Research diagnostic criteria for mild cognitive impairment with Lewy bodies: A systematic review and meta-analysis.

INTRODUCTION: Operationalized research criteria for mild cognitive impairment with Lewy bodies (MCI-LB) were published in 2020. The aim of this systematic review and meta-analysis was to review the evidence for the diagnostic clinical features and biomarkers in MCI-LB set out in the criteria. METHODS: MEDLINE, PubMed, and Embase were searched on 9/28/22 for relevant articles. Articles were included if they presented original data reporting the rates of diagnostic features in MCI-LB. RESULTS: Fifty-seven articles were included. The meta-analysis supported the inclusion of the current clinical features in the diagnostic criteria. Evidence for striatal dopaminergic imaging and meta-iodobenzylguanidine cardiac scintigraphy, though limited, supports their inclusion. Quantitative electroencephalogram (EEG) and fluorodeoxyglucose positron emission tomography (PET) show promise as diagnostic biomarkers. DISCUSSION: The available evidence largely supports the current diagnostic criteria for MCI-LB. Further evidence will help refine the diagnostic criteria and understand how best to apply them in clinical practice and research. HIGHLIGHTS: A meta-analysis of the diagnostic features of MCI-LB was carried out. The four core clinical features were more common in MCI-LB than MCI-AD/stable MCI. Neuropsychiatric and autonomic features were also more common in MCI-LB. More evidence is needed for the proposed biomarkers. FDG-PET and quantitative EEG show promise as diagnostic biomarkers in MCI-LB.

Actigraphic and melatonin alignment in older adults with varying dementia risk.

Circadian rhythms alter with ageing and may be aetiologically linked to neurodegeneration. This study explored the association between clinical markers and 1) dim light melatonin onset (DLMO) time and 2) phase angle derived from sleep midpoint, in older adults with varying dementia risks. Participants completed 14 days of actigraphy followed by in-lab measurement of salivary melatonin, from which DLMO time and phase angle were computed. Eighty participants (age = 65.5, SD = 9.6), 44 males (55%), MMSE (28.6, SD = 1.5) were included in the analysis. Sex (t = 2.15, p = .04), sleep onset (r = 0.49, p < .001) and midpoint (r = 0.44, p < .001) also correlated with DLMO time. Multiple linear regression showed chronotype, average actigraphy-derived light exposure during the DLMO window (window 2 h prior to DLMO to 2 h post), early biological day (6-10 h post DLMO time) and late biological day (10-14 h post DLMO time) were predictive of DLMO time (adjusted R2 = 0.75). Sleep offset, depression severity, average light exposure during the early biological night and early and late biological day were shown to be predictive variables in the estimation of phase angle (adjusted R2 = 0.78). The current study highlights the potential use of clinical variables, such as actigraphy-derived light, as circadian markers in ageing which could be easily implemented into existing clinical practice and could yield potential targets focusing on chronotherapeutic interventions.

REM sleep behaviour disorder: not just a bad dream.

Rapid eye movement (REM) sleep behaviour disorder (RBD) is a parasomnia characterised by the loss of the normal atonia during the REM stage of sleep, resulting in overt motor behaviours that usually represent the enactment of dreams. Patients will seek medical attention due to sleep-related injuries or unpleasant dream content. Idiopathic RBD which occurs independently of any other disease occurs in up to 2% of the older population. Meanwhile, secondary RBD is very common in association with certain neurodegenerative conditions. RBD can also occur in the context of antidepressant use, obstructive sleep apnoea and narcolepsy. RBD can be diagnosed with a simple screening question followed by confirmation with polysomnography to exclude potential mimics. Treatment for RBD is effective and involves treatment of underlying causes, modification of the sleep environment, and pharmacotherapy with either clonazepam or melatonin. An important finding in the past decade is the recognition that almost all patients with idiopathic RBD will ultimately go on to develop Parkinson disease or dementia with Lewy bodies. This suggests that idiopathic RBD represents a prodromal phase of these conditions. Physicians should be aware of the risk of phenoconversion. They should educate idiopathic RBD patients to recognise the symptoms of these conditions and refer as appropriate for further testing and enrolment into research trials focused on neuroprotective measures.

Fifty years of Parkinson's disease: one step forwards, two steps back?

The first issue of the British Journal of Hospital Medicine was published in October 1966 and included a symposium covering the neuropathology and treatment of Parkinson's disease. Could things have really changed that much in just 50 brief years?

Abnormal connectivity between the default mode and the visual system underlies the manifestation of visual hallucinations in Parkinson's disease: a task-based fMRI study.

BACKGROUND: The neural substrates of visual hallucinations remain an enigma, due primarily to the difficulties associated with directly interrogating the brain during hallucinatory episodes. AIMS: To delineate the functional patterns of brain network activity and connectivity underlying visual hallucinations in Parkinson's disease. METHODS: In this study, we combined functional magnetic resonance imaging (MRI) with a behavioral task capable of eliciting visual misperceptions, a confirmed surrogate for visual hallucinations, in 35 patients with idiopathic Parkinson's disease. We then applied an independent component analysis to extract time series information for large-scale neuronal networks that have been previously implicated in the pathophysiology of visual hallucinations. These data were subjected to a task-based functional connectivity analysis, thus providing the first objective description of the neural activity and connectivity during visual hallucinations in patients with Parkinson's disease. RESULTS: Correct performance of the task was associated with increased activity in primary visual regions; however, during visual misperceptions, this same visual network became actively coupled with the default mode network (DMN). Further, the frequency of misperception errors on the task was positively correlated with the strength of connectivity between these two systems, as well as with decreased activity in the dorsal attention network (DAN), and with impaired connectivity between the DAN and the DMNs, and ventral attention networks. Finally, each of the network abnormalities identified in our analysis were significantly correlated with two independent clinical measures of hallucination severity. CONCLUSIONS: Together, these results provide evidence that visual hallucinations are due to increased engagement of the DMN with the primary visual system, and emphasize the role of dysfunctional engagement of attentional networks in the pathophysiology of hallucinations.

The relationships between mild cognitive impairment and phenotype in Parkinson's disease.

BACKGROUND: The concept of differing clinical phenotypes within Parkinson's disease (PD) is well represented in the literature. However, there is no consensus as to whether any particular disease phenotype is associated with an increased risk of mild cognitive impairment (MCI) using the newly proposed Movement Disorders Society diagnostic criteria for this feature. AIMS: To explore the expression of PD-MCI in relation to the heterogeneity of idiopathic PD. METHODS: A cluster analysis incorporating a range of specific demographic, clinical and cognitive variables was performed on 209 patients in the early stages of PD (between Hoehn and Yahr stages I-III). Post hoc analyses exploring variables not included in the clustering solution were performed to interrogate the veracity of the subgroups generated. RESULTS: This study identified four distinct PD cohorts: a younger disease-onset subgroup, a tremor dominant subgroup, a non-tremor dominant subgroup, and a subgroup with rapid disease progression. The present study identified a differential expression of PD-MCI across these subgroups, with the highest frequency observed in the non-tremor dominant cluster. The non-tremor dominant subgroup was also associated with a higher prevalence of freezing of gait, hallucinations, daytime somnolence, and rapid eye movement sleep behavior disorder compared with other subgroups. CONCLUSIONS: This study confirms the existence of heterogeneity within the early clinical stages of PD and for the first time highlights the differential expression of PD-MCI using the newly defined diagnostic criteria for this feature. An improved understanding of PD-MCI and its clinical relationships may lead to an improved understanding of the pathophysiology underlying heterogeneity in PD.