Efficacy and safety of donepezil in patients with dementia with Lewy bodies: results from a 12-week multicentre, randomised, double-blind, and placebo-controlled phase IV study.

BACKGROUND: Donepezil has been approved in Japan for the treatment of dementia with Lewy bodies (DLB) based on clinical trials showing its beneficial effects on cognitive impairment. This phase IV study evaluated the efficacy of donepezil by focusing on global clinical status during a 12-week double-blind phase. METHODS: Patients with probable DLB were randomly assigned to the placebo (n = 79) or 10 mg donepezil (n = 81) groups. The primary endpoint was changes in global clinical status, assessed using the Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus). We also assessed four CIBIC-plus domains (general condition, cognitive function, behaviour, and activities of daily living) and changes in cognitive impairment and behavioural and neuropsychiatric symptoms measured using the Mini-Mental State Examination (MMSE) and the Neuropsychiatric Inventory (NPI), respectively. RESULTS: Although donepezil's superiority was not shown in the global clinical status, a significant favourable effect was detected in the cognitive domain (P = 0.006). MMSE scores improved in the donepezil group after adjustments in post hoc analysis (MMSE mean difference, 1.4 (95% confidence interval (CI), 0.42-2.30), P = 0.004). Improvements in NPIs were similar between the groups (NPI-2: -0.2 (95% CI, -1.48 to 1.01), P = 0.710; NPI-10: 0.1 (95% CI, -3.28 to 3.55), P = 0.937). CONCLUSION: The results support the observation that the efficacy of 10 mg donepezil in improving cognitive function is clinically meaningful in DLB patients. The evaluation of global clinical status might be affected by mild to moderate DLB patients enrolled in this study. No new safety concerns were detected.

Evaluating depression in cognitively healthy elderly people by using Mini-Mental State Examination.

AIM: We examined a method for evaluating depression with the Mini-Mental State Examination in cognitively healthy elderly people and employed the projective perspective. METHODS: In MMSE three groups-normal, depressed tendency, and depressed-completed the Mini-Mental State Examination (MMSE) and a Japanese version of the 15-item Geriatric Depression Scale. The Mini-Mental State Examination evaluated individuals' writing based on a sentence, the number of written words, and sentence content; it also assessed their copying of drawn figures. RESULTS: In the depressed group, the proportion corresponding to the characteristics of (i) to (iii) was higher than in the other two groups: (i) the calculation score was 0 or 1; (ii) subjects scored above the median in sentence writing relative to similar subjects with the same language and clinical setting; and (iii) subjects expressed feelings in their writing. One point was given for each characteristic, and we calculated the sum. Depressed subjects had a score ≥2. CONCLUSIONS: This evaluation method can differentiate depressed subjects with high accuracy (sensitivity: 77.8%, specificity: 76.4%) without placing an extra burden on the subjects.

123I-MIBG myocardial scintigraphy for the diagnosis of DLB: a multicentre 3-year follow-up study.

BACKGROUND AND PURPOSE: We previously reported the usefulness of iodine-123 metaiodobenzylguanidine (123I-MIBG) myocardial scintigraphy for differentiation of dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) in a cross-sectional multicentre study. The aim of this study was, by using reassessed diagnosis after 3-year follow-up, to evaluate the diagnostic accuracy of 123I-MIBG scintigraphy in differentiation of probable DLB from probable AD. METHODS: We undertook 3-year follow-up of 133 patients with probable or possible DLB or probable AD who had undergone 123I-MIBG myocardial scintigraphy at baseline. An independent consensus panel made final diagnosis at 3-year follow-up. Based on the final diagnosis, we re-evaluated the diagnostic accuracy of 123I-MIBG scintigraphy performed at baseline. RESULTS: Sixty-five patients completed 3-year follow-up assessment. The final diagnoses were probable DLB (n=30), possible DLB (n=3) and probably AD (n=31), and depression (n=1). With a receiver operating characteristic curve analysis of heart-to-mediastinum (H/M) ratios for differentiating probable DLB from probable AD, the sensitivity/specificity were 0.77/0.94 for early images using 2.51 as the threshold of early H/M ratio, and 0.77/0.97 for delayed images using 2.20 as the threshold of delayed H/M ratio. Five of six patients who were diagnosed with possible DLB at baseline and with probable DLB at follow-up had low H/M ratio at baseline. CONCLUSIONS: Our follow-up study confirmed high correlation between abnormal cardiac sympathetic activity evaluated with 123I-MIBG myocardial scintigraphy at baseline and the clinical diagnosis of probable DLB at 3-year follow-up. Its diagnostic usefulness in early stage of DLB was suggested. TRIAL REGISTRATION NUMBER: UMIN00003419.

123I-FP-CIT SPECT findings and its clinical relevance in prodromal dementia with Lewy bodies.

PURPOSE: Evidence for the prodromal stage of dementia with Lewy bodies (DLB) is very limited. To address this issue, we investigate the 123I-FP-CIT SPECT measure of dopamine transporter binding finding and its clinical relevance. METHODS: We enrolled subjects into a prodromal DLB group (PRD-DLB) (n = 20) and clinical DLB group (CLIN-DLB) (n = 18) and compared these groups with an Alzheimer's disease control group (AD) (n = 10). PRD-DLB was defined as patients having the non-motor symptoms associated with Lewy body disease (LBD) [i.e. REM sleep behavior disorder (RBD), olfactory dysfunction, autonomic dysfunction, and depression] and showing characteristic diffuse occipital hypometabolism in 18F-FDG PET. CLIN-DLB was defined as patients fulfilling the established criteria of probable DLB. Striatal specific binding ratio (SBR) of 123I-FP-CIT SPECT was used for objective group comparisons. The correlations between SBR and cognitive function (MMSE), motor symptoms (UPDRS3), and duration of LBD-associated non-motor symptoms were compared between the two DLB groups. RESULTS: Mean SBR scores of both PRD-DLB and CLIN-DLB were significantly lower than those of AD. No correlation was found between SBR and MMSE scores. Both in the CLIN-DLB and total DLB groups, SBR scores were negatively correlated with UPDRS3 scores, whereas no correlation was found in PRD-DLB. Among the LBD-related non-motor symptoms, duration of olfactory dysfunction, and RBD demonstrated negative correlation with SBR scores in PRD-DLB. CONCLUSION: 123I-FP-CIT SPECT may play a role for detecting DLB among the subjects in prodromal stage. During this stage, long-term olfactory dysfunction and/or RBD may indicate more severe degeneration of the nigro-striatal dopaminergic pathway.

Adequacy of Using Consensus Guidelines for Diagnosis of Dementia with Lewy Bodies in Clinical Trials for Drug Development.

BACKGROUND/AIMS: To evaluate the adequacy of using the consensus diagnostic criteria for dementia with Lewy bodies (DLB) to recruit patients with homogeneous characteristics in future clinical trials, where multiple departments of multinational centres are expected to participate with a long enrolment period, and additionally, to contribute to the possible future criteria revision. METHODS: Using data from 2 trials of donepezil for DLB, conducted 3 years apart, characteristics in patients with probable DLB were analysed and compared between studies and between psychiatric and neurological centres. RESULTS: In 273 patients (phase II: 135, phase III: 138; psychiatric: 73, neurological: 184), clinical characteristics overall were very similar between studies, and between specialty centres, excluding distinctive parkinsonism in the neurological versus psychiatric centres: incidence of parkinsonism (91.8 vs. 71.2%, p < 0.001), Hoehn and Yahr stage (III: 55.0 vs. 21.2%, p < 0.001), and concomitant anti-Parkinson medication (24.5 vs. 11.0%, p = 0.017). Rapid eye movement sleep behaviour disorder, depression, and delusion, suggestive or supportive features, were observed in 35-40%. Additionally, a high prevalence (55.3%) of anxiety was observed. CONCLUSION: Employing the consensus criteria is adequate to enrol homogeneous DLB patients into future clinical trials regardless of the specialty of centres and time. Further discussion could involve adding anxiety to future criteria.

Cognitive dysfunction in patients with very mild Alzheimer's disease and amnestic mild cognitive impairment showing hemispheric asymmetries of hypometabolism on ¹8F-FDG PET.

OBJECTIVE: We investigated cognitive dysfunction in patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) who present hemispheric asymmetries of cerebral metabolic rate of glucose (CMRglc) decrease on (18) F-fluorodeoxyglucose positron emission tomography. METHODS: Based on the hemispheric asymmetries of CMRglc decrease in the posterior cingulate cortex, precuneus, and parietotemporal cortex, the patients were divided into three groups (a left-dominant hypometabolism group, a right-dominant hypometabolism group, and a non-dominant hypometabolism group). CMRglc decrease in the whole brain was controlled among the three groups. All the patients underwent mini-mental state examination (MMSE), Wechsler Memory Scale-Revised (WMS-R), and Wechsler Adult Intelligent Scale-Third (WAIS-III). RESULTS: There were no significant differences in MMSE and WAIS-III scores among the three groups. In WMS-R, the results indicated that the left-dominant group demonstrated significantly lower scores in verbal memory than the other two groups. Furthermore, the left-dominant group had a greater tendency to be diagnosed with AD rather than aMCI. CONCLUSIONS: Patients with AD and aMCI showing left-dominant hypometabolism tend to show severer impairment in verbal memory function and to be diagnosed with AD dementia.

Characteristics of depression in community-dwelling elderly people as indicated by the tree-drawing test.

BACKGROUND: The tree-drawing test (TDT) is a typical projective method, but previous studies have paid little attention to it for elderly people. We investigated the characteristics of depression in community-dwelling elderly people as indicated by the TDT. METHODS: This study was a complete enumeration survey of elderly people conducted through home visits. The contents of the survey included gender, age, presence or absence of housemates, frequency of going out, the 15-item Geriatric Depression Scale, and TDT. The subjects were divided into three groups (normal, depressed tendency, and depressed) according to the total 15-item Geriatric Depression Scale score. RESULTS: In TDT, no significant difference was observed in drooping crown, shadow of the whole tree, or shadow near the base, which have been regarded as indices of depression in younger people. However, the values concerning the size of the tree, such as the height and width of the whole tree, height and width of the crown, and number of occupied areas (of the paper), were significantly lower in the depressed group than in the other groups. In addition, the width of the trunk was significantly smaller in the depressed group than in the normal group. Subjects were classified as being in a 'depressed state' if they used 40 or fewer areas for drawing (i.e. occupied areas) and a 'non-depressed state' if they used 41 or more areas. This enabled depression to be detected (sensitivity: 71.4%; specificity: 79.9%). CONCLUSIONS: The size of the tree in TDT is suggested to reflect characteristics of depression in elderly people, such as introversion, reserve, antisocial attitude, a feeling of inferiority, weakness of ego, and lack of vigour. Furthermore, the numbers of occupied areas were found to be relatively useful in detecting depression in elderly people.

Clinical profiles of dementia with Lewy bodies with and without Alzheimer's disease-like hypometabolism.

OBJECTIVES: It is well known that Alzheimer's disease (AD)-type pathology is commonly present in dementia with Lewy bodies (DLB) brains and that the degree of AD-type pathology has an influence on the clinical characteristics of DLB. Although significant hypometabolism in the temporoparietal/precuneus on [(18)F]fluoro-d-glucose ((18)F-FDG) positron emission tomography (PET) scans is considered to support a diagnosis of AD, some DLB patients also exhibit this metabolic pattern. The clinical significance of the metabolic pattern on DLB remains unknown. METHODS: Twenty-three DLB patients, 10 AD patients, and 11 controls underwent (18)F-FDG PET scans. According to the degree of hypometabolism in the parietal/precuneus regions, representing the AD-like metabolic pattern, 12 patients were placed in the DLB-AD(+) group and 11 patients were placed in the DLB-AD(-) group. The demographics and clinical variables were compared among the four groups. RESULTS: In addition to the parietal/precuneus regions, the DLB-AD(+) group exhibited significantly greater posterior cingulate hypometabolism than the DLB-AD(-) group, although occipital metabolism did not differ. The prevalence of visual hallucinations and extracampine hallucinations, and the Bender-Gestalt test score were significantly higher in the DLB-AD(+) group than the DLB-AD(-) group, although there were no differences in the demographics and other examined clinical variables between the two DLB groups. These clinical differences were absent in the DLB-AD(-) group, AD group, and controls. CONCLUSIONS: Parietal/precuneus hypometabolism may be associated with clinical characteristics in DLB patients. Further multiple imaging modalities that are sensitive to AD-type pathology are needed to reveal the neurobiological basis of the AD-like metabolic pattern.

An autopsied case of corticobasal degeneration showing severe cerebral atrophy over a protracted disease course of 16 years.

The patient was a 72-year-old Japanese woman. At the age of 57, she started having difficulty performing daily work and developed agraphia. She also exhibited restlessness and loss of interest, and began to speak less. Thereafter, stereotypical behavior, gait disturbance and dysphagia were noted. CT scan demonstrated left-dominant frontal and temporal lobe atrophy. She died at the age of 72, about 16 years after the onset of symptoms. Neuropathologically, the brain weighed 867 g, and showed remarkable cerebral atrophy with degeneration of the white matter, predominantly in the left dorsal frontal lobe and anterior temporal lobe. Microscopically, severe neuronal loss and gliosis with rarefaction were found in the cerebral cortex, and severe destruction of myelin and axons was observed in the cerebral white matter. Moderate neuronal loss with gliosis was also found in the pallidum and substantia nigra. Gallyas-Braak staining and tau immunostaining revealed pretangle neurons, NFTs, ballooned neurons and astrocytic plaques in the cerebral cortex, subcortical nuclei and brainstem, and argyrophilic threads and coiled bodies in the subcortical white matter. Tau isoform-specific immunostaining revealed that most tau-immunoreactive structures were positive for 4-repeat (4R) tau, but some of the NFTs were positive for 3-repeat (3R) tau in the cerebral neocortex. Immunoblotting demonstrated an accumulation of 4R tau in the cerebral cortex and subcortical white matter. The patient was pathologically diagnosed as having corticobasal degeneration. Her long survival course likely accounts for the severe white matter degeneration and accumulation of 3R tau in NFTs.

[Assessment of Inspection Technology of Dopamine Transporter Imaging with ¹²³I-Ioflupane].

Imaging start time of single-photon emission computed tomography (SPECT) scan is recommended between 3 hours and 6 hours after injection of ¹²³I-ioflupane in Ioflupane clinical practice guidelines. But image includes the effect of physiological actions of the human body and the attenuation at 13.27 hours physical half-life of ¹²³I. Therefore, we evaluated the effect of the image by the elapsed time of imaging start time. Optimal cut-off frequency of Butterworth filter were examined phantom by normalized mean square error. Count was reduced by 23.1% in 5 hours, but cut-off frequency of Butterworth filter was 0.11 cycle/pixel in 0-5 hours from phantom data. Ten subjects (age 55-85 years) were injected with ¹²³I-ioflupane of 110-199 MBq into the vein only once. And we examined the specific binding ratio (SBR) in inspection of injection after 5. 5 hours and 3 hours. Decrease of counts value increased the coefficient of variance (CV) between 3 hours and 5.5 hours after injection, but the improvement of statistical noise by pre-processing filter reduced the CV. No significant difference in the result of SBR was found between 3 hours and 5. 5 hours after injection. Our results suggest that imaging start time of SPECT scan is recommended between 3 hours and 5.5 hours after injection of ¹²³I-ioflupane.

Primary visual cortical metabolism and rapid eye movement sleep behavior disorder in dementia with Lewy bodies.

AIM: Significant glucose hypometabolism in the primary visual cortex (PVC) is considered to support a diagnosis of dementia with Lewy bodies (DLB), but its relationship to the clinical features remains unknown. The purpose of this study was to assess the association between the metabolic pattern and clinical variables in DLB. METHODS: A total of 27 DLB patients who underwent [18F]fluoro-d-glucose (18F-FDG) positron emission tomography scans were examined. Demographics and clinical variables were compared between patients with and without glucose hypometabolism in the PVC. The correlations between the cerebral metabolic rate of glucose in the PVC and clinical variables were also investigated. RESULTS: Only the onset age of probable rapid eye movement sleep behavior disorder (RBD) was significantly different between patients with and withoutglucose hypometabolism in the PVC, being younger in patients with the metabolic pattern; there were no other differences in clinical variables. The onset age of probable RBD was significantly correlated with the cerebral metabolic rate of glucose in the PVC. CONCLUSIONS: Glucose hypometabolism in the PVC provides a potential mechanism for the link between antecedent RBD and the subsequent development of dementia in DLB patients. Glucose hypometabolism in the PVC may represent the effect of the pathophysiological process of DLB on RBD rather than a distinct condition in the disease progression. The physiological aspects of the link between this metabolic pattern and the onset of RBD remain unclear.

Three presenile patients in which neuropsychological and neuroimaging examinations suggest possible progression to dementia with Lewy bodies.

We report three presenile patients who were initially suspected of having Alzheimer's disease (AD) or being in the prodromal stage of AD, regardless of visuoperceptual dysfunctions in daily living, because they lacked the core features and prodromal non-motor symptoms of dementia with Lewy bodies. Subsequently, progression to dementia with Lewy bodies was suspected based on neuropsychological and neuroimaging findings; additionally, one of the three patients suffered from visual hallucinations. Neuropsychological examinations such as subjective contours, cube copying and block design in the Wechsler Adult Intelligence Scale-III revealed visuoperceptual dysfunction in all three patients even when other cognitive functions were rather preserved. Brain magnetic resonance imaging revealed no significant brain atrophy, including in the parieto-occipital area and the hippocampus, while brain (18)F-fluorodeoxyglucose positron emission tomography demonstrated right dominant metabolic reductions in the occipital lobe, including the primary visual cortex, in all three patients. We suggest the possibility of progression to dementia with Lewy bodies, but not AD or posterior cortical atrophy. Regardless of the presence of core features and prodromal non-motor symptoms, this progression is suggested when there are difficulties only in higher-level visual processing such as subjective contours and block design in the Wechsler Adult Intelligence Scale-III, no significant atrophy of the parieto-occipital area and hippocampus on brain magnetic resonance imaging, and hypometabolism in the occipital lobe including the primary visual cortex on brain (18)F-fluorodeoxyglucose positron emission tomography.

Autopsy case of concurrent Huntington's disease and neurofibromatosis type 1.

We report here an autopsy case of concurrent Huntington's disease (HD) and neurofibromatosis type 1 (NF1), also known as von Recklinghausen's disease. The patient was a Japanese woman with a significant hereditary burden: seven of her family members within four generations were affected by either NF1 or concurrent HD and NF1. She was diagnosed as having NF1 at age 24. At age 40, she showed signs of irritability, aggressive and childish behaviour, which became progressively worse. At age 48, rigidity and spastic gait were observed. One year later, choreoathetoid involuntary movements became apparent. Diagnosis of HD was made by identification of the abnormally expanded cytosine-adenine-guanine repeats in the Huntington's disease gene. Her condition deteriorated gradually to an apallic state and she died at age 60. Post-mortem examination revealed extensive brain atrophy, which was particularly severe in the frontal and temporal cortices and the striatum. The degree of neurodegenerative change seemed to correspond to grade IV. Polyglutamine positive inclusions were seen frequently in all layers of the cerebral cortex and in the amygdala and hippocampus. Inclusions were also present in the striatum, but there were fewer than in the cortex. Remarkably, neuronal intranuclear inclusions were present in the cerebellum, although they are usually not seen in HD. Features associated with the central nervous system involvement of NF1 were not found in the brain, but HD pathology might have been accelerated by the concurrence of NF1. This is the third report of a case with concurrent HD and NF1 in the world, and the first study in which occurrence of polyglutamine inclusions was confirmed on post-mortem examination.

Long-term safety and efficacy of donepezil in patients with dementia with Lewy bodies: results from a 52-week, open-label, multicenter extension study.

BACKGROUND/AIMS: To investigate the safety and efficacy of long-term administration (52 weeks) of donepezil in patients with dementia with Lewy bodies (DLB). METHODS: This was a 52-week, multicenter, open-label extension study. Up to 8 weeks after the completion of the preceding randomized, placebo-controlled trial (RCT), patients started treatment with 3 mg of donepezil daily for 2 weeks, followed by 5 mg daily for the remaining 50 weeks. Cognitive function, behavioral and psychiatric symptoms, cognitive fluctuations, and caregiver burden were assessed using the Mini-Mental State Examination, Neuropsychiatric Inventory, Cognitive Fluctuation Inventory, and the Zarit Caregiver Burden Interview, respectively. Safety parameters were monitored throughout. RESULTS: In total, 108 patients were enrolled in the study. Cognitive function and dementia-related behavioral symptoms, including cognitive fluctuations, were improved after the start of donepezil treatment, and improvement was maintained for 52 weeks. Reduction in caregiver burden observed in the preceding RCT returned to the baseline level at 52 weeks. There was no significant imbalance in the incidence of adverse events (AEs) by onset time, and delayed AE onset induced by the long-term administration of donepezil was unlikely to appear. CONCLUSION: The long-term administration of donepezil at 5 mg/day was well tolerated in patients with DLB and is expected to exhibit lasting effects, improving impaired cognitive function and psychiatric symptoms up to 52 weeks.

Three patients with mood disorders showing catatonia and frontotemporal lobes atrophy.

Here we report the cases of three patients with mood disorders showing catatonia and frontotemporal lobe atrophy. Catatonia is a syndrome linked to frontal dysfunction that most frequently occurs in patients with mood disorders. The diagnostic criteria of catatonia and frontotemporal dementia partly overlap. In the present patients, catatonia might be closely related to frontal dysfunction caused by frontotemporal lobe atrophy. With regard to therapeutics for catatonia, we found that administering a low dose of lorazepam alone or after electroconvulsive therapy may be useful for treating and preventing catatonia. We also found that administering glutaminate antagonists such as memantine may be useful for treating lorazepam-resistant catatonia.

Intelligence or years of education: which is better correlated with memory function in normal elderly Japanese subjects?

BACKGROUND: We compared differences in intelligence and memory function between normal elderly Japanese subjects with more years of education and those with fewer years of education. We also investigated clinical and neuropsychological factors that are strongly correlated with memory function. METHODS: There were 118 normal elderly subjects who underwent the Mini-Mental State Examination, Wechsler Adult Intelligence Scale, 3rd edition (WAIS-III), and Wechsler Memory Scale Revised. Subjects with at least 13 years of education were categorized as the H group, and those with 12 years of education or less were categorized as the L group. RESULTS: Age and Mini-Mental State Examination scores were not significantly different between the two groups. On the WAIS-III, there were significant differences between the two groups in Verbal IQ and Full Scale IQ. On the Wechsler Memory Scale Revised, there were significant differences between the two groups in Visual Memory, General Memory, and Delayed Recall. Correlation coefficients between memory function and the other factors demonstrated significant but weak correlations between years of education and General Memory (R = 0.22) and between years of education and Delayed Recall (R = 0.20). Strong correlations were found between Verbal IQ and Verbal Memory (R = 0.45), between Verbal IQ and General Memory (R = 0.49), between Full Scale IQ and General Memory (R = 0.50) and between Full Scale IQ and Delayed Recall (R = 0.48). CONCLUSIONS: In normal elderly Japanese subjects, years of education weakly correlated with memory function while Verbal IQ, Full Scale IQ and Verbal Comprehension on WAIS-III had stronger correlations with memory function. Verbal IQ and Verbal Comprehension on WAIS-III were found to be insusceptible to the cognitive decline characteristic of Alzheimer's disease or amnestic mild cognitive impairment. Therefore, verbal intelligence, as measured by Verbal IQ and Verbal Comprehension, may be the most useful factor for inferring premorbid memory function in Alzheimer's disease or amnestic mild cognitive impairment patients.

Dementia with Lewy bodies: early diagnostic challenges.

Dementia with Lewy bodies (DLB) is defined pathologically as neurodegeneration associated with Lewy bodies (LB). LB-related symptoms, including olfactory dysfunction, dysautonomia, and mood and sleep disorders, are increasingly recognized as clinical signs that enable the early detection of DLB, because these symptoms often antedate dementia by years or even decades. It remains unknown if the clinical history of LB-related symptoms is sufficient for the prodromal state of DLB to be suspected in memory clinics. We retrospectively investigated the clinical courses, including olfactory dysfunction, dysautonomia, depression, and rapid eye movement sleep behaviour disorder, of 90 patients with probable DLB. The timing of LB-related symptoms that preceded or followed relative to the onset of memory loss was calculated. LB-related symptoms were present in 79 of 90 patients (87.8%) with probable DLB before or at the time of memory loss onset. These symptoms preceded the onset of memory loss between 1.2 and 9.3 years. We also report on four non-demented patients with a clinical history of LB-related symptoms in our memory clinic. All four patients showed reduced cardiac [(123) I]-metaiodobenzylguanidine levels. Moreover, [(18) F]fluoro-D-glucose positron emission tomography scans revealed glucose hypometabolism in the occipital cortex in two patients. One patient converted to probable DLB with the development of parkinsonism 2 years after major depression was diagnosed. Based on a clinical history of LB-related symptoms, we propose a conceptual framework to identify these symptomatic but non-demented individuals that led us to suspect the underlying pathophysiology of Lewy body disease. Further prospective study is warranted to determine the clinical significance of LB-related symptoms in non-demented patients.

A simple method to evaluate the pentagon copy test of the Mini-Mental State Examination for the differentiation of dementia with Lewy bodies.

There are many commonalities between the clinical symptoms of dementia with Lewy bodies (DLB) and those of Alzheimer's disease (AD). The accurate differentiation of these two diseases is an important neuropsychological issue. The Mini-Mental State Examination (MMSE) is often used as a screening test for dementing disorders. We created evaluation items for the pentagon copy test of MMSE and developed a simple, highly accurate evaluation method for differentiating DLB in combination with conventional evaluation items such as the Qualitative Scoring MMSE Pentagon Test (QSPT). Subjects were divided into three groups: DLB (n = 119), AD (n = 50), and Normal (n = 26). The severities of DLB and AD ranged from mild cognitive impairment (MCI) to mild dementia. We compared the results of the pentagon copy test. We found that the rates of patients with abnormalities in "motor incoordination" and "gestalt destruction" were higher in the DLB group than the AD group. Furthermore, receiver operating characteristic curve analysis suggested the differentiation of DLB with high accuracy (sensitivity: 0.70, specificity: 0.78) using the criterion of patients meeting one of the following three characteristics: "the number of angles on QSPT: scores other than 4," "major tremor (Parkinsonism-related tremor) is present," and "gestalt destruction (distortion in overall coherence) is present." This evaluation method may be clinically useful for evaluating MCI to mild DLB patients because the burden on patients is low.

Retrospective survey of prodromal symptoms in dementia with Lewy bodies: comparison with Alzheimer's disease.

BACKGROUND: Non-motor symptoms are recognized to enable the early detection of Parkinson's disease (PD). It remains unknown when those symptoms appear in dementia with Lewy bodies (DLB). METHOD: We investigated the prevalence of 15 non-motor symptoms of PD at the onset of memory loss based on a standardized worksheet in 34 patients with DLB, 32 patients with Alzheimer's disease (AD) and 30 normal controls. RESULTS: DLB patients exhibited a significantly higher prevalence of olfactory dysfunction, constipation, increased saliva and signs of rapid eye movement sleep behavior disorder at the onset of memory loss than AD patients and normal controls. CONCLUSIONS: Paying attention to non-motor symptoms of PD may help DLB diagnosis in the early stage, especially in terms of its differentiation from AD.

Glucose hypometabolism in primary visual cortex is commonly associated with clinical features of dementia with Lewy bodies regardless of cognitive conditions.

BACKGROUND: Although metabolic reduction in the primary visual cortex on [(18) F]-fluoro-d-glucose (FDG) positron emission tomographic (PET) scans is the hallmark of dementia with Lewy bodies (DLB) for differential diagnosis from Alzheimer's disease, the clinical significance of the metabolic pattern in patients without dementia remains unknown. The purpose of this study was to investigate the clinical profiles of patients without dementia with the metabolic pattern and its relevance to DLB. METHODS: Of 145 individuals who underwent (18) F-FDG PET, 25 patients with glucose hypometabolism in the primary visual cortex were identified based on three-dimensional stereotactic surface projection images through comparison with a normative database. The frequency of core and suggestive clinical features of DLB was compared between the groups with and without the metabolic pattern. RESULTS: Of 25 patients with glucose hypometabolism in the primary visual cortex, 12 exhibited more than two core features of DLB (probable DLB group) and 6 had rapid eye movement sleep behavior disorder (possible DLB group). Three patients exhibited memory loss without any core or suggestive features but with reduced cardiac iodine-123 metaiodobenzylguanidine uptake. Ten of these 21 patients exhibited no dementia. The proportion of individuals in the probable and possible DLB groups was significantly higher in the group with glucose hypometabolism in the primary visual cortex. CONCLUSION: Glucose hypometabolism in the primary visual cortex is commonly associated with the clinical features of DLB regardless of cognitive conditions. Continued follow-up of these patients without dementia with the metabolic pattern is warranted to determine if they represent the prodromal state of DLB.