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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.

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 [18F]‐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 [ABSTRACT FROM AUTHOR]

To investigate hypothalamic atrophy and its clinical correlates in multiple system atrophy (MSA) in-vivo. 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. 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. 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. 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. • MSA is characterized by autonomic dysfunction and parkinsonian/cerebellar symptoms. • The hypothalamus role in MSA has been investigated pathologically, yet not in vivo. • We performed a structural MRI study investigating hypothalamic subregional volumes. • A reduction in posterior hypothalamus volume was found in MSA compared to PD and HC. • Posterior hypothalamus volume was associated with MoCA scores in MSA and PD. [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: The aim of this work was to investigate the cortical and white matter changes that underlie cognitive impairment in patients with incident Parkinson's disease (PD) disease using voxel-based morphometry and diffusion tensor imaging.Methods: Newly diagnosed nondemented PD (n = 125) and control subjects (n = 50) were recruited from the Incidence of Cognitive Impairment in Cohorts with Longitudinal Evaluation in Parkinson's Disease Study and completed cognitive assessments and 3T structural and diffusion tensor MR imaging. Voxel-based morphometry was performed to investigate the relationship between gray matter volume and cognitive ability. Microstructural white matter changes were assessed with diffusion tensor imaging measures of fractional anisotropy and mean diffusivity using tract-based spatial statistics.Results: Increased mean diffusivity was observed bilaterally in subjects with PD, relative to controls (P = 0.019). Increased mean diffusivity was associated with performance on the semantic fluency and Tower of London tasks in frontal and parietal white matter tracts, including the cingulum, superior longitudinal fasciculus, inferior longitudinal fasciculus, and inferior fronto-occipital fasciculus. There was no difference in total gray matter volume between groups; however, bilateral reductions in frontal and parietal gray matter volume were associated with reduced performance on measures of executive function in PD subjects.Conclusions: At the earliest stages of PD, regionally specific increases in central white matter mean diffusivity are present and suggest early axonal damage. Such changes are not accompanied by significant gray matter volume loss and are consistent with proposed models of pathological progression of the disease. Structural MRI, especially diffusion tensor imaging analysis, offers potential as a noninvasive biomarker reflecting cognitive impairment in PD. [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]

ABSTRACT Background Rapid eye movement sleep behavior disorder has poor prognostic implications for Parkinson's disease. The authors recruited 124 patients with early Parkinson's disease to compare clinical and neuroimaging findings based on the presence of this sleep disorder. Methods The presence of rapid eye movement sleep behavior disorder was assessed with the Mayo Sleep Questionnaire. Magnetic resonance imaging sequences were obtained for voxel-based morphometry and diffusion tensor imaging. Results Patients with sleep disorder had more advanced disease, but groups had similar clinical characteristics and cognitive performance. Those with sleep disorder had areas of reduced cortical grey matter volume and white matter changes compared with those who did not have sleep disorder. However, differences were slight and were not significant when the analyses were adjusted for multiple comparisons. Conclusions Rapid eye movement sleep behavior disorder was associated with subtle changes in white matter integrity and grey matter volume in patients with early Parkinson's disease. © 2013 Movement Disorder Society [ABSTRACT FROM AUTHOR]

ABSTRACT Dementia is a frequent and disabling complication of Parkinson's disease (PD). Clinicians and researchers lack a biomarker capable of tracking the structural and functional changes that underlie the evolution of cognitive dysfunction in PD. Magnetic resonance imaging (MRI) has been adopted as a biomarker in natural history and interventional studies of Alzheimer's disease (AD) and amnestic mild cognitive impairment (MCI), but its utility as a biomarker for PD and Parkinson's disease dementia (PDD) is unclear. In this review, the authors summarize the studies that have used MRI to investigate cognitive decline in PD, outline limitations of those studies, and suggest directions for future research. PD dementia is associated with extensive cortical atrophy, which may be quantified with structural MRI. More promisingly, patterns of atrophy may be present in those who have PD with MCI (PD-MCI). Subcortical white matter tract degeneration is detectable early in the disease with diffusion tensor imaging and may precede changes observed on conventional structural MRI. Although less well studied, other MR techniques, such as functional MRI, MR perfusion imaging with arterial spin labeling, and MR spectroscopy, have demonstrated differences in activation and metabolism between PD and PDD. In this review, the ability to compare studies was limited by the heterogeneity of study populations, cognitive testing methods, and imaging protocols. Future work should adopt agreed scan protocols, should be adequately powered, and should use carefully phenotyped patients to fully maximize the contribution of MRI as a biomarker for PDD. © 2013 Movement Disorder Society [ABSTRACT FROM AUTHOR]

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]

Abstract: Introduction: : Alterations in cholinergic function have been reported to be associated with dementia. The aim of this study was to investigate differences in the distribution of muscarinic acetylcholine receptors (mAChRs) using (R,R) 123I-iodo-quinuclidinyl-benzilate (QNB) and single photon emission computed tomography (SPECT) in dementia with Lewy bodies (DLB), Parkinson’s disease dementia (PDD) and age-matched controls. 123I-QNB binding was also compared to the corresponding cerebral perfusion changes in the same subjects. Methods: : 63 subjects (24 controls, 14 DLB, 25 PDD) underwent 123I-QNB and perfusion 99mTc-exametazine SPECT scanning. Image analysis, using statistical parametric mapping (SPM99), involved spatial normalisation of each image to a customised template, followed by smoothing and intensity normalisation of each image to its corresponding mean whole brain uptake. Group effects and correlations were assessed using two sample t tests and linear regression respectively. Results: : Relative to controls, significant elevation of 123I-QNB binding was apparent in the right occipital lobe in DLB and right and left occipital lobes in PDD (height threshold p ≤0.001 uncorrected). PDD also showed significant loss in uptake in frontal regions and temporal lobes bilaterally that was not present in DLB. These patterns appeared to be independent of any corresponding rCBF changes. Conclusion: : Significant elevation of mAChRs in the occipital lobe was associated with DLB and PDD. This may relate to the visual disturbances that are prevalent in these disorders. Further studies are required in order to establish the role of mAChRs in visual function. [Copyright &y& Elsevier]

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]

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. [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]