Osamu Iizuka

Diagnostic accuracy of 123I-meta-iodobenzylguanidine myocardial scintigraphy in dementia with Lewy bodies: a multicenter study.

Background and Purpose Dementia with Lewy bodies (DLB) needs to be distinguished from Alzheimer’s disease (AD) because of important differences in patient management and outcome. Severe cardiac sympathetic degeneration occurs in DLB, but not in AD, offering a potential system for a biological diagnostic marker. The primary aim of this study was to investigate the diagnostic accuracy, in the ante-mortem differentiation of probable DLB from probable AD, of cardiac imaging with the ligand 123I-meta-iodobenzylguanidine (MIBG) which binds to the noradrenaline reuptake site, in the first multicenter study. Methods We performed a multicenter study in which we used 123I-MIBG scans to assess 133 patients with clinical diagnoses of probable (n = 61) or possible (n = 26) DLB or probable AD (n = 46) established by a consensus panel. Three readers, unaware of the clinical diagnosis, classified the images as either normal or abnormal by visual inspection. The heart-to-mediastinum ratios of 123I-MIBG uptake were also calculated using an automated region-of-interest based system. Results Using the heart-to-mediastinum ratio calculated with the automated system, the sensitivity was 68.9% and the specificity was 89.1% to differentiate probable DLB from probable AD in both early and delayed images. By visual assessment, the sensitivity and specificity were 68.9% and 87.0%, respectively. In a subpopulation of patients with mild dementia (MMSE ≥ 22, n = 47), the sensitivity and specificity were 77.4% and 93.8%, respectively, with the delayed heart-to-mediastinum ratio. Conclusions Our first multicenter study confirmed the high correlation between abnormal cardiac sympathetic activity evaluated with 123I-MIBG myocardial scintigraphy and a clinical diagnosis of probable DLB. The diagnostic accuracy is sufficiently high for this technique to be clinically useful in distinguishing DLB from AD, especially in patients with mild dementia.

White matter involvement in idiopathic normal pressure hydrocephalus: a voxel-based diffusion tensor imaging study

The aim of this study was to characterise the white matter damage involved in idiopathic normal pressure hydrocephalus (INPH) using diffusion tensor imaging (DTI) and the relationship between this damage and clinical presentation. Twenty patients with INPH, 20 patients with Alzheimer’s disease and 20 patients with idiopathic Parkinson’s disease (as disease control groups) were enrolled in this study. Mean diffusivity (MD) and fractional anisotropy (FA) were determined using DTI, and these measures were analysed to compare the INPH group with the control groups and with certain clinical correlates. On average, the supratentorial white matter presented higher MD and lower FA in the INPH group than in the control groups. In the INPH group, the mean hemispheric FA correlated with some of the clinical measures, whereas the mean hemispheric MD did not. On a voxel-based statistical map, white matter involvement with high MD was localised to the periventricular regions, and white matter involvement with low FA was localised to the corpus callosum and the subcortical regions. The total scores on the Frontal Assessment Battery were correlated with the FA in the frontal and parietal subcortical white matter, and an index of gait disturbance was correlated with the FA in the anterior limb of the left internal capsule and under the left supplementary motor area. DTI revealed the presence of white matter involvement in INPH. Whereas white matter regions with high MD were not related to symptom manifestation, those with low FA were related to motor and cognitive dysfunction in INPH.

Cognitive Profile of Idiopathic Normal Pressure Hydrocephalus

Background/Aims: Frontal lobe dysfunction is believed to be a primary cognitive symptom in idiopathic normal pressure hydrocephalus (iNPH); however, the neuropsychology of this disorder remains to be fully investigated. The objective of this study was to delineate a comprehensive profile of cognitive dysfunction in iNPH and evaluate the effects of cerebrospinal fluid (CSF) shunt surgery on cognitive dysfunction. Methods: A total of 32 iNPH patients underwent neuropsychological testing of memory, attention, language, executive function, and visuoperceptual and visuospatial abilities. Of these 32 patients, 26 were reevaluated approximately 1 year following CSF shunt surgery. The same battery of tests was performed on 32 patients with Alzheimer’s disease (AD) and 30 healthy elderly controls. Results: The iNPH patients displayed baseline deficits in attention, executive function, memory, and visuoperceptual and visuospatial functions. Impairments of attention, executive function, and visuoperceptual and visuospatial abilities in iNPH patients were more severe than in those with AD, whereas the degree of memory impairment was comparable to that in AD patients. A significant improvement in executive function was observed following shunt surgery. Conclusion: Patients with iNPH are impaired in various aspects of cognition involving both ‘frontal’ executive functions and ‘posterior cortical’ functions. Shunt treatment can ameliorate executive dysfunction.

A Validation Study of the Japanese Version of the Addenbrooke's Cognitive Examination-Revised.

The aim of this study was to validate the Japanese version of the Addenbrooke’s Cognitive Examination-Revised (ACE-R) [Mori: Japanese Edition of Hodges JR’s Cognitive Assessment for Clinicians, 2010] designed to detect dementia, and to compare its diagnostic accuracy with that of the Mini-Mental State Examination. The ACE-R was administered to 85 healthy individuals and 126 patients with dementia. The reliability assessment revealed a strong correlation in both groups. The internal consistency was excellent (α-coefficient = 0.88). Correlation with the Clinical Dementia Rating sum of boxes score was significant (rs = –0.61, p < 0.001). The area under the curve was 0.98 for the ACE-R and 0.96 for the Mini-Mental State Examination. The cut-off score of 80 showed a sensitivity of 94% and a specificity of 94%. Like the original ACE-R and the versions designed for other languages, the Japanese version of the ACE-R is a reliable and valid test for the detection of dementia.

Hallucinators find meaning in noises: pareidolic illusions in dementia with Lewy bodies.

By definition, visual illusions and hallucinations differ in whether the perceived objects exist in reality. A recent study challenged this dichotomy, in which pareidolias, a type of complex visual illusion involving ambiguous forms being perceived as meaningful objects, are very common and phenomenologically similar to visual hallucinations in dementia with Lewy bodies (DLB). We hypothesise that a common psychological mechanism exists between pareidolias and visual hallucinations in DLB that confers meaning upon meaningless visual information. Furthermore, we believe that these two types of visual misperceptions have a common underlying neural mechanism, namely, cholinergic insufficiency. The current study investigated pareidolic illusions using meaningless visual noise stimuli (the noise pareidolia test) in 34 patients with DLB, 34 patients with Alzheimer׳s disease and 28 healthy controls. Fifteen patients with DLB were administered the noise pareidolia test twice, before and after donepezil treatment. Three major findings were discovered: (1) DLB patients saw meaningful illusory images (pareidolias) in meaningless visual stimuli, (2) the number of pareidolic responses correlated with the severity of visual hallucinations, and (3) cholinergic enhancement reduced both the number of pareidolias and the severity of visual hallucinations in patients with DLB. These findings suggest that a common underlying psychological and neural mechanism exists between pareidolias and visual hallucinations in DLB.

Changes in the volumes of the brain and cerebrospinal fluid spaces after shunt surgery in idiopathic normal-pressure hydrocephalus

OBJECTIVES To investigate volumetric changes of the brain and cerebrospinal fluid (CSF) spaces after shunt surgery in shunt-responsive idiopathic normal-pressure hydrocephalus (iNPH), and correlations between the changes and postoperative clinical improvements. METHODS Twenty-one patients with shunt-responsive iNPH were studied. Magnetic resonance imaging (MRI) of the brain was performed before and 1year after surgery, and clinical symptoms were assessed by the iNPH Grading Scale, a validated assessment tool of the triad of iNPH, the Modified Rankin Scale, the Timed Up and Go Test, and neuropsychological tests including the Mini-Mental State Examination. The volumes of the left cerebral hemisphere, infratentorial brain, ventricles, and suprasylvian and infrasylvian subarachnoid CSF spaces were measured using an MRI-based volumetric technique. RESULTS The volumes of the cerebral hemisphere and infratentorial brain did not change significantly after shunt surgery (p=0.231, 0.109, respectively). The volumes of the ventricles and infrasylvian subarachnoid CSF spaces were significantly decreased (p<0.0001, <0.05, respectively), with a mean change rate of -26.1% and -4.5%, respectively. The volumes of the suprasylvian subarachnoid CSF spaces increased significantly (p<0.0001), with a mean change rate of 43.5%. The decrease in ventricular volumes was significantly correlated with clinical improvement.

Amyloid deposits and response to shunt surgery in idiopathic normal-pressure hydrocephalus.

OBJECTIVES In previous studies, patients with idiopathic normal-pressure hydrocephalus (iNPH) occasionally showed Alzheimers pathology in frontal lobe cortical biopsy during cerebrospinal fluid shunt surgery or intracranial pressure monitoring. In clinical practice, the differential diagnosis of iNPH from Alzheimers disease (AD) can be problematic, particularly because some iNPH cases exhibit AD comorbidity. In this study, we evaluated amyloid deposition in the brains of patients with iNPH before shunt surgery, and investigated the association between brain amyloid deposits and clinical improvement following the surgery. MATERIALS & METHODS Amyloid imaging was performed in patients with iNPH or AD and also in healthy control subjects by using positron emission tomography (PET) and a radiolabeled pharmaceutical compound, (11)C-BF227. Using the cerebellar hemispheres as reference regions, the standard uptake value ratio (SUVR) of the neocortex was estimated and used as an index for amyloid deposition. In patients with iNPH, clinical symptoms were assessed before shunt surgery and 3 months after surgery. RESULTS Five of the 10 patients with iNPH had neocortical SUVRs that were as high as those of AD subjects, whereas the SUVRs of the 5 patients were as low as those of healthy controls. A significant inverse correlation between neocortical SUVRs and cognitive improvements after shunt surgery was observed in iNPH. CONCLUSIONS The amount of amyloid deposits ranges widely in the brains of patients with iNPH and is associated with the degree of cognitive improvement after shunt surgery.

Pure word deafness and pure anarthria in a patient with frontotemporal dementia.

A 66‐year‐old right‐handed man developed pure anarthria following pure word deafness. In addition to language disorders, his behavior gradually changed and finally included violence against his wife. Brain magnetic resonance imagings revealed atrophy of the left perisylvian area, which included the inferior half of the precentral gyrus and the upper portion of the superior temporal gyrus, consistent with frontotemporal dementia (FTD). It has been documented as either a disorder of expressive language or as an impaired understanding of word meaning. Unlike with pure anarthria, pure word deafness is not included in the clinical diagnostic current criteria for FTD. However, a large variety of language symptoms can appear in FTD according to the distribution of pathological changes in the frontotemporal cortices. This case suggests that pure word deafness could be a prodomal symptom of FTD.

On the Utility of MIBG SPECT/CT in Evaluating Cardiac Sympathetic Dysfunction in Lewy Body Diseases

Background Abnormal cardiac uptake of 123I-metaiodobenzylguanidine (123I-MIBG) is a diagnostic marker of Lewy body diseases (LBDs), e.g., Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Planar imaging is generally used to assess cardiac sympathetic dysfunction in 123I-MIBG scintigraphy; however, its clinical utility requires further improvement. We hypothesized that the co-registration of single-photon emission tomography (SPECT) and computed tomography (CT) images would improve the diagnostic accuracy of 123I-MIBG cardiac scintigraphy for LBDs. This study sought to evaluate the effects of SPECT/CT imaging on 123I-MIBG cardiac scintigraphy for diagnosing LBDs. Methods We retrospectively investigated data of 54 patients (consecutive 18 patients in each PD, DLB, and idiopathic normal pressure hydrocephalus [iNPH] groups) who underwent 123I-MIBG cardiac scintigraphy (planar and SPECT/CT) because of suspected LBDs at the Tohoku University hospital from June 2012 to June 2015. We compared the diagnostic accuracies of the conventional planar 123I-MIBG method and SPECT/CT methods (manual and semi-automatic). Results In the conventional planar analysis, 123I-MIBG uptake decreased only in the DLB group compared with the iNPH group. In contrast, the SPECT/CT analysis revealed significantly lower 123I-MIBG uptake in both the PD and DLB groups compared with the iNPH group. Furthermore, a receiver operating characteristic analysis revealed that both the manual and semi-automatic SPECT/CT methods were superior to the conventional planar method in differentiating the 3 disorders. Conclusions SPECT/CT 123I-MIBG cardiac scintigraphy can detect mild cardiac sympathetic dysfunction in LDBs. Our results suggest that the SPECT/CT technique improves diagnostic accuracy for LBDs.

The effects of aging and Alzheimer’s disease on associative recognition memory

We investigated the effects of aging and Alzheimer’s disease (AD) on item and associative recognition memory. Three groups of participants (younger adults, elderly adults, and AD patients) studied photographs of common objects that were located on either the left or the right side of a black computer screen inside either a red or a blue square. In a subsequent old/new recognition memory test, the participants were presented with four kinds of stimuli: “intact” stimuli, which were presented as they were during the study phase; “location-altered” stimuli, which were presented in a different location; “color-altered” stimuli, which were presented with a different surrounding color; and “new” stimuli, which consisted of photographs that had not been presented during the study phase. Compared with younger adults, the older adults showed equivalent performance in simple item recognition but worse performance in discriminating location-altered and color-altered stimuli. Compared with older adults, the AD patients showed equivalent performance in discriminating color-altered stimuli but worse performance in simple item recognition and the discrimination of location-altered stimuli. We speculate that distinct structural and functional changes in specific brain regions that are caused by aging and AD are responsible for the different patterns of memory impairment.