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Objective: The present study aimed to clarify the neuropsychological profile of the emergent diagnostic category of Mild Cognitive Impairment with Lewy bodies (MCI-LB) and determine whether domain-specific impairments such as in memory were related to deficits in domain-general cognitive processes (executive function or processing speed). Method: Patients (n = 83) and healthy age- and sex-matched controls (n = 34) underwent clinical and imaging assessments. Probable MCI-LB (n = 44) and MCI-Alzheimer's disease (AD) (n = 39) were diagnosed following National Institute on Aging-Alzheimer's Association (NIA-AA) and dementia with Lewy bodies (DLB) consortium criteria. Neuropsychological measures included cognitive and psychomotor speed, executive function, working memory, and verbal and visuospatial recall. Results: MCI-LB scored significantly lower than MCI-AD on processing speed [Trail Making Test B: p =.03, g =.45; Digit Symbol Substitution Test (DSST): p =.04, g =.47; DSST Error Check: p <.001, g =.68] and executive function [Trail Making Test Ratio (A/B): p =.04, g =.52] tasks. MCI-AD performed worse than MCI-LB on memory tasks, specifically visuospatial (Modified Taylor Complex Figure: p =.01, g =.46) and verbal (Rey Auditory Verbal Learning Test: p =.04, g =.42) delayed recall measures. Stepwise discriminant analysis correctly classified the subtype in 65.1% of MCI patients (72.7% specificity, 56.4% sensitivity). Processing speed accounted for more group-associated variance in visuospatial and verbal memory in both MCI subtypes than executive function, while no significant relationships between measures were observed in controls (all ps >.05) Conclusions: MCI-LB was characterized by executive dysfunction and slowed processing speed but did not show the visuospatial dysfunction expected, while MCI-AD displayed an amnestic profile. However, there was considerable neuropsychological profile overlap and processing speed mediated performance in both MCI subtypes. [ABSTRACT FROM AUTHOR]

Objectives: Previous research has identified that dementia with Lewy bodies (DLB) has abnormal pareidolic responses which are associated with severity of visual hallucinations (VH), and the pareidolia test accurately classifies DLB with VH. We aimed to assess whether these findings would also be evident at the earlier stage of mild cognitive impairment (MCI) with Lewy bodies (MCI‐LB) in comparison to MCI due to AD (MCI‐AD) and cognitively healthy comparators. Methods: One‐hundred and thirty‐seven subjects were assessed prospectively in a longitudinal study with a mean follow‐up of 1.2 years (max = 3.7): 63 MCI‐LB (22% with VH) and 40 MCI‐AD according to current research diagnostic criteria, and 34 healthy comparators. The pareidolia test was administered annually as a repeated measure. Results: Probable MCI‐LB had an estimated pareidolia rate 1.2–6.7 times higher than MCI‐AD. Pareidolia rates were not associated with concurrent VH, but had a weak association with total score on the North East Visual Hallucinations Inventory. The pareidolia test was not an accurate classifier of either MCI‐LB (Area under curve (AUC) = 0.61), or VH (AUC = 0.56). There was poor sensitivity when differentiating MCI‐LB from controls (41%) or MCI‐AD (27%), though specificity was better (91% and 89%, respectively). Conclusions: Whilst pareidolic responses are specifically more frequent in MCI‐LB than MCI‐AD, sensitivity of the pareidolia test is poorer than in DLB, with fewer patients manifesting VH at the earlier MCI stage. However, the high specificity and ease of use may make it useful in specialist clinics where imaging biomarkers are not available. Key Points: Pareidolia responses to ambiguous visual stimuli may be a surrogate for visual hallucinationsPareidolias are more common in dementia with Lewy bodies than in Alzheimer's disease (AD)We found an increased rate of pareidolias in mild cognitive impairment (MCI) with Lewy bodies than in AD or healthy comparatorsMisperceptions in the pareidolia test are reasonably specific to MCI with Lewy bodies, but these may lack sensitivity at early stages [ABSTRACT FROM AUTHOR]

Introduction: Diagnostic criteria for prodromal dementia with Lewy bodies have recently been published. These include the use of imaging biomarkers to distinguish mild cognitive impairment with Lewy bodies (MCI-LB) from MCI due to other causes. Two potential biomarkers listed, though not formally included in the diagnostic criteria, due to insufficient evidence, are relatively preserved hippocampi, and atrophy of the insula cortex on structural brain imaging.Methods: In this report, we sought to investigate these imaging biomarkers in 105 research subjects, including well characterised groups of patients with MCI-LB (n = 38), MCI with no core features of Lewy body disease (MCI-AD; n = 36) and healthy controls (N = 31). Hippocampal and insula volumes were determined from T1 weighted structural MRI scans, using grey matter segmentation performed with SPM software.Results: Adjusting for age, sex and intracranial volume, there were no differences in hippocampal or insula volume between MCI-AD and MCI-LB, although in both conditions volumes were significantly reduced relative to controls.Conclusion: Our results do not support the use of either hippocampal or insula volume to identify prodromal dementia with Lewy bodies. [ABSTRACT FROM AUTHOR]

Objective: To use arterial spin labelling to investigate differences in perfusion in mild cognitive impairment with Lewy bodies (MCI-LB) compared to Alzheimer type MCI (MCI-AD) and healthy controls. Methods: We obtained perfusion images on 32 MCI-LB, 30 MCI-AD and 28 healthy subjects of similar age. Perfusion relative to cerebellum was calculated, and we aimed to examine differences in relative perfusion between MCI-LB and the other groups. This included whole brain voxelwise comparisons, as well as using predefined region-of-interest ratios of medial occipital to medial temporal, and posterior cingulate to precuneus. Differences in occipital perfusion in eyes open vs eyes closed conditions were also examined. Results: Compared to controls, the MCI-LB showed reduced perfusion in the precuneus, parietal, occipital and fusiform gyrus regions. In our predefined regions, the ratio of perfusion in occipital/medial temporal was significantly lower, and the posterior cingulate/precuneus ratio was significantly higher in MCI-LB compared to controls. Overall, the occipital perfusion was greater in the eyes open vs closed condition, but this did not differ between groups. Conclusion: We found patterns of altered perfusion in MCI-LB which are similar to those seen in dementia with Lewy bodies, with reduction in posterior parietal and occipital regions, but relatively preserved posterior cingulate. [ABSTRACT FROM AUTHOR]

We performed a clinicopathological study to assess the burden of small vessel disease (SVD) type of pathological changes in elderly demented subjects, who had clinical evidence of autonomic dysfunction, either carotid sinus hypersensitivity or orthostatic hypotension or both or had exhibited unexpected repeated falls. Clinical and neuropathological diagnoses in 112 demented subjects comprised dementia with Lewy bodies (DLB), Parkinson's disease with dementia (PDD), Alzheimer's disease (AD), Mixed dementia (mostly AD‐DLB) and vascular dementia (VaD). Of these, 12 DLB subjects had no recorded unexpected falls in life and therefore no evidence of concomitant autonomic dysfunction. A further 17 subjects were assessed as aging controls without significant pathology or signs of autonomic dysfunction. We quantified brain vascular pathological changes and determined severities of neurodegenerative lesions including α‐synuclein pathology. We found moderate‐severe vascular changes and high‐vascular pathology scores (P < 0.01) in all neurodegenerative dementias and as expected in VaD compared to similar age controls. Arteriolosclerosis, perivascular spacing and microinfarcts were frequent in the basal ganglia and frontal white matter (WM) across all dementias, whereas small infarcts (<5 mm) were restricted to VaD. In a sub‐set of demented subjects, we found that vascular pathology scores were correlated with WM hyperintensity volumes determined by MRI in life (P < 0.02). Sclerotic index values were increased by ~50% in both the WM and neocortex in all dementias compared to similar age controls. We found no evidence for increased α‐synuclein deposition in subjects with autonomic dysfunction. Our findings suggest greater SVD pathological changes occur in the elderly diagnosed with neurodegenerative dementias including DLB and who develop autonomic dysfunction. SVD changes may not necessarily manifest in clinically overt symptoms but they likely confound motor or cognitive dysfunction. We propose dysautonomia promotes chronic cerebral hypoperfusion to impact upon aging‐related neurodegenerative disorders and characterize their end‐stage clinical syndromes. [ABSTRACT FROM AUTHOR]

Background: Lewy body dementia (LBD) and Alzheimer's disease (AD) are common forms of degenerative dementia. While they are characterized by different clinical profiles, attentional deficits are a common feature. The objective of this study was to investigate how attentional problems in LBD and AD differentially affect different aspects of reaction time performance and to identify possible structural neural correlates. Methods: We studied reaction time data from an attention task comparing 39 LBD patients, 28 AD patients, and 22 age-matched healthy controls. Data were fitted to an ex-Gaussian model to characterize different facets of the reaction time distribution (mean reaction time, reaction time variability, and the subset of extremely slow responses). Correlations between ex-Gaussian parameters and grey and white matter volume were assessed by voxel-based morphometry. Results: Both dementia groups showed an increase in extremely slow responses. While there was no difference between AD and controls with respect to mean reaction time and variability, both were significantly increased in LBD patients compared to controls and AD. There were widespread correlations between mean reaction time and variability and grey matter loss in AD, but not in LBD. Conclusions: This study shows that different aspects of reaction time performance are differentially affected by AD and LBD, with a difference in structural neural correlates underlying the observed behavioural deficits. While impaired attentional performance is linked to brain atrophy in AD, in LBD it might be related to functional or microstructural rather than macrostructural changes. [ABSTRACT FROM AUTHOR]

Abstract: A significant symptom of Lewy body dementia (LBD) is slow cognitive processing or bradyphrenia. In a previous fMRI task‐based study, we found slower responses in LBD, accompanied by greater deactivation in the default mode network. In this study, we investigated the timing and magnitude of the activations and deactivations with respect to reaction time to determine whether the slower responses in LBD were associated with delayed neuronal activity. Using fMRI, we examined the magnitude and latency of activations and deactivations during an event‐related attention task in 32 patients with LBD and 23 healthy controls using predefined regions of interest. Default mode network deactivations did not significantly differ in their timing between groups or task conditions, while the task‐related activations in the parietal, occipital, frontal, and motor cortex were all significantly later in the LBD group. Repeating the analysis with reaction time as a parametric modulator of activation magnitude produced similar findings, with the reaction time modulator being significant in a number of regions including the default mode network, suggesting that the increased deactivation in LBD is partly explained by slower task completion. Our data suggest that the default mode network deactivation is initiated at the start of the task, and remains deactivated until its end, with the increased magnitude of deactivation in LBD reflecting the more prolonged cognitive processing in these patients. These data add substantially to our understanding of the neural origins of bradyphrenia, which will be essential for determining optimum therapeutic strategies for cognitive impairment in LBD. Hum Brain Mapp 39:633–643, 2018. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Visual hallucinations are common in dementia with Lewy bodies (DLB), although their etiology is unclear. This study aimed to investigate the relationship between severity and frequency of hallucinations and regional brain glucose metabolism. We performed brain FDG-PET scanning on 28 subjects with DLB (mean age 76). The neuropsychiatric index (NPI) was used to assess frequency and severity of hallucinations. We used the SPM package to investigate voxelwise correlations between NPI hallucination score (severity x frequency) and FDG uptake relative to the cerebellum. There was a bilateral medial occipital region where reduced FDG was associated with increased hallucination severity and frequency. We conclude that the reduced occipital metabolism frequently seen in DLB is associated with frequency and severity of visual hallucinations. Further studies are required to investigate whether this is the result of deficits in top-down or bottom-up visual processing pathways. [ABSTRACT FROM AUTHOR]

Background: Imaging biomarkers for Alzheimer's disease include medial temporal lobe atrophy (MTLA) depicted on computed tomography (CT) or magnetic resonance imaging (MRI) and patterns of reduced metabolism on fluorodeoxyglucose positron emission tomography (FDG-PET).Aims: To investigate whether MTLA on head CT predicts the diagnostic usefulness of an additional FDG-PET scan.Method: Participants had a clinical diagnosis of Alzheimer's disease (n = 37) or dementia with Lewy bodies (DLB; n = 30) or were similarly aged controls (n = 30). We visually rated MTLA on coronally reconstructed CT scans and, separately and blind to CT ratings, abnormal appearances on FDG-PET scans.Results: Using a pre-defined cut-off of MTLA ⩾5 on the Scheltens (0-8) scale, 0/30 controls, 6/30 DLB and 23/30 Alzheimer's disease had marked MTLA. FDG-PET performed well for diagnosing Alzheimer's disease v DLB in the low-MTLA group (sensitivity/specificity of 71%/79%), but in the high-MTLA group diagnostic performance of FDG-PET was not better than chance.Conclusions: In the presence of a high degree of MTLA, the most likely diagnosis is Alzheimer's disease, and an FDG-PET scan will probably not provide significant diagnostic information. However, in cases without MTLA, if the diagnosis is unclear, an FDG-PET scan may provide additional clinically useful diagnostic information. [ABSTRACT FROM AUTHOR]

Background: Individuals with Lewy body dementia (LBD) typically exhibit impairments in attentional and executive function. Current pharmacological treatments have limited efficacy, with associated side effects. Transcranial direct current stimulation (tDCS) may represent an alternative treatment, as cognitive improvements have been demonstrated in healthy individuals. However, no studies to date have assessed the feasibility of tDCS in an LBD population. The aim of this preliminary study, therefore, was to assess the tolerability of tDCS, as well as its effects upon attentional and visuoperceptual performance, in LBD patients.Methods: Thirteen participants completed attentional (simple reaction time, choice reaction time, and digit vigilance) and forced-choice visuoperceptual (angle and motion perception) tasks before and after one 20-min session of active tDCS (0.08 mA/cm2). The anodal electrode was applied to the left dorsolateral prefrontal cortex and the cathodal electrode was applied to the right deltoid. Attentional (task accuracy and reaction time to correct answers) and visuoperceptual (task accuracy and difficulty) outcome measures were compared using paired t-tests.Results: All participants tolerated stimulation and did not report any side effects during or immediately after stimulation. Post-stimulation improvements were observed in the choice reaction time (increased percentage of correct answers; p = 0.01) and digit vigilance (reduced mean reaction time to correct answers; p = 0.02) attention tasks. Visuoperceptual task performance did not improve (all p-values > 0.05).Conclusions: Attentional, but not visuoperceptual, improvements were observed following stimulation in LBD patients. Larger-scale, placebo-controlled trials are needed to confirm whether tDCS is a useful treatment option for attentional deficits in LBD. [ABSTRACT FROM AUTHOR]

Objective: Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are two dementias with overlapping phenotypes. Clinically, these are differentiated by the one-year precedence rule between the onset of dementia with respect to Parkinsonism. In this report we aimed to find differences between DLB and PDD in functional connectivity (FC) using resting state functional magnetic resonance imaging, which we hypothesised would reflect the underlying pathological differences between DLB and PDD.Methods: The study cohort comprised of 18 patients with DLB, 12 with PDD and 17 healthy control (HC) groups. Eight cortical and four subcortical seeds were chosen, and time series extracted to estimate correlation maps. We also implemented a voxel-based morphometry (VBM) analysis to assess regional grey matter differences. FC analysis was corrected for age, sex and regional grey matter differences.Results: The FC analysis showed greater alterations in DLB than in PDD for seeds placed within the fronto-parietal network (FPN), whilst in contrast, for the supplementary motor area seed FC alterations were more apparent in PDD than in DLB. However, when comparing DLB and PDD, no significant differences were found. In addition, VBM analysis revealed greater atrophy in PDD than HC and DLB in the bilateral motor cortices and precuneus respectively.Conclusions: PDD and DLB demonstrate similar FC alterations in the brain. However, attention- and motor-related seeds revealed subtle differences between both conditions when compared with HC, which may relate to the neuropathology and chronological precedence of core symptoms in the Lewy body dementias. [ABSTRACT FROM AUTHOR]

Background: Resting-state functional magnetic resonance imaging (fMRI) can be used to measure correlations in spontaneous low-frequency fluctuations in the blood oxygen level-dependent (BOLD) signal which represent functional connectivity between key brain areas.Aims: To investigate functional connectivity with regions hypothesised to be differentially affected in dementia with Lewy bodies (DLB) compared with Alzheimer's disease and controls.Method: Fifteen participants with probable DLB, 16 with probable Alzheimer's disease and 16 controls were scanned in the resting-state using a 3T scanner. The BOLD signal time-series of fluctuations in seed regions were correlated with all other voxels to measure functional connectivity.Results: Participants with DLB and Alzheimer's disease showed greater caudate and thalamic connectivity compared with controls. Those with DLB showed greater putamen connectivity compared with those with Alzheimer's disease and the controls. No regions showed less connectivity in DLB or Alzheimer's disease v. controls, or in DLB v. Alzheimer's disease.Conclusions: Altered connectivity in DLB and Alzheimer's disease provides new insights into the neurobiology of these disorders and may aid in earlier diagnosis. [ABSTRACT FROM AUTHOR]

Objectives Visuo-perceptual abnormalities are a prominent feature in dementia with Lewy bodies (DLB) and also occur in Alzheimer's disease (AD) to a lesser extent. We studied the progression of visuo-perceptual abnormalities over a 12-month period in DLB and AD by using a novel computerised test battery. Methods Following our previous work using the Newcastle Visual Perception (NEVIP) battery, we re-assessed 16 AD, 12 DLB and 28 similar-aged comparison participants 12 months after initial baseline assessment. Results DLB visual perception at follow-up showed worse performance than AD ( U = 43, p = 0.027); however, there were no significant changes in visuo-perceptual scores between baseline assessment and 12-month assessment within groups. A poor baseline score on the NEVIP predicted subsequent deterioration on the Bristol Activities of Daily Living Scale ( rs = −0.725, p = 0.014) in DLB participants but not in the AD group. Conclusions The NEVIP is a reliable test of visuo-perception, relatively independent of cognitive decline, with predictive value in identifying DLB participants at risk of functional decline. Visuo-perceptual dysfunction is a core feature of the disorder for some DLB patients and was stable over the 12-month period examined here. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

We examined 99mTc-exametazime brain blood flow single-photon emission computed tomography (SPECT) images using a spatial covariance analysis (SCA) approach to assess its diagnostic value in distinguishing dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). Voxel SCA was simultaneously applied to a set of preprocessed images (AD, n=40; DLB, n=26), generating a series of eigenimages representing common intercorrelated voxels in AD and DLB. Linear regression derived a spatial covariance pattern (SCP) that discriminated DLB from AD. To investigate the diagnostic value of the model SCP, the SCP was validated by applying it to a second, independent, AD and DLB cohort (AD, n=34; DLB, n=29). Mean SCP expressions differed between AD and DLB (F1,64=36.2, P<0.001) with good diagnostic accuracy (receiver operating characteristic (ROC) curve area 0.87, sensitivity 81%, specificity 88%). Forward application of the model SCP to the independent cohort revealed similar differences between groups (F1,61=38.4, P<0.001), also with good diagnostic accuracy (ROC 0.86, sensitivity 80%, specificity 80%). Multivariate analysis of blood flow SPECT data appears to be robust and shows good diagnostic accuracy in two independent cohorts for distinguishing DLB from AD. [ABSTRACT FROM AUTHOR]

Background: Visual hallucinations and visuoperceptual deficits are common in dementia with Lewy bodies, suggesting that cortical visual function may be abnormal.Aims: To investigate: (1) cortical visual function using functional magnetic resonance imaging (fMRI); and (2) the nature and severity of perfusion deficits in visual areas using arterial spin labelling (ASL)-MRI.Method: In total, 17 participants with dementia with Lewy bodies (DLB group) and 19 similarly aged controls were presented with simple visual stimuli (checkerboard, moving dots, and objects) during fMRI and subsequently underwent ASL-MRI (DLB group n = 15, control group n = 19).Results: Functional activations were evident in visual areas in both the DLB and control groups in response to checkerboard and objects stimuli but reduced visual area V5/MT (middle temporal) activation occurred in the DLB group in response to motion stimuli. Posterior cortical perfusion deficits occurred in the DLB group, particularly in higher visual areas.Conclusions: Higher visual areas, particularly occipito-parietal, appear abnormal in dementia with Lewy bodies, while there is a preservation of function in lower visual areas (V1 and V2/3). [ABSTRACT FROM AUTHOR]

Abstract: White matter changes have been investigated in Alzheimer''s disease (AD) in a number of studies using diffusion imaging. Fewer studies have investigated dementia with Lewy bodies (DLB). We used diffusion-weighted magnetic resonance imaging (MRI) and high-resolution (0.3 mm in-plane) coronal 3T MRI of the medial temporal lobe in 16 subjects with AD, 16 with DLB and 16 similarly aged healthy subjects. We found increased mean diffusivity in the temporal lobe of AD, and reduced fractional anisotropy (FA) in a small cluster in the right postcentral gyrus region in the DLB group. Mean FA in this cluster correlated with UPDRS (Unified Parkinson''s Disease Rating Scale) motor score. We had previously reported reduced visibility in the AD group of a dark appearing layer of the hippocampus in the high-resolution images. In an SPM analysis on all subjects, there were significant clusters of reduced FA in the corpus callosum, fornix and stria terminalis that correlated with the visual rating of the hippocampus. These results suggest that changes to the hippocampus are associated with structural changes to the white matter fibres of the hippocampus output, and that changes in motor function are associated with changes in white matter underlying somatosensory cortex. [Copyright &y& Elsevier]

We used high resolution (0.3 mm in-plane) coronal 3T magnetic resonance (MR) imaging of the medial temporal lobe in 16 subjects with Alzheimer's disease (AD), 16 with dementia with Lewy bodies (DLB), and 16 similarly aged healthy subjects. On the anterior section of the hippocampus body, regions of interest were manually drawn blind to diagnosis on the CA1, CA2, and CA3/4 subregions, and the width of the subiculum and entorhinal cortex was measured. Controlling for intracranial volume, age, and years of education, we found the subiculum thickness was significantly reduced in AD (2.03 ± 0.29 mm) compared to both control (2.37 ± 0.28 mm, p = 0.008) and DLB (2.35 ± 0.24 mm, p = 0.001) subjects. The area of CA1 was likewise reduced in AD compared to controls and DLB. In the hippocampus images, a hypointense line is visible between CA1 and CA3/4. This line was significantly less distinct in AD, suggesting disease related changes to this region. Future studies should investigate whether subiculum thickness or the hypointense line could be a diagnostic feature to help discriminate AD from DLB. [ABSTRACT FROM AUTHOR]

99mTc-exametazime single photon emission computed tomography (SPECT) scans of 36 patients with Alzheimer's disease (AD) and 30 with dementia with Lewy bodies (DLB) underwent region of interest (ROI) and principal component analysis (PCA). Principal component analysis was performed on the entire ROI data set. Principal components (PCs) were obtained, representing common intercorrelated regions in AD and DLB. Topographic expression that signified the extent to which a participant expressed the topographic covariance pattern was derived and used as a discriminatory variable. Principal components were identified, accounting for 77% of total data variance. Significant (PC × group) interaction was observed (P < .001). Topographic expression was significantly higher in DLB than AD (F1,64 = 21.6, P < .001), and differentiated DLB from AD with sensitivity 73% specificity 72%. Calculating the topographic expression in an independent data set of 48 patients with AD and 23 with DLB gave sensitivity = 70%, specificity = 67%. Principal component analysis captures additional sources of variance and if perfusion SPECT is the only scan available, this procedure may offer extra information. [ABSTRACT FROM AUTHOR]

Abstract: Hippocampal atrophy and posterior cingulate hypometabolism are common features of both Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB). These regions show correlated activity at rest as part of the ‘default network’, and they are connected by the cingulum, a white matter (WM) tract. We hypothesised that hippocampal atrophy would be associated with disruption of the cingulum, as determined by diffusion tensor imaging. We recruited 15 people with AD, 16 with DLB, and 15 healthy control subjects of similar age. They were scanned on a 1.5 T MRI system with a T1 weighted 3D sequence and diffusion tensor FLAIR imaging. The T1 images were segmented into grey and white matter and spatially normalised using SPM. Hippocampal atrophy was estimated by calculating the mean grey matter (GM) volume from a region of interest in standard space and global atrophy from the total CSF segmentation. Fractional anisotropy (FA) maps were calculated and also spatially normalised. Using SPM, a multivariate correlation of FA against hippocampal GM, global atrophy and disease group was performed. We found a bilateral region adjacent to the posterior cingulate and encompassing a branch of the cingulum where global atrophy correlated with fractional anisotropy, after controlling for diagnosis and hippocampal GM. The results suggest that dementia disease progression as measured by global atrophy is associated with disruption of the white matter which connects posterior cingulate and lateral parietal regions. Hence, in addition to the hypometabolism in these regions in AD and DLB, there is also disruption to the white matter connecting them. Future studies are needed to determine whether the disruption precedes or is consequent on atrophy or hypometabolism. [Copyright &y& Elsevier]

Background People with Parkinson's disease (PD) have an increased risk of developing dementia (PDD), which often has clinical features similar to dementia with Lewy bodies (DLB). Whilst perfusion studies have shown parieto-occipital hypoperfusion in DLB and PDD relative to controls, there have not been any longitudinal studies of perfusion changes in PDD and DLB. Methods In this study, we measured brain perfusion using Tc99m HMPAO SPECT over one year in 17 PDD, 18 DLB and 34 healthy subjects. We used SPM99 to compare perfusion changes in the two dementia groups against the control group. Results We did not see any reductions in perfusion in either of the dementia groups. However, in the DLB, but not PDD group, there was a significant increase in putamen perfusion relative to controls over the year. In both DLB and PDD groups, there was a correlation between striatal perfusion increase over the year, and worsening of parkinsonism. Perfusion changes were not secondary to changes in antiparkinsonian medication. Conclusion The increase in striatal perfusion may be a compensatory change related to decreasing striatal dopaminergic input from the substantia nigra in PDD and DLB, consistent with the increased predominance of rigidity over tremor symptoms in these groups compared with non-demented PD. Copyright © 2005 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

• In the differential diagnosis of dementia with Lewy body and Alzhiemer's disease, spatial covariance analysis of FDG-PET significantly outperforms that of HMPAO-SPECT. • With a relatively small derivation group, spatial covariance analysis of FDG-PET performed similarly to visual interpretation and a univariate quantification method. • Unlike the univariate method, there was little concordance between spatial covariance analysis and visual interpretation of FDG-PET scans, implying that spatial covariance analysis and visual interpretation rely on different sources of variance to separate disease subgroups. We investigated diagnostic characteristics of spatial covariance analysis (SCA) of FDG-PET and HMPAO-SPECT scans in the differential diagnosis of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), in comparison with visual ratings and region of interest (ROI) analysis. Sixty-seven patients (DLB 29, AD 38) had both HMPAO-SPECT and FDG-PET scans. Spatial covariance patterns were used to separate AD and DLB in an initial derivation group (DLB n=15, AD n=19), before being forward applied to an independent group (DLB n=14, AD n=19). Visual ratings were by consensus, with ROI analysis utilising medial occipital/medial temporal uptake ratios. SCA of HMPAO-SPECT performed poorly (AUC 0.59±0.10), whilst SCA of FDG-PET (AUC 0.83±0.07) was significantly better. For FDG-PET, SCA showed similar diagnostic performance to ROI analysis (AUC 0.84±0.08) and visual rating (AUC 0.82±0.08). In contrast to ROI analysis, there was little concordance between SCA and visual ratings of FDG-PET scans. We conclude that SCA of FDG-PET outperforms that of HMPAO-SPECT. SCA of FDG-PET also performed similarly to the other analytical approaches, despite the limitations of a relatively small SCA derivation group. Compared to visual rating, SCA of FDG-PET relies on different sources of group variance to separate DLB from AD. [ABSTRACT FROM AUTHOR]

• Lewy body disease (LBD) includes dementia with Lewy bodies and Parkinson's disease. • We meta-analyzed anatomical/cognitive studies of visual hallucinations (VH) in LBD. • VH were associated with reduced occipital, temporal, frontal, and parietal grey matter. • VH without dementia were associated with deficits in verbal immediate memory. Visual hallucinations (VH) are common in Parkinson's disease and dementia with Lewy bodies, two forms of Lewy body disease (LBD), but the neural substrates and mechanisms involved are still unclear. We conducted meta-analyses of voxel-based morphometry (VBM) and neuropsychological studies investigating the neuroanatomical and cognitive correlates of VH in LBD. For VBM (12 studies), we used Seed-based d Mapping with Permutation of Subject Images (SDM-PSI), including statistical parametric maps for 50% of the studies. For neuropsychology (35 studies), we used MetaNSUE to consider non-statistically significant unreported effects. VH were associated with smaller grey matter volume in occipital, frontal, occipitotemporal, and parietal areas (peak Hedges' g -0.34 to -0.49). In patients with Parkinson's disease without dementia, VH were associated with lower verbal immediate memory performance (Hedges' g -0.52). Both results survived correction for multiple comparisons. Abnormalities in these brain regions might reflect dysfunctions in brain networks sustaining visuoperceptive, attention, and executive abilities, with the latter also being at the basis of poor immediate memory performance. [ABSTRACT FROM AUTHOR]

Abstract Although dementia with Lewy bodies (DLB) is a synucleinopathy, it is frequently accompanied by beta amyloid (Aβ) accumulation. Elucidating the relationships of Aβ with gray matter atrophy in DLB may yield insights regarding the contributions of comorbid Alzheimer's disease to its disease progression. Twenty healthy controls and 25 DLB subjects underwent clinical assessment, [18F]-Florbetapir, and 3T magnetic resonance imaging. FreeSurfer was used to estimate cortical thickness and subcortical volumes, and PetSurfer was used to quantify [18F]-Florbetapir standardized uptake value ratio. Principal component analysis was used to identify the dominant Aβ component for correlations with regional cortical thickness, hippocampal subfields, and subcortical structures. Relative to healthy controls, the DLB group demonstrated increased Aβ in widespread regions encompassing the frontal and temporoparietal cortices, whereas cortical thinning was restricted to the temporal lobe. Among DLB subjects, the Aβ component was significantly associated with more severe hippocampal and subiculum atrophy. These findings may reflect an early process of superimposed AD-like atrophy in DLB, thereby conferring support for the therapeutic potential of anti-Aβ interventions in people with DLB. [ABSTRACT FROM AUTHOR]

Neuropsychiatric symptoms (NPS) in Lewy body dementias (LBD) occur frequently and early in disease progression. Such symptoms are associated with worse quality of life, caregiver burden and functional limitations. Limited evidence exists, however, outlining the longitudinal relationship between NPS and cognitive decline in prodromal LBD. 123 participants were derived from three cohort studies. Patients with mild cognitive impairment (MCI) relating to probable dementia with Lewy bodies (MCI-LB, n = 67) and Parkinson's disease (PD-MCI, n = 56) completed comprehensive cognitive and neuropsychiatric assessment and were followed up longitudinally. Linear regression and mixed effects models assessed the relationship between baseline NPS and cognition at baseline and over time. In MCI-LB, overall NPS burden was associated with declines over time in executive function (p = 0.026) and processing speed (p = 0.028) and baseline aberrant motor behaviour was associated with declines in attention (p < 0.025). Anxiety was significantly associated with poorer visuospatial functioning (p = 0.016) at baseline and poorer attention both at baseline (p = 0.017) and across time points (p = 0.024). In PD-MCI, psychosis was associated with poorer executive functioning at baseline (p = 0.008) and across time points (p = 0.002) but had no association with changes longitudinally. Core neuropsychiatric components of LBD are not strongly associated with cognition in prodromal disease. This may suggest that neuropathological mechanisms underlying NPS may not be the same as those underlying cognitive impairment. Non-core NPS, however, may be more directly associated with cognitive change. Future studies utilising neuroimaging techniques are needed to explore the neuropathological basis of NPS in prodromal LBD. • Neuropsychiatric symptoms may be mechanistically independent of cognitive decline. • Common core symptoms are unrelated to cognitive decline in prodromal Lewy body dementia. • MCI-LB demonstrated significantly greater neuropsychiatric symptom severity and prevelence compared to PD-MCI participants. [ABSTRACT FROM AUTHOR]

Dopaminergic loss can be visualised using 123I-FP-CIT single photon emission computed tomography (SPECT) in several disorders including Parkinson''s disease (PD) and dementia with Lewy bodies (DLB). Most previous SPECT studies have adopted region of interest (ROI) methods for analysis, which are subjective and operator-dependent. The purpose of this study was to investigate differences in striatal binding of 123I-FP-CIT SPECT using the automated technique of statistical parametric mapping (SPM99) in subjects with DLB, Alzheimer''s disease (AD), PD and healthy age-matched controls. This involved spatial normalisation of each subject''s image to a customised template, followed by smoothing and intensity normalisation of each image to its corresponding mean occipital count per voxel. Group differences were assessed using a two-sample t test. Applying a height threshold of P ≤ 0.05 corrected, the SPM{t} maps showed a significant bilateral reduced uptake in caudate, anterior and posterior putamen in DLB and PD subjects compared to AD subjects and controls. Significant reduction in binding was also observed bilaterally in the caudate nucleus in AD compared to controls. Striatal binding was indistinguishable between patients with DLB and PD. To investigate the usefulness of SPM as a decision aid in the evaluation of visually rated normal and abnormal patterns of uptake, receiver operator characteristic (ROC) curve analysis was performed using data from single-subject SPMs. The areas under the ROC curves were greater than 0.92, demonstrating comparable discriminatory power with visual rating. The automated voxel-based approach is a viable alternative to the subjective and often time-consuming method of ROI and, in addition, may have the potential to differentiate between normal and abnormal patterns of uptake in a manner similar to visual inspection. [Copyright &y& Elsevier]