Visual Hallucinations In Dementia With Lewy Bodies Research Articles

Behavioral and neural correlates of pareidolic illusions in dementia with Lewy bodies

IntroductionPareidolia, 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. MethodsForty-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. ResultsFactor 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. ConclusionsAt 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.

Free water imaging of the cholinergic system in dementia with Lewy bodies and Alzheimer's disease.

Degeneration of cortical cholinergic projections from the nucleus basalis of Meynert (NBM) is characteristic of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), whereas involvement of cholinergic projections from the pedunculopontine nucleus (PPN) to the thalamus is less clear. We studied both cholinergic projection systems using a free water-corrected diffusion tensor imaging (DTI) model in the following cases: 46 AD, 48 DLB, 35 mild cognitive impairment (MCI) with AD, 38 MCI with Lewy bodies, and 71 controls. Free water in the NBM-cortical pathway was increased in both dementia and MCI groups compared to controls and associated with cognition. Free water along the PPN-thalamus tract was increased only in DLB and related to visual hallucinations. Results were largely replicated in an independent cohort. While NBM-cortical projections degenerate early in AD and DLB, the thalamic cholinergic input from the PPN appears to be more selectively affected in DLB and might associate with visual hallucinations. Free water in the NBM-cortical cholinergic pathways is increased in AD and DLB. NBM-cortical pathway integrity is related to overall cognitive performance. Free water in the PPN-thalamus cholinergic pathway is only increased in DLB, not AD. PPN-thalamus pathway integrity might be related to visual hallucinations in DLB.

Exploration of visual hallucinations – FDG‐PET associations in DLB and MCI‐LB with and without visual hallucinations

AbstractBackgroundSeveral hypotheses exist regarding the neurologic substrate underlying visual hallucinations (VH) in Dementia with Lewy Bodies (DLB). Studies have suggested an association with regional cerebral hypometabolism in the primary visual or visual association cortices on FDG‐PET. We compared regional cerebral glucose metabolism and posterior cingulate island sign (CIS) ratios in DLB and in Mild Cognitive Impairment with Lewy Bodies (MCI‐LB) participants with (VH+) and without (VH‐) VH.MethodParticipants with clinically probable DLB or MCI‐LB and an FDG‐PET scan were identified from the Mayo ADRC database. Responses on the Visual Hallucinations and Delusions Questionnaire and Neuropsychiatric Inventory were used to assess presence or absence of VH. Standardized uptake value ratios (SUVr) were used to calculate regional cerebral glucose hypometabolism in the primary visual cortex (PVC), lateral occipital cortex (LOC), and whole occipital cortex (WOC). The CIS ratio was defined as posterior cingulate divided by the sum of the precuneus plus cuneus FDG‐PET uptake ratio.ResultTwo cohorts were identified (27 DLB and 18 MCI‐LB, 87% male). Eighteen DLB participants were VH+ and 9 were VH‐, whereas 5 MCI‐LB were VH+ and 13 were VH‐. There were no statistically significant differences in demographic (age, sex, education) and clinical features (MoCA, CDR, presence of other core DLB features, and UPDRS) between VH+ vs VH‐ in those with DLB, and between VH+ vs VH‐ in those with MCI‐LB. Similarly, there were no statistically significant differences in DLB between VH+ vs VH‐ in PVC (1.55±0.14 vs 1.58±0.15), LOC (1.22±0.16 vs 1.28±0.12), WOC (1.29±0.15 vs 1.34±0.11), or CIS ratio (1.16±0.08 vs 1.14±0.10), nor in MCI‐LB between VH+ vs VH‐ in PVC (1.68±0.19 vs 1.58±0.14), LOC (1.40±0.21 vs 1.32±0.14), WOC (1.45±0.20 vs 1.37±0.14), or CIS ratio (1.17±0.08 vs 1.19±0.10) (P>0.05 for all comparisons).ConclusionThese findings do not support a direct correlation between regional cerebral glucose metabolism and VH in DLB or MCI‐LB. Further work in DLB and MCI‐LB with larger numbers is warranted. Other neurologic substrates and mechanisms, such as REM sleep intrusions during wakefulness, neurotransmitter dysfunction, and disruption of functional connectivity across brain regions should be explored as contributors to VH in DLB.

Event-related oscillations differentiate between cognitive, motor and visual impairments.

Parkinson's disease (PD) and dementia with Lewy bodies (DLB) share pathological and clinical similarities while differing in the timing and severity of motor cognitive and visual impairment. Previous EEG studies found abnormal neural oscillations in PD, mild cognitive impairment (MCI) and Alzheimer's disease, however, the electrophysiological signature of clinical symptoms is still unclear. We assessed the specificity of event-related oscillations in distinguishing between cognitive, motor and visual involvement in patients with neurodegenerative conditions. EEG was recorded during a visual oddball task in 30 PD, 28 DLB, 30 MCI patients and 32 age-matched healthy controls. Target and non-target event-related power were examined in the time-frequency domain using complex Morlet wavelet convolution and compared within and between the study groups. MCI (z = -1.8, p = 0.04, Cohen's d = -0.5) and DLB (z = -3.1, p < 0.001, d = -1.0) patients showed decreased delta-band target event-related synchronization compared to participants with normal cognition. PD (z = 1.6, p = 0.05, d = 0.5) and DLB (z = 2.7, p < 0.01, d = 0.9) patients showed decreased beta suppression compared to MCI patients and controls. DLB patients with visual hallucinations (VH) showed decreased early-alpha suppression (z = 2.08, p = 0.019, d = 3.19, AUC = 1.0 ± 0.0) compared to DLB-VH-. Decreased event-related delta-band synchronization, reflecting a decline in information processing ability, was characteristic of cognitive impairment due to any cause. Decreased event-related beta suppression, reflecting impaired execution of motor action, was specific to PD and DLB. Decreased event-related early-alpha suppression was characteristic of the presence of VH in DLB. These findings show that specific oscillations may reflect specific clinical symptoms, being a marker of network dysfunction.

Cognitive correlates and baseline predictors of future development of visual hallucinations in dementia with Lewy bodies

Visual hallucinations (VH) are common in dementia with Lewy bodies (DLB), and are among the core symptoms for its clinical diagnosis. VH have been associated with cognitive alterations, although research findings in this area are still limited. The present study aimed at investigating the cognitive correlates of VH in DLB, and the baseline neuropsychological features predicting the future development of VH. A cross sectional study compared the cognitive profile of 18 DLB patients with VH with that of 32 DLB without VH. A longitudinal study involved 34 DLB patients with no VH at baseline, among whom 17 developed VH and 17 remained without VH at follow-up. Logistic regression analyses were carried out to investigate what baseline cognitive variables independently predicted the development of VH at follow-up. DLB patients with VH had worse performance on the copy of the Rey complex figure, assessing visual construction/perception, than those without VH in the cross-sectional study (p = .001). Significant impairments in attention and visual memory delayed recall were also present. Baseline performance on the immediate prose memory was the only significant predictor of VH development in the longitudinal study (p = .03). DLB patients are more at risk of developing VH if presenting more severe immediate verbal memory impairment, and this might be related to a combination of (a) DMN-related dysfunctions, (b) impairment in medial temporal lobe-related functions, and (c) frontal abilities including long-term encoding of information and working memory. Differences between hallucinating and non-hallucinating patients in visual construction/perception, typical of DLB symptomatology, may be essential for VH to emerge in individuals with an at risk cognitive profile.

Changes of Metabolic Connectivity in Dementia with Lewy Bodies with Visual Hallucinations: A 18F-Fluorodeoxyglucose Positron Emission Tomography/Magnetic Resonance Study.

Background: Recurrent complex visual hallucinations (VHs) are common in dementia with Lewy bodies (DLB). Previous investigations suggest that VHs are associated with connectivity changes within and between large scale networks involved in visual processing and attention. Aim: To examine more directly whether VH in DLB reflects direct changes in neuronal activity between cortical regions assessing metabolic connectivity with 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/magnetic resonance and graph theory. Methods: Twenty-six patients with probable DLB (13 VHs and 13 no-VHs; mean age: 72.9 ± 6.87 years vs. 70.2 ± 7.96 years) were enrolled. T1-weighted 3T-MR images and FDG-PET data were coacquired using an integrated PET/MR scanner. MR images defined cortical parcels of the Shaefer-Yeo atlas for multiple functional networks. We computed in each parcel the regional standardized-uptake-values (SUV) corrected for partial volume and normalized to the cerebellar cortex. Strength degree, clustering coefficient, characteristic path length, and hubs were analyzed with graph analysis. Results: The mean 18F-FDG-PET SUVr of parcels belonging to the visual and dorsal attention networks (DANs) were significantly lower in the VH group (p = 0.01). Metabolism in the right temporoparietal cortex correlated with VH severity (R = -0.58; p < 0.01). VH patients showed weaker metabolic connectivity in the parietal, temporal, and occipital cortex of the default mode network, DAN, and visual networks, but more robust connectivity in the right insula and orbitofrontal cortex. A lower global efficiency characterized the VH group, except for ventral attention network and limbic network. Conclusions: VHs in DLB correlate with lower glucose metabolism and weaker metabolic connectivity in the parietal-occipital cortex, but stronger connectivity in the limbic system. Impact statement This study shows that application of the graph theory to 18F-fluorodeoxyglucose-positron emission tomography data, commonly acquired during the diagnostic workflow in neurodegenerative diseases, could be used to obtain information of functional connectivity at a group level, with results that are consistent with other data commonly used in brain functional investigation (e.g., electroencephalography or functional magnetic resonance). New network-based methods of metabolic image analyses, such as graph analysis, are a recent area of research with a potential capacity to extract information on alterations of metabolic connectivity that may become pharmacological and neuromodulation targets of the physiopathology of recurrent complex visual hallucinations.

Functional Brain Connectivity Patterns Associated with Visual Hallucinations in Dementia with Lewy Bodies.

Background:The presence of recurrent, complex visual hallucinations (VH) is among the core clinical features of dementia with Lewy bodies (DLB). It has been proposed that VH arise from a disrupted organization of functional brain networks. However, studies are still limited, especially investigating the resting-state functional brain features underpinning VH in patients with dementia.Objective:The aim of the present pilot study was to investigate whether there were any alterations in functional connectivity associated with VH in DLB.Methods:Seed-based analyses and independent component analysis (ICA) of resting-state fMRI scans were carried out to explore differences in functional connectivity between DLB patients with and without VH.Results:Seed-based analyses reported decreased connectivity of the lateral geniculate nucleus, the superior parietal lobule and the putamen with the medial frontal gyrus in DLB patients with VH. Visual areas showed a pattern of both decreased and increased functional connectivity. ICA revealed between-group differences in the default mode network (DMN).Conclusion:Functional connectivity analyses suggest dysfunctional top-down and bottom-up processes and DMN-related alterations in DLB patients with VH. This impairment might foster the generation of false visual images that are misinterpreted, ultimately resulting in VH.

Associations between visual hallucinations and impaired visuo-spatial abilities in dementia with Lewy bodies.

Objectives: In dementia with Lewy bodies (DLB) recurrent visual hallucinations (VH) often coexist or occur consecutively to impaired visual perception. Since in-depth neuropsychological testing is time-consuming, and therefore, not routinely performed in clinical settings, we aimed to explore whether standard cognitive screening tests may be helpful to alert a clinician to the presence of VH in DLB by exploring association between visuo-spatial dysfunction and VH. Method: The clock drawing, cube, and pentagons copying items from Montreal Cognitive Assessment and Mini-Mental State Exam and nonmotor Hooper visual organization test (HVOT) have been scored in DLB patients with and without VH using traditional and extended scoring methods. Results: Forty-five of 69 (65%) DLB patients were VH-positive (VH+). VH+ patients performed worse on the clock drawing (8.8/16 vs. 11.9/16, p = .016) with a higher rate of misrepresentation of time (69% vs. 29%, p = .002) and numbers (53% vs. 25%, p = .024). Likewise, VH+ patients performed worse on the HVOT (13.3/30 vs. 15.7/30, p = .009) having more isolated (6.2/30 vs. 4.4/30, p = .012) types of responses compared to VH- patients. Both groups had similar copying ability (p > .05). The VH discriminative accuracy of the clock drawing was comparable to that of the more elaborate test of visual perception, the HVOT. Conclusions: In DLB impaired drawing and visual organization, but not copying ability is associated with the presence of VH. The simple clock drawing test can be helpful to alert a clinician to the possibility of VH in DLB. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

423 - Visual Hallucinations in Parkinson Disease and Dementia with Lewy Bodies: a review

Visual Hallucinations (VH) are a common psychiatric symptom of Parkinson’s Disease (PD) and Dementia with Lewy Bodies (DLB). According to the Perception-Attention Deficits Model, VH stem from impaired perceptual (bottom-up), including dorsal (DVS) and ventral visual streams (VVS), and attentional (top-down) processes, with a persistent Default Mode Network (DMN) activity and a dysfunctional imbalance of Dorsal (DAN) and Ventral Attentional Networks (VAN).We review the literature on the neurobiological underpinnings of VH in DLB and PD, concerning overlapping and different mechanisms.In DLB hallucinators, PET-scan findings of disconnection between higher and primary visual areas and dysfunctional recruitment of the VVS, corroborate other imaging and neuropathologic studies which document inferior longitudinal fasciculus damage and increased temporal lobe Lewy body (LB) pathology. The alteration of network topography is more pronounced in the DAN and DMN. The involvement of anterior cortical regions, clustering around attentional networks, is demonstrated in neuropathologic, volumetric and perfusion studies. VH severity closely correlates with anterior cingulate cortex and inferior temporal cortex hypoperfusion, structural changes in the DVS (superior parietal gyrus and precuneus) and increased diffusivity of the right thalamic projections to parieto-occipital cortices. Thalamocortical dysfunction alongside decreased cholinergic activity in reticular nucleus, which receive projections from the nucleus basalis of Meynert, seems to play a crucial role.Both DLB and demented PD hallucinators have more frontal cortical atrophy, yet greater in DLB, supporting top-down mechanisms.Regarding PD hallucinators, findings of cortical atrophy in inferior parietal lobule, cuneus, lingual lobule, and precentral gyrus correlated with hallucination scores. However, some studies did not evidence volumetric cortical differences between hallucinators and non-hallucinators. Moreover, LB are not necessarily present in hallucinators, suggesting other neuropathologic mechanisms in the genesis of VH, namely altered neurochemical circuitry. Volume loss in pedunculopontine nucleus and right-thalamus support the hypothesis of a dysfunctional cholinergic brainstem control of the cortex. PET-scan studies discovered higher 5-HT2A receptor levels in the inferolateral temporal and prefrontal cortices. A greater nigrostriatal impairment is documented in the right-caudate of hallucinators. Therefore, VH may arise from an inability to activate DAN (in which caudate is involved) and consequent faulty visuo-perceptual processing by DMN and VAN.

Frontal and subcortical contribution to visual hallucinations in dementia with Lewy bodies and Parkinson’s disease

ABSTRACTObjectives: Visual hallucinations (VH) are common in Lewy body disease (LBD), and have been associated with cognitive and structural brain alterations. Evidence so far concerns mainly Parkinson’s disease (PD), but little is known about symptom-specific pathophysiological mechanisms across the LBD spectrum, especially related to the presence of dementia. The aim of the present pilot study was to investigate the neuroanatomical, and neuropsychological characteristics related to VH in two forms of LBD, namely dementia with Lewy bodies (DLB) and PD without dementia.Methods: Whole brain voxel-based morphometry (VBM) analyses on 3D MRI acquired structural brain scans, and neuropsychological testing were performed on 28 clinically diagnosed DLB (11 with VH, 17 NVH), and 24 PD (9 with VH, and 15 NVH) patients. In order to assess differences in gray matter (GM) regional volumes, and cognitive performance, hallucinating patients for each group were compared with corresponding non-hallucinating ones.Results: DLB patients with VH presented significantly worse visual attention deficits compared to those without, which persisted even when controlling for visual perception. Whole brain VBM analysis revealed decreased GM volume in DLB with VH in the right superior and medial frontal gyri, putamen, caudate nucleus and insula. Subcortical regional volumes were also significantly associated with visual attention performance. Hallucinating PD patients, instead, presented more severe executive dysfunction, but VBM showed no volumetric differences between the two PD subgroups. Post hoc region of interest analyses revealed striatal GM loss in PD with VH.Conclusion: Frontal and striatal GM atrophy may contribute to the emergence of VH in DLB, which may be fostered by the more severe attention deficits. Striatal GM loss and executive dysfunction, instead, appeared to underlie VH in PD without dementia.

060 Impaired color discrimination is associated with hallucinations in dementia with lewy bodies

IntroductionEmerging evidence indicates that color discrimination impairments can predict the development of dementia across a range of prodromal Lewy body conditions. However, color vision deficits are not seen uniformly in patients with Dementia with Lewy Bodies (DLB), suggesting a more nuanced association. Visual hallucinations(VH) represent a discriminating feature of DLB, and recent evidence implicates visual pathway dysfunction as a significant contributor to this phenomenon. We therefore hypothesized that color impairment will more closely associate with VH in DLB rather than general cognition.MethodsIn this study, we examined the relationship between color vision impairment and VH, along with other clinical and neuropsychological features in 24 patients with DLB alongside 25 age-matched controls. Color discrimination was assessed using the Farnsworth-Munsell-100 Hue (FM-100) test.ResultsColor discrimination impairment was seen in 16/24 DLB participants (67%) with a higher error score relative to controls(p=0.001). We demonstrate for the first time a strong association between color discrimination errors and both the presence and severity of VH in DLB based on clinician-derived(p=0.008) and questionnaire-derived(p=0.03) measures. Correlation with clinical and neuropsychological variables revealed that color discrimination is significantly related to visuospatial impairment(p=0.02) but not to global measures of cognition, motor severity, age or disease duration. Factor analysis confirmed a unique relationship between color discrimination, visual hallucinations and visuospatial function.ConclusionOur results suggest that color impairments may be a specific biomarker of visual hallucinations and associated visuoperceptual deficits in evolving Lewy body disorders rather than dementia per se and thus providing insight into a shared pathophysiological substrate.

The brain metabolic signature of visual hallucinations in dementia with Lewy bodies

Visual hallucinations (VH) are a core clinical feature of dementia with Lewy bodies (DLB), but their specific neural substrate remains elusive. We used 18F-FDG-PET to study the neural dysfunctional signature of VH in a group of 38 DLB patients (mean age±SD 72.9 ± 7.5) with available anamnestic records, cognitive and neurological examination and NeuroPsychiatric Inventory assessing VH. We tested the voxel-wise correlation between 18F-FDG-PET hypometabolism and VH NPI scores at the whole-group level, then adopting inter-regional correlation analysis to explore the resting-state networks (RSNs) metabolic connectivity in DLB patients with and without visual hallucinations, as compared to N = 38 age-matched healthy controls (HCs) (mean age±SD 71.5 ± 6.9). At the whole-group level, we found a negative correlation between VH NPI scores and 18F-FDG-PET hypometabolism in the right occipito-temporal cortex (p < .001 uncorrected, p < .05 Family-Wise Error cluster-corrected). Then, splitting the group according to VH presence, we found that DLB non-hallucinators presented a pattern of connectivity seeding from this occipito-temporal cluster and extending to the ventral visual stream. At difference, the DLB hallucinators showed a metabolic connectivity pattern limited to the occipital-dorsal parietal regions. As for RSNs, both the DLB subgroups showed a markedly reduced extent of attention and visual networks compared to HCs, with a variable alteration in the topography. DLB-VH patients showed a more pronounced shrinkage of the primary visual network, which was disconnected from the higher visual hubs, at difference with both HC and DLB non-hallucinators. These findings suggest that an altered brain metabolic connectivity within and beyond visual systems may promote VH in DLB. These results support the most recent neurocognitive models interpreting VH as the result of an inefficient recruitment of the ventral visual stream and of a large-scale multi-network derangement.

Gender difference in the association and presentation of visual hallucinations in dementia with Lewy bodies: a cross-sectional study.

Visual hallucinations (VHs) are among the most striking features of dementia with Lewy bodies (DLB). We investigated gender differences in the association and presentation of VHs in DLB. A cross-sectional analysis of baseline data from a prospective, longitudinal study on dementia was performed. Cumulative frequency, 1-month frequency, and phenomenology of VHs were summarized and compared between female and male patients with DLB. Gender differences in the factors associated with VHs were investigated in patients with and without hallucinations. A total of 152 patients including 65 (42.8%) women and 87 (57.2%) men were analyzed. The cumulative and 1-month frequencies of VHs were 60% and 55.4%, respectively, in women and 44.8% and 41.4%, respectively, in men. Adjusting for age and disease severity resulted in the inclusion of more women in the VH group [odds ratio (OR)=2.33, p=0.028)] than in the non-VH group. In female participants, older age (OR=9.16, p=0.003) and higher neuropsychiatric inventory score (OR=4.89, p=0.009) were associated with VHs, whereas in male participants, more severe dementia stage (clinical dementia rating 2-3 versus clinical dementia rating 0.5, OR=6.22, p=0.008) and higher rates of using antipsychotics (OR=9.64, p=0.047) were associated with VHs. The frequencies of 1-month and cumulative VHs were high in DLB, which indicated a high prevalence as well as a high persistency of VHs in DLB. The patterns of factors associated with VHs differed between female and male patients. Copyright © 2017 John Wiley & Sons, Ltd.

Neuronal Loss and Α-Synuclein Pathology in the Superior Colliculus and Its Relationship to Visual Hallucinations in Dementia with Lewy Bodies

Patients with dementia with Lewy bodies (DLB) often experience visual hallucinations, which are related to decreased quality of life for patients and increased caregiver distress. The pathologic changes that contribute to visual hallucinations are not known, but several hypotheses implicate deficient attentional processing. The superior colliculus has a role in visual attention and planning eye movements and has been directly implicated in several models of visual hallucinations. Therefore, the present study sought to identify neurodegenerative changes that may contribute to hallucinations in DLB. Postmortem superior colliculus tissue from 13 comparison, 10 DLB, and 10 Alzheimer disease (AD) cases was evaluated using quantitative neuropathologic methods. α-Synuclein and tau deposition were more severe in deeper layers of the superior colliculus. DLB cases had neuronal density reductions in the stratum griseum intermedium, an important structure in directing attention toward visual targets. In contrast, neuronal density was reduced in all laminae of the superior colliculus in AD. These findings suggest that regions involved in directing attention toward visual targets are subject to neurodegenerative changes in DLB. Considering several hypotheses of visual hallucinations implicating dysfunctional attention toward external stimuli, these findings may provide evidence of pathologic changes that contribute to the manifestation of visual hallucinations in DLB.

The Pareidolia Test: A Simple Neuropsychological Test Measuring Visual Hallucination-Like Illusions.

BackgroundVisual hallucinations are a core clinical feature of dementia with Lewy bodies (DLB), and this symptom is important in the differential diagnosis and prediction of treatment response. The pareidolia test is a tool that evokes visual hallucination-like illusions, and these illusions may be a surrogate marker of visual hallucinations in DLB. We created a simplified version of the pareidolia test and examined its validity and reliability to establish the clinical utility of this test.MethodsThe pareidolia test was administered to 52 patients with DLB, 52 patients with Alzheimer’s disease (AD) and 20 healthy controls (HCs). We assessed the test-retest/inter-rater reliability using the intra-class correlation coefficient (ICC) and the concurrent validity using the Neuropsychiatric Inventory (NPI) hallucinations score as a reference. A receiver operating characteristic (ROC) analysis was used to evaluate the sensitivity and specificity of the pareidolia test to differentiate DLB from AD and HCs.ResultsThe pareidolia test required approximately 15 minutes to administer, exhibited good test-retest/inter-rater reliability (ICC of 0.82), and moderately correlated with the NPI hallucinations score (rs = 0.42). Using an optimal cut-off score set according to the ROC analysis, and the pareidolia test differentiated DLB from AD with a sensitivity of 81% and a specificity of 92%.ConclusionsOur study suggests that the simplified version of the pareidolia test is a valid and reliable surrogate marker of visual hallucinations in DLB.

Changes to the lateral geniculate nucleus in Alzheimer's disease but not dementia with Lewy bodies.

AimsComplex visual hallucinations occur in 70% of dementia with Lewy bodies (DLB) cases and significantly affect patient well‐being. Visuo‐cortical and retinal abnormalities have been recorded in DLB and may play a role in visual hallucinations. The present study aimed to investigate the lateral geniculate nucleus (LGN), a visual relay centre between the retina and visual cortex, to see if changes to this structure underlie visual hallucinations in DLB.MethodsFifty‐one [17 probable DLB, 19 control and 15 probable Alzheimer's disease (AD)] cases were recruited for a functional magnetic resonance imaging study, in which patients' response to a flashing checkerboard stimulus was detected and measured in the LGN, before comparison across experimental groups. Additionally, post mortem LGN tissue was acquired for a cross‐sectional study using 20 (six DLB, seven control and seven AD) cases and analysed using stereology. α‐Synuclein, phosphorylated tau and amyloid‐β pathology was also assessed in all cases.Results DLB cases did not significantly differ from controls on neuroimaging, morphometry or pathology. However, a significant increase in amyloid‐β pathology, a reduction in number of parvocellular neurones and magnocellular gliosis was found in AD cases compared with control and DLB cases.ConclusionsThese findings suggest that the early visual system is relatively spared in DLB, which implies that upstream visual structures may be largely responsible for the generation of hallucinatory percepts. The significance of the degeneration of the LGN in AD cases is uncertain.

Relevance of subcortical visual pathways disruption to visual symptoms in dementia with Lewy bodies

Visual hallucinations represent a core diagnostic criterion for dementia with Lewy bodies (DLB). We hypothesized that thalamic regions, which are critically involved in the modulation of visual transmission, may be differentially disrupted in DLB as compared to Alzheimer's Disease (AD) and that these deficits could relate to visual dysfunction in DLB patients.Magnetic Resonance and Diffusion Tensor Imaging (DTI) were performed with a 3 T scanner on a sample population of 15 DLB patients, 15 AD patients and 13 healthy volunteers. Regional thalamic micro-structural changes were assessed by parcelling the thalamus based on its connectivity to cortex and to amygdala and by measuring the mean diffusivity (MD) in each connectivity-defined sub-region.Micro-structural grey matter damage associated to higher MD values was found bilaterally in DLB compared to controls in the sub-regions projecting from thalamus to prefrontal and parieto-occipital cortices. Right thalamic sub-region projecting to amygdala and left thalamic sub-region projecting to motor cortex were also affected in DLB compared to controls. Higher MD values were found bilaterally in AD compared to controls in the thalamic sub-regions projecting to temporal cortex. Specific comparison between the two forms of dementia found differences: the sub-regions which project from thalamus to parieto-occipital cortex and to amygdala showed higher MD values in DLB compared to AD patients. In DLB patients, correlation analysis showed a significant correlation between NPI hallucinations item scores and MD values in the right thalamic sub-regions projecting to parietal and occipital cortices.The present study demonstrates how thalamic connectivity alterations between higher and lower visual areas may be relevant in explaining visual hallucinations in DLB.

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.

Improved Visual Hallucination by Donepezil and Occipital Glucose Metabolism in Dementia with Lewy Bodies: The Osaki-Tajiri Project

Deficits in the cholinergic system are pronounced in dementia with Lewy bodies (DLB) and are more severe in patients with visual hallucinations (VHs). The aim is to identify the occipital glucose metabolism patterns by positron emission tomography (PET) and the changes following donepezil treatment. 13 DLB patients with VHs were enrolled in the study. After the first FDG-PET study, 5 mg/day donepezil was administered orally, and a second PET study was performed 3 months later. After donepezil administration, VHs disappeared completely in 6 patients, and the PET studies revealed significantly decreased glucose metabolism in the medial occipital cortex. These results suggest that VHs in DLB were associated with impaired glucose metabolism in the medial occipital cortex. Donepezil treatment may modify regional glucose metabolism.

Frontal and associative visual areas related to visual hallucinations in dementia with Lewy bodies and Parkinson's disease with dementia

Visual Hallucinations (VH) are among the core features of Dementia with Lewy Bodies (DLB), but are also very frequent in demented patients with Parkinson's Disease (PDD). The purpose of this study was to investigate the pattern of gray matter and cognitive impairment underlying VH in DLB and PDD. We applied voxel-based morphometry and behavioral assessment to 12 clinically diagnosed DLB patients and 15 PDD patients. Subjects with VH showed greater gray matter loss than non-hallucinators, specifically in the right inferior frontal gyrus (BA 45) in the DLB patients and in the left orbitofrontal lobe (BA 10) in the PDD patients. Comparing the two subgroups with VH, DLB patients had greater decrease of the bilateral premotor area (BA 6) than PDD patients. Furthermore, decreased volume in associative visual areas, namely left precuneus and inferior frontal lobe, correlated with VH in the DLB but not in PDD patients. VH were related to impaired verbal fluency, inhibitory control of attention and visuoperception in the DLB group and to visual memory in the PDD group. In conclusion, DLB and PDD patients with VH had more frontal gray matter atrophy than non-hallucinators, the impairment being greater in the DLB group. The patterns of structural and functional correlations were different in both pathologies.