In this narrative review, we delved into the intricate interplay between Apolipoprotein E (APOE) alleles (typically associated with Alzheimer\'s disease-AD) and alpha-synucleinopathies (aS-pathies), involving Parkinson\'s disease (PD), Parkinson\'s disease dementia (PDD), dementia with Lewy bodies (DLB), and multiple-system atrophy (MSA). First, in-vitro, animal, and human-based data on the exacerbating effect of APOE4 on LB pathology were summarized. We found robust evidence that APOE4 carriage constitutes a risk factor for PDD-APOE2, and APOE3 may not alter the risk of developing PDD. We confirmed that APOE4 copies confer an increased hazard towards DLB, as well. Again APOE2 and APOE3 appear unrelated to the risk of conversion. Of note, in individuals with DLB APOE4, carriage appears to be intermediately prevalent between AD and PDD-PD (AD > DLB > PDD > PD). Less consistency existed when it came to PD; APOE-PD associations tended to be markedly modified by ethnicity. Finally, we failed to establish an association between the APOE gene and MSA. Phenotypic associations (age of disease onset, survival, cognitive-neuropsychiatric- motor-, and sleep-related manifestations) between APOE alleles, and each of the aforementioned conditions were also outlined. Finally, a synopsis of literature gaps was provided followed by suggestions for future research.

Lewy body dementia (LBD) is situated at the convergence of neurodegenerative disorders, posing an intricate and diverse clinical dilemma. The accumulation of abnormal protein in the brain, namely, the Lewy body causes disturbances in typical neural functioning, leading to a range of cognitive, motor, and mental symptoms that have a substantial influence on the overall well-being and quality of life of affected individuals. There is no definitive cure for the disease; however, several nonpharmacological and pharmacological modalities have been tried with questionable efficacies. The aim of this study is to figure out the role of different interventional strategies in the disease. Donepezil, rivastigmine, memantine, and galantamine were the commonly used drugs for LBD. Together with that, levodopa, antipsychotics, armodafinil, piracetam, and traditional medications like yokukansan were also used, when indicated. Talking about nonpharmacological measures, exercise, physical therapy, multicomponent therapy, occupational therapy, psychobehavioral modification, transcranial stimulation, and deep brain stimulation have been used with variable efficacies. Talking about recent advances in the treatment of LBD, various disease-modifying therapies like ambroxol, neflamapimod, irsenontrine, nilotinib, bosutinib, vodobatinib, clenbuterol, terazosin, elayta, fosgonimeton, and anle138b are emerging out. However, there drugs are still in the different phases of clinical trials and are not commonly used in clinical practice. With the different pharmacological and nonpharmacological modalities we have for treatment of LBD, all of them offer symptomatic relief only. Being a degenerative disease, definite cure of the disease can only be possible with regenerative measures.

Lewy body disease (LBD) is the second most common neurodegenerative disorder in patients older than 65 years. LBD is characterized by heterogeneous symptoms like fluctuation in attention, visual hallucinations, Parkinsonism, and REM sleep behaviour disorders. Considering the relevant social impact of the disease, identifying effective non-pharmacological treatments is becoming a priority. The aim of this systematic review was to provide an up-to-date literature review of the most effective non-pharmacological treatments in patients with LBD, focussing on evidence-based interventions.
Following PRISMA criteria, we carried out a systematic search through three databases (PubMed, Cochrane Libraries, and PEDro) including physical therapy (PT), cognitive rehabilitation (CR), light therapy (LT), transcranial direct current stimulation (tDCS), transcranial magnetic stimulation (TMS), electroconvulsive therapy (ECT), deep brain stimulation (DBS). All studies were qualitatively assessed using standardized tools (CARE and EPHPP).
We obtained a total of 1,220 studies of which 23 original articles met eligibility criteria for inclusion. The total number of LBD patients included was 231; mean age was 69.98, predominantly men (68%). Some PT studies highlighted improvements in motor deficits. CR produced significant improvements in mood, cognition, and patient\'s quality of life and satisfaction. LT outlined a partial trend of improvements in mood and sleep quality. DBS, ECT, and TMS showed some partial improvements mainly on neuropsychiatric symptoms, whereas tDCS provided partial improvements in attention.
This review highlights the efficacy of some evidence-based rehabilitation studies in LBD; however, further randomized controlled trials with larger samples are needed to provide definitive recommendations.

UNASSIGNED: Cognitive impairment is common in the course of Parkinson\'s disease (PD) and displays a continuum from subjective cognitive impairment to dementia. Illuminating the pathophysiological processes associated with the continuum may help create follow-up and new treatment approaches. In this context, large-scale intrinsic connectivity networks are widely investigated to elucidate the neural processes underlying PD and are promising as non-invasive biomarkers. This systematic review aims to examine the alterations in large-scale intrinsic connectivity networks in the continuum of PD-associated cognitive impairment.
UNASSIGNED: ScienceDirect, Web of Science, and PubMed databases were searched with the specified keywords. The studies obtained as a result of this review were investigated by the PRISMA criteria, which were taken as a basis for the systematic review and writing of meta-analyses.
UNASSIGNED: A total of 974 studies were obtained from three databases. Twenty studies were included in the systematic review based on predetermined eligibility criteria. Among the large-scale connectivity networks examined in these studies, it was found that sensory-motor networks decreased their connectivity in the continuum of PD-associated cognitive impairment, and there were conflicting results in terms of cognitive networks.
UNASSIGNED: Well-designed longitudinal studies are needed to clarify the alterations in the intrinsic connectivity networks in the PD cognitive impairment continuum. In these studies, it is necessary to define the cognitive disorder groups well, to control the connectivity changes that may occur due to dopaminergic treatment, and to evaluate Parkinson\'s patients with subjective cognitive impairment and dementia within the continuum.

Lewy body dementia (LBD) refers to both dementia with Lewy bodies (DLB) and Parkinson\'s disease with dementia (PDD). Sleep disturbances are common in LBD, and can include poor sleep quality, excessive daytime sleepiness (EDS), and rapid eye movement behaviour disorder (RBD). Despite the high clinical prevalence of sleep disturbances in LBD, they are under-studied relative to other dementias. The aim of the present systematic review was to examine the nature of sleep disturbances in LBD, summarise the effect of treatment studies upon sleep, and highlight specific and necessary directions for future research.
Published studies in English were located by searching PubMED and PSYCArticles databases (until 10 June 2022). The search protocol was pre-registered in PROSPERO (CRD42021293490) and performed in accordance with PRISMA guidelines.
Following full-text review, a final total of 70 articles were included. These included 20 studies focussing on subjective sleep, 14 on RBD, 8 on EDS, 7 on objective sleep, and 1 on circadian rhythms. The majority of the 18 treatment studies used pharmacological interventions (n = 12), had an open-label design (n = 8), and were of low-to-moderate quality. Most studies (n = 55) included only patients with DLB. Due to the heterogeneity of the studies, we reported a narrative synthesis without meta-analysis.
At least one form of sleep disturbance may be present in as many as 90% of people with LBD. Subjectively poor sleep quality, excessive daytime sleepiness, and RBD are more common and severe in LBD relative to other dementias.

Lewy body dementia (LBD) is the second most common neurodegenerative dementia, and it causes earlier mortality and more morbidity than Alzheimer\'s disease. Reviewing current evidence on its pharmacological management is essential for developing evidence-based clinical guidelines, and for improving the quality of its clinical care. Hence, we systematically reviewed all studies that investigated the efficacy of any medication for managing various symptoms of LBD.
We identified eligible studies by searching 15 databases comprehensively. We completed quality assessment, extracted relevant data, and performed GRADE assessment of available evidence. We conducted meta-analyses when appropriate (PROSPERO:CRD42020182166).
We screened 18,884 papers and included 135 studies. Our meta-analyses confirmed level-1 evidence for Donepezil\'s efficacy of managing cognitive symptoms of dementia with Lewy bodies (DLB) (SMD = 0.63; p < 0.001) and Parkinson\'s Disease Dementia (PDD) (SMD = 0.43; p < 0.01), and managing hallucinations in DLB (SMD=-0.52; p = 0.02). Rivastigmine and Memantine have level-2 evidence for managing cognitive and neuropsychiatric symptoms of DLB. Olanzapine and Yokukansan have similar evidence for managing DLB neuropsychiatric symptoms. Level-2 evidence support the efficacy of Rivastigmine and Galantamine for managing cognitive and neuropsychiatric symptoms of PDD.
We list evidence-based recommendations for the pharmacological management of DLB and PDD, and propose specific clinical guidelines for improving their clinical management.
Supplemental data for this article can be accessed online at https://doi.org/10.1080/13607863.2022.2032601 .

Despite improvements in diagnostic criteria for dementia with Lewy bodies (DLB), the ability to discriminate DLB from Alzheimer\'s disease (AD) and other dementias remains suboptimal. Electroencephalography (EEG) is currently a supportive biomarker in the diagnosis of DLB. We performed a systematic review to better clarify the diagnostic and prognostic role of EEG in DLB and define the clinical correlates of various EEG features described in DLB. MEDLINE, EMBASE, and PsycINFO were searched using search strategies for relevant articles up to 6 August 2020. We included 43 studies comparing EEG in DLB with other diagnoses, 42 of them included a comparison of DLB with AD, 10 studies compared DLB with Parkinson\'s disease dementia, and 6 studies compared DLB with other dementias. The studies were visual EEG assessment (6), quantitative EEG (35) and event-related potential studies (2). The most consistent observation was the slowing of the dominant EEG rhythm (<8 Hz) assessed visually or through quantitative EEG, which was observed in ~90% of patients with DLB and only ~10% of patients with AD. Other findings based on qualitative rating, spectral power analyses, connectivity, microstate and machine learning algorithms were largely heterogenous due to differences in study design, EEG acquisition, preprocessing and analysis. EEG protocols should be standardized to allow replication and validation of promising EEG features as potential biomarkers in DLB.

Parkinson\'s disease (PD) is a prevalent neurodegenerative disorder, which relates to not only motor symptoms, but also cognitive, autonomic, and mood impairments. The literature suggests that pharmacological or surgical treatment has a limited effect on providing relief of the symptoms and also restricting its progression. Recently, research on non-pharmacological interventions for people living with PD (pwPD) that alleviate their motor and non-motor features has shown a new aspect in treating this complex disease. Numerous studies are supporting exercise intervention as being effective in both motor and non-motor facets of PD, such as physical functioning, strength, balance, gait speed, and cognitive impairment. Via the lens of the physical profession, this paper strives to provide another perspective for PD treatment by presenting exercise modes categorized by motor and non-motor PD symptoms, along with its effects and mechanisms. Acknowledging that there is no \"one size fits all\" exercise prescription for such a variable and progressive disease, this review is to outline tailored physical activities as a credible approach in treating pwPD, conceivably enhancing overall physical capacity, ameliorating the symptoms, reducing the risk of falls and injuries, and, eventually, elevating the quality of life. It also provides references and practical prescription applications for the clinician.

Patients with Lewy body disease (LBD) frequently experience visual hallucinations (VH), well-formed images perceived without the presence of real stimuli. The structural and functional brain mechanisms underlying VH in LBD are still unclear. The present review summarises the current literature on the neural correlates of VH in LBD, namely Parkinson\'s disease (PD), and dementia with Lewy bodies (DLB). Following a systematic literature search, 56 neuroimaging studies of VH in PD and DLB were critically reviewed and evaluated for quality assessment. The main structural neuroimaging results on VH in LBD revealed grey matter loss in frontal areas in patients with dementia, and parietal and occipito-temporal regions in PD without dementia. Parietal and temporal hypometabolism was also reported in hallucinating PD patients. Disrupted functional connectivity was detected especially in the default mode network and fronto-parietal regions. However, evidence on structural and functional connectivity is still limited and requires further investigation. The current literature is in line with integrative models of VH suggesting a role of attention and perception deficits in the development of VH. However, despite the close relationship between VH and cognitive impairment, its associations with brain structure and function have been explored only by a limited number of studies.

BACKGROUND: Parkinson\'s disease dementia (PDD) is a major cause of morbidity and mortality in Parkinson\'s disease (PD), which severely affects patient functioning and quality of life and increases the risk for nursing home admission. Unfortunately, current treatment options for PDD are limited and have only marginal therapeutic effects. As novel treatments are developed, there will be a need to assess their efficacy in well-designed randomized controlled trials. However, there is no consensus on the optimal outcome measures for use in PDD clinical trials.
METHODS: A systematic review of PDD clinical trials and empiric studies of outcome measures used in PDD was performed. Outcome measures were divided into five categories: 1) cognitive; 2) behavioral and mood; 3) activities of daily living and quality of life; 4) global; and 5) caregiver burden.
RESULTS: A total of 20 PDD pharmacologic clinical trials were identified. These trials incorporated a broad array of outcome measures, which were used inconsistently across trials. We summarize the psychometric properties and other relevant data on outcome measures used, including their diagnostic utility, inter-rater reliability, test-retest reliability, responsiveness, clinically meaningful change, and availability of alternate forms.
CONCLUSIONS: We have identified the best-evidenced PDD outcome measures in each domain. Further research is needed to assess the validity, reliability, and clinically meaningful change of these measures in PDD to inform the design of future clinical trials and enhance the ability of clinicians, researchers and policy-makers to interpret study results. In addition, the development of outcome measures specific to PDD may be warranted.