Cognitive and executive impairments in Parkinson's disease psychosis: a Bayesian meta-analysis.

BACKGROUND: Cognitive and executive deficits lead to worsening of quality of life and are a risk factor for developing dementia in people with Parkinson's disease (PD) with psychosis (PDP). However, which key cognitive domains are differentially affected in PDP compared with those without (PDnP), remains unclear. Here, we examined this using a Bayesian meta-analytical approach. METHODS: Searches were conducted on PubMed, Web of Science, SCOPUS, Medline and PsycINFO. Hedges' g effect-size estimates were extracted from eligible studies as a measure of standard mean differences between PDP and PDnP participants. Meta-analyses were conducted separately for each cognitive domain and subdomain, we examined the effect of age, PD medications, PD duration and severity, depression and psychosis severity for all major domains with meta-regressions. RESULTS: Effect-size estimates suggest worse performance on all major domains (k=105 studies) in PDP compared with PDnP participants, with global cognition (k=103 studies, g=-0.57), processing speed (k=29 studies, g=-0.58), executive functions (k=33, g=-0.56), episodic memory (k=30 studies, g=-0.58) and perception (k=34 studies, g=-0.55) as the most likely affected domains. Age, depression and PD duration had moderating effects on task-related performance across most of the major nine domains. CONCLUSIONS: We report extensive deficits across nine domains as well as subdomains in PD psychosis, with global cognition, processing speed and executive functions as the most likely impaired. The presence of depression may influence task-related performance in PDP, alongside age and PD duration, but not dose of dopamine replacement treatments.

Wrist-worn actigraphy in agitated late-stage dementia patients: A feasibility study on digital inclusion.

BACKGROUND: Wrist-worn actigraphy can be an objective tool to assess sleep and other behavioral and psychological symptoms in dementia (BPSD). We investigated the feasibility of using wearable actigraphy in agitated late-stage dementia patients. METHODS: Agitated, late-stage Alzheimer's dementia care home residents in Greater London area (n = 29; 14 females, mean age ± SD: 80.8 ± 8.2; 93.1% White) were recruited to wear an actigraphy watch for 4 weeks. Wearing time was extracted to evaluate compliance, and factors influencing compliance were explored. RESULTS: A high watch-acceptance (96.6%) and compliance rate (88.0%) was noted. Non-compliance was not associated with age or BPSD symptomatology. However, participants with "better" cognitive function (R = 0.42, p = 0.022) and during nightshift (F1.240, 33.475 = 8.075, p = 0.005) were less compliant. Female participants were also marginally less compliant (F1, 26 = 3.790, p = 0.062). DISCUSSIONS: Wrist-worn actigraphy appears acceptable and feasible in late-stage agitated dementia patients. Accommodating the needs of both the patients and their carers may further improve compliance.

The association between visual hallucinations and secondary psychosis: a systematic review and meta-analysis.

INTRODUCTION: Visual hallucinations are often considered to be suggestive of a secondary cause of psychosis, however, this association has never been assessed meta-analytically. We aimed to compare the presence of visual hallucinations in patients with psychosis due to a primary or secondary cause. METHOD: We conducted a meta-analysis of case-control studies directly comparing primary and secondary psychosis. A random-effects model, following the DerSimonian and Laird method, was used to pool studies and generate overall odds ratios (OR), 95% confidence intervals (CI) and prediction intervals (PI). RESULTS: Fourteen studies (904 primary and 804 secondary psychosis patients) were included. Visual hallucinations were significantly associated with secondary psychosis (OR = 3.0, 95% CI = 1.7-5.1, p < 0.001) with moderate between-study heterogeneity (I2 = 70%). Subgroup analysis by type of secondary psychosis (organic, drug-induced, mixed) was non-significant. Analysis of the content of visual hallucinations (51 primary and 142 secondary psychosis patients) found hallucinations of inanimate objects were significantly more likely to be associated with secondary psychosis (OR = 0.1, 95% CI = 0.01-0.8, p = 0.03). CONCLUSIONS: Visual hallucinations were strongly associated with a secondary cause of psychosis. The presence of visual hallucinations in a patient presenting with psychosis may serve as a potential "red flag" for a secondary cause and warrant further investigation.

Neuropathological correlates of neuropsychiatric symptoms in dementia.

INTRODUCTION: Neuropsychiatric symptoms (NPS) are common in Lewy body disease (LBD), but their etiology is poorly understood. METHODS: In a population-based post mortem study neuropathological data was collected for Lewy body (LB) neuropathology, neurofibrillary tangles (NFT), amyloid beta burden, TDP-43, lacunar infarcts, cerebral amyloid angiopathy (CAA), and hyaline atherosclerosis. Post mortem interviews collected systematic information regarding NPS and cognitive status. A total of 1038 cases were included: no pathology (NP; n = 761), Alzheimer's disease (AD; n = 189), LBD (n = 60), and AD+LBD (n = 28). RESULTS: Hallucinations were associated with higher LB Braak stages, while higher NFT Braak staging was associated with depression, agitation, and greater number of symptoms in the Neuropsychiatric Inventory. Cases with dual AD+LBD pathology had the highest risk of hallucinations, agitation, apathy, and total symptoms but a multiplicative interaction between these pathologies was not significant. DISCUSSION: LB and AD pathology contribute differentially to NPS likely with an additive process contributing to the increased burden of NPS.

Transcranial Direct Current Stimulation in the Treatment of Visual Hallucinations in Charles Bonnet Syndrome: A Randomized Placebo-Controlled Crossover Trial.

OBJECTIVE: To investigate the potential therapeutic benefits and tolerability of inhibitory transcranial direct current stimulation (tDCS) on the remediation of visual hallucinations in Charles Bonnet syndrome (CBS). DESIGN: Randomized, double-masked, placebo-controlled crossover trial. PARTICIPANTS: Sixteen individuals diagnosed with CBS secondary to visual impairment caused by eye disease experiencing recurrent visual hallucinations. INTERVENTION: All participants received 4 consecutive days of active and placebo cathodal stimulation (current density: 0.29 mA/cm2) to the visual cortex (Oz) over 2 defined treatment weeks, separated by a 4-week washout period. MAIN OUTCOME MEASURES: Ratings of visual hallucination frequency and duration following active and placebo stimulation, accounting for treatment order, using a 2 × 2 repeated-measures model. Secondary outcomes included impact ratings of visual hallucinations and electrophysiological measures. RESULTS: When compared with placebo treatment, active inhibitory stimulation of visual cortex resulted in a significant reduction in the frequency of visual hallucinations measured by the North East Visual Hallucinations Interview, with a moderate-to-large effect size. Impact measures of visual hallucinations improved in both placebo and active conditions, suggesting support and education for CBS may have therapeutic benefits. Participants who demonstrated greater occipital excitability on electroencephalography assessment at the start of treatment were more likely to report a positive treatment response. Stimulation was found to be tolerable in all participants, with no significant adverse effects reported, including no deterioration in preexisting visual impairment. CONCLUSIONS: Findings indicate that inhibitory tDCS of visual cortex may reduce the frequency of visual hallucinations in people with CBS, particularly individuals who demonstrate greater occipital excitability prior to stimulation. tDCS may offer a feasible intervention option for CBS with no significant side effects, warranting larger-scale clinical trials to further characterize its efficacy.

Light, sleep-wake rhythm, and behavioural and psychological symptoms of dementia in care home patients: Revisiting the sundowning syndrome.

OBJECTIVES: It is believed that inadequate environmental light, especially in facilities such as care homes, contribute to the diurnal changes of behavioural and psychological symptoms of dementia (BPSD) historically referred to as "sundowning syndrome". Conceptual models of sundowning phenomena have shifted emphasis from the role of light in vision (image forming) to its role in circadian rhythm modulation. However, the grounds for this change are unclear and the evidence on which it is based has not been examined comprehensively. METHODS: We have searched literature on sundowning syndrome and its association with light and studies evaluating BPSD, behavioural rhythm and environmental light in care homes in four databases (PubMed, Web of Science, Embase and Cochrane Library) from inception to 31 January 2021. RESULTS: Of the nine studies investigating light, behavioural rhythm and BPSD in care homes identified, we found evidence that insufficient natural light exposure was associated with worsening of BPSD and disrupted activity rhythm but it was not clear whether this related to image forming or disrupted circadian rhythm. There was a paucity of evidence in relation to the role of low levels of light for image forming in the context of a specific BPSD symptom: visual hallucinations. We also found literature on the possible role of light outside the visible spectrum influencing cognition. Based on the evidence, we proposed a new model integrating different components of light in BPSD and sundowning syndrome that combines its image forming and circadian roles. CONCLUSIONS: Inadequate light may be a risk factor for BPSD and sundowning syndrome for dementia patients through a range of different mechanisms. It is recommended that multiple neuro-endocrinological and socio-environmental factors relevant to light such as adjusting the environmental setting, increasing light exposure, and scheduling activities should be considered when treating dementia patients with BPSD.

Cognition, hallucination severity and hallucination-specific insight in neurodegenerative disorders and eye disease.

Introduction: Hallucinations occur across neurodegenerative disorders, with increasing severity, poorer cognition and impaired hallucination-specific insight associated with worse outcomes and faster disease progression. It remains unclear how changes in cognition, temporal aspects of hallucinations, hallucination-specific insight and distress relate to each other.Methods: Extant samples of patients experiencing visual hallucinations were included in the analyses: Parkinson's Disease (n = 103), Parkinson's Disease Dementia (n = 41), Dementia with Lewy Bodies (n = 27) and Eye Disease (n = 113). We explored the relationship between factors of interest with Spearman's correlations and random-effect linear models.Results: Spearman's correlation analyses at the whole-group level showed that higher hallucination-specific insight was related to higher MMSE score (rs = 0.39, p < 0.001) and less severe hallucinations (rs = -0.28, p < .01). Linear mixed-models controlling for diagnostic group showed that insight was related to higher MMSE (p < .001), to hallucination severity (p = 0.003), and to VH duration (p = 0.04). Interestingly, insight was linked to the distress component but not the frequency component of severity. No significant relationship was found between MMSE and hallucination severity in these analyses.Conclusion: Our findings highlight the importance of hallucination-specific insight, distress and duration across groups. A better understanding of the role these factors play in VH may help with the development of future therapeutic interventions trans-diagnostically.

Disrupted connectivity within visual, attentional and salience networks in the visual snow syndrome.

Here we investigate brain functional connectivity in patients with visual snow syndrome (VSS). Our main objective was to understand more about the underlying pathophysiology of this neurological syndrome. Twenty-four patients with VSS and an equal number of gender and age-matched healthy volunteers attended MRI sessions in which whole-brain maps of functional connectivity were acquired under two conditions: at rest while watching a blank screen and during a visual paradigm consisting of a visual-snow like stimulus. Eight unilateral seed regions were selected a priori based on previous observations and hypotheses; four seeds were placed in key anatomical areas of the visual pathways and the remaining were derived from a pre-existing functional analysis. The between-group analysis showed that patients with VSS had hyper and hypoconnectivity between key visual areas and the rest of the brain, both in the resting state and during a visual stimulation, compared with controls. We found altered connectivity internally within the visual network; between the thalamus/basal ganglia and the lingual gyrus; between the visual motion network and both the default mode and attentional networks. Further, patients with VSS presented decreased connectivity during external sensory input within the salience network, and between V5 and precuneus. Our results suggest that VSS is characterised by a widespread disturbance in the functional connectivity of several brain systems. This dysfunction involves the pre-cortical and cortical visual pathways, the visual motion network, the attentional networks and finally the salience network; further, it represents evidence of ongoing alterations both at rest and during visual stimulus processing.

Localised increase in regional cerebral perfusion in patients with visual snow syndrome: a pseudo-continuous arterial spin labelling study.

OBJECTIVES: We aimed to investigate changes in regional cerebral blood flow (rCBF) using arterial spin labelling (ASL) in patients with visual snow syndrome (VSS), in order to understand more about the underlying neurobiology of the condition, which remains mostly unknown. METHODS: We performed an MRI study in which whole-brain maps of rCBF were obtained using pseudo-continuous ASL. Twenty-four patients with VSS and an equal number of gender and age-matched healthy volunteers took part in the study. All subjects were examined with both a visual paradigm consisting of a visual-snow like stimulus, simulating key features of the snow, and a blank screen at rest, randomly presented. RESULTS: Patients with VSS had higher rCBF than controls over an extensive brain network, including the bilateral cuneus, precuneus, supplementary motor cortex, premotor cortex and posterior cingulate cortex, as well as the left primary auditory cortex, fusiform gyrus and cerebellum. These areas were largely analogous comparing patients either at rest, or when looking at a 'snow-like' visual stimulus. This widespread, similar pattern of perfusion differences in either condition suggests a neurophysiological signature of visual snow. Furthermore, right insula rCBF was increased in VSS subjects compared with controls during visual stimulation, reflecting a greater task-related change and suggesting a difference in interoceptive processing with constant perception of altered visual input. CONCLUSION: The data suggest VSS patients have marked differences in brain processing of visual stimuli, validating its neurobiological basis.

Visual hallucinations in neurological and ophthalmological disease: pathophysiology and management.

Visual hallucinations are common in older people and are especially associated with ophthalmological and neurological disorders, including dementia and Parkinson's disease. Uncertainties remain whether there is a single underlying mechanism for visual hallucinations or they have different disease-dependent causes. However, irrespective of mechanism, visual hallucinations are difficult to treat. The National Institute for Health Research (NIHR) funded a research programme to investigate visual hallucinations in the key and high burden areas of eye disease, dementia and Parkinson's disease, culminating in a workshop to develop a unified framework for their clinical management. Here we summarise the evidence base, current practice and consensus guidelines that emerged from the workshop.Irrespective of clinical condition, case ascertainment strategies are required to overcome reporting stigma. Once hallucinations are identified, physical, cognitive and ophthalmological health should be reviewed, with education and self-help techniques provided. Not all hallucinations require intervention but for those that are clinically significant, current evidence supports pharmacological modification of cholinergic, GABAergic, serotonergic or dopaminergic systems, or reduction of cortical excitability. A broad treatment perspective is needed, including carer support. Despite their frequency and clinical significance, there is a paucity of randomised, placebo-controlled clinical trial evidence where the primary outcome is an improvement in visual hallucinations. Key areas for future research include the development of valid and reliable assessment tools for use in mechanistic studies and clinical trials, transdiagnostic studies of shared and distinct mechanisms and when and how to treat visual hallucinations.

Visual hallucinations in dementia and Parkinson's disease: A qualitative exploration of patient and caregiver experiences.

OBJECTIVES: Visual hallucinations (VHs) can occur in several clinical conditions, of which the dementias, broadly defined, and Parkinson's disease rank among the most common. There is limited research on the lived experience of hallucinations among affected individuals and therefore a lack of evidence-based management strategies. This study used qualitative methods to explore the VH experience of individuals with dementia or Parkinson's disease and their informal caregivers. METHODS: In-depth interviews were conducted with 10 individuals with VHs and dementia and 11 informal caregivers, and 11 individuals with VHs and Parkinson's disease and 9 informal caregivers. Interviews were analysed using an inductive thematic approach. RESULTS: Three themes emerged from the data: "Insight and distress," "Caregiver approach: challenging v reassurance," and "Normality and stigma." Insight appeared to affect whether hallucinations were perceived as threatening and whether acceptance occurred over time. Emotional reactions and management strategies varied as insight changed with disease progression. Concerns around stigmatisation negatively influenced help-seeking and acceptance of the hallucinations. CONCLUSIONS: Degree of insight and cognitive ability appear fundamental to the lived experience of hallucinations. Irrespective of the clinical context, support in early stages should focus on raising awareness of VH, symptom disclosure, stigma reduction, and contact with others affected. In later stages, the focus shifts to informal caregiver needs and a flexible approach to reassuring those affected.

Risk factors for early psychosis in PD: insights from the Parkinson's Progression Markers Initiative.

BACKGROUND: Parkinson's Disease (PD) psychosis refers to the spectrum of illusions, formed hallucinations and delusions that occur in PD. Visual hallucinations and illusions are thought to be caused by specific cognitive and higher visual function deficits and patients who develop such symptoms early in the disease course have greater rates of cognitive decline and progression to dementia. To date, no studies have investigated whether such deficits are found prior to the onset of PD psychosis. METHOD: Here we compare baseline cognitive, biomarker (structural imaging and cerebrospinal fluid) and other PD psychosis risk factor data in patients who go on to develop illusions or hallucinations within 3-4 years of follow-up in the Parkinson's Progression Markers Initiative cohort of newly diagnosed PD. RESULTS: Of n=423 patients with PD, n=115 (27%) reported predominantly illusions with the median time of onset at 19.5 months follow-up. At study entry these patients had reduced CSF amyloid Aß1-42, lower olfaction scores, higher depression scores and increased REM sleep behaviour disorder symptoms compared to patients without early onset PD psychosis but no differences in cognitive, higher visual or structural imaging measures. A subset of patients with early onset formed hallucinations (n=21) had reduced higher visual function at baseline, cortical thinning in parietal, occipital and frontal cortex and reduced hippocampal volume. CONCLUSIONS: The findings suggest early onset illusions and formed hallucinations are linked to amyloid pathology in PD and point to a difference in the underlying pathophysiological mechanism of illusions and formed hallucinations, with implications for their respective links to future cognitive decline.

New Therapeutic Strategies for Lewy Body Dementias.

This article reviews current treatment strategies and recent advances for the Lewy body dementias (LBDs). Current available symptom treatment strategies are based on monoaminergic, cholinergic and glutaminergic neurotransmitter systems. Relatively robust evidence exists for cholinesterase inhibitors for cognitive impairment in LBD and in Parkinson's disease for antidepressants, clozapine and recently pimavanserin for psychosis. interpidine (RVT 101) and nelotanserin are currently under investigation. Non-pharmacological interventions, such as cognitive stimulation, physical exercises and neuromodulation strategies, may be useful in Parkinson's disease but have not yet been tested in dementias. Disease-modifying approaches are aimed at preventing, slowing or ameliorating the production, aggregation and deposition of pathological proteins, including immunotherapy targeting α-synuclein and an ongoing trial using ambroxol which increases glucocerebrosidase activity to lower the levels of the protein alpha-synuclein. Other disease-modifying clinical trials are using agents to augment insulin signalling, stem cell therapy, reducing amyloid pathology and gene therapy.

Are stroke survivors with delirium at higher risk of post-stroke dementia? Current evidence and future directions.

OBJECTIVES: The idea that delirium is a risk factor for dementia, broadly defined, is derived from heterogeneous patient samples. We reviewed available evidence as to whether stroke survivors who developed delirium during the acute phase of treatment are at a higher prospective risk of incident post-stroke cognitive impairment or dementia. DESIGN: We searched 8721 records in the Cochrane database for reviews or protocols dealing with the study objective, Medline, EMBASE, PsycInfo and CINAHL for observational studies in the general adult population and PubMed for in-process articles. Additional searches of the reference lists of retrieved articles were also undertaken. Qualitative syntheses and meta-analysis were conducted according to conventional guidelines. RESULTS: Twelve relevant articles were fully appraised. Four out of these studies, comprising 743 stroke survivors, including 199 with delirium, met criteria for qualitative syntheses. Overall, the studies presented low to moderate level evidence suggesting an association between post-stroke delirium and dementia. CONCLUSIONS: There is a need for further studies to investigate the association of post-stroke delirium and dementia using well-defined cohorts of patients and controlling for factors such as pre-stroke cognition, stroke severity and location and the presence of persistent delirium. Such studies will help understand the place of delirium identification and prevention in reducing the risk of dementia after stroke. © 2016 The Authors. International Journal of Geriatric Psychiatry Published by John Wiley & Sons Ltd.

Cognitive phenotype of psychotic symptoms in Alzheimer's disease: evidence for impaired visuoperceptual function in the misidentification subtype.

BACKGROUND: Establishing the cognitive phenotype of psychotic symptoms in Alzheimer's disease (AD) could localise discrete pathology and target symptomatic treatment. This study aimed to establish whether psychotic symptoms would be associated with poorer performance on neuropsychological tests known to correlate with striatal dopaminergic function and to investigate whether these differences would be attributed to the paranoid (persecutory delusions) or misidentification (misidentification phenomena +/- hallucinations) subtype. METHODS: Seventy patients with probable AD (34 psychotic and 36 nonpsychotic) were recruited to the study. Analysis of covariance was used to compare motor speed and the rapid visual processing test of sustained visual attention, after adjusting for potential confounding factors. Multivariate analyses were used to compare performance across other cognitive domains. Significant findings were explored by separating patients on the basis of subtype. RESULTS: Rapid visual processing performance accuracy was reduced in patients with psychotic symptoms (F1,58 = 5.94, p = 0.02) and differed significantly across subtypes (F2,51 = 3.94, p = 0.03), largely because of poorer performance in the misidentification compared with nonpsychotic group. Multivariate analyses (corrected for multiple comparisons) showed poorer performance on the incomplete letters task in psychotic patients (F1,63 = 8.77, p = 0.004) and across subtypes (F2,55 = 10.90, p < 0.001), similarly attributed to the misidentification subtype. CONCLUSIONS: These findings provide further support of the involvement of dopaminergic networks in the psychosis endophenotype in AD and, in addition, implicate the ventral (temporo-occipital) pathway in the misidentification subtype. Future studies should investigate the early trajectory of neuropathological change in vivo across psychosis subtypes.

Art and the brain: a view from dementia.

OBJECTIVE: Art making encompasses a range of perceptual and cognitive functions involving widely distributed brain systems. The dementias impact on these systems in different ways, raising the possibility that each dementia has a unique artistic signature. DESIGN: Here we use a review of the visual art of 14 artists with dementia (five Alzheimer's disease, seven fronto-temporal dementia and two dementia with Lewy bodies) to further our understanding of the neurobiological constituents of art production and higher artistic function. RESULTS: Artists with Alzheimer's disease had prominent changes in spatial aspects of their art and attributes of colour and contrast. These qualities were preserved in the art of fronto-temporal dementia, which was characterised by perseverative themes and a shift towards realistic representation. The art of dementia with Lewy Bodies was characterised by simple, bizarre content. CONCLUSIONS: The limitations of using visual aspects of individual artworks to infer the impact of dementia on art production are discussed with the need for a wider perspective encompassing changes in cognition, emotion, creativity and artistic personality. A novel classificatory scheme is presented to help characterise neural mechanisms of higher artistic functions in future studies.

A clinico-anatomical dissection of the magnocellular and parvocellular pathways in a patient with the Riddoch syndrome.

KEY MESSAGE: The Riddoch syndrome is thought to be caused by damage to the primary visual cortex (V1), usually following a vascular event. This study shows that damage to the anatomical input to V1, i.e., the optic radiations, can result in selective visual deficits that mimic the Riddoch syndrome. The results also highlight the differential susceptibility of the magnocellular and parvocellular visual systems to injury. Overall, this study offers new insights that will improve our understanding of the impact of brain injury and neurosurgery on the visual pathways. The Riddoch syndrome, characterised by the ability to perceive, consciously, moving visual stimuli but not static ones, has been associated with lesions of primary visual cortex (V1). We present here the case of patient YL who, after a tumour resection surgery that spared his V1, nevertheless showed symptoms of the Riddoch syndrome. Based on our testing, we postulated that the magnocellular (M) and parvocellular (P) inputs to his V1 may be differentially affected. In a first experiment, YL was presented with static and moving checkerboards in his blind field while undergoing multimodal magnetic resonance imaging (MRI), including structural, functional, and diffusion, acquired at 3 T. In a second experiment, we assessed YL's neural responses to M and P visual stimuli using psychophysics and high-resolution fMRI acquired at 7 T. YL's optic radiations were partially damaged but not severed. We found extensive activity in his visual cortex for moving, but not static, visual stimuli, while our psychophysical tests revealed that only low-spatial frequency moving checkerboards were perceived. High-resolution fMRI revealed strong responses in YL's V1 to M stimuli and very weak ones to P stimuli, indicating a functional P lesion affecting V1. In addition, YL frequently reported seeing moving stimuli and discriminating their direction of motion in the absence of visual stimulation, suggesting that he was experiencing visual hallucinations. Overall, this study highlights the possibility of a selective loss of P inputs to V1 resulting in the Riddoch syndrome and in hallucinations of visual motion.

Parkinson's disease psychosis associated with accelerated multidomain cognitive decline.

BACKGROUND: Cognitive deficits are associated with poor quality of life and increased risk of development of dementia in patients with Parkinson's disease (PD) psychosis. The trajectory of cognitive decline in PD psychosis remains however unclear. OBJECTIVE: We examined this using data from the Parkinson's Progression Markers Initiative study. METHODS: We analysed data from patients with drug-naïve PD (n=676) and healthy controls (HC, n=187) over 5 years, and examined all cognitive measures assessed at each time point. We classified patients with PD into those who developed psychosis over the course of the study (PDP) and those without psychosis throughout (PDnP) using the Movement Disorders Society Unified Parkinson's Disease Rating Scale part I hallucinations/psychosis item. We used linear mixed-effect models with restricted maximum likelihood. Age, sex, ethnicity, education and neuropsychiatric and PD-specific symptoms were entered as covariates of interest. FINDINGS: There were no baseline cognitive differences between PD patient groups. There were differences in cognitive performance between PD and HC across the majority of the assessments.Patients with PDP exhibited greater cognitive decline over 5 years compared with PDnP across most domains even after controlling for sociodemographics, depression, sleepiness, rapid eye movement sleep behaviour disorder and motor symptom severity (immediate recall, b=-0.288, p=0.003; delayed recall, b=-0.146, p=0.003; global cognition, Montreal Cognitive Assessment, b=-0.206, p<0.001; visuospatial, b=-0.178, p=0.012; semantic fluency, b=-0.704, p=0.002; processing speed, b=-0.337, p=0.029). CONCLUSIONS: Patients with PD psychosis exhibited decline in semantic aspects of language, processing speed, global cognition, visuospatial abilities and memory, regardless of sociodemographic characteristics, neuropsychiatric and motor symptoms. These cognitive domains, particularly semantic aspects of language may therefore play an important role in PD psychosis and warrant further investigation. TRIAL REGISTRATION NUMBER: NCT01141023.

Distinct grey and white matter changes are associated with the phenomenology of visual hallucinations in Lewy Body Disease.

Visual hallucinations in Lewy body disease (LBD) can be differentiated based on phenomenology into minor phenomena (MVH) and complex hallucinations (CVH). MVH include a variety of phenomena, such as illusions, presence and passage hallucinations occurring at early stages of LBD. The neural mechanisms of visual hallucinations are largely unknown. The hodotopic model posits that the hallucination state is due to abnormal activity in specialized visual areas, that occurs in the context of wider network connectivity alterations and that phenomenology of VH, including content and temporal characteristics, may help identify brain regions underpinning these phenomena. Here we investigated both the topological and hodological neural basis of visual hallucinations integrating grey and white matter imaging analyses. We studied LBD patients with VH and age matched healthy controls (HC). VH were assessed using a North-East-Visual-Hallucinations-Interview that captures phenomenological detail. Then we applied voxel-based morphometry and tract based spatial statistics approaches to identify grey and white matter changes. First, we compared LBD patients and HC. We found a reduced grey matter volume and a widespread damage of white tracts in LBD compared to HC. Then we tested the association between CVH and MVH and grey and white matter indices. We found that CVH duration was associated with decreased grey matter volume in the fusiform gyrus suggesting that LBD neurodegeneration-related abnormal activity in this area is responsible for CVH. An unexpected finding was that MVH severity was associated with a greater integrity of white matter tracts, specifically those connecting dorsal, ventral attention networks and visual areas. Our results suggest that networks underlying MVH need to be partly intact and functional for MVH experiences to occur, while CVH occur when cortical areas are damaged. The findings support the hodotopic view and the hypothesis that MVH and CVH relate to different neural mechanisms, with wider implications for the treatment of these symptoms in a clinical context.

A novel method for reducing the effect of tonic muscle activity on the gamma band of the scalp EEG.

Neural oscillations in the gamma band are of increasing interest, but separating them from myogenic electrical activity has proved difficult. A novel algorithm has been developed to reduce the effect of tonic scalp and neck muscle activity on the gamma band of the EEG. This uses mathematical modelling to fit individual muscle spikes and then subtracts them from the data. The method was applied to the detection of motor associated gamma in two separate groups of eight subjects using different sampling rates. A reproducible increase in high gamma (65-85 Hz) magnitude occurred immediately after the motor action in the left central area (p = 0.02 and p = 0.0002 for the two cohorts with individually optimized algorithm parameters, compared to p = 0.03 and p = 0.16 before correction). Whilst the magnitude of this event-related gamma synchronisation was not reduced by the application of the EMG reduction algorithm, the baseline left central gamma magnitude was significantly reduced by an average of 23 % with a faster sampling rate (p < 0.05). In comparison, at left and right temporo-parietal locations the gamma amplitude was reduced by 60 and 54 % respectively (p < 0.05). The reduction of EMG contamination by fitting and subtraction of individual spikes shows promise as a method of improving the signal to noise ratio of high frequency neural oscillations in scalp EEG.