Kazumi Ota

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.

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 [123I]‐metaiodobenzylguanidine levels. Moreover, [18F]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 follow up study of non-demented patients with primary visual cortical hypometabolism: Prodromal dementia with Lewy bodies

We previously reported non-demented patients with glucose hypometabolism in the primary visual cortex (PVC), which is the preferentially affected region in patients with dementia with Lewy bodies (DLB). It remains unknown, however, whether these patients represent a prodromal DLB state. Eleven non-demented patients who attended our memory clinic for more than three years (mean follow-up period: 44 ± 5 months) were examined. All the patients had glucose hypometabolism in the PVC on [(18)F]-fluoro-d-glucose (FDG) positron emission tomography (PET) scans at baseline. Four patients, including one with a clinical history of occipital bleeding, exhibited no core or suggestive features of DLB. Seven patients reported recurrent nocturnal dream-enactment behavior, which is consistent with probable rapid eye movement (REM) sleep behavior disorder (RBD). The condition of the patient with occipital bleeding was stable, which is consistent with an underlying non-neurodegenerative disorder. Of the remaining 10 patients, 5 had stable cognitive conditions (non-converters) and 5 exhibited progression to dementia (converters). The clinical diagnoses of 4 patients with probable RBD were changed to probable DLB. Despite no differences in psychological profiles at baseline between non-converters and converters, the initial pattern of cortical metabolism differed: converters had lower glucose hypometabolism in the parietal and the lateral occipital cortex compared to non-converters. The metabolic reduction in the PVC is present in patients with prodromal DLB. Moreover, the spatial profiles of reduced glucose metabolism at baseline could help to define the distinct prognostic subgroup that has a greater risk of conversion to DLB.

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

Although metabolic reduction in the primary visual cortex on [18F]‐fluoro‐d‐glucose (FDG) positron emission tomographic (PET) scans is the hallmark of dementia with Lewy bodies (DLB) for differential diagnosis from Alzheimers 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.

Detection of early amnestic mild cognitive impairment without significantly objective memory impairment : a case-controlled study

Background:  We encountered eight early amnestic mild cognitive impairment (aMCI) patients (early MCI group) who did not fulfill the diagnostic criteria for aMCI. We compared the scores of neuropsychological examinations as well as the cerebral metabolic rate for glucose consumption (CMRglc) decrease on 18F‐FDG PET examination between the early MCI group and 10 aMCI patients (MCI group) or six normal elderly subjects (normal group), to examine whether the current diagnostic criteria can detect early‐stage aMCI.

ORIGINAL ARTICLE: Detection of early amnestic mild cognitive impairment without significantly objective memory impairment: a case-controlled study

Background:  We encountered eight early amnestic mild cognitive impairment (aMCI) patients (early MCI group) who did not fulfill the diagnostic criteria for aMCI. We compared the scores of neuropsychological examinations as well as the cerebral metabolic rate for glucose consumption (CMRglc) decrease on 18F‐FDG PET examination between the early MCI group and 10 aMCI patients (MCI group) or six normal elderly subjects (normal group), to examine whether the current diagnostic criteria can detect early‐stage aMCI.

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

It is well known that Alzheimers 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 [18F]fluoro‐d‐glucose (18F‐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.

Neuropsychological Detection of the Early Stage of Amnestic Mild Cognitive Impairment without Objective Memory Impairment

Aim: We investigate the assessment method to detect the early stage of amnestic mild cognitive impairment (aMCI) using Wechsler Memory Scale – Revised (WMS-R) and Wechsler Adult Intelligence Scale – Third Edition (WAIS-III). Methods: Three groups (normal group, aMCI group, and early aMCI group), controlled for age and years of education, underwent brain 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET), WAIS-III, WMS-R, and other tests. The early aMCI group does not fulfill the clinical diagnostic criteria of aMCI because patients do not have objective memory impairment, but their clinical symptoms and results of 18F-FDG PET indicate that they should be included in the category of aMCI. Results: The discrepancy of scores between Verbal IQ and General Memory had the highest accuracy in discriminating between normal and early aMCI groups. Conclusion: The cutoff point determined in this study is useful to detect an early stage of aMCI, which may be distinguished from aMCI using the current criteria.

Visuoperceptual Assessments for Differentiating Dementia with Lewy Bodies and Alzheimer's Disease: Illusory Contours and Other Neuropsychological Examinations

We examined the utility of illusory contours (ICs) for the differentiation of dementia with Lewy bodies (DLB) from Alzheimers disease (AD). Thirty-five probable DLB patients, 35 probable AD patients controlled by age, years of education, and Mini-Mental State Examination (MMSE) score, and 30 cognitively normal subjects controlled by age and years of education underwent visuoperceptual examinations including ICs, pentagon copying in MMSE, overlapping figures, clock drawing test, cube copying, and line orientation. Four items in ICs (ICs-4) were found to be significantly impaired in DLB compared with AD, and a sensitivity and a specificity of total score of ICs-4 were 88.6% and 37.1%, respectively. When a score of ICs-4 is combined with a 10-point scaled score of pentagon copying in MMSE, a sensitivity and a specificity were 77.1% and 82.9%, respectively. The present study suggests that ICs-4 can be included in neuropsychological examinations to assess visuoperceptual impairment in DLB.

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

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.