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Background: Previous studies suggest that posterior cortical atrophy may be a useful marker for early onset Alzheimer's disease (AD). Dementia with Lewy bodies (DLB) is associated with less temporal lobe atrophy than AD, though posterior cortical atrophy may be greater. Therefore, we assessed whether visual rating scales for assessing posterior atrophy (PA), medial temporal lobe atrophy (MTA), and ventricular enlargement (VEn) aid in the discrimination between AD, DLB, and normal aging.Methods: T1-weighted MRI scans acquired at 3 Tesla were visually rated for PA (range 0-3), MTA (range 0-4), and VEn (range 0-3) in older subjects with AD (n = 36), DLB (n = 35), and healthy controls (n = 35). The diagnostic utility of MTA, PA, and VEn visual ratings in distinguishing AD and DLB from controls as well as AD from DLB was investigated.Results: Significantly higher MTA ratings were associated with AD and DLB compared to controls (p < 0.001). MTA ratings were greater in AD relative to DLB (U = 384.5, p = 0.004). For PA ratings, scores did not differ between groups (p = 0.20). VEn ratings were significantly higher in AD and DLB compared to controls (p = 0.003), but similar between AD and DLB (U = 384.5, p = 0.4).Conclusions: Unlike findings reported in younger subjects, visual ratings for PA are not a reliable marker at older ages for distinguishing AD from controls, or for distinguishing DLB from AD. However, visual ratings of MTA and VEn may be useful markers in distinguishing both AD and DLB from older subjects without dementia. [ABSTRACT FROM AUTHOR]

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]

BACKGROUND: Growing evidence suggests that cerebral white-matter changes and depressive symptoms are linked directly along the causal pathway. We investigated whether baseline severity of cerebral white-matter changes predict longer-term future depressive outcomes in a community sample of non-disabled older adults. METHOD: In the Leukoaraiosis and Disability in the Elderly (LADIS) study, a longitudinal multi-centre pan-European study, 639 older subjects underwent baseline structural magnetic resonance imaging (MRI) and clinical assessments. Baseline severity of white-matter changes was quantified volumetrically. Depressive outcomes were assessed in terms of depressive episodes and depressive symptoms, as measured by the Geriatric Depression Scale (GDS). Subjects were clinically reassessed annually for up to 3 years. Regression models were constructed to determine whether baseline severity of white-matter changes predicted future depressive outcomes, after controlling for confounding factors. RESULTS: Baseline severity of white-matter changes independently predicted depressive symptoms at both 2 (p<0.001) and 3 years (p=0.015). Similarly, white-matter changes predicted incident depression (p=0.02). Over the study period the population became significantly more disabled (p<0.001). When regression models were adjusted to account for the influence of the prospective variable transition to disability, baseline severity of white-matter changes no longer predicted depressive symptoms at 3 years (p=0.09) or incident depression (p=0.08). CONCLUSIONS: Our results support the vascular depression hypothesis and strongly implicate white-matter changes in the pathogenesis of late-life depression. Furthermore, the findings indicate that, over time, part of the relationship between white-matter changes and depression may be mediated by loss of functional activity. [ABSTRACT FROM AUTHOR]

(99m)Tc-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 x group) interaction was observed (P < .001). Topographic expression was significantly higher in DLB than AD (F(1,64) = 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]

Background: The aim of this study is to investigate the diagnostic value of perfusion 99mTc-exametazime single photon emission computed tomography (SPECT) in the diagnosis of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) in comparison with dopaminergic 123I-2beta-carbomethoxy-3beta-(4-iodophenyl)-n-(3-fluoropropyl) nortropane (FP-CIT) SPECT imaging.Methods: Subjects underwent 99mTc-exametazime scanning (39 controls, 36 AD, 30 DLB) and 123I-FP-CIT scanning (33 controls, 33 AD, 28 DLB). For each scan, five raters performed visual assessments blind to clinical diagnosis on selected transverse 99mTc-exametazime images in standard stereotactic space. Diagnostic accuracy of 99mTc-exametazime was compared to 123I-FP-CIT results for the clinically relevant subgroups AD and DLB using receiver operating characteristic (ROC) curve analysis.Results: Inter-rater agreement for categorizing uptake was "moderate" (mean kappa = 0.53) for 99mTc-exametazime and "excellent" (mean kappa = 0.88) for 123I-FP-CIT. For AD and DLB, consensus rating matched clinical diagnosis in 56% of cases using 99mTc-exametazime and 84% using 123I-FP-CIT. In distinguishing AD from DLB, ROC analysis revealed superior diagnostic accuracy with 123I-FP-CIT (ROC curve area 0.83, sensitivity 78.6%, specificity 87.9%) compared to occipital 99mTc-exametazime (ROC curve area 0.64, sensitivity 64.3%, specificity 63.6%) p = 0.03.Conclusion: Diagnostic accuracy was superior with 123I-FP-CIT compared to 99mTc-exametazime in the differentiation of DLB from AD. [ABSTRACT FROM AUTHOR]

BACKGROUND: White matter hyperintensities have been associated with the development of depression in older subjects, though the details of this relationship are not fully understood. METHODS: In a pan-European multicentre study of 629 older subjects, we examined the relationship between MRI white matter hyperintensities (WMH), depressive symptoms and self perceived health quality of life (QOL). WMH were rated using a three-point scale. RESULTS: We found depressive symptoms as assessed by the geriatric depression 15-item scale to be associated with WMH rating (Spearman's rho 0.11, p = 0.008) and also with the Euro-QOL health score (Spearman's rho -0.5, p < 0.001). In a ordinal logistic regression model, QOL was found to strongly predict GDS score (p < 0.001) and severe vs mild WMH were associated with increased depression (p = 0.028). The relationship between history of severe depression and WMH score was examined, but there were no differences either between those with and without a history of severe depression, or those with an early vs late onset of depression. CONCLUSIONS: The results suggest that WMH play a role in increasing depressive symptoms, even when perceived quality of life is controlled for as a possible mediating factor. [ABSTRACT FROM AUTHOR]

REM sleep behaviour disorder (RBD) is a parasomnia characterised by dream-enacting behaviour with loss of muscle atonia during REM sleep and is a prodromal feature of α-synucleinopathies like Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Although cortical-to-subcortical connectivity is well-studied in RBD, cerebellar and subcortical nuclei reciprocal connectivity is less established. Nonetheless, it could be relevant since RBD pathology involves brainstem structures with an ascending gradient. In this study, we utilised resting-state functional MRI to investigate 13 people with isolated RBD (iRBD), 17 with Parkinson's disease and 16 healthy controls. We investigated the connectivity between the basal ganglia, thalamus and regions of the cerebellum. The cerebellum was segmented using a functional atlas, defined by a resting-state network-based parcellation, rather than an anatomical one. Controlling for age, we found a significant group difference (F 4,82 = 5.47, p FDR = 0.017) in cerebellar-thalamic connectivity, with iRBD significantly lower compared to both control and Parkinson's disease. Specifically, cerebellar areas involved in this connectivity reduction were related to the default mode, language and fronto-parietal resting-state networks. Our findings show functional connectivity abnormalities in subcortical structures that are specific to iRBD and may be relevant from a pathophysiological standpoint. Further studies are needed to investigate how connectivity changes progress over time and whether specific changes predict disease course or phenoconversion., (© 2024. The Author(s).)

Background and Objectives: Retrospective studies indicate that dementia with Lewy bodies (DLB) may be preceded by a mild cognitive impairment (MCI) prodrome. Research criteria for the prospective identification of MCI with Lewy bodies (MCI-LB) have been developed. We aimed to assess the prognosis of a prospectively identified MCI-LB cohort at 2 key milestones, 3- and 5 years after diagnosis, to examine classification stability over time and rates of adverse outcomes (dementia or death)., Methods: This was a retrospective examination of data from 2 longitudinal observational cohort studies where participants with MCI were prospectively recruited from North East England and differentially classified as MCI due to Alzheimer disease (MCI-AD), possible MCI-LB, or probable MCI-LB. Adverse outcomes (DLB/other dementia or death) and stability of disease-specific classifications were examined in each group., Results: Of 152 participants with baseline MCI (54 MCI-AD, 29 possible MCI-LB, and 69 probable MCI-LB), 126 were followed for up to 3 years (mean age 75.3 years; 40% female). We found that prospective probable MCI-LB classifications were both sensitive (91%) and specific (94%) to classifications either remaining as probable MCI-LB or progressing to DLB (in some cases autopsy confirmed) for 3 or more years after. Classifications were at least as stable as those in MCI-AD. In this cohort with disease-specific MCI classifications, rates of progression to dementia were high: 55% of MCI-LB had developed DLB within 3 years. Dementia occurred in 47% of MCI-AD over the same duration (odds ratio 1.68, 95% CI 0.66-4.26, p = 0.278). Premature death was a common competing risk, occurring in 9% of MCI-AD and 11% of MCI-LB within 3 years., Discussion: These findings support that prospectively identified probable MCI-LB is a prodromal presentation of DLB and that disease-specific classifications of MCI may reliably identify different prodromal dementias.

Objective: To investigate hypothalamic atrophy and its clinical correlates in multiple system atrophy (MSA) in-vivo., Background: MSA is characterized by autonomic dysfunction and parkinsonian/cerebellar manifestations. The hypothalamus regulates autonomic and homeostatic functions and is also involved in memory and learning processes., Methods: 11 MSA, 18 Parkinson's Disease (PD) and 18 Healthy Controls (HC) were included in this study. A validated and automated hypothalamic segmentation tool was applied to 3D-T1-weighted images acquired on a 3T MRI scanner. MSA hypothalamic volumes were compared to those of PD and HC. Furthermore, the association between hypothalamic volumes and scores of autonomic, depressive, sleep and cognitive manifestations were investigated., Results: Posterior hypothalamus volume was reduced in MSA compared to controls (t = 2.105, p = 0.041) and PD (t = 2.055, p = 0.046). Total hypothalamus showed a trend towards a reduction in MSA vs controls (t = 1.676, p = 0.101). Reduced posterior hypothalamus volume correlated with worse MoCA scores in the parkinsonian (MSA + PD) group and in each group separately, but not with autonomic, sleep, or depression scores., Conclusions: In-vivo structural hypothalamic involvement may be present in MSA. Reduced posterior hypothalamus volume, which includes the mammillary bodies and lateral hypothalamus, is associated with worse cognitive functioning. Larger studies on hypothalamic involvement in MSA and its clinical correlates are needed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Visual hallucinations are a common, potentially distressing experience of people with Lewy body disease (LBD). The underlying brain changes giving rise to visual hallucinations are not fully understood, although previous models have posited that alterations in the connectivity between brain regions involved in attention and visual processing are critical., Methods: Data from 41 people with LBD and visual hallucinations, 48 with LBD without visual hallucinations and 60 similarly aged healthy comparator participants were used. Connections were investigated between regions in the visual cortex and ventral attention, dorsal attention and default mode networks., Results: Participants with visual hallucinations had worse cognition and motor function than those without visual hallucinations. In those with visual hallucinations, reduced functional connectivity within the ventral attention network and from the visual to default mode network was found. Connectivity strength between the visual and default mode network correlated with the number of correct responses on a pareidolia task, and connectivity within the ventral attention network with visuospatial performance., Conclusions: Our results add to evidence of dysfunctional connectivity in the visual and attentional networks in those with LBD and visual hallucinations., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Introduction: 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., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: Declaration of competing interest Dr Paul Donaghy has received grant support by the Medical Research Council, the Lewy Body Society and Alzheimer's Research UK. Dr Donaghy has also received payment for lectures by the Neurology Academy and has an unpaid leadership role on the Lewy Body Society Specialist Advisory Committee. Professor John-Paul Taylor is supported by the NIHR Newcastle Biomedical Research Centre. Professor John O'Brien has received grant support from Alliance Medical and Merck, consulting fees from Roche and Biogen and lecture fees from GE Healthcare. Professor O'Brien also participates on advisory boards for TauRx, Novo Nordisk and chairs the research strategy board for UK Alzheimer's Society. Dr Alison Yarnall has received grant support from the Dunhill Medical Trust, EU IMI, NIHR, Parkinson's UK, Michael J Fox Foundation, Weston Brain Institute and Intercept pharmaceuticals. Dr Yarnall has also received funding and/or honoraria from Britannia, UCB, Abbvie, GSK, Teva-Lundbeck, GE Healthcare and Genus for attending educational events. The remaining authors have no competing interests to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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 p s > .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.

Multiple system atrophy (MSA) is a neurodegenerative disease characterized by autonomic failure, ataxia, and/or parkinsonism. Its prominent pathological alterations can be investigated using diffusion magnetic resonance imaging (dMRI), a technique that exploits the characteristics of water random motion inside brain tissue. The aim of this report was to review currently available literature on the application of dMRI in MSA and to describe microstructural abnormalities, diagnostic applications, and pathophysiological correlates. Sixty-four published studies involving microstructural investigation using dMRI in MSA were included. Widespread microstructural abnormalities of white matter were described, especially in the middle cerebellar peduncle, corticospinal tract, and hemispheric fibers. Gray matter degeneration was identified as well, with diffuse involvement of subcortical structures, especially in the putamina. Diagnostic applications of dMRI were mostly explored for the differential diagnosis between MSA parkinsonism and Parkinson's disease. Recently, machine learning algorithms for image processing and disease classification have demonstrated high diagnostic accuracy, showing potential for translation into clinical practice. To a lesser extent, clinical correlates of microstructural abnormalities have also been investigated, and abnormalities related to motor, ocular, and cognitive impairments were described. dMRI in MSA has contributed to in vivo identification of known pathological abnormalities. Translation into clinical practice of the latest advancements for the differential diagnosis between MSA and other forms of parkinsonism seems feasible. Current limitations involve the possibility of correctly diagnosing MSA in the very early stages, when the clinical diagnosis is most uncertain. Furthermore, pathophysiological correlates of microstructural abnormalities remain understudied. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Objective cognitive impairment is a feature of Lewy body dementia (LBD), and computerised attentional tasks are commonly used as outcome measures in interventional trials. However, the reliability of these measures, in the absence of interventions, are unknown. This study examined the reliability of these attentional measures at short-term and longer-term follow-up stages. LBD patients (n = 36) completed computerised attentional tasks [simple and choice reaction time, and digit vigilance (SRT, CRT, DV)] at short-term (Day 0-Day 5) and longer-term (4 and 12 weeks) follow-up. Intra-class correlations (ICCs) were calculated to assess test-retest reliability. At short-term, the reciprocal SRT, CRT and DV mean reaction time to correct answers, the reciprocal DV coefficient of variation, and reciprocal power of attention (PoA) all showed excellent levels of reliability (all ICCs > 0.90). The reciprocal PoA showed the highest level of reliability (ICC = 0.978). At longer-term follow-up, only the reciprocal PoA had excellent levels of reliability (ICC = 0.927). Reciprocal SRT, CRT and DV reaction time to correct answers, and the CRT coefficient of variation values, showed good levels of test-retest reliability (ICCs ≥ 0.85). Contrary to expectations, most attentional measures demonstrated high levels of test-retest reliability at both short-term and longer-term follow-up time points. The reciprocal PoA composite measure demonstrated excellent levels of test-retest reliability, both in the short-term and long-term. This indicates that objective attentional tasks are suitable outcome measures in LBD studies and that the composite PoA measure may offer the highest levels of reliability., (© 2022. The Author(s).)

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., (Copyright © 2022. Published by Elsevier B.V.)

Background: Gait impairments are characteristic motor manifestations and significant predictors of poor quality of life in Parkinson's disease (PD). Neuroimaging biomarkers for gait impairments in PD could facilitate effective interventions to improve these symptoms and are highly warranted., Objective: The aim of this study was to identify neural networks of discrete gait impairments in PD., Methods: Fifty-five participants with early-stage PD and 20 age-matched healthy volunteers underwent quantitative gait assessment deriving 12 discrete spatiotemporal gait characteristics and [ 18 F]-2-fluoro-2-deoxyglucose-positron emission tomography measuring resting cerebral glucose metabolism. A multivariate spatial covariance approach was used to identify metabolic brain networks that were related to discrete gait characteristics in PD., Results: In PD, we identified two metabolic gait-related covariance networks. The first correlated with mean step velocity and mean step length (pace gait network), which involved relatively increased and decreased metabolism in frontal cortices, including the dorsolateral prefrontal and orbital frontal, insula, supplementary motor area, ventrolateral thalamus, cerebellum, and cuneus. The second correlated with swing time variability and step time variability (temporal variability gait network), which included relatively increased and decreased metabolism in sensorimotor, superior parietal cortex, basal ganglia, insula, hippocampus, red nucleus, and mediodorsal thalamus. Expression of both networks was significantly elevated in participants with PD relative to healthy volunteers and were not related to levodopa dosage or motor severity., Conclusions: We have identified two novel gait-related brain networks of altered glucose metabolism at rest. These gait networks could serve as a potential neuroimaging biomarker of gait impairments in PD and facilitate development of therapeutic strategies for these disabling symptoms. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background and Objectives: In Charles Bonnet Syndrome (CBS), visual hallucinations (VH) are experienced by people with sight loss due to eye disease or lesional damage to early visual pathways. The aim of this cross-sectional study was to investigate structural brain changes using magnetic resonance imaging (MRI) in CBS., Methods: Sixteen CBS patients, 17 with eye disease but no VH, and 19 normally sighted people took part. Participants were imaged on a 3T scanner, with 1 mm resolution T1 weighted structural imaging, and diffusion tensor imaging with 64 diffusion directions., Results: The three groups were well matched for age, sex and cognitive scores (MMSE). The two eye disease groups were matched on visual acuity. Compared to the sighted controls, we found reduced grey matter in the occipital cortex in both eye disease groups. We also found reductions of fractional anisotropy and increased diffusivity in widespread areas, including occipital tracts, the corpus callosum, and the anterior thalamic radiation. We did not find any significant differences between the eye disease participants with VH versus without VH, but did observe a negative association between hippocampal volume and VH severity in the CBS group., Discussion: Our findings suggest that although there are cortical and subcortical effects associated with sight loss, structural changes do not explain the occurrence of VHs. CBS may relate instead to connectivity or excitability changes in brain networks linked to vision., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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., (© 2021 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)

Objective: To provide evidence that cardiac I-123-metaiodobenzylguanidine sympathetic innervation imaging (MIBG) scintigraphy differentiates probable mild cognitive impairment with Lewy bodies (MCI-LB) from mild cognitive impairment due to Alzheimer disease (MCI-AD), we scanned patients with MCI and obtained consensus clinical diagnoses of their MCI subtype. We also performed baseline FP-CIT scans to compare the accuracy of MIBG and FP-CIT., Methods: We conducted a prospective cohort study into the accuracy of cardiac MIBG scintigraphy in the diagnosis of MCI-LB. Follow-up clinical assessment was used to diagnose MCI-AD (no core features of MCI-LB and normal FP-CIT), probable MCI-LB (2 or more core features, or 1 core feature with abnormal FP-CIT), or possible MCI-LB (1 core feature or abnormal FP-CIT). For the comparison between MIBG and FP-CIT, only core clinical features were used for diagnosis., Results: We recruited 95 people with mild cognitive impairment. Cardiac MIBG was abnormal in 22/37 probable and 2/15 possible MCI-LB cases and normal in 38/43 MCI-AD cases. The sensitivity in probable MCI-LB was 59% (95% confidence interval [CI], 42%-75%), specificity 88% (75%-96%), and accuracy 75% (64%-84%). The positive likelihood ratio was 5.1 and negative likelihood ratio 0.46. With symptom-only diagnoses, the accuracies were 79% for MIBG (95% CI, 68%-87%) and 76% for FP-CIT (95% CI, 65%-85%)., Conclusions: Cardiac MIBG appears useful in early disease, with an abnormal scan highly suggestive of MCI-LB. Validation in a multicenter setting is justified., Classification of Evidence: This study provides Class I evidence that cardiac MIBG distinguishes MCI-LB from MCI-AD., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

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., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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.

Background and Aims: Consensus is lacking on whether light to moderate consumption of alcohol compared to abstinence is neuroprotective. In this study, we investigated the relationship between self-reported alcohol use and brain volume change over 2 years in middle-aged subjects., Methods: A sample of 162 subjects (aged 40-59 at baseline) from the PREVENT-Dementia programme underwent MRI scans on two separate occasions (mean interval 734 days; SD 42 days). We measured longitudinal rates of brain atrophy using the FSL Siena toolbox, and change in hippocampal volume from segmentation in SPM., Results: Controlling for age and sex, there were no significant associations of either total brain, ventricular, or hippocampal volume change with alcohol consumption. Adjusting for lifestyle, demographic and vascular risk factors did not alter this., Conclusions: We did not find any evidence of influence of alcohol consumption on changes in brain volume over a 2-year period in 40-60-year-olds.

Objective: Significant amyloid deposition is present in approximately half of all cases of dementia with Lewy bodies (DLB). We sought to determine whether amyloid deposition was associated with more rapid clinical decline over 1 year., Methods: Twenty-eight participants had a baseline clinical assessment and amyloid PET scan, followed by a further clinical assessment after 1 year. Changes in clinical measures were compared with amyloid deposition assessed by visual rating and cortical standardized uptake value ratio., Results: Amyloid deposition on visual rating was associated with greater decline in Mini-Mental State Examination and daily function over 1 year. There was no correlation between cortical standardized uptake value ratio and clinical measures., Conclusions: This study provides further evidence for a link between amyloid deposition and clinical progression in DLB. Pathologies such as amyloid, and their interaction with α-synuclein, remain possible treatment targets in DLB., (Copyright © 2020 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Increased rates of brain atrophy on serial MRI are frequently used as a surrogate marker of disease progression in Alzheimer's disease and other dementias. However, the extent to which they are associated with future risk of dementia in asymptomatic subjects is not clear. In this study, we investigated the relationship between the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) risk score and longitudinal atrophy in middle-aged subjects., Materials and Methods: A sample of 167 subjects (aged 40-59 at baseline) from the PREVENT-Dementia programme underwent MRI scans on two separate occasions (mean interval 735 days; SD 44 days). We measured longitudinal rates of brain atrophy using the FSL Siena toolbox., Results: Annual percentage rates of brain volume and ventricular volume change were greater in those with a high (>6) vs low CAIDE score-absolute brain volume percentage loss 0.17% (CI 0.07 to 0.27) and absolute ventricular enlargement 1.78% (CI 1.14 to 2.92) higher in the at risk group. Atrophy rates did not differ between subjects with and without a parental history of dementia, but were significantly correlated with age. Using linear regression, with covariates of age, sex and education, CAIDE score >6 was the only significant predictor of whole brain atrophy rates (p=0.025) while age (p=0.009), sex (p=0.002) and CAIDE>6 (p=0.017) all predicted ventricular expansion rate., Conclusion: Our results show that progressive brain atrophy is associated with increased risk of future dementia in asymptomatic middle-aged subjects, two decades before dementia onset., Competing Interests: Competing interests: JTO’B has no conflicts related to this study. Unrelated to this work, he has received honoraria for work as DSMB chair or member for TauRx, Axon, Eisai, has acted as a consultant for Lilly and has received honorarium for talks from GE Healthcare and research support from Alliance Medical., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2019 International Society of Neuropathology.)

The cingulate island sign (CIS) refers to the relative sparing of metabolism in the posterior cingulate cortex (PCC) and represents an important biomarker in distinguishing dementia with Lewy bodies (DLB) from Alzheimer disease (AD). The underlying basis of the CIS is unknown; therefore, our aim was to investigate which neurodegenerative changes underpin the formation of CIS. Using quantitative neuropathology, α-synuclein, phosphorylated Tau, and amyloid-β pathology was assessed in 12 DLB, 9 AD and 6 age-matched control patients in the anterior cingulate (ACC), midcingulate, PCC, precuneus/cuneus and parahippocampal gyrus. All participants had undergone 99mTc-hexamethylpropyleneamine oxime (HMPAO) single-photon emission computed tomography imaging during life to define the presence or absence of CIS. In the DLB group, no significant correlations were observed between CIS ratios and neurodegenerative pathology in PCC. In DLB, however, the ACC showed lower HMPAO uptake, as well as significantly higher α-synuclein and amyloid-β burden compared with PCC, possibly underlying the relative preservation of perfusion in PCC when compared with ACC. Our findings suggest that neurodegenerative pathology does not directly correlate with the CIS in DLB, and other metabolic or pathological changes are therefore more likely to be relevant for the development of the CIS., (© 2019 American Association of Neuropathologists, Inc.)

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.

Background: Complex visual hallucinations are common in Lewy body dementia (LBD) and can cause significant patient and caregiver distress. Current treatments are primarily pharmacological in nature and have limited efficacy and associated side effects. The objective of this study was to assess the effects of consecutive sessions of transcranial direct current stimulation (tDCS) on visual hallucination frequency and severity in LBD, at short-term and long-term follow-up stages., Methods: The study was a randomised, double-blind, placebo-controlled trial involving 40 participants with LBD (M age  = 75.52 years, SD age  = 8.69 years) which was conducted at a single site between November 2013 and December 2017. Participants received two consecutive 20-min sessions of active (0.048 mA/cm 2 ) or placebo tDCS, separated by a 30-min break, over 5 consecutive days. The anodal electrode was applied to the right parietal cortex (P4) and the cathodal electrode was applied to the occipital cortex (O z ). The primary outcome measure was the Neuropsychiatric Inventory (NPI) hallucinations subscale, as completed by a caregiver/informant at baseline and day 5 (short-term) follow-up, and month 1 and month 3 (long-term) follow-up. Secondary outcome measures included visual cortical excitability, as measured using transcranial magnetic stimulation, computerised attentional and visuoperceptual tasks, and measures of global cognition and cognitive fluctuations., Results: Complete study data were obtained from 36 participants. There was an overall improvement in visual hallucinations (NPI) for both groups at day 5 relative to baseline, with a medium-to-large effect size; however, compared to placebo, active tDCS did not result in any improvements in visual hallucinations (NPI) at day 5 relative to baseline, or at month 1 or month 3 follow-up time points. Additionally, comparisons of secondary outcome measures showed that active tDCS did not result in any improvements on any measure (visual cortical excitability, attentional and visuoperceptual tasks or cognitive measures) at any time point., Conclusions: Repeated consecutive sessions of parietal anodal tDCS, and occipital cathodal tDCS, do not improve visual hallucinations or visuoperceptual function, or alter visual cortical excitability in LBD., Trial Registration: ISRCTN, ISRCTN40214749 . Registered on 25 October 2013.

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, [ 18 F]-Florbetapir, and 3T magnetic resonance imaging. FreeSurfer was used to estimate cortical thickness and subcortical volumes, and PetSurfer was used to quantify [ 18 F]-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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Lewy body dementia (LBD) and Alzheimer's disease (AD) are common forms of dementia that have different clinical profiles but are both commonly associated with attentional deficits. The aim of this study was to investigate efficiency of different attentional systems in LBD and AD and its association with brain structural abnormalities. We studied reaction time (RT) data from 45 LBD, 31 AD patients and 22 healthy controls (HCs) using the Attention Network Test (ANT) to assess the efficiency of three different attentional systems: alerting, orienting and executive conflict. Voxel-based morphometry (VBM) was used to investigate relations between different attention components and cortical volume. Both dementia groups showed slower overall RTs than controls, with additional slowing in LBD relative to AD. There was a significant alerting effect in controls which was absent in the dementia groups, the executive conflict effect was greater in both dementia groups compared to controls, but the orienting effect did not differ between groups. Mean RT in AD was negatively correlated with occipital gray matter (GM) volume and in LBD orienting efficiency was negatively related to occipital white matter (WM) volume. Given that previous studies in less impaired patients suggest a maintenance of the alerting effect, the absent alerting effect in our study suggests a loss of alerting efficiency with dementia progression. While orienting was largely preserved, it might be related to occipital structural abnormalities in LBD. Executive function was markedly impaired in both dementia groups, however, the absence of relations to brain volume suggests that it might be more related to functional rather than macrostructural pathophysiological changes.

Objective: To investigate the relationship between visual hallucinations in Parkinson disease (PD) and levels of γ-aminobutyric acid (GABA) in the primary visual cortex., Methods: We utilized magnetic resonance spectroscopy to investigate occipital GABA levels in 36 participants with PD, 19 with and 17 without complex visual hallucinations, together with 20 healthy controls without hallucinations. In addition, we acquired T1-weighted MRI, whole-brain fMRI during a visual task, and diffusion tensor imaging., Results: We found lower GABA+/creatine in PD with visual hallucinations (0.091 ± 0.010) vs those without (0.101 ± 0.010) and controls (0.099 ± 0.010) ( F 2,49 = 4.5; p = 0.016). Reduced gray matter in the hallucinations group was also observed in the anterior temporal lobe. Although there were widespread reductions in white matter integrity in the visual hallucinations group, this was no longer significant after controlling for cognitive function., Conclusions: The data suggest that reduced levels of GABA are associated with visual hallucinations in PD and implicate changes to the ventral visual stream in the genesis of visual hallucinations. Modulation of visual cortical excitability through, for example, pharmacologic intervention, may be a promising treatment avenue to explore., (Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: Amyloid deposition is common in dementia with Lewy bodies, but its pathophysiological significance is unclear., Objective: The objective of this study was to investigate the relationship between amyloid deposition and clinical profile, gray matter volume, and brain perfusion in dementia with Lewy bodies., Methods: Dementia with Lewy bodies (n = 37), Alzheimer's disease (n = 20), and controls (n = 20) underwent a thorough clinical assessment, 3T MRI, and early- and late-phase 18 F-Florbetapir PET-CT to assess cortical perfusion and amyloid deposition, respectively. Amyloid scans were visually categorized as positive or negative. Image analysis was carried out using statistical parametric mapping (SPM) 8., Results: There were no significant differences between amyloid-positive and amyloid-negative dementia with Lewy bodies cases in age (P = .78), overall cognitive impairment (P = .83), level of functional impairment (P = .80), or any other clinical or cognitive scale. There were also no significant differences in hippocampal or gray matter volumes. However, amyloid-positive dementia with Lewy bodies cases had lower medial temporal lobe perfusion (P = .03) than amyloid-negative cases, although a combination of medial temporal lobe perfusion, hippocampal volume, and cognitive measures was unable to accurately predict amyloid status in dementia with Lewy bodies., Conclusions: Amyloid deposition was not associated with differences in clinical or neuropsychological profiles in dementia with Lewy bodies, but was associated with imaging evidence of medial temporal lobe dysfunction. The presence of amyloid in dementia with Lewy bodies cannot be identified on the basis of clinical and other imaging features and will require direct assessment via PET imaging or CSF. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society., (© 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.)

ABSTRACTThe ventromedial prefrontal cortex's (vMPFC) role in regulating emotions in late life depression (LLD) remains unclarified. We assessed vMPFC activation in an emotional valence blood oxygenation level-dependent (BOLD) functional magnetic neuroimaging (fMRI) task and related the findings to extent of white matter hyperintensities (WMH). Sixteen participants with mild to moderate LLD were compared to 14 similar aged comparison participants. Participants in the scanner viewed words matched for length and arousal, indicated the perceived valence by pressing one of the three buttons i.e. "positive, negative, or neutral." WMH volume was greater in LLD participants than comparison participants. There were no differences in activations between groups to any valence contrast. Female LLD participants showed greater activation for negative versus positive and negative versus neutral words as compared to female comparison participants. Female LLD participants respond differently to emotionally laden words compared to comparison participants. WMH could play a role in etiopathology of emotional perception in female LLD participants.

Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) require differential management despite presenting with symptomatic overlap. Currently, there is a need of inexpensive DLB biomarkers which can be fulfilled by electroencephalography (EEG). In this regard, an established electrophysiological difference in DLB is a decrease of dominant frequency (DF)-the frequency with the highest signal power between 4 and 15 Hz. Here, we investigated network connectivity in EEG signals acquired from DLB patients, and whether these networks were able to differentiate DLB from healthy controls (HCs) and associated dementias. We analysed EEG recordings from old adults: HCs, AD, DLB and Parkinson's disease dementia (PDD) patients. Brain networks were assessed with the minimum spanning tree (MST) within six EEG bands: delta, theta, high-theta, alpha, beta and DF. Patients showed lower alpha band connectivity and lower DF than HCs. DLB and PDD showed a randomised MST compared with HCs and AD in high-theta and alpha but not in DF. The MST randomisation in DLB and PDD reflects decreased brain efficiency as well as impaired neural synchronisation. However, the lack of network topology differences at the DF between all dementia groups and HCs may indicate a compensatory response of the brain to the neuropathology.

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., (© 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.)

Background: Alzheimer's disease (AD) is associated with atrophy in entorhinal cortex (ERC), the hippocampus, and its subfields Cornu Ammonis 1 (CA1) and subiculum, which predict conversion from mild cognitive impairment (MCI) to clinical AD. The stratum radiatum, lacunosum, and moleculare (SRLM) are also important gateways involving ERC and CA1, which are affected by early AD pathology., Objective: To assess whether the SRLM is affected in MCI and AD., Methods: In this proof-of-concept study, 27 controls, 13 subjects with AD, and 22 with MCI underwent 3T MRI. T1 maps were used for whole-hippocampal volumetry, T2 maps were segmented for hippocampal subfield areas, entorhinal cortex and subiculum thickness, and evaluated for SRLM integrity., Results: Significant CA1 atrophy and subiculum thinning were found in both AD and MCI compared to similarly aged controls. However, SRLM integrity was only significantly reduced in AD but not in MCI compared to controls. There were no significant differences in other hippocampal subfields (CA2, CA3/dentate gyrus) or ERC thickness between the groups. Finally, CA1 and CA3/DG areas and SRLM clarity were correlated with clinical and cognitive measurements of disease severity., Conclusion: Although this study was cross sectional, it suggests a progression of specific subfield changes from MCI to established AD that is associated with the reduced integrity of SRLM, which may reflect more widespread hippocampal involvement as the disease progresses and the relative preservation of SRLM in MCI. These results provide new MRI biomarkers for disease staging and understanding of the neurobiology in AD.

We investigated whole-brain atrophy and ventricular enlargement over 18 months in nondemented Parkinson's disease (PD) and examined their associations with clinical measures and baseline CSF markers. PD subjects (n = 100) were classified at baseline into those with mild cognitive impairment (MCI; PD-MCI, n = 36) and no cognitive impairment (PD-NC, n = 64). Percentage of whole-brain volume change (PBVC) and ventricular expansion over 18 months were assessed with FSL-SIENA and ventricular enlargement (VIENA) respectively. PD-MCI showed increased global atrophy (-1.1% ± 0.8%) and ventricular enlargement (6.9 % ± 5.2%) compared with both PD-NC (PBVC: -0.4 ± 0.5, p < 0.01; VIENA: 2.1% ± 4.3%, p < 0.01) and healthy controls. In a subset of 35 PD subjects, CSF levels of tau, and Aβ42/Aβ40 ratio were correlated with PBVC and ventricular enlargement respectively. The sample size required to demonstrate a 20% reduction in PBVC and VIENA was approximately 1/15th of that required to detect equivalent changes in cognitive decline. These findings suggest that longitudinal MRI measurements have potential to serve as surrogate markers to complement clinical assessments for future disease-modifying trials in PD., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To assess reductions of cerebral glucose metabolism in Parkinson's disease (PD) with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), and their associations with cognitive decline., Methods: FDG-PET was performed on a cohort of 79 patients with newly diagnosed PD (mean disease duration 8 months) and 20 unrelated controls. PD participants were scanned while on their usual dopaminergic medication. Cognitive testing was performed at baseline, and after 18 months using the Cognitive Drug Research (CDR) and Cambridge Neuropsychological Test Automated Battery (CANTAB) computerised batteries, the Mini-Mental State Examination (MMSE), and the Montreal Cognitive Assessment (MoCA). We used statistical parametric mapping (SPM V.12) software to compare groups and investigate voxelwise correlations between FDG metabolism and cognitive score at baseline. Linear regression was used to evaluate how levels of cortical FDG metabolism were predictive of subsequent cognitive decline rated with the MMSE and MoCA., Results: PD participants showed reduced glucose metabolism in the occipital and inferior parietal lobes relative to controls. Low performance on memory-based tasks was associated with reduced FDG metabolism in posterior parietal and temporal regions, while attentional performance was associated with more frontal deficits. Baseline parietal to cerebellum FDG metabolism ratios predicted MMSE (β=0.38, p=0.001) and MoCA (β=0.3, p=0.002) at 18 months controlling for baseline score., Conclusions: Reductions in cortical FDG metabolism were present in newly diagnosed PD, and correlated with performance on neuropsychological tests. A reduced baseline parietal metabolism is associated with risk of cognitive decline and may represent a potential biomarker for this state and the development of PD dementia., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Mild cognitive impairment (MCI) is prevalent in 15%-40% of Parkinson's disease (PD) patients at diagnosis. In this investigation, we study brain intra- and inter-network alterations in resting state functional magnetic resonance imaging (rs-fMRI) in recently diagnosed PD patients and characterise them as either cognitive normal (PD-NC) or with MCI (PD-MCI). Patients were divided into two groups, PD-NC (N = 62) and PD-MCI (N = 37) and for comparison, healthy controls (HC, N = 30) were also included. Intra- and inter-network connectivity were investigated from participants' rs-fMRIs in 26 resting state networks (RSNs). Intra-network differences were found between both patient groups and HCs for networks associated with motor control (motor cortex), spatial attention and visual perception. When comparing both PD-NC and PD-MCI, intra-network alterations were found in RSNs related to attention, executive function and motor control (cerebellum). The inter-network analysis revealed a hyper-synchronisation between the basal ganglia network and the motor cortex in PD-NC compared with HCs. When both patient groups were compared, intra-network alterations in RSNs related to attention, motor control, visual perception and executive function were found. We also detected disease-driven negative synchronisations and synchronisation shifts from positive to negative and vice versa in both patient groups compared with HCs. The hyper-synchronisation between basal ganglia and motor cortical RSNs in PD and its synchronisation shift from negative to positive compared with HCs, suggest a compensatory response to basal dysfunction and altered basal-cortical motor control in the resting state brain of PD patients. Hum Brain Mapp 38:1702-1715, 2017. © 2016 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

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.

Aims: Complex 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., Methods: Fifty-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., Conclusions: These 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., (© 2015 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.)