Understanding the nature and impact of cognitive fluctuations and sleep disturbances in dementia with Lewy bodies: A qualitative caregiver study.

Objectives: Dementia with Lewy bodies is characterised by rapid fluctuations in attention, which are known as "cognitive fluctuations." Despite the fact that cognitive fluctuations are considered to be a core dementia with Lewy bodies symptom, they are very difficult to define and measure using existing quantitative subjective measurement tools, which are typically completed by caregivers. Cognitive fluctuations are also likely to be influenced by various aspects of sleep, but this is as yet unexplored. The primary aim of this qualitative study was to investigate the phenomenology of cognitive fluctuations in dementia with Lewy bodies by understanding caregiver experiences. Methods: Seven caregivers of people with dementia with Lewy bodies completed one-to-one semistructured interviews, which were conducted by telephone. Caregivers were asked to describe the nature, frequency, duration and potential triggers of cognitive fluctuations that were experienced by the individual with dementia with Lewy bodies. Caregivers were also asked about the subjective sleep experience of the individual with dementia with Lewy bodies, and about their own sleep experiences. Interviews were audio recorded, transcribed verbatim and analysed using Thematic Analysis. Results: Caregivers reported that there was a great deal of individual variation in the frequency, duration and severity of cognitive fluctuations. Patient sleep disturbances, including excessive daytime sleepiness, nocturnal awakenings, restless legs and sleep apnoea, were common. However, the impact of sleep alterations or experiences upon the fluctuations was reported to be less clear. Caregivers also reported that their own sleep was negatively affected, potentially due to actively listening for overnight events and behaviours. Conclusions: Qualitatively, caregivers report that dementia with Lewy bodies cognitive fluctuations show large individual variations in terms of their frequency, duration and severity, but that subjectively, sleep may not consistently influence this symptom. Specific, caregiver-focussed interventions are likely to be necessary to maintain good sleep health in dementia with Lewy bodies caregivers.

Post-hospitalisation COVID-19 cognitive deficits at one year are global and associated with elevated brain injury markers and grey matter volume reduction.

The spectrum, pathophysiology, and recovery trajectory of persistent post-COVID-19 cognitive deficits are unknown, limiting our ability to develop prevention and treatment strategies. We report the one-year cognitive, serum biomarker, and neuroimaging findings from a prospective, national study of cognition in 351 COVID-19 patients who had required hospitalisation, compared to 2,927 normative matched controls. Cognitive deficits were global and associated with elevated brain injury markers, and reduced anterior cingulate cortex volume one year after COVID-19. The severity of the initial infective insult, post-acute psychiatric symptoms, and a history of encephalopathy were associated with greatest deficits. There was strong concordance between subjective and objective cognitive deficits. Longitudinal follow-up in 106 patients demonstrated a trend toward recovery. Together, these findings support the hypothesis that brain injury in moderate to severe COVID-19 may be immune-mediated, and should guide the development of therapeutic strategies.

EEG Functional Connectivity Differences Predict Future Conversion to Dementia in Mild Cognitive Impairment With Lewy Body or Alzheimer Disease.

BACKGROUND: Predicting which individuals may convert to dementia from mild cognitive impairment (MCI) remains difficult in clinical practice. Electroencephalography (EEG) is a widely available investigation but there is limited research exploring EEG connectivity differences in patients with MCI who convert to dementia. METHODS: Participants with a diagnosis of MCI due to Alzheimer's disease (MCI-AD) or Lewy body disease (MCI-LB) underwent resting state EEG recording. They were followed up annually with a review of the clinical diagnosis (n = 66). Participants with a diagnosis of dementia at year 1 or year 2 follow up were classed as converters (n = 23) and those with a diagnosis of MCI at year 2 were classed as stable (n = 43). We used phase lag index (PLI) to estimate functional connectivity as well as analysing dominant frequency (DF) and relative band power. The Network-based statistic (NBS) toolbox was used to assess differences in network topology. RESULTS: The converting group had reduced DF (U = 285.5, p = 0.005) and increased relative pre-alpha power (U = 702, p = 0.005) consistent with previous findings. PLI showed reduced average beta band synchrony in the converting group (U = 311, p = 0.014) as well as significant differences in alpha and beta network topology. Logistic regression models using regional beta PLI values revealed that right central to right lateral (Sens = 56.5%, Spec = 86.0%, -2LL = 72.48, p = 0.017) and left central to right lateral (Sens = 47.8%, Spec = 81.4%, -2LL = 71.37, p = 0.012) had the best classification accuracy and fit when adjusted for age and MMSE score. CONCLUSION: Patients with MCI who convert to dementia have significant differences in EEG frequency, average connectivity and network topology prior to the onset of dementia. The MCI group is clinically heterogeneous and have underlying physiological differences that may be driving the progression of cognitive symptoms. EEG connectivity could be useful to predict which patients with MCI-AD and MCI-LB convert to dementia, regardless of the neurodegenerative aetiology.

Cerebrovascular and Alzheimer's disease biomarkers in dementia with Lewy bodies and other dementias.

Co-pathologies are common in dementia with Lewy bodies and other dementia disorders. We investigated cerebrovascular and Alzheimer's disease co-pathologies in patients with dementia with Lewy bodies in comparison with patients with mild cognitive impairment, Alzheimer's disease, mixed dementia, vascular dementia or Parkinson's disease with dementia and cognitively unimpaired participants. We assessed the association of biomarkers of cerebrovascular and Alzheimer's disease co-pathologies with medial temporal atrophy and global cognitive performance. Additionally, we evaluated whether the findings were specific to dementia with Lewy bodies. We gathered a multi-cohort dataset of 4549 participants (dementia with Lewy bodies = 331, cognitively unimpaired = 1505, mild cognitive impairment = 1489, Alzheimer's disease = 708, mixed dementia = 268, vascular dementia = 148, Parkinson's disease with dementia = 120) from the MemClin Study, Karolinska Imaging in Dementia Study, Gothenburg H70 Birth Cohort Studies and the European DLB Consortium. Cerebrovascular co-pathology was assessed with visual ratings of white matter hyperintensities using the Fazekas scale through structural imaging. Alzheimer's disease biomarkers of ß-amyloid and phosphorylated tau were assessed in the cerebrospinal fluid for a subsample (N = 2191). Medial temporal atrophy was assessed with visual ratings and global cognition with the mini-mental state examination. Differences and associations were assessed through regression models, including interaction terms. In dementia with Lewy bodies, 43% had a high white matter hyperintensity load, which was significantly higher than that in cognitively unimpaired (14%), mild cognitive impairment (26%) and Alzheimer's disease (27%), but lower than that in vascular dementia (62%). In dementia with Lewy bodies, white matter hyperintensities were associated with medial temporal atrophy, and the interaction term showed that this association was stronger than that in cognitively unimpaired and mixed dementia. However, the association between white matter hyperintensities and medial temporal atrophy was non-significant when ß-amyloid was included in the model. Instead, ß-amyloid predicted medial temporal atrophy in dementia with Lewy bodies, in contrast to the findings in mild cognitive impairment where medial temporal atrophy scores were independent of ß-amyloid. Dementia with Lewy bodies had the lowest performance on global cognition, but this was not associated with white matter hyperintensities. In Alzheimer's disease, global cognitive performance was lower in patients with more white matter hyperintensities. We conclude that white matter hyperintensities are common in dementia with Lewy bodies and are associated with more atrophy in medial temporal lobes, but this association depended on ß-amyloid-related pathology in our cohort. The associations between biomarkers were overall stronger in dementia with Lewy bodies than in some of the other diagnostic groups.

Multivariate brain-cognition associations in euthymic bipolar disorder.

BACKGROUND: People with bipolar disorder (BD) tend to show widespread cognitive impairment compared to healthy controls. Impairments in processing speed (PS), attention and executive function (EF) may represent 'core' impairments that have a role in wider cognitive dysfunction. Cognitive impairments appear to relate to structural brain abnormalities in BD, but whether core deficits are related to particular brain regions is unclear and much of the research on brain-cognition associations is limited by univariate analysis and small samples. METHODS: Euthymic BD patients (n = 56) and matched healthy controls (n = 26) underwent T1-weighted MRI scans and completed neuropsychological tests of PS, attention and EF. We utilised public datasets to develop normative models of cortical thickness (n = 5977) to generate robust estimations of cortical abnormalities in patients. Canonical correlation analysis was used to assess multivariate brain-cognition associations in BD, controlling for age, sex and premorbid IQ. RESULTS: BD showed impairments on tests of PS, attention and EF, and abnormal cortical thickness in several brain regions compared to healthy controls. Impairments in tests of PS and EF were most strongly associated with cortical thickness in the left inferior temporal, right entorhinal and right temporal pole areas. CONCLUSION: Impairments in PS, attention and EF can be observed in euthymic BD and may be related to abnormal cortical thickness in temporal regions. Future research should continue to leverage normative modelling and multivariate methods to examine complex brain-cognition associations in BD. Future research may benefit from exploring covariance between traditional brain structural morphological metrics such as cortical thickness, cortical volume and surface area.

The contribution of short-term memory for sound features to speech-in-noise perception and cognition.

Speech-in-noise (SIN) perception is a fundamental ability that declines with aging, as does general cognition. We assess whether auditory cognitive ability, in particular short-term memory for sound features, contributes to both. We examined how auditory memory for fundamental sound features, the carrier frequency and amplitude modulation rate of modulated white noise, contributes to SIN perception. We assessed SIN in 153 healthy participants with varying degrees of hearing loss using measures that require single-digit perception (the Digits-in-Noise, DIN) and sentence perception (Speech-in-Babble, SIB). Independent variables were auditory memory and a range of other factors including the Pure Tone Audiogram (PTA), a measure of dichotic pitch-in-noise perception (Huggins pitch), and demographic variables including age and sex. Multiple linear regression models were compared using Bayesian Model Comparison. The best predictor model for DIN included PTA and Huggins pitch (r2 = 0.32, p < 0.001), whereas the model for SIB included the addition of auditory memory for sound features (r2 = 0.24, p < 0.001). Further analysis demonstrated that auditory memory also explained a significant portion of the variance (28 %) in scores for a screening cognitive test for dementia. Auditory memory for non-speech sounds may therefore provide an important predictor of both SIN and cognitive ability.

Advanced qEEG analyses discriminate between dementia subtypes.

BACKGROUND: Dementia is caused by neurodegenerative conditions and characterized by cognitive decline. Diagnostic accuracy for dementia subtypes, such as Alzheimer's Disease (AD), Dementia with Lewy Bodies (DLB) and Parkinson's Disease with dementia (PDD), remains challenging. METHODS: Here, different methods of quantitative electroencephalography (qEEG) analyses were employed to assess their effectiveness in distinguishing dementia subtypes from healthy controls under eyes closed (EC) and eyes open (EO) conditions. RESULTS: Classic Fast-Fourier Transform (FFT) and autoregressive (AR) power analyses differentiated between all conditions for the 4-8 Hz theta range. Only individuals with dementia with Lewy Bodies (DLB) differed from healthy subjects for the wider 4-15 Hz frequency range, encompassing the actual dominant frequency of all individuals. FFT results for this range yielded wider significant discriminators vs AR, also detecting differences between AD and DLB. Analyses of the inclusive dominant / peak frequency range (4-15 Hz) indicated slowing and reduced variability, also discriminating between synucleinopathies vs controls and AD. Dissociation of periodic oscillations and aperiodic components of AR spectra using Fitting-Oscillations-&-One-Over-F (FOOOF) modelling delivered a reliable and subtype-specific slowing of brain oscillatory peaks during EC and EO for all groups. Distinct and robust differences were particularly strong for aperiodic parameters, suggesting their potential diagnostic power in detecting specific changes resulting from age and cognitive status. CONCLUSION: Our findings indicate that qEEG methods can reliably detect dementia subtypes. Spectral analyses comprising an integrated, multi-parameter EEG approach discriminating between periodic and aperiodic components under EC and EO conditions may enhance diagnostic accuracy in the future.

Brain Morphology Normative modelling platform for abnormality and Centile estimation: Brain MoNoCle.

Normative models of brain structure estimate the effects of covariates such as age and sex using large samples of healthy controls. These models can then be applied to smaller clinical cohorts to distinguish disease effects from other covariates. However, these advanced statistical modelling approaches can be difficult to access, and processing large healthy cohorts is computationally demanding. Thus, accessible platforms with pre-trained normative models are needed. We present such a platform for brain morphology analysis as an open-source web application https://cnnplab.shinyapps.io/normativemodelshiny/, with six key features: (i) user-friendly web interface, (ii) individual and group outputs, (iii) multi-site analysis, (iv) regional and whole-brain analysis, (v) integration with existing tools, and (vi) featuring multiple morphology metrics. Using a diverse sample of 3,276 healthy controls across 21 sites, we pre-trained normative models on various metrics. We validated the models with a small clinical sample of individuals with bipolar disorder, showing outputs that aligned closely with existing literature only after applying our normative modelling. Further validation with a cohort of temporal lobe epilepsy showed agreement with previous group-level findings and individual-level seizure lateralisation. Finally, with the ability to investigate multiple morphology measures in the same framework, we found that biological covariates are better explained in specific morphology measures, and for clinical applications, only some measures are sensitive to the disease process. Our platform offers a comprehensive framework to analyse brain morphology in clinical and research settings. Validations confirm the superiority of normative models and the advantage of investigating a range of brain morphology metrics together.

Outcomes of Patients With Mild Cognitive Impairment With Lewy Bodies or Alzheimer Disease at 3 and 5 Years After Diagnosis.

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.

Subjective hearing loss is not associated with an increased risk of Alzheimer's disease dementia.

Hearing loss is a risk-factor for dementia but the reasons for this are unclear. Subjective hearing loss is related to increased future dementia risk, however, this metric has not been previously examined with cognitive, neuroimaging and biochemical measures that are relevant to Alzheimer's disease. We assessed Cognitively Normal and Mild Cognitively Impaired participants from the Alzheimer's Disease Neuroimaging Initiative with subjective hearing loss to examine if they had faster decline in episodic memory scores, hippocampal volume and greater pTau positivity. The likelihood of a dementia diagnosis in hearing impaired participants over a 5-year period was also assessed. There were no statistically significant differences between the hearing subgroups over a 5-year period nor were there in conversions to a dementia diagnosis. Objective hearing loss metrics may provide a more reliable link between hearing loss and dementia risk.

Associations between multimorbidity and neuropathology in dementia: consideration of functional cognitive disorders, psychiatric illness and dementia mimics.

BACKGROUND: Multimorbidity, the presence of two or more health conditions, has been identified as a possible risk factor for clinical dementia. It is unclear whether this is due to worsening brain health and underlying neuropathology, or other factors. In some cases, conditions may reflect the same disease process as dementia (e.g. Parkinson's disease, vascular disease), in others, conditions may reflect a prodromal stage of dementia (e.g. depression, anxiety and psychosis). AIMS: To assess whether multimorbidity in later life was associated with more severe dementia-related neuropathology at autopsy. METHOD: We examined ante-mortem and autopsy data from 767 brain tissue donors from the UK, identifying physical multimorbidity in later life and specific brain-related conditions. We assessed associations between these purported risk factors and dementia-related neuropathological changes at autopsy (Alzheimer's-disease related neuropathology, Lewy body pathology, cerebrovascular disease and limbic-predominant age-related TDP-43 encephalopathy) with logistic models. RESULTS: Physical multimorbidity was not associated with greater dementia-related neuropathological changes. In the presence of physical multimorbidity, clinical dementia was less likely to be associated with Alzheimer's disease pathology. Conversely, conditions which may be clinical or prodromal manifestations of dementia-related neuropathology (Parkinson's disease, cerebrovascular disease, depression and other psychiatric conditions) were associated with dementia and neuropathological changes. CONCLUSIONS: Physical multimorbidity alone is not associated with greater dementia-related neuropathological change; inappropriate inclusion of brain-related conditions in multimorbidity measures and misdiagnosis of neurodegenerative dementia may better explain increased rates of clinical dementia in multimorbidity.

Cholinergic changes in Lewy body disease: implications for presentation, progression and subtypes.

Cholinergic degeneration is significant in Lewy body disease, including Parkinson's disease, dementia with Lewy bodies, and isolated REM sleep behaviour disorder. Extensive research has demonstrated cholinergic alterations in the CNS of these disorders. More recently, studies have revealed cholinergic denervation in organs that receive parasympathetic denervation. This enables a comprehensive review of cholinergic changes in Lewy body disease, encompassing both central and peripheral regions, various disease stages and diagnostic categories. Across studies, brain regions affected in Lewy body dementia show equal or greater levels of cholinergic impairment compared to the brain regions affected in Lewy body disease without dementia. This observation suggests a continuum of cholinergic alterations between these disorders. Patients without dementia exhibit relative sparing of limbic regions, whereas occipital and superior temporal regions appear to be affected to a similar extent in patients with and without dementia. This implies that posterior cholinergic cell groups in the basal forebrain are affected in the early stages of Lewy body disorders, while more anterior regions are typically affected later in the disease progression. The topographical changes observed in patients affected by comorbid Alzheimer pathology may reflect a combination of changes seen in pure forms of Lewy body disease and those seen in Alzheimer's disease. This suggests that Alzheimer co-pathology is important to understand cholinergic degeneration in Lewy body disease. Thalamic cholinergic innervation is more affected in Lewy body patients with dementia compared to those without dementia, and this may contribute to the distinct clinical presentations observed in these groups. In patients with Alzheimer's disease, the thalamus is variably affected, suggesting a different sequential involvement of cholinergic cell groups in Alzheimer's disease compared to Lewy body disease. Patients with isolated REM sleep behaviour disorder demonstrate cholinergic denervation in abdominal organs that receive parasympathetic innervation from the dorsal motor nucleus of the vagus, similar to patients who experienced this sleep disorder in their prodrome. This implies that REM sleep behaviour disorder is important for understanding peripheral cholinergic changes in both prodromal and manifest phases of Lewy body disease. In conclusion, cholinergic changes in Lewy body disease carry implications for understanding phenotypes and the influence of Alzheimer co-pathology, delineating subtypes and pathological spreading routes, and for developing tailored treatments targeting the cholinergic system.

Delirium is more common and associated with worse outcomes in Parkinson's disease compared to older adult controls: results of two prospective longitudinal cohort studies.

BACKGROUND: Inpatient prevalence of Parkinson's disease (PD) delirium varies widely across the literature. Delirium in general older populations is associated with adverse outcomes, such as increased mortality, dementia, and institutionalisation. However, to date there are no comprehensive prospective studies in PD delirium. This study aimed to determine delirium prevalence in hospitalised PD participants and the association with adverse outcomes, compared to a control group of older adults without PD. METHODS: Participants were hospitalised inpatients from the 'Defining Delirium and its Impact in Parkinson's Disease' and the 'Delirium and Cognitive Impact in Dementia' studies comprising 121 PD participants and 199 older adult controls. Delirium was diagnosed prospectively using the Diagnostic and Statistical Manual of Mental Disorders 5th Edition criteria. Outcomes were determined by medical note reviews and/or home visits 12 months post hospital discharge. RESULTS: Delirium was identified in 66.9% of PD participants compared to 38.7% of controls (p < 0.001). In PD participants only, delirium was associated with a significantly higher risk of mortality (HR = 3.3 (95% confidence interval [CI] = 1.3-8.6), p = 0.014) and institutionalisation (OR = 10.7 (95% CI = 2.1-54.6), p = 0.004) 12 months post-discharge, compared to older adult controls. However, delirium was associated with an increased risk of developing dementia 12 months post-discharge in both PD participants (OR = 6.1 (95% CI = 1.3-29.5), p = 0.024) and in controls (OR = 13.4 (95% CI = 2.5-72.6), p = 0.003). CONCLUSION: Delirium is common in hospitalised PD patients, affecting two thirds of patients, and is associated with increased mortality, institutionalisation, and dementia. Further research is essential to understand how to accurately identify, prevent and manage delirium in people with PD who are in hospital.

Instrumental variables in real-world clinical studies of dementia and neurodegenerative disease: Systematic review of the subject-matter argumentation, falsification test, and study design strategies to justify a valid instrument.

OBJECTIVES: We systematically reviewed how investigators argued for and justified the validity of their instrumental variables (IV) in clinical studies of dementia and neurodegenerative disease. METHODS: We included studies using IV analysis with observational data to investigate causal effects in clinical research studies of dementia and neurodegenerative disease. We reported the subject-matter argumentation, falsification test, and study design strategies used to satisfy the three assumptions of a valid IV: relevance, exclusion restriction, and exchangeability. RESULTS: Justification for the relevance assumption was performed in all 12 included studies, exclusion restriction in seven studies, and exchangeability in nine studies. Two subject-matter argumentation strategies emerged from seven studies on the relevance of their IV. All studies except one provided quantitative evidence for the strength of the association between the IV and exposure variable. Four argumentation strategies emerged for exclusion restriction from six studies. Four falsification tests were performed across three studies. Three argumentation strategies emerged for exchangeability across four studies. Nine falsification tests were performed across nine studies. Two notable study design strategies were reported. CONCLUSION: Our results reinforce IV analysis as a feasible option for clinical researchers in dementia and neurodegenerative disease by clarifying known strategies used to validate an IV.

Identifying parkinsonism in mild cognitive impairment.

INTRODUCTION: Clinical parkinsonism is a core diagnostic feature for mild cognitive impairment with Lewy bodies (MCI-LB) but can be challenging to identify. A five-item scale derived from the Unified Parkinson's Disease Rating Scale (UPDRS) has been recommended for the assessment of parkinsonism in dementia. This study aimed to determine whether the five-item scale is effective to identify parkinsonism in MCI. METHODS: Participants with MCI from two cohorts (n = 146) had a physical examination including the UPDRS and [123I]-FP-CIT SPECT striatal dopaminergic imaging. Participants were classified as having clinical parkinsonism (P+) or no parkinsonism (P-), and with abnormal striatal dopaminergic imaging (D+) or normal imaging (D-). The five-item scale was the sum of UPDRS tremor at rest, bradykinesia, action tremor, facial expression, and rigidity scores. The ability of the scale to differentiate P+D+ and P-D- participants was examined. RESULTS: The five-item scale had an AUROC of 0.92 in Cohort 1, but the 7/8 cut-off defined for dementia had low sensitivity to identify P+D+ participants (sensitivity 25%, specificity 100%). Optimal sensitivity and specificity was obtained at a 3/4 cut-off (sensitivity 83%, specificity 88%). In Cohort 2, the five-item scale had an AUROC of 0.97, and the 3/4 cut-off derived from Cohort 1 showed sensitivity of 100% and a specificity of 82% to differentiate P+D+ from P-D- participants. The five-item scale was not effective in differentiating D+ from D- participants. CONCLUSIONS: The five-item scale is effective to identify parkinsonism in MCI, but a lower threshold must be used in MCI compared with dementia.

Lewy body dementia: Overcoming barriers and identifying solutions.

Despite its high prevalence among dementias, Lewy body dementia (LBD) remains poorly understood with a limited, albeit growing, evidence base. The public-health burden that LBD imposes is worsened by overlapping pathologies, which contribute to misdiagnosis, and lack of treatments. For this report, we gathered and analyzed public-domain information on advocacy, funding, research outputs, and the therapeutic pipeline to identify gaps in each of these key elements. To further understand the current gaps, we also conducted interviews with leading experts in regulatory/governmental agencies, LBD advocacy, academic research, and biopharmaceutical research, as well as with funding sources. We identified wide gaps across the entire landscape, the most critical being in research. Many of the experts participated in a workshop to discuss the prioritization of research areas with a view to accelerating therapeutic development and improving patient care. This white paper outlines the opportunities for bridging the major LBD gaps and creates the framework for collaboration in that endeavor. HIGHLIGHTS: A group representing academia, government, industry, and consulting expertise was convened to discuss current progress in Dementia with Lewy Body care and research. Consideration of expert opinion,natural language processing of the literature as well as publicly available data bases, and Delphi inspired discussion led to a proposed consensus document of priorities for the field.

Functional connectivity in Lewy body disease with visual hallucinations.

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.