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Introduction: Pareidolia, a form of visual illusions phenomenologically similar to complex visual hallucinations, is a phenomenon that is associated with visual hallucinations in dementia with Lewy bodies (DLB). This study aimed to identify commonalities and differences in behavioral and neural correlates between pareidolic illusions and visual hallucinations in DLB., Methods: Forty-three patients with DLB underwent the scene pareidolia test, which evokes and measures pareidolic illusions, and standardized neuropsychological and behavioral assessments. Regional cerebral blood flow (rCBF) was measured by single-photon emission computed tomography. Factor analysis was performed to assess the relationships among pareidolic illusions, cognitive functions, and behavioral symptoms. Partial least squares correlation analysis was used to investigate the relationship between these symptoms and rCBF., Results: Factor analysis yielded three behavior factors: the first factor (hallucinations/fluctuations) consisted of pareidolic illusions, visual hallucinations, and fluctuating cognition; the second factor (general cognitive function) consisted of general cognitive function and working memory; and the third factor (visual processing) consisted of visual processing and pareidolic illusions. Partial least squares correlation analysis identified two brain-behavior correlation patterns: (1) rCBF reduction in the frontal and perisylvian/periventricular regions was associated with lower general cognitive function and lower visual processing; and (2) rCBF reduction in the bilateral occipitotemporal cortex was associated with more severe hallucinations/fluctuations and lower visual processing., Conclusions: At the behavioral level, pareidolic illusions are associated with visual hallucinations, fluctuating cognition, and visual processing in DLB. At the neural level, pareidolic illusions may arise from the synergistic effects of global neuropathological changes and occipitotemporal cortical dysfunctions., Competing Interests: Declaration of competing interest Nothing to report., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background and Purpose: We previously reported the usefulness of iodine-123 metaiodobenzylguanidine ( 123 I-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 123 I-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 123 I-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 123 I-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 123 I-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., Competing Interests: Competing interests: HeA, TAr and KW received honoraria for sponsored lectures from Fujifilm RI Pharma. TAs and SY received honoraria for sponsored lectures and research grant from Fujifilm RI Pharma Co and Nihon Medi-Physics. HF, SN, SO, JT and MYo received honoraria for sponsored lectures from Fujifilm RI Pharma and Nihon Medi-Physics. HH and KUt received honoraria for sponsored lectures from Nihon Medi-Physics. EI received honoraria for consultancies, sponsored lectures and presiding at lecture meetings from Nihon Medi-Physics. OI received honoraria for sponsored lectures and travel costs from Nihon Medi-Physics. KKo received honoraria for sponsored lectures, writing and editing from Fujifilm RI Pharma, and honoraria for sponsored lectures from Nihon Medi-Physics. HM received honoraria for sponsored lectures and travel costs from Fujifilm RI Pharma and Nihon Medi-Physics. KNakaj has collaborative research works with Fujifilm RI Pharma and received research funds for joint research and honoraria for lectures and writing. KNakas received sponsored scholarship and honoraria for presiding at meetings from Fujifilm RI Pharma and honoraria for presiding at lecture meetings from Nihon Medi-Physics. EM received research grant from Fujifilm RI Pharma and honoraria for sponsored lectures from Nihon Medi-Physics and Fujifilm RI Pharma. TT received honoraria for sponsored lectures and presiding at lecture meetings from Nihon Medi-Physics. KUr received research grant from Fujifilm RI Pharma and honoraria for sponsored lectures from Nihon Medi-Physics. MYa received honoraria for sponsored lectures and research grant from Fujifilm RI Pharma. JY received sponsored scholarship, honoraria for sponsored lectures and travel costs from Fujifilm RI Pharma, and honoraria for sponsored lectures and research grant from Nihon Medi-Physics. JK, HiA, EI, KKa, KM, YM, HN, YN, MS, AT and YW declare that they have no conflicts of interest., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: There is increasing evidence for predictive coding theories of psychosis, which state that hallucinations arise from abnormal perceptual priors or biases. However, psychological processes that foster abnormal priors/biases in patients suffering hallucinations have been largely unexplored. The widely recognized relationship between affective disorders and psychosis suggests a role for mood and emotion., Methods: Thirty-six patients with dementia with Lewy bodies (DLB), a representative condition associated with psychosis of neurological origin, and 12 patients with Alzheimer's disease (AD) were enrolled. After an experimental mood induction, the participants underwent the pareidolia test, in which visual hallucination-like illusions were evoked and measured., Results: In DLB patients, the number of pareidolic illusions was doubled under negative mood compared to that under neutral mood. In AD patients, there was no significant difference in the number of pareidolic responses between negative and neutral mood conditions. A signal detection theory analysis demonstrated that the observed affective modulation of pareidolic illusions was mediated through heightened perceptual bias, not sensory deterioration., Conclusions: The current findings demonstrated that abnormal perceptual priors in psychotic false perception have an affective nature, which we suggest are a type of cognitive feeling that arises in association with perception and cognition., Competing Interests: The authors have declared that no competing interests exist.

Pareidolias are visual illusions of meaningful objects, such as faces and animals, that arise from ambiguous forms embedded in visual scenes. Pareidolias and visual hallucinations have been suggested to have a common underlying neural mechanism in patients with dementia with Lewy bodies (DLB). The aim of the present study was to find an externally observable physiological indicator of pareidolias. Using a pareidolia test developed by Uchiyama and colleagues, we evoked pareidolias in patients with DLB and recorded the resultant changes in the diameters of their pupil. The time frequencies of changes in pupil diameters preceding pareidolic utterances and correct utterances by the patients, as well as correct utterances by healthy control participants, were analyzed by a fast Fourier transform program. The power at time frequencies of 0-0.46 Hz was found to be greatest preceding pareidolic utterances in patients with DLB, followed by that preceding correct utterances in control participants, followed by that preceding correct utterances in patients with DLB. When the changes in power preceding the utterance were greater than the median value of correct utterances by the control group, the frequency of pareidolic utterances was significantly greater than that of correct utterances and when the changes were the same as or lower than the median value, the frequency of correct utterances was significantly greater than that of pareidolic utterances. Greater changes in power preceding the utterance at time frequencies of 0-0.46 Hz may thus be an externally observable physiological indicator of the occurrence of pareidolias.

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.

Background: Comorbidity of idiopathic normal pressure hydrocephalus and neurodegenerative diseases presents a diagnostic challenge. The aim of this study was to elucidate the clinical features of iNPH patients who are possibly comorbid with Lewy body diseases., Methods: In this study, we retrospectively analyzed the records of consecutive 127 patients with definite idiopathic normal pressure hydrocephalus. (123)I-Metaiodobenzylguanidine myocardial scintigraphy was undertaken to 21 patients with idiopathic normal pressure hydrocephalus because of suspicion for comorbid Lewy body diseases., Results: As a result, 7 of the 21 patients with idiopathic normal pressure hydrocephalus exhibited cardiac sympathetic abnormality. Idiopathic normal pressure hydrocephalus patients with cardiac sympathetic dysfunction had the constellation of clinical findings, such as younger onset, less severe urinary dysfunction, kinesie paradoxale, and cogwheel rigidity., Conclusions: Our results suggested that comorbidity of idiopathic normal pressure hydrocephalus and Lewy body diseases are not rare condition and careful screening for potentially-curative surgery is important especially in atypical cases., (Copyright © 2015 Elsevier B.V. All rights reserved.)

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.

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., (Copyright © 2014 Elsevier Ltd. All rights reserved.)