disease, although Japanese data in this study which failed to support such a relation would indicate an ethnic variation.

The association between the apolipoprotein E epsilon 4 (APOE E4) allele and a wide spectrum of behavioral symptoms of Alzheimer's disease (AD) was investigated. Neither the severity nor the presence of any behavioral changes was associated with the number of APOE E4 alleles, even after controlling for the effects of age at onset, sex, education level, duration of illness, and severity of dementia. The findings do not support the hypothesis that neuropsychiatric manifestations of AD are different in patients with the APOE E4 allele.

Everyday experience suggests that highly emotional events are often the most memorable. Experimental work in animals and humans has demonstrated that the amygdaloid complex plays a crucial role in emotional memory, i.e., memory of events arousing strong emotions. The aim of this study was to elucidate the relationship between medial temporal damage and impaired memory of real-life emotional events in patients with Alzheimer's disease.In 36 patients with probable Alzheimer's disease who experienced the 1995 earthquake in Kobe, Japan, memories of events surrounding the earthquake were examined as an index of emotional memory with the use of a semistructured interview, and amygdalar and hippocampal volumes were quantified by magnetic resonance imaging. The effects of the atrophy of these structures on recall performance were determined by multiple regression analysis.Irrespective of generalized brain atrophy and cognitive impairments, emotional memory was correlated more with normalized amygdalar volume (right and left averaged) than with normalized hippocampal volume. General knowledge of the earthquake was correlated with neither amygdalar nor hippocampal volume.The results indicate that impairment of emotional event memory in patients with Alzheimer's disease is related to intensity of amygdalar damage and provide evidence of the amygdala's involvement in emotional memory in humans.

Parietal cerebral glucose metabolism is reduced before substantial impairments appeared in subjects carrying the apolipoprotein E (APOE) epsilon4 allele, but the effect of the APOE epsilon4 allele on cerebral metabolism in Alzheimer disease (AD) is still undetermined. To investigate the effect of the APOE epsilon4 allele on cerebral metabolism in AD, we examined regional cerebral glucose metabolism in 83 patients with AD by using 18F-fluorodeoxyglucose and positron emission tomography. Cerebral glucose metabolism in the fronto-parieto-temporal association and limbic cortices was significantly decreased in the AD patients compared with 26 age- and sex-matched normal controls. Regional cerebral glucose metabolic rate was not correlated significantly with the number of APOE epsilon4 alleles in any region, which was consistent even after controlling the effects of age, sex, and severity of dementia, and in a subgroup analysis of those aged between 60 and 75. These results supported the view that the APOE epsilon4 allele is not associated with specific deficits in brain metabolism in AD despite evidence of preclinical alterations.

The authors examined 65 patients with Alzheimer's disease for delusions and explored the relationship of delusions with regional cerebral glucose metabolism determined by [18F]fluorodeoxyglucose PET. In patients with delusions (n = 26), normalized glucose metabolism was significantly increased in the left inferior temporal gyrus and significantly decreased in the left medial occipital region as compared with those without delusions (n = 39). The two groups were similar in age, sex, and dementia severity. These results suggest that delusions in Alzheimer's disease are attributable to a dysfunction in specific brain areas rather than a simple reaction to intellectual deficits.

BackgroundEmotional memory is a special category of memory for events arousing strong emotions. To investigate the effects of emotional involvement on memory retention in individuals with Alzheimer's disease we studied peoples' memories of distressing experiences during a devastating earthquake.MethodFifty-one subjects with probable Alzheimer's disease who experienced the Kobe earthquake at home in the greater Kobe area were studied. Memories of the earthquake were assessed 6 and 10 weeks after the disaster in semi-structured interviews, and were compared with memories of a magnetic resonance imaging (MRI) examination given after the earthquake.ResultsForty-four (86.3%) of the subjects remembered the earthquake and 16 (31.4%) of subjects remembered the MRI experience. Factual content of the earthquake was lost in most of the subjects.ConclusionsFear reinforces memory retention of an episode in subjects with Alzheimer's disease but does not enhance retention of its context, despite repeated exposure to the information.

The diagnostic utility of the Fuld cholinergic deficit profile (Fuld, 1984) to dementia of the Alzheimer type (DAT) was evaluated on the Japanese version of the WAIS-R. Profiles were calculated for groups of subjects with DAT(n = 236), vascular dementia (n = 29), frontotemporal dementia (n = 22), and hydrocephalic dementia (n = 10). The frequency of positive profile occurrence for the subject groups was as follows: 23/236 for DAT (9.7%), 2/29 (6.9%) for vascular dementia, 2/22 (9.1%) for frontotemporal dementia, and 2/10 (20%) for hydrocephalic dementia. No significant difference in the frequency of positive profile occurrence was revealed across four types of dementia. We conclude from these findings that the Fuld profile lacks the diagnostic utility on the Japanese WAIS-R.

Objective: Both the magnitude of brain atrophy and premorbid brain size determine the volume of the brain affected by Alzheimer’s disease. To examine the possibility that premorbid brain volume is a determinant of cognitive reserve in patients with Alzheimer’s disease, the relation between diffuse brain atrophy and cognitive decline and the impact of premorbid brain size on cognitive decline were studied in patients with Alzheimer’s disease. Method: By measuring whole brain volume and intracranial volume in 60 patients with probable Alzheimer’s disease, mild to moderate in severity, with the use of high-resolution magnetic resonance imaging and image processing, the authors studied the impact of premorbid brain volume and magnitude of diffuse brain atrophy on cognitive functions. On the basis of the normative brain-calvarium relationship derived from data an 28 healthy adults and the total intracranial volume measure of each patient, the magnitude of brain atrophy and premorbid brain volume were estimated. Results: After control for the effects of age, sex, and education as confounding factors, it was found that the Alzheimer’s disease patients’ intelligence was correlated both positively with premorbid brain volume and negatively with magnitude of brain atrophy, while impairments in language and memory were correlated with magnitude of brain atrophy but not with premorbid brain volume. Conclusions: These findings partially support the hypothesis that premorbid brain volume is a determinant of reserves against intellectual decline in Alzheimer’s disease. (Am J Psychiatry 1997; 154:18‐24)

Motor, perceptual, and cognitive skill learning abilities of mild Alzheimer's 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.

Thirty-one patients with mild-to-moderate Alzheimer's disease (AD) underwent a test battery of complex visual tasks. We assessed the scores using a principal-factor analysis to elucidate the underlying deficits. There were three independent factors: The first factor included the tasks of identifying and comparing forms of visual stimuli. The second factor consisted of digit span and digit symbol tasks, and the third factor consisted of a specified visual counting task. We considered these three factors as representing the dysfunctions of object recognition, general attention and spatial recognition, respectively. These results underline the disturbances of the two visual systems, object vision and spatial vision, in early-AD patients.

Neuropsychiatric disturbances are common and burdensome symptoms of dementia. Assessment and measurement of neuropsychiatric disturbances are indispensable to the management of patients with dementia. Neuropsychiatric Inventory (NPI) is a comprehensive assessment tool that evaluates psychiatric symptoms in dementia. The Nursing Home Version (NPI-NH) of NPI was developed for use in extended care facilitate caring for residents with dementia. We translated the NPI-NH into Japanese and examined their validity and reliability.The subjects were 100 demented inpatients and the nurses in charge of them. The Mini-Mental State Examination (MMSE) was conducted with all patients and NPI-NH, Cohen-Mansfield Agitation Inventory (CMAI), Cornell Scale for Depression in Dementia (CSDD), and Behavior Pathology in Alzheimer's Disease (BEHAVE-AD) Rating Scale were conducted with the nurses. We examined validity of NPI-NH by comparing its score with the CMAI, CSDD, and BEHAVE-AD. In order to evaluate test-retest reliability, NPI-NH was re-adopted to 30 randomly selected nurses in charge inpatients by a different examiner 1 week later.The frequency score, severity score and occupational disruptiveness score in each NPI-NH item were significantly correlated with the score of the correspondent item in BEHAVE-AD. The agitation score of NPI-NH was significantly correlated with CMAI and the depression score of NPI-NH was significantly correlated with CSDD. Test-retest reliability of the scores of NPI-NH was acceptably high.The Japanese version of NPI-NH demonstrated sufficient validity and reliability as well as the original version of them. It is a useful tool for evaluating psychiatric symptoms in demented inpatients.

Background: Apathy and depression may be strongly associated with executive dysfunction in Alzheimer's disease (AD). The Frontal Assessment Battery (FAB) is an instrument for assessing executive function. The dual task paradigm is also useful for assessing divided attention. However, the association between apathy/depression and these tasks is unclear.Methods: Both the FAB and the dual task were used to evaluate AD patients. A two-way analysis of variance was then conducted between the FAB and dual task results and the absence versus the presence of depression or the absence versus the presence of apathy.Results: Of 88 patients with AD, 26 had both apathy and depression, 26 had depression only, 18 had apathy only, and 18 had neither. Total FAB scores and dual task scores differed significantly between the AD patients with depression and those without depression; the scores were also different between those with apathy and those without apathy. Also, a significant interaction between depression and apathy was noted for the total FAB and dual task scores.Conclusions: The deficits in the total FAB and dual task scores were larger in AD patients with both apathy and depression compared with patients with either apathy or depression alone. AD patients with both symptoms may have greater deficits in frontal lobe function relative to AD patients with either apathy or depression alone.

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.

By using [(18)F]-2-fluoro-deoxy-d-glucose and positron emission tomography, the authors studied changes in regional glucose metabolism after a 1-year interval in patients with mild Alzheimer's disease (AD). Glucose metabolism declined over time in the bilateral precuneus and posterior cingulate gyri and in the frontal, temporal, and parietal cortices. Glucose metabolism in these regions may be a useful measure of the progression of AD and a valid surrogate outcome measure of clinical drug trials.

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.

The decision of long-term institutionalization of patients with Alzheimer's disease (AD) is based on multiple patients' and caregivers' characteristics. It is very important to find out factors associated with institutionalization for the timely institutionalization, i.e. for the prevention of premature institutionalization. Among those factors, caregiver burden is reportedly one of the most important factors in Europe and North America. However, no studies have been carried out in Japan. In order to address this issue, we studied outcome of patients with AD.Subjects were 211 patients who fulfilled the criteria of the National Institute of Neurological Disease and Stroke/Alzheimer's Disease and Related Disorders Association for probable AD. Diagnosis of AD was made through extensive examinations including MRI and PET/SPECT of the brain. The patients included 149 women and 62 men; the mean age was 73.1 +/- 8.0 (SD) years. The Japanese version of Zarit Caregiver Burden Interview (ZBI), which is a validated tool for assessment of the burden of caregivers for dementia patients, was used to evaluate caregivers' burden through the interview of a principal caregiver by trained nurses. Cognitive, functional, and neuropsychiatric impairments were assessed with standardized instruments of the Mini-Mental State Examination (MMSE), Hyogo Activities of Daily Living Scale (HADLS), Neuropsychiatric Inventory (NPI), respectively. We annually sent a questionnaire to the caregivers to collect information on the patients' status. It included questions whether and when they died or were institutionalized and whether they had used formal social supports such as home care, day care, and respite care services.Time to death or institutionalization.One-hundred and fifty subjects were followed for at least one year and 51 of them met either end point. The Cox proportional hazard model demonstrated that the baseline caregiver burden was a significant predictor of the end point even after controlling possible confounders. Among these, the use of day care and home care services during the course were significant protective factors. The baseline cognitive and functional disturbances but not neuropsychiatric manifestations were significantly associated with the end point.The caregiver burden is a significant predictor for the death or institutionalization of the patients with AD. The caregiver education which decrease the caregiver burden and prompt the usage of the social care services are necessary to protect premature institutionalization.

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 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). The everyday disability caused by the impairment of memory function was also assessed with the Memory Checklist (CL), and was correlated with the RBMT scores. In addition, the diagnostic value of the RBMT was examined in 46 pairs of AD patients and healthy subjects; the patients were chosen from the present subjects and the healthy subjects from the participants in the previous RBMT standardization study as one-by-one matched for age, sex, and educational level.Both of the total screening score and profile score of RBMT were significantly correlated with all of the weighted sum scores of verbal, visual, general, and delayed memory tests of the WMS-R and the word recall subtest score of the ADAS-J Cog. Both of the RBMT scores were also highly correlated with the CL score and the memory subscale of the CDR. In the analysis of the diagnostic accuracy, both of the RBMT scores correctly classified 98% of AD patients and 96% of normal volunteers by setting the cut-off scores of 6/5 for the total screening score and of 14/13 for the total profile score.The RBMT is a useful tool in evaluating everyday memory function in patients with mild AD. This test also accurately differentiates AD patients from healthy individuals.

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 53.9 and 72.7 years. Groups of age-matched normal subjects were used as controls. A regional relative cerebral glucose metabolic image of each subject was obtained by 2-[ 18 F] fluoro-2-deoxy- d -glucose (FDG) positron emission tomography (PET). NEUROSTAT program was used for spatial normalization and voxel-based statistical parametric mapping (SPM) 99 was used for statistical analyses. Results : Both AD groups had significant hypometabolic regions in the bilateral parieto-temporal regions compared with the age-matched groups. The EO group had more severe hypometabolism in the bilateral parietal and posterior cingulate cortices and precuneus region than the LO group. However, LO group showed no significant hypometabolic regions compared to the EO group. Conclusion : The effects of time of AD onset were delineated as a double dissociation, that is, EO AD patients have a more severe reduction of glucose metabolism. Our finding suggests the existence of biological subtypes of AD.

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 18F-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.

Purpose. To determine whether the Short-Memory Questionnaire (SMQ) being administered by caregivers to patients with Alzheimer's disease (AD) is also valid when given to patients with vascular dementia (VaD). Methods. Subjects were 58 patients with VaD, 26 patients with cerebrovascular disorders free of cognitive deficit (CVD) and 62 healthy controls. All subjects received the Mini-Mental State Examination (MMSE), and their primary caregivers (or family members with same household) received the SMQ. Results. In the VaD patients, the SMQ score was highly correlated with the MMSE score. When 39/40 was defined as a cutoff point based on the results of previous study, the SMQ properly classified 55 of the 58 VaD patients and 61 of the 62 controls, but only about half of the 26 CVD patients, as cases. Conclusion. The SMQ, a simple quantitative rating test for memory disturbance, is useful for the assessment and screening of VaD patients as well as AD patients, although careful attention should be paid to the assessment of CVD patients. Copyright © 2000 John Wiley & Sons, Ltd.

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 18F-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.

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.

Background and Purpose —The clinical significance of the apoE ε4 allele in white matter changes in patients with dementia has been a subject of debate. We studied the association between the apoE ε4 allele and white matter hyperintensities (WMHs) before and after control for (1) potential vascular risk factors and (2) the presence of lacunar infarcts in patients with dementia. Methods —The subjects were 131 patients with dementia who had either Alzheimer’s disease or vascular dementia, or a combination of these 2 types of dementia, with or without WMHs, lacunar infarcts, or both. The association of the ε4 allele with WMHs was examined before and after control for age, sex, duration of symptoms, education level, severity of dementia, presence of lacunar infarcts, and potential vascular risk factors, including hypertension, diabetes mellitus, lipid disorders, smoking habit, drinking habit, and cardiac diseases. Results —WMHs were observed in 73 (55.7%) of the patients. Neither the number of apoE ε4 alleles nor their presence was significantly associated with WMHs before or after control for the potential confounding factors. Multiple logistic regression analyses revealed that age, the presence of hypertension, and the presence of lacunar infarcts were independently associated with WMHs. Conclusions —The apoE ε4 allele was not associated with WMHs in patients with dementia. The fact that WMHs were significantly associated with hypertension and lacunar infarcts may indicate an ischemic origin of WMHs.

A study was performed to assess interrater reliability of the Japanese version of the Short-Memory Questionnaire (SMQ), which is an easily-administered, informant-based scale of cognitive function. The subjects were 18 consecutive patients with Alzheimer's disease who were outpatients of Department of Neuropsychiatry in Ehime University School of Medicine and their principal caregivers. One neuropsychiatrist (NP) administered the SMQ, and all sessions were videotaped. Then one nurse (Ns), one clinical psychologist (CP), one occupational therapist (OT), and one neurologist (NL) from another institution viewed the videotape and performed reassessments independently. Interrater reliability between the NP and Ns, CP, OT, or NL were all extremely good. Interrater reliability between the Ns and CP, between the Ns and OT, between the Ns and NL, between the CP and OT, between the CP and NL, and between the OT and NL were also extremely good. The SMQ is a convenient, quantitative scale, and in this study it showed good interrater reliability between personnel from different fields. Therefore, it is a very useful test for everyday medical consultations and for clinical research. Copyright © 2000 John Wiley & Sons, Ltd.

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.

To investigate the neurobiological bases of visual hallucinations in dementia with Lewy bodies (DLB), regional cerebral glucose metabolism was compared among three patient groups; DLB with visual hallucinations, DLB without visual hallucinations and Alzheimer's disease (AD) without visual hallucinations. The regional metabolism was significantly lower in both DLB groups than in the AD group in the primary visual area and the posterior temporal, parietal and lateral occipital association areas. The hypometabolism in the right posterior temporal and parietal areas was significantly milder in DLB with visual hallucinations than in DLB without hallucinations. The hypometabolism in the primary visual cortex and the relatively preserved metabolism in the right temporoparietal association cortices may be associated with the occurrence of visual hallucinations in DLB patients.

We found 15 patients with dementia with Lewy bodies (DLB) and 232 patients with Alzheimer’s disease (AD) among 327 consecutive patients with mild to moderate dementia in a Japanese dementia registry, using the clinical criteria of the Consortium on DLB International Workshop. The percentage of females was significantly lower in DLB than in AD (p < 0.01), while age at examination, Mini-Mental State Examination score and duration of cognitive symptoms were comparable between the two diseases. Eight of the 15 DLB patients (53%) had spontaneous parkinsonism, which was observed in 6 of the 232 AD patients (2.6%). Visual hallucinations were reported by 11 of the 15 DLB patients (73%) and 8 of the 232 AD patients (3.4%). Cognitive fluctuation was positive in 13 of the 15 DLB patients (87%). We found two types of episodic cognitive deterioration: one was characterized by pronounced disturbances of attention and alertness (inattention type), and the other was characterized by marked and bizarre disturbances of orientation in time and places, and misidentification of persons (disorientation type). Systematized delusion was observed in 8 DLB patients, and 5 patients showed neuroleptic sensitivity. Patients with DLB have a unique dementia syndrome even in the stage of mild to moderate cognitive impairments. Further studies are recommended to establish diagnosis, treatment and management.

Background Dementia with Lewy bodies (DLB) is emerging as a common cause of degenerative dementia. Some preliminary evidence exists that the pattern of cognitive impairment in DLB is different from that in Alzheimer disease (AD). Objective To delineate features of cognitive impairment of DLB on standardized neuropsychological tests. Methods We performed neuropsychological assessments of 26 patients with probable DLB (based on criteria of the consortium on DLB international workshop) and of 52 patients with probable AD (based on criteria of the National Institute of Neurological and Communicative Disorders and Stroke [now the National Institute of Neurological Disorders and Stroke])–Alzheimer's Disease and Related Disorders Association) who were matched to the patients with DLB 2:1 by age, sex, education, and Mini-Mental State Examination score. Results Compared with the group with probable AD, the group with probable DLB scored significantly lower on the picture arrangement, block design, object assembly, and digit symbol substitution subtests of the Wechsler Adult Intelligence Scale–Revised and on the Raven Colored Progressive Matrices test and significantly higher on the Mini-Mental State Examination locational orientation subtest and the Alzheimer's Disease Assessment Scale word recall subtest. A discriminant analysis revealed that the word recall score on the Alzheimer's Disease Assessment Scale and the block design score on the Wechsler Adult Intelligence Scale–Revised were the best discriminant factors. Conclusions The disproportionately severe visuoperceptual, visuoconstructive, and visuospatial dysfunction and the disproportionately mild memory impairment in DLB compared with AD, which likely reflect the distribution of the pathologic changes in DLB, can help to differentiate DLB from AD.

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 Raven's 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.

Objective: Dementia with Lewy bodies (DLB) is emerging as a common cause of degenerative dementia. A recent pathologic study has indicated that the medial temporal lobe in patients with DLB was less atrophic than that in patients with AD. The purpose of this study was to examine whether medial temporal MRI volumetry was useful to differentiate DLB from AD clinically.Methods: We compared the volumes of the hippocampal formation, amygdaloid complex, and whole brain in 27 patients with probable DLB (based on the criteria of the Consortium on DLB International Workshop), 27 patients with probable AD(based on criteria of the National Institute of Neurological Disease and Stroke/Alzheimer's Disease and Related Disorders Association), and 27 normal elderly subjects using an MRI-based volumetric technique. The three groups were matched for age and sex. Severity of cognitive disturbances represented by their Mini-Mental State Examination score was comparable between the DLB and AD groups.Results: Hippocampal volume (normalized to intracranial volume) in the DLB group was significantly larger than that in the AD group, but significantly smaller than that in the normal control group. There were no significant differences in the amygdala and whole-brain volume between the DLB group and the AD group, but the atrophies of the amygdala and whole brain were more severe in the DLB group than those in the control group.Conclusions: These findings indicate the usefulness of MRI hippocampal volumetry in clinically discriminating patients with DLB from patients with AD.

To determine the features of cortical atrophy in frontotemporal dementia (FTD) and Alzheimer disease by using a hemispheric surface display generated with magnetic resonance (MR) images.The extent of cortical atrophy was evaluated with automated MR hemispheric surface display and volumetry in 18 patients with FTD and in 18 matched patients with Alzheimer disease. Results were compared with those in 18 healthy, matched control subjects.Most cortical regions were significantly atrophic in FTD and Alzheimer disease. The frontal and anterior temporal lobes were significantly more atrophic in FTD than in Alzheimer disease. The mean hemispheric-to-intracranial volume ratio in patients with FTD (56.2%) and those with Alzheimer disease (58.4%) was significantly smaller than the ratio in the control subjects (66.0%). Asymmetry of hemispheric volume was significantly larger in the FTD group than in the Alzheimer disease and control groups.Cortical atrophy in FTD is more widespread than was previously thought. Asymmetric frontal and anterior temporal atrophy is a distinctive feature of FTD and distinguishes it from Alzheimer disease. Hemispheric surface display is a useful complement to tomographic images and is useful for the evaluation of focal cortical atrophy in degenerative dementias, especially FTD.