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Introduction: The extent to which the Big Five personality traits and subjective well-being (SWB) are discriminatory predictors of clinical manifestation of dementia versus dementia-related neuropathology is unclear., Methods: Using data from eight independent studies (N total = 44,531; N dementia = 1703; baseline M age = 49 to 81 years, 26 to 61% female; M follow-up range = 3.53 to 21.00 years), Bayesian multilevel models tested whether personality traits and SWB differentially predicted neuropsychological and neuropathological characteristics of dementia., Results: Synthesized and individual study results indicate that high neuroticism and negative affect and low conscientiousness, extraversion, and positive affect were associated with increased risk of long-term dementia diagnosis. There were no consistent associations with neuropathology., Discussion: This multistudy project provides robust, conceptually replicated and extended evidence that psychosocial factors are strong predictors of dementia diagnosis but not consistently associated with neuropathology at autopsy., Highlights: N(+), C(-), E(-), PA(-), and NA(+) were associated with incident diagnosis. Results were consistent despite self-report versus clinical diagnosis of dementia. Psychological factors were not associated with neuropathology at autopsy. Individuals with higher conscientiousness and no diagnosis had less neuropathology. High C individuals may withstand neuropathology for longer before death., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: The relationship between cerebrospinal fluid pressure (CSFP) and cognition has received little research attention. The purpose of this study was to explore the relationship between CSFP and cognition in patients with Alzheimer's disease (AD) and patients with Lewy body dementia (LBD)., Method: We included 178 participants, including 137 patients with AD and 41 patients with LBD (including dementia with Lewy bodies (DLBs) and Parkinson's disease dementia (PDD)). CSFP was measured by lumbar puncture, and a patient-reported history and laboratory test data were collected. Logistic and linear regression analyses were used to evaluate the associations between CSFP and cognition, the cerebrospinal fluid (CSF) / serum albumin ratio (Qalb), and CSF biomarkers of AD., Results: The mean age of the included patients was 63.58 ± 8.77 years old, and the mean CSFP was 121 ± 33.72 mmH2O. A total of 76.9% of the patients had a CSFP distribution of [90-170) mmH2O, 46 patients (25.8%) had severe dementia, 83 patients (46.6%) had moderate dementia, 28 patients (15.7%) had mild dementia, and 21 patients (11.8%) had mild cognitive impairment (MCI) (including 16 patients with MCI due to AD and 5 patients with MCI due to LBD). In all patients (p value < 0.001) and in patients with AD (p value = 0.01), the mean cerebrospinal fluid pressure (CSFP) was higher in patients with MCI than in patients with dementia. In multivariate analysis, in all patients (OR: 6.37, 95% confidential interval (CI): 1.76-23.04, p = 0.005) and patients with AD (odds ratio (OR): 5.43, 95% CI: 1.41-20.87, p = 0.005), a CSFP in the lowest quartile ([50-90) mmH2O) was associated with a higher level of severe dementia than a CSFP in the highest quartile ([170-210) mmH2O). In addition, there was a significant linear correlation between CSFP and the Mini-Mental State Examination (MMSE) score in all patients with dementia (r = 0.43, p = 0.04, Durbin-Watson test (D-W test) = 0.75)., Conclusion: In patients with AD, the mean cerebrospinal fluid pressure was higher in patients with MCI than in patients with dementia, and the decrease in CSFP was related to a more serious dementia level. However, no such relationship was found in patients with LBD., (© 2024. The Author(s).)

Background: Attention-deficit/hyperactivity disorder (ADHD), a common neurodevelopmental condition now recognized to persist into older adulthood, has been postulated to be a risk factor for neurocognitive disorders given the overlap in clinical features and neurobiology, as well as the complex interplay between ADHD and known risk factors for dementia. Studies have emerged assessing this relationship, but there has not yet been a comprehensive systematic review addressing this topic., Objective: To assess whether ADHD is a risk factor for neurocognitive disorders and to explore possible mechanisms for such an association., Methods: A systematic review of the literature was conducted using Medline, Embase, and PsycINFO from inception until June 4, 2023. Studies were included if they assessed whether or how ADHD may be a risk factor for neurocognitive disorders. Studies were excluded if they were not primary literature, not published in a peer-reviewed journal, not in English, and/or used non-human subjects. Study quality was assessed using the QualSyst tool., Results: Sixteen studies met inclusion criteria. Seven studies found a positive association between ADHD and neurocognitive disorders (all-cause dementia in four studies, Alzheimer's disease in three studies, Lewy body dementia in two studies, and mild cognitive impairment in one study). Four studies did not find an association. Five studies pertained to possible mechanisms for an association, including genetics, with minimal significant findings., Conclusions: ADHD may be a risk factor for certain neurocognitive disorders, although the evidence base is limited, and the absolute risk is small. Possible explanations include genetic and lifestyle factors.

Objective: To assess the changes in effective connectivity of important regions of the visual network (VIS) and dorsal attention network (DAN) underlying visual hallucinations (VHs) in Dementia with Lewy Bodies (DLB), Parkinson's Disease (PD) and Parkinson's Disease Dementia (PDD), as measured by a transcranial magnetic stimulation-electroencephalographic technique (TMS-EEG)., Methods: We stimulated the right visual cortex (V1/V2), the right intraparietal sulcus and the right frontal eye fields, two key regions of the DAN, and measured TMS-evoked cortical activation within the VIS and the DAN. We compared 11 patients with VHs and 15 patients without VHs., Results: Patients with VHs showed lower TMS-evoked cortical activation within the DAN following intraparietal sulcus and frontal eye fields stimulation than patients without VHs. No difference was found between patients with and without cognitive impairment. Also, when considering only patients with cognitive impairment, VHs were associated with lower TMS-evoked cortical activation following intraparietal sulcus stimulation., Conclusions: DLB, PD, and PDD patients with VHs had less effective connectivity of the right intraparietal sulcus within the DAN than patients without VHs., Significance: We provided the first evidence that VHs are associated with specific intraparietal sulcus dysfunction within the DAN in patients with PDD, PD, and DLB., (Copyright © 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: White matter hyperintensities (WMHs) are associated with cognitive deficits and worse clinical outcomes in dementia, but rare studies have been carried out of cognitive impairment in Lewy body disease (CI-LB) patients. The objective was to investigate the associations between WMHs and clinical manifestations in patients with CI-LB., Methods: In this retrospective multicentre cohort study, 929 patients (486 with dementia with Lewy bodies [DLB], 262 with Parkinson's disease dementia [PDD], 74 with mild cognitive impairment [MCI] with Lewy bodies [MCI-LB] and 107 with Parkinson's disease with MCI [PD-MCI]) were analysed from 22 memory clinics between January 2018 and June 2022. Demographic and clinical data were collected by reviewing medical records. WMHs were semi-quantified according to the Fazekas method. Associations between WMHs and clinical manifestations were investigated by multivariate linear or logistic regression models., Results: Dementia with Lewy bodies patients had the highest Fazekas scores compared with PDD, MCI-LB and PD-MCI. Multivariable regressions showed the Fazekas score was positively associated with the scores of Unified Parkinson's Disease Rating Scale Part III (p = 0.001), Hoehn-Yahn stage (p = 0.004) and total Neuropsychiatric Inventory (p = 0.001) in MCI-LB and PD-MCI patients. In patients with DLB and PDD, Fazekas scores were associated with the absence of rapid eye movement sleep behaviour disorder (p = 0.041) and scores of Unified Parkinson's Disease Rating Scale Part III (p < 0.001), Hoehn-Yahn stage (p < 0.001) and the Montreal Cognitive Assessment (p = 0.014)., Conclusion: White matter hyperintensity burden of DLB was higher than for PDD, MCI-LB and PD-MCI. The greater WMH burden was significantly associated with poorer cognitive performance, worse motor function and more severe neuropsychiatric symptoms in CI-LB., (© 2023 European Academy of Neurology.)

Introduction: We examined the progression of extrapyramidal symptoms and signs in autopsy-confirmed dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD), and Alzheimer's disease dementia (AD)., Methods: Longitudinal data were obtained from Arizona Study of Aging and Neurodegenerative Disease, with PDD (n = 98), AD (n = 47) and DLB (n = 48) further sub-grouped as with or without parkinsonism (DLB+ and DLB-). Within-group Unified Parkinson's Disease Rating Scale (UPDRS) -II and UPDRS-III trajectories were analyzed using non-linear mixed effects models., Results: In DLB, 65.6% had parkinsonism. Baseline UPDRS-II and III scores (off-stage) were highest (P < 0.001) for PDD (mean ± SD 14.3 ± 7.8 and 27.4 ± 16.3), followed by DLB+ (6.0 ± 8.8 and 17.2 ± 17.1), DLB- (1.1 ± 1.3 and 3.3 ± 5.5) and AD (3.2 ± 6.1 and 8.2 ± 13.6). Compared to PDD, the DLB+ group had faster UPDRS-III progression over 8-years (Cohen's-d range 0.98 to 2.79, P < 0.001), driven by gait (P < 0.001) and limb bradykinesia (P = 0.02) subscales., Discussion: Motor deficits progress faster in DLB+ than PDD, providing insights about expected changes in motor function., Highlights: Dementia with Lewy bodies has faster motor progression than Parkinson's disease dementia Linear and non-linear mixed modeling analysis of longitudinal data was utilized Findings have implications for clinical prognostication and trial design., (© 2023 the Alzheimer's Association.)

Objectives: Neuropsychiatric symptom could be useful for detecting patients with prodromal dementia. Similarities and differences in the NPSs between preclinical/prodromal Alzheimer's disease (AD) and prodromal Parkinson's disease dementia (PDD)/Dementia with Lewy bodies (DLB) may exist. This study aimed to compare the NPSs between preclinical/prodromal AD and prodromal PDD/DLB., Methods: One hundred and three participants without dementia aged ≥50 years were included in this study. The mild behavioral impairment (MBI) total score and the MBI scores for each domain were calculated using the neuropsychiatric inventory questionnaire score. Participants were divided into five groups based on the clinical diagnosis by neurologists or psychiatrists in each institution based on the results of the amyloid positron emission tomography and dopamine transporter single photon emission computed tomography (DAT-SPECT): Group 1: amyloid-positive and abnormal DAT-SPECT, Group 2: amyloid-negative and abnormal DAT-SPECT, Group 3: amyloid-positive and normal DAT-SPECT, Group 4: mild cognitive impairment unlikely due to AD with normal DAT-SPECT, and Group 5: cognitively normal with amyloid-negative and normal DAT-SPECT., Results: The MBI abnormal perception or thought content scores were significantly higher in Group 1 than Group 5 (Bonferroni-corrected p = 0.012). The MBI total score (Bonferroni-corrected p = 0.011) and MBI impulse dyscontrol score (Bonferroni-corrected p = 0.033) in Group 4 were significantly higher than those in Group 5., Conclusion: The presence of both amyloid and putative Lewy body pathologies may be associated with psychotic symptoms., (© 2023 John Wiley & Sons Ltd.)

Objectives: People with dementia can face barriers when trying to access care after a diagnosis, particularly in young-onset dementia (YOD). Little is known about the effects of ethnicity on the use of anti-dementia medication and variations between age groups. The aim of this study was to analyze national data on variations in the uptake of anti-dementia medication between people with YOD and late-onset dementia (LOD)., Design: Cross-sectional longitudinal cohort study., Setting: Data from the U.S. National Alzheimer's Coordinating Centre were obtained from September 2005 to March 2019., Participants: First visits of people with a diagnosis of Alzheimer's disease (AD) dementia, Lewy body dementia (LBD), and Parkinson's disease dementia (PDD) were included., Measurements: Logistic regression was used to analyze the effects of education and ethnicity on use of cholinesterase inhibitors and memantine, accounting for YOD/LOD, gender, living situation, severity stage, and comorbidities., Results: In total, 15,742 people with AD dementia and LBD/PDD were included, with 11,019 PwD having completed a first follow-up visit. Significantly more people with YOD used memantine than those with LOD, while fewer used cholinesterase inhibitors. PwD from minority ethnic backgrounds used memantine and cholinesterase inhibitors less often than those from a White ethnic background. Logistic regression analysis showed that ethnicity was a significant determinant of both memantine and cholinesterase inhibitors usage, while education was only a significant determinant for memantine usage., Conclusions: Findings highlight the impact of social factors on current usage of anti-dementia medication and the need for more resources to enable equitable use of anti-dementia medication.

Aggregation of misfolded α-synuclein (α-syn) protein in the periphery and central nervous system (CNS) gives rise to a group of disorders, which are labeled collectively as synucleinopathies. These clinically distinct disorders are known as pure autonomic failure, Parkinson's disease (PD), Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). In the case of PD, it has been demonstrated that toxic aggregates of α-syn protein not only cause apoptosis of dopamine neurons but its accumulation in the neocortex and limbic area principally contributes to dementia. In our multifunctional drug discovery research for PD, we converted one of our catechol-containing lead dopamine agonist molecules D-520 into its prodrug D-685 . The prodrug exhibited higher in vivo anti-Parkinsonian efficacy in a reserpinized PD animal model than the parent D-520 and exhibited facile brain penetration. In our study with an α-syn transgenic animal model (D line) for PD and dementia with Lewy bodies (DLB), we have shown that 1 month of chronic treatment with the compound D-685 was sufficient to reduce the accumulation of α-syn and phospho-α-syn in the cortex, hippocampus, and striatum areas significantly compared to the control tg mice. Furthermore, D-685 did not exhibit any deleterious effect in the CNS as was evident from the neuron and microglia studies. Future studies will further explore in depth the potential of D-685 to modify disease progression while addressing symptomatic deficits.

Purpose: Identifying the associated clinical conditions in patients with newly diagnosed dementia with Lewy bodies (DLB) may contribute to the disease management. This study aimed to examine the clinical features and coexisting geriatric syndromes of patients with newly diagnosed DLB., Method: This cross-sectional study included newly diagnosed DLB participants who were admitted to a tertiary geriatric outpatient clinic. Of the 857 patients with dementia, 116 DLB diagnoses were eligible for analysis. The core and supportive clinical features of DLB were recorded. Geriatric syndromes including polypharmacy, depression, insomnia, dependency, a history of delirium, falls, malnutrition, urinary incontinence, functional impairment, and living alone, were assessed and recorded at baseline., Results: The mean age was 79.0 ± 6.9 years, and 50.9% of the participants were female. The majority (63.8%) had mild dementia, 31.9% had moderate, and 4.3% had severe disease. Cognitive fluctuations (78.4%), visual hallucinations (77.6%), and Parkinsonism (73.3%) were the most common clinical features. Functional impairment (59.5%) and urinary incontinence (59.5%) were the leading geriatric syndromes, followed by polypharmacy (56.9%), depressive symptoms (54.7%), falls (52.6%), insomnia (49.1%), malnutrition (24.3%), and delirium (6.0%). Women had more functional impairment and depressive symptoms than men., Conclusion: Although most patients had mild dementia, three-quarters of the DLB cohort had hallucinations, and nearly two-thirds were functionally impaired. The proportion of other serious health conditions also increased, indicating a high comorbidity and geriatric syndrome burden. Comprehensive geriatric assessment is strongly recommended for DLB patients from the time of diagnosis until death to reduce disability and comorbidities., The Clinical Trial Registration Number: NCT05052450., (© 2022. The Author(s), under exclusive licence to European Geriatric Medicine Society.)

Lewy body dementia is the third most common and costliest type of dementia. It is an umbrella term for dementia with Lewy bodies and Parkinson's disease dementia, both of which place a substantial burden on the person and society. Recent findings outline ethnoracial differences in dementia risk. Delayed and misdiagnosis across ethnoracial groups contribute to higher levels of burden. In this context, we aimed to summarize current knowledge, gaps, and unmet needs relating to race and ethnicity in Lewy body dementia. In this narrative review, we provide an overview of studies on Lewy body dementia focusing on differences across ethnoracial groups and outline several recommendations for future studies. The majority of the findings comparing different ethnoracial groups were from North American sites. There were no differences in clinical prevalence and progression across ethnoracial groups. Compared to people identifying as non-Hispanic White, co-pathologies were more common and clinical diagnostic accuracy was lower for people identifying as Black. Co-morbidities (e.g., diabetes, hypertension) were more common and medication use rates (e.g., antidepressants, antiparkinsonian agents) were lower for people identifying as Black or Hispanic compared to people identifying as White. More than 90% of clinical trial participants identified as non-Hispanic White. Despite increasing efforts to overcome disparities in Alzheimer's disease and related dementias, inclusion of individuals from minoritized communities in Lewy body dementia studies continues to be limited and the findings are inconclusive. Representation of diverse populations is crucial to improve the diagnostic and therapeutic efforts in Lewy body dementia.

Objective: To determine the minimum duration of electroencephalography (EEG) data necessary to differentiate EEG features of Lewy body dementia (LBD), that is, dementia with Lewy bodies and Parkinson disease dementia, from non-LBD patients, that is, Alzheimer disease and Parkinson disease., Methods: We performed quantitative EEG analysis for 16 LBD and 14 non-LBD patients. After artifact removal, a fast Fourier transform was performed on 90, 60, and thirty 2-second epochs to derive dominant frequency; dominant frequency variability; and dominant frequency prevalence., Results: In LBD patients, there were no significant differences in EEG features derived from 90, 60, and thirty 2-second epochs (all P >0.05). There were no significant differences in EEG features derived from 3 different groups of thirty 2-second epochs (all P >0.05). When analyzing EEG features derived from ninety 2-second epochs, we found that LBD had significantly reduced dominant frequency, reduced dominant frequency variability, and reduced dominant frequency prevalence alpha compared with the non-LBD group (all P <0.05). These same differences were observed between the LBD and non-LBD groups when analyzing thirty 2-second epochs., Conclusions: There were no differences in EEG features derived from 1 minute versus 3 minutes of EEG data, and both durations of EEG data equally differentiated LBD from non-LBD., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: From an ongoing multicenter effort toward differentiation of Parkinsonian spectrum disorders (PSD) from other types of neurodegenerative disorders, the sleep biomarker non-rapid-eye-movement sleep with hypertonia (NRH) emerged., Methods: This study included in the PSD group patients with dementia with Lewy bodies/Parkinson disease dementia (DLB/PDD = 16), Parkinson disease (PD = 16), and progressive supranuclear palsy (PSP = 13). The non-PSD group included patients with Alzheimer disease dementia (AD = 24), mild cognitive impairment (MCI = 35), and a control group with normal cognition (CG = 61). In-home, multi-night Sleep Profiler studies were conducted in all participants. Automated algorithms detected NRH, characterized by elevated frontopolar electromyographic power. Between-group differences in NRH were evaluated using Logistic regression, Mann-Whitney U and Chi-squared tests., Results: NRH was greater in the PSD group compared to non-PSD (13.9 ± 11.0% vs. 3.1 ± 4.7%, P < 0.0001). The threshold NRH≥5% provided the optimal between-group differentiation (AUC = 0.78, P < 0.001). NRH was independently associated with the PSD group after controlling for age, sex, and SSRI/SNRI use (P < 0.0001). The frequencies of abnormal NRH by subgroup were PSP = 92%, DLB/PDD = 81%, PD = 56%, MCI = 26%, AD = 17%, and CG = 16%. The odds of abnormal NRH in each PSD subgroup ranged from 3.7 to 61.2 compared to each non-PSD subgroup. The night-to-night and test-retest intraclass correlations were excellent (0.78 and 0.84, both P < 0.0001)., Conclusions: In this pilot study, NRH appeared to be a novel candidate sleep biomarker for PSD-related neurodegeneration. Future studies in larger cohorts are needed to confirm these findings, understand the etiology of NRH magnitude/duration, and determine whether it is an independent prodromal marker for specific neurodegenerative pathologies., Competing Interests: Declaration of competing interest As shareholders in Advanced Brain Monitoring, Inc. Mr. Levendowski, Ms. Berka and Dr. Westbrook would financially benefit if the SP intellectual property was acquired by a third party. Dr. Boeve has served as an investigator for clinical trials sponsored by Biogen, Alector, and EIP Pharma. He receives royalties from the publication of a book entitled Behavioral Neurology Of Dementia (Cambridge Medicine, 2009, 2017). He serves on the Scientific Advisory Board of the Tau Consortium. Dr. Salat is a consultant to Cyclerion and Amylyx, has a financial interest in Niji Corp and has served as an investigator on research sponsored by Renew Research. Dr. Lee-Iannotti serves as a paid advisor to and speaker for Jazz Pharmaceuticals. Dr Shprecher received research support from the Arizona Alzheimer's Consortium, Abbvie, Acadia, Aptinyx, Axovant, Biogen, Eisai, Eli Lilly, Enterin, Neurocrine, Michael J Fox Foundation, NIH, Nuvelution and Teva; consultant fees from Amneal, Forensis and Neurocrine; speaker honoraria from Acorda, Amneal, Intermountain Healthcare, Neurocrine, Sunovion, Teva and US World Meds. Dr. Mazeika serves as the Medical Director of Advanced Brain Monitoring, Inc. None of the other authors reported financial conflicts., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: It is unclear whether people with dementia (PwD) have more negative attitudes toward own aging (ATOA) than people without dementia and what factors influence ATOA among PwD. We investigated whether PwD have more negative ATOA than individuals without dementia and whether cognition and dementia subtype are associated with ATOA in PwD., Methods: Data from the IDEAL and PROTECT studies were used to compare ATOA between 1502 PwD (mean (SD) age = 76.3 (8.5)) and 6377 individuals without dementia (mean (SD) age = 66.1 (7.1)). Linear regressions and ANOVA were used., Results: PwD reported slightly more negative ATOA than people without dementia; this relationship disappeared after controlling for depression and self-rated health. In PwD more positive ATOA showed negligible associations with better general cognition, memory performance, verbal fluency, and visuospatial ability. However, after adjusting for covariates only better visuospatial ability predicted more positive ATOA. Additional analyses showed that before and after controlling for covariates, individuals with poorer self-reported visual acuity have more negative ATOA. Amongst dementia subtypes, people with Parkinson's disease dementia and dementia with Lewy bodies reported most negative ATOA., Conclusions: ATOA between PwD and people without dementia do not differ. ATOA in PwD appear to be affected not by cognitive impairment but by other characteristics that vary across dementia subtypes. Among PwD, those with Parkinson's disease dementia and dementia with Lewy bodies may have higher risk of experiencing negative ATOA due to the motor and visual impairments that they experience., (© 2022. The Author(s).)

Background and Purpose: Lewy body dementia (LBD), including dementia with Lewy bodies (DLB) and Parkinson's disease dementia, is a common form of neurodegenerative dementia. The frequency and influence of comorbid cerebrovascular disease is not understood but has potentially important clinical management implications., Methods: A systematic literature search was conducted (MEDLINE and Embase) for studies including participants with DLB and/or Parkinson's disease dementia assessing cerebrovascular lesions (imaging and pathological studies). They included white matter changes, cerebral amyloid angiopathy, cerebral microbleeds (CMB), macroscopic infarcts, microinfarcts and intracerebral haemorrhage., Results: Of 4411 articles, 63 studies were included. Cerebrovascular lesions commonly studied included white matter changes (41 studies) and CMB (18 studies). There was an increased severity of white matter changes on magnetic resonance imaging (visualized as white matter hyperintensities), but not neuropathology, in LBD compared to Parkinson's disease without dementia and age-matched controls. CMB prevalence in DLB was highly variable but broadly similar to Alzheimer's disease (0%-48%), with a lobar predominance. No relationship was found between large cortical or small subcortical infarcts or intracerebral haemorrhage and the presence of LBD., Conclusion: The underlying mechanisms of white matter hyperintensities in LBD require further exploration, as their increased severity in LBD was not supported by neuropathological examination of white matter. CMB in LBD had a similar prevalence to Alzheimer's disease. There is a need for larger studies assessing the influence of cerebrovascular lesions on clinical symptoms, disease progression and outcomes., (© 2021 European Academy of Neurology.)

Individuals with dementia with Lewy bodies (DLB) commonly die from dementia-related causes, but little is known regarding caregiver experiences during the end-of-life period in DLB. This reflects a critical knowledge gap given the high frequency of informal caregiving for individuals with dementia, high caregiver burden in DLB, and the fact that most individuals with DLB die from this disease. Investigators conducted telephone interviews with family members of individuals who died with DLB in the last 5 years. Investigators used a qualitative descriptive approach to analyze interview transcripts. Participants included 15 children, 13 spouses, and 2 other family members. Interviews averaged 31 min. Major themes included caregivers as the main drivers of care for individuals with DLB throughout the disease course and at the end of life, the impact of DLB features (e.g., fluctuations, hallucinations, and delusions) on end-of-life experiences, experiences relating to the caregiving role, death and post-death experiences, and supports employed by caregivers in the end-of-life period. End-of-life experiences for caregivers of individuals with DLB built on the accumulated burden of the disease course, where caregivers were often responsible for driving DLB care-from making the diagnosis to educating healthcare professionals and double-checking medical decisions. While some end-of-life experiences were consistent with those described in dementia palliative care more generally (e.g., financial stresses, poor sleep, being overwhelmed, and needing increased education and support), many DLB features specifically affected end-of-life caregiver experiences, such as the presence of delusions. Improving caregiver experiences at the end of life in DLB will require improved diagnosis and care for individuals with DLB throughout the disease course and also better strategies for treating behavioral symptoms. More research is needed regarding drivers of quality end-of-life experiences for individuals with DLB and their families and how drivers and strategies may differ between dementias.

Objectives: Psychosocial support for people with dementia with Lewy bodies (DLB) and family care partners is frequently lacking, despite the need expressed by those with lived experience. Our objective was to examine the feasibility and acceptability of an intervention designed to build coping capability., Design: The design was non-randomised with all participants receiving the intervention., Setting: The setting was a Memory Assessment and Management Service in the Northeast of England., Participants: Participants comprised 19 dyads consisting of a person with DLB and a family care partner., Intervention: The intervention was group-based, with weekly sessions attended for up to four successive weeks. It was informed by Social Cognitive Theory., Measurements: Data were collected on recruitment, attendance and attrition, self-efficacy, mood, stress and participant experience., Results: Recruitment was achieved with minimal attrition and three successive groups were delivered. Care partners felt more in control and able to cope in at least 3 of 13 areas with 73% feeling this way in eight or more areas. Three themes were identified from post-intervention interviews: people like us, outcomes from being a group member and intervention design., Conclusions: A DLB-specific group intervention is acceptable to people with DLB and family care partners, and recruitment is feasible within a specialist service. Participation may enhance understanding of this condition and reduce social isolation. It may improve care partners' coping capability particularly if targeted towards those with low prior understanding of DLB and more stress. Means of evaluating outcomes for people with DLB need further development.

Aim: Lewy body dementia is a common neurodegenerative dementia with unique challenges in managing day-to-day life. A more in-depth multifaceted picture of the Lewy body dementia lived experience will enable identification of best practice and future research direction. The review aim was to explore experiences of people living with Lewy body dementia and their family carers., Design: Integrative review method informed by Whittemore and Knafl, supported by the information retrieval framework PALETTE. A convergent integrated approach enabled synthesis of key findings and theme identification., Data Sources: Medline, CINAHL, PsycINFO, AMED, and ALOIS databases were systematically searched to find studies published between 1995 and 2020., Review Methods: Twenty-six articles from twenty studies were synthesized (from 1583 retrieved). Quality and relevance were appraised using the Mixed-Methods Appraisal Tool and Gough's 'Weight of Evidence' framework. Data management was supported by ATLAS.ti 8 and COVIDENCE software., Results: Four themes were identified: living with an uncertain diagnosis and prognosis; fear of the now - worry for the future; living with behavioural and psychiatric symptoms; and maintaining a social and emotional life. People reported difficulty finding information and support around diagnosis, disease progression and managing complex symptoms. The result is increased caregiver burden, grief and stress and reduced quality of life., Conclusion: Delayed diagnosis and complex symptom burden means people are not getting the timely support and information they need to live and die well. Current evidence is largely quantitative, with a focus on family caregiver burden and unmet need. The challenge remains in how to capture a more holistic picture of the lived experience for people living with Lewy body dementia and those who care for them., Impact: This review highlighted current knowledge and identified gaps in exploring the lived experience for people with Lewy body dementia and their families., (© 2021 The Authors. Journal of Advanced Nursing published by John Wiley & Sons Ltd.)

Individuals with dementia may come to forensic autopsy, partly because of non-natural deaths (e.g. fall-related), and/or concerns of abuse/neglect. At the New York City Office of Chief Medical Examiner (NYC OCME), brains from such cases are submitted for neurodegenerative disease (ND) work-up. Seventy-eight sequential cases were evaluated using a recently published condensed protocol for the NIA-AA guidelines for the neuropathologic assessment of Alzheimer disease (AD), a cost-cutting innovation in diagnostic neuropathology. ND was identified in 74 (94.9%) brains; the most common were AD (n = 41 [52.5%]), primary age-related tauopathy (n = 26 [33.3%]), and Lewy body disease ([LBD], n = 25 [32.1%]). Others included age-related tau astrogliopathy, hippocampal sclerosis of aging, progressive supranuclear palsy, multiple system atrophy, amyotrophic lateral sclerosis, argyrophilic grain disease, and Creutzfeldt-Jakob disease. 26.8% of AD cases involved a non-natural, dementia-related death, versus 40.0% for LBD. Finally, 70 (89.7%) cases had chronic cerebrovascular disease, 53 (67.9%) being moderate-to-severe. We present a diverse distribution of NDs notable for a high rate of diagnoses associated with falls (e.g. LBD), a potential difference from the hospital neuropathology experience. We also report a high burden of cerebrovascular disease in demented individuals seen at the NYC OCME. Finally, we demonstrate that the aforementioned condensed protocol is applicable for a variety of ND diagnoses., (© 2021 American Association of Neuropathologists, Inc. All rights reserved.)

The association between hearing impairment and dementia has emerged as a major public health challenge, with significant opportunities for earlier diagnosis, treatment and prevention. However, the nature of this association has not been defined. We hear with our brains, particularly within the complex soundscapes of everyday life: neurodegenerative pathologies target the auditory brain, and are therefore predicted to damage hearing function early and profoundly. Here we present evidence for this proposition, based on structural and functional features of auditory brain organization that confer vulnerability to neurodegeneration, the extensive, reciprocal interplay between 'peripheral' and 'central' hearing dysfunction, and recently characterized auditory signatures of canonical neurodegenerative dementias (Alzheimer's disease, Lewy body disease and frontotemporal dementia). Moving beyond any simple dichotomy of ear and brain, we argue for a reappraisal of the role of auditory cognitive dysfunction and the critical coupling of brain to peripheral organs of hearing in the dementias. We call for a clinical assessment of real-world hearing in these diseases that moves beyond pure tone perception to the development of novel auditory 'cognitive stress tests' and proximity markers for the early diagnosis of dementia and management strategies that harness retained auditory plasticity., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Evidence-based recommendations on the optimal evaluation approach for dementia diagnostics are limited. This impedes a harmonized workup across clinics and nations., Objective: To evaluate the diagnostic performance of a multidisciplinary consensus conference compared to a single clinician approach., Methods: In this prospective study, we enrolled 457 patients with suspected cognitive decline, from two European memory clinics. A diagnostic evaluation was performed at baseline independently in two ways: 1) by a single clinician and 2) at a multidisciplinary consensus conference. A syndrome diagnosis and an etiological diagnosis was made. The confidence in the diagnosis was recorded using a visual analogue scale. An expert panel re-evaluation diagnosis served as reference for the baseline syndrome diagnosis and a 12-24-month follow-up diagnosis for the etiological diagnosis., Results: 439 patients completed the study. We observed 12.5%discrepancy (k = 0.81) comparing the baseline syndrome diagnoses of the single clinician to the consensus conference, and 22.3%discrepancy (k = 0.68) for the baseline etiological diagnosis. The accuracy of the baseline etiological diagnosis was significantly higher at the consensus conference and was driven mainly by increased accuracy in the MCI group. Confidence in the etiological diagnosis at baseline was significantly higher at the consensus conference (p < 0.005), especially for the frontotemporal dementia diagnosis., Conclusion: The multidisciplinary consensus conference performed better on diagnostic accuracy of disease etiology and increased clinicians' confidence. This highlights the importance of a multidisciplinary diagnostic evaluation approach for dementia diagnostics, especially when evaluating patients in the MCI stage.

Dementia is a collection of symptoms affecting a person's cognition. Dementia is debilitating, and therefore, finding an effective treatment is of utmost importance. Resveratrol, which exhibits neuroprotective effects, has low bioavailability. However, its glucoside polydatin is more bioavailable. Here, the evidence that supports the protective role of polydatin against dementia- related diseases such as Alzheimer's disease, vascular dementia, alcohol-related dementia, and Lewy body dementias is presented. The beneficial effects of polydatin from a mechanistic perspective are specifically emphasized in this review. Future directions in this area of research are also discussed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This report describes the evaluation of the psychometric and clinimetric properties of nine self-report measures completed by informal care partners of individuals with mild cognitive impairment or dementia in Parkinson's disease and dementia with Lewy bodies. One hundred thirty-six care partners completed measures on relationship satisfaction, burden, stress, mood, resilience, health, quality of life, and feelings related to care provision. Psychometric properties, such as internal consistency, convergent validity, floor and ceiling effects, completion rate and data missingness, as well as clinimetric properties, such as time to administer, ease of scoring, readability and availability of the scales, were examined. Additionally, the design of the measure development studies was assessed with the 2018 COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) Risk of Bias checklist. Participants were mostly married women (>85%) with a mean age of 69.4 years. The methodological quality of the design of all measure development studies was "inadequate." Five widely applied measures (Zarit Burden Interview, Hospital Anxiety and Depression Scale, Short Form 12 Health Survey, Relatives' Stress Scale, and EuroQoL-5D) and two less researched instruments (Brief Resilience Scale and Relationship Satisfaction Scale) had high internal consistency and completion rates, moderate to strong convergent validity, low missingness and floor effects, and excellent clinical utility ratings. Two scales (Dyadic Relationship Scale and Family Caregiving Role) received poor psychometric ratings, and their usage among informal care partners is not recommended. In conclusion, well-validated and widely used measures received strong psychometric and clinimetric ratings. Future studies are required to determine the most reliable, valid and robust caregiver-reported measures.

Aim: Dementia with Lewy bodies (DLB) is a common but underdiagnosed type of cognitive impairment and dementia. The current diagnostic criteria for research purposes have a high specificity but lack sensitivity. Moreover, patients who live alone are not always aware that they have core clinical features such as cognitive fluctuations, visual hallucinations, and parasomnia. Anxiety is a common and early manifestation in DLB., Methods: We matched 41 DLB patients with 41 patients with Alzheimer's disease (AD) according to gender, age, and cognitive status and retrospectively analyzed their files for the presence of anxiety, depression, constipation, and the core clinical features of DLB in the documented period before diagnosis., Results: Anxiety, but not depression, occurred significantly more frequently in DLB than in AD (63.4% vs 26.8%). It appears up to 4-5 years before the diagnosis of DLB and is associated with depression and living at home. Anxiety in DLB was often described as intermittent panic attacks without reason or during states of delirium; it was also severe enough to require medical treatment and inpatient or outpatient psychiatric care. It was often mistaken for a psychiatric illness or a manifestation of other common forms of dementia. Anxiety in AD seemed much milder, was often related to the patient's coping with cognitive dysfunction, and was never cited as a specific reason for medical help. The concomitant presence of anxiety with at least one core clinical criterion of DLB enabled us to differentiate it from AD in our study, with a sensitivity of 63.4% but a specificity of 100%., Conclusions: In all patients over 50 who present with cognitive problems and anxiety, DLB should be considered. Patients and informants should be carefully questioned regarding the presence of other typical signs and symptoms of DLB., (© 2019 Japanese Psychogeriatric Society.)

Background: Research concerning the potential roles of cardiovascular disease (CaVD) and diabetes mellitus (DM) as risk factors for Lewy body disease (LBD) is limited. These disorders are, however, established risk factors for vascular dementia (VaD) and have been proposed as risk factors for Alzheimer's disease (AD)., Objective: The aim of this study was to investigate the prevalence of CaVD and DM in LBD and compare the results with previous findings in cases with AD, VaD, and mixed AD-VaD (MD)., Methods: Autopsy reports at the Clinical Department of Pathology in Lund from 2001-2018 were analyzed. All cases with a complete neuropathological diagnosis of LBD were selected, not distinguishing between subjects with clinical Parkinson disease dementia and dementia with Lewy bodies, on the condition of a clinical diagnosis of dementia. Clinical data were retrieved through the patients' medical records and the Swedish National Diabetes Register (NDR) and compared with those of the AD, VaD, and MD cases., Results: In LBD, there was less CaVD, significantly less DM (p = 0.002) and likewise significantly less hypertension (p < 0.001) than in VaD. The results of the LBD group were consistent with the results of the AD group., Conclusion: Our findings of a low prevalence of CaVD and CaVD risk factors in LBD and in AD argue against the association between these risk factors and their contribution to the development of neurodegenerative diseases.

Aim: To assess the clinical utility of FDG-PET as a diagnostic aid for differentiating Alzheimer's disease (AD; both typical and atypical forms), dementia with Lewy bodies (DLB), frontotemporal lobar degeneration (FTLD), vascular dementia (VaD) and non-degenerative pseudodementia., Methods: A comprehensive literature search was conducted using the PICO model to extract evidence from relevant studies. An expert panel then voted on six different diagnostic scenarios using the Delphi method., Results: The level of empirical study evidence for the use of FDG-PET was considered good for the discrimination of DLB and AD; fair for discriminating FTLD from AD; poor for atypical AD; and lacking for discriminating DLB from FTLD, AD from VaD, and for pseudodementia. Delphi voting led to consensus in all scenarios within two iterations. Panellists supported the use of FDG-PET for all PICOs-including those where study evidence was poor or lacking-based on its negative predictive value and on the assistance it provides when typical patterns of hypometabolism for a given diagnosis are observed., Conclusion: Although there is an overall lack of evidence on which to base strong recommendations, it was generally concluded that FDG-PET has a diagnostic role in all scenarios. Prospective studies targeting diagnostically uncertain patients for assessing the added value of FDG-PET would be highly desirable.

Dementia has become a serious disease in elderly population. Graph theory based brain network analysis method is considered as a popular and universal technique in the field of the neurosciences. It can help neuroscientists to investigate the neuropathology of dementia, especially to understand dementia subtypes. However, brain network analysis for various dementia subtypes at the same time is still limited. The aim at this study is to investigate the similarities and differences in brain network modular parameters of three dementia subtypes: Alzheimer's disease (AD), Parkinson's disease dementia (PDD), Lewy body dementia (DLB). Health control has also been compared. All subjects of health control(HC), AD, PDD and DLB groups were from Huashan Hospital. Using topological analysis algorithms, we found that HC brain was divided into 4 modules; AD brain was divided into 4 modules; PDD brain was divided into 6 modules; and DLB brain was divided into 10 modules, which demonstrated differences in these dementia subtypes. We also found that right thalamus area was scattered in all dementia subtypes. After using the seed point correlation analysis, it can be seen that the connections between right thalamus and subcortical, frontal gyrus were enhanced and the connections with the occipital gyrus was attenuated in dementia subtypes. As a result, findings in this paper are expected to be useful for neuroscientists to further understand the pathology of AD, PDD and DLB.

In Parkinson's disease and dementia with Lewy bodies, neuronal α-synuclein aggregates (Lewy bodies and Lewy neurites) are distributed throughout the nervous system, including the brain, spinal cord, sympathetic ganglia, enteric nervous system, cardiac and pelvic plexuses, submandibular gland, adrenal medulla, and skin. Lewy bodies also occur in 10-20% of neurologically asymptomatic individuals older than 60 years. These cases are called incidental Lewy body disease (ILBD). In ILBD, Lewy bodies can be found in the brain, spinal cord, sympathetic ganglia, visceral autonomic nervous system and skin. In addition, neuronal loss in the substantia nigra is observed in ILBD. Thus, ILBD represents pre-symptomatic Parkinson's disease and/or dementia with Lewy bodies. The pathological process of Lewy body disease may affect the peripheral and central nervous systems at the same time.