Symptoms In Dementia With Lewy Bodies Research Articles

Digital Biomarkers for the Assessment of Non-Cognitive Symptoms in Patients with Dementia with Lewy Bodies: A Systematic Review.

Portable digital health technologies (DHTs) could help evaluate non-cognitive symptoms, but evidence to support their use in patients with dementia with Lewy bodies (DLB) is uncertain. 1) To describe portable or wearable DHTs used to obtain digital biomarkers in patients with DLB, 2) to assess the digital biomarkers' ability to evaluate non-cognitive symptoms, and 3) to assess the feasibility of applying digital biomarkers in patients with DLB. We systematically searched databases MEDLINE, Embase, and Web of Science from inception through February 28, 2023. Studies assessing digital biomarkers obtained by portable or wearable DHTs and related to non-cognitive symptoms were eligible if including patients with DLB. The quality of studies was assessed using a modified check list based on the NIH Quality assessment tool for Observational Cohort and Cross-sectional Studies. A narrative synthesis of data was carried out. We screened 4,295 records and included 20 studies. Seventeen different DHTs were identified for assessment of most non-cognitive symptoms related to DLB. No thorough validation of digital biomarkers for measurement of non-cognitive symptoms in DLB was reported. Studies did not report on aspects of feasibility in a systematic way. Knowledge about feasibility and validity of individual digital biomarkers remains extremely limited. Study heterogeneity is a barrier for establishing a broad evidence base for application of digital biomarkers in DLB. Researchers should conform to recommended standards for systematic evaluation of digital biomarkers.

Association of Plasma Amyloid, P-Tau, GFAP, and NfL With CSF, Clinical, and Cognitive Features in Patients With Dementia With Lewy Bodies.

Plasma β-amyloid-1-42/1-40 (Aβ42/40), phosphorylated-tau (P-tau), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) have been widely examined in Alzheimer disease (AD), but little is known about their reflection of copathologies, clinical importance, and predictive value in dementia with Lewy bodies (DLB). We aimed to evaluate associations of these biomarkers with CSF amyloid, cognition, and core features in DLB. This cross-sectional multicenter cohort study with prospective component included individuals with DLB, AD, and healthy controls (HCs), recruited from 2002 to 2020 with an annual follow-up of up to 5 years, from the European-Dementia With Lewy Bodies consortium. Plasma biomarkers were measured by single-molecule array (Neurology 4-Plex E kit). Amyloid status was determined by CSF Aβ42 concentrations, and cognition was assessed by Mini-Mental State Examination (MMSE). Biomarker differences across groups, associations with amyloid status, and clinical core features were assessed by analysis of covariance. Associations with cognitive impairment and decline were assessed by linear regression and linear mixed-effects models. In our cohort consisting of 562 individuals (HC n = 89, DLB n = 342, AD n = 131; 250 women [44.5%], mean [SD] age of 71 [8] years), sex distribution did not differ between groups. Patients with DLB were significantly older, and had less years of education and worse baseline cognition than HC, but not AD. DLB participants stratified for amyloid status differed significantly in plasma Aβ42/40 ratio (decreased in amyloid abnormal: β = -0.008, 95% CI -0.016 to -0.0003, p = 0.01) and P-tau (increased in amyloid abnormal, P-tau181: β = 0.246, 95% CI 0.011-0.481; P-tau231: β = 0.227, 95% CI 0.035-0.419, both p < 0.05), but not in GFAP (β = 0.068, 95% CI -0.018 to 0.153, p = 0.119), and NfL (β = 0.004, 95% CI -0.087 to 0.096, p = 0.923) concentrations. Higher baseline GFAP, NfL, and P-tau concentrations were associated with lower MMSE scores in DLB, and GFAP and NfL were associated with a faster cognitive decline (GFAP: annual change of -2.11 MMSE points, 95% CI -2.88 to -1.35 MMSE points, p < 0.001; NfL: annual change of -2.13 MMSE points, 95% CI -2.97 to -1.29 MMSE points, p < 0.001). DLB participants with parkinsonism had higher concentrations of NfL (β = 0.08, 95% CI 0.02-0.14, p = 0.006) than those without. Our study suggests a possible utility of plasma Aβ42/40, P-tau181, and P-tau231 as a noninvasive biomarkers to assess amyloid copathology in DLB, and plasma GFAP and NfL as monitoring biomarkers for cognitive symptoms in DLB.

Neuroanatomical substrates of depression in dementia with Lewy bodies and Alzheimer's disease.

Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) are often associated with depressive symptoms from the prodromal stage. The aim of the present study was to investigate the neuroanatomical correlates of depression in prodromal to mild DLB patients compared with AD patients. Eighty-three DLB patients, 37 AD patients, and 18 healthy volunteers were enrolled in this study. Depression was evaluated with the Mini International Neuropsychiatric Interview (MINI), French version 5.0.0. T1-weighted three-dimensional anatomical images were acquired for all participants. Regression and comparison analyses were conducted using a whole-brain voxel-based morphometry (VBM) approach on the grey matter volume (GMV). DLB patients presented a significantly higher mean MINI score than AD patients (p = 0.004), 30.1% of DLB patients had clinical depression, and 56.6% had a history of depression, while 0% of AD patients had clinical depression and 29.7% had a history of depression. VBM regression analyses revealed negative correlations between the MINI score and the GMV of right prefrontal regions in DLB patients (p < 0.001, uncorrected). Comparison analyses between DLB patients taking and those not taking an antidepressant mainly highlighted a decreased GMV in the bilateral middle/inferior temporal gyrus (p < 0.001, uncorrected) in treated DLB patients. In line with the literature, our behavioral analyses revealed higher depression scores in DLB patients than in AD patients. We also showed that depressive symptoms in DLB are associated with decreased GMV in right prefrontal regions. Treated DLB patients with long-standing depression would be more likely to experience GMV loss in the bilateral middle/inferior temporal cortex. These findings should be taken into account when managing DLB patients.

Eating problems in people with dementia with Lewy bodies: Associations with various symptoms and the physician's understanding.

Eating problems frequently occur in people with dementia with Lewy bodies (DLB), but few studies have investigated the clinical background of this phenomenon. This study examined the relationship between eating problems and various symptoms of DLB and the relation between the treatment needs for DLB people with eating problems and the understanding of their eating problems by caregivers and physicians. This was a subanalysis of a cross-sectional, questionnaire-based survey study. Two hundred sixty-one subjects with DLB were divided into subjects with or without eating problems. Logistic or linear regression analysis was used to investigate the factors influencing eating problems. The treatment needs of DLB people for their eating problems and the understanding of these needs by caregivers and physicians were calculated as participant-caregiver and participant-physician kappa coefficient. Of the 261 participants, 27% suffered from eating problems. The presence of eating problems in participants with DLB was related to depression (p = 0.01, OR : 2.19, 95% CI: 1.23-3.91) and apathy (p = 0.01, OR 2.15, 95% CI: 1.20-3.87), while the worsening of eating problems was related to dysphagia (β = 0.24, p = 0.03), apathy (β = 0.23, p = 0.05), and nighttime behavior (β = 0.24, p = 0.04). The participant-physician kappa coefficient for physician understanding of constipation, weight loss, dysphagia, weight gain, and increase in appetite was significantly lower than the corresponding participant-caregiver kappa coefficient (p-value of five symptoms < 0.01). Physicians need to pay more attention to eating problems and their neuropsychiatric background in the long-term support and management of DLB subjects.

GBA1 rs3115534 Is Associated with REM Sleep Behavior Disorder in Parkinson's Disease in Nigerians.

Rapid eye movement (REM) sleep behavior disorder (RBD) is an early feature of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Damaging coding variants in Glucocerebrosidase (GBA1) are a genetic risk factor for RBD. Recently, a population-specific non-coding risk variant (rs3115534) was found to be associated with PD risk and earlier onset in individuals of African ancestry. We aimed to investigate whether the GBA1 rs3115534 PD risk variant is associated with RBD in persons with PD. We studied 709 persons with PD and 776 neurologically healthy controls from Nigeria. All DNA samples were genotyped and imputed, and the GBA1 rs3115534 risk variant was extracted. The RBD screening questionnaire (RBDSQ) was used to assess symptoms of possible RBD. RBD was present in 200 PD (28.2%) and 51 (6.6%) controls. We identified that the non-coding GBA1 rs3115534 risk variant is associated with possible RBD in individuals of Nigerian origin (β, 0.3640; standard error [SE], 0.103, P = 4.093e-04), as well as in all samples after adjusting for PD status (β, 0.2542; SE, 0.108; P = 0.019) suggesting that although non-coding, this variant may have the same downstream consequences as GBA1 coding variants. Our results indicate that the non-coding GBA1 rs3115534 risk variant is associated with an increasing number of RBD symptoms in persons with PD of Nigerian origin. Further research is needed to assess if this variant is also associated with polysomnography-defined RBD and with RBD symptoms in DLB. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Alpha-Synuclein Pre-Formed Fibrils Injected into Prefrontal Cortex Primarily Spread to Cortical and Subcortical Structures.

Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) are characterized by diffuse spread of alpha-synuclein (α-syn) throughout the brain. Patients with PDD and DLB have a neuropsychological pattern of deficits that include executive dysfunction, such as abnormalities in planning, timing, working memory, and behavioral flexibility. The prefrontal cortex (PFC) plays a major role in normal executive function and often develops α-syn aggregates in DLB and PDD. To investigate the long-term behavioral and cognitive consequences of α-syn pathology in the cortex and characterize pathological spread of α-syn. We injected human α-syn pre-formed fibrils into the PFC of wild-type male mice. We then assessed the behavioral and cognitive effects between 12- and 21-months post-injection and characterized the spread of pathological α-syn in cortical, subcortical, and brainstem regions. We report that PFC PFFs: 1) induced α-syn aggregation in multiple cortical and subcortical regions with sparse aggregation in midbrain and brainstem nuclei; 2) did not affect interval timing or spatial learning acquisition but did mildly alter behavioral flexibility as measured by intraday reversal learning; and 3) increased open field exploration. This model of cortical-dominant pathology aids in our understanding of how local α-syn aggregation might impact some symptoms in PDD and DLB.

Clinical correlates of Dopamine transporter imaging and EEG biomarkers in Dementia with Lewy bodies

AbstractBackgroundDiagnostic value of dopamine transporter (DAT) imaging and electroencephalography (EEG) biomarkers in Dementia with Lewy bodies (DLB) is well studied, but their relationships with clinical symptoms in DLB are not elusive. We investigated the association between DAT imaging and EEG biomarkers and clinical characteristics of DLB.MethodWe evaluated the 120 patients with DLB retrospectively. Quantitative analysis of DAT imaging was performed and uptakes for caudate, putamen, and ventral striatum (VST) were assessed. Frequency of posterior dominant rhythm and theta/beta ratio (TBR) were used as EEG biomarkers. Four core clinical features of DLB were assessed. Firstly, correlation analysis between biomarkers and clinical symptoms were assessed. Regression analyses with significantly correlated biomarkers as model variable were performed to investigate the association between clinical characteristics and biomarkers. Age, sex, and education were used as covariates.ResultParietal TBR (B = 0.498, P = 0.023) and putaminal DAT uptake (B = ‐0.609, P = 0.010) were related to the presence of fluctuation. The severity of visual hallucination was associated with the higher parietal TBR (B = 0.391, P = 0.045) and lower DAT uptake in putamen (B = ‐0.520, P = 0.010) and. Putaminal DAT uptake was related to the presence of REM sleep behavior disorder (B = ‐0.646, P = 0.010). Severity of parkinsonism was associated with the frontal TBR (B = 3.353, P &lt; 0.001).ConclusionDAT imaging and EEG biomarkers were related to the clinical symptoms in DLB differently. In addition, TBR reflects characteristics of DLB better than posterior slow activity.

Underlying mechanisms, clinical manifestation, and methodological considerations of functional connectivity in Dementia with Lewy Bodies

AbstractBackgroundFunctional connectivity disturbances are potential disease mechanisms related to observable symptoms in Dementia with Lewy Bodies (DLB). Despite several existing theories, the exact relationship between functional connectivity, underlying mechanisms of the DLB, and symptomatology is yet not clear. The present review addresses this gap by summarising research findings of functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) research while considering the impact of different methodological choices causing mixed findings.MethodWe performed a systematic literature review of resting‐state functional connectivity in DLB following PRISMA. We searched multiple databases from January 2000 to November 2022. Keywords included “DLB”, “connectivity”, “EEG”, and “fMRI”, their synonyms and acronyms, and related terms of network analysis. The final sample contained 6 EEG and 14 fMRI studies.ResultThe main methodological choices of fMRI articles included a data‐driven approach (i.e., Independent Component Analysis or Graph Theory; 43%), seed‐based or regions of interest (50%), or their combination (7%) with most studies focusing on large‐scale resting‐state networks (71%). The overall trend of connectivity findings showed a decrease, yet more subtle changes in the directionality of connectivity were observed when using a hypothesis‐driven approach (Fig 1A). The Default Mode Network (DMN) was the most studied network with 75% of relevant articles reporting decreased connectivity. Other networks with a consistent decrease in connectivity included Executive and Sensorimotor Networks (80% and 100% of relevant studies respectively). The inter‐network connectivity revealed the mixed relationship between the DMN, executive, attentional and visual networks (VN; Fig 1B). EEG studies showed a consistent decrease in connectivity on alpha and beta bands (100% and 66% of relevant studies respectively) and disorganisation in graph properties in regions overlapping with findings from large‐scale networks.ConclusionDysfunctions in large‐scale networks likely contribute to progressive degenerative mechanisms and are consistent with visual attention and perception processing theories of psychotic symptoms in the DLB. Hence, connectivity measures can capture brain disturbances in the DLB and remain crucial in uncovering underlying relationships between the networks’ disorganisation and disease mechanisms resulting in psychotic, motor, and cognitive symptoms in DLB. The choice of analytical approach might contribute to the directionality and mixed findings in the literature.

123I‐Ioflupane SPECT Striatal Binding Ratio Predicts Progression of Parkinsonism in a Dementia with Lewy Bodies Cohort

AbstractBackgroundThe criteria for diagnosis of dementia with Lewy bodies (DLB) remain predominantly clinical. However, use of striatal dopamine transporter visualization is suggested as an “indicative” biomarker for DLB under the most recent published DLB criteria (McKeith, Neurology, 2017). The objective of this study is to determine if 123I‐ioflupane SPECT (DaTscan) striatal binding ratio (SBR) correlates with parkinsonian symptoms measured on the Movement Disorder Society – Unified Parkinson’s Disease Rating Scale Part III (MDS‐UPDRS‐III) in patients with either probable DLB or high‐likelihood DLB individuals with mild cognitive impairment (MCI). A secondary aim of this study is to determine if DaTscan SBR measured at baseline can predict progression of parkinsonian symptoms over 2 years in this study population.MethodsThis is a retrospective cohort study using the U.S. Dementia with Lewy Bodies Consortium (DLBC) dataset (U01 NS100610). The sample group included in this study are individuals with either probable DLB (McKeith, Neurology, 2017) or MCI‐LB (McKeith, 2020). Each participant had a baseline DaTscan analyzed with DaTQUANT software and physical examination scored with MDS‐UPDRS‐III. Participants without these data were excluded. Mixed effect models were fit with UPDRS score as the dependent variable and SBR z‐score as the primary independent variable. Data were adjusted for age, gender, diagnosis, and dopaminergic medication at time of examination.ResultsAn analysis between 53 participants’ baseline MDS‐UPDRS‐III and SBR z‐scores revealed a moderate negative correlation, indicating SBR is a significant predictor of baseline MDS‐UPDRS‐III score. An analysis between 23 participants’ baseline SBR z‐scores and 24‐month MDS‐UPDRS‐III revealed a moderate negative correlation, indicating that baseline SBR is a significant predictor of 24‐month MDS‐UPDRS‐III scores.ConclusionThese data reveal a significant relationship between DaTscan SBR and motor examination in DLB. Additionally, there is a significant relationship between baseline SBR and progression of parkinsonian features. We conclude that in DLB, DaTscan at time of diagnosis could be used to confirm underlying dopamine deficiency in the context of clinical parkinsonism and predict progression of parkinsonian symptoms in DLB. This could aid in guiding therapies and prognostication of symptom progression.

Depression in dementia with Lewy bodies: a critical update.

Depression with an estimated prevalence of 35% is a frequent manifestation of dementia with Lewy bodies (DLB), having negative effects on cognitive performance and life expectancy, yet the underlying neurobiology is poorly understood and most likely heterogeneous. Depressive symptoms in DLB can occur during the clinical course and, together with apathy, is a common prodromal neuropsychiatric symptom of this neurocognitive disorder in the group of Lewy body synucleinopathies. There are no essential differences in the frequency of depression in DLB and Parkinson disease-dementia (PDD), while its severity is up to twice as high as in Alzheimer disease (AD). Depression in DLB that is frequently underdiagnosed and undertreated, has been related to a variety of pathogenic mechanisms associated with the basic neurodegenerative process, in particular dysfunctions of neurotransmitter systems (decreased monoaminergic/serotonergic, noradrenergic and dopaminergic metabolism), α-synuclein pathology, synaptic zinc dysregulation, proteasome inhibition, gray matter volume loss in prefrontal and temporal areas as well as dysfunction of neuronal circuits with decreased functional connectivity of specific brain networks. Pharmacotherapy should avoid tricyclic antidepressants (anticholinergic adverse effects), second-generation antidepressants being a better choice, while modified electroconvulsive therapy, transcranial magnetic stimulation therapy and deep brain stimulation may be effective for pharmacotherapy-resistant cases. Since compared to depression in other dementias like Alzheimer disease and other parkinsonian syndromes, our knowledge of its molecular basis is limited, and further studies to elucidate the heterogeneous pathogenesis of depression in DLB are warranted.

123I-Ioflupane SPECT Striatal Binding Ratio Predicts Progression of Parkinsonism in a Dementia with Lewy Bodies Cohort (P11-6.004)

<h3>Objective:</h3> This research aims to determine if 123I-ioflupane SPECT (DaTscan) striatal binding ratio (SBR) correlates with parkinsonian symptoms measured on the Movement Disorder Society – Unified Parkinson’s Disease Rating Scale Part III (MDS-UPDRS-III) in patients with either probable dementia with Lewy bodies (DLB) or high-likelihood DLB individuals with mild cognitive impairment (MCI). Additionally, it aims to determine if DaTscan SBR predicts progression of parkinsonian symptoms over 2 years in this patient population. <h3>Background:</h3> The criteria for diagnosis of DLB remain predominantly clinical. Striatal dopamine transporter visualization using DaTscan is used to aid in diagnosis when exam findings of parkinsonism are equivocal. Further clinical utility of DaTscan in DLB, such as for screening or confirmatory tests or monitoring of disease progression or response to therapy, remains unclear. <h3>Design/Methods:</h3> This is a retrospective cohort study using the Dementia with Lewy Bodies Consortium (DLBC) dataset. The sample group included in this study are individuals with either probable DLB (based on 2017 McKeith Criteria) or high-likelihood DLB individuals with MCI. Each participant had a baseline and 24-month DaTscan analyzed with DaTQUANT software and physical examination scored with MDS-UPDRS-III. Participants without these data were excluded. <h3>Results:</h3> An analysis between baseline MDS-UPDRS-III and SBR z-scores revealed a moderate negative correlation, indicating SBR is a significant predictor of baseline MDS-UPDRS-III score. An analysis between baseline SBR z-scores and 24-month MDS-UPDRS-III revealed a moderate negative correlation, indicating that baseline SBR is a significant predictor of 24-month MDS-UPDRS-III scores. <h3>Conclusions:</h3> These data reveal a significant relationship between DaTscan SBR and motor examination in DLB. Additionally, there is a relationship between baseline SBR and progression of parkinsonian features. We conclude that DaTscan at time of diagnosis could be used to predict progression of parkinsonian symptoms in DLB which can aid in guiding therapies and prognostication of symptom progression. <b>Disclosure:</b> Dr. Maly has nothing to disclose. Dr. Leverenz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia. Dr. Leverenz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Leverenz has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai. The institution of Dr. DiFilippo has received research support from NIH. Dr. DiFilippo has received personal compensation in the range of $500-$4,999 for serving as a Reviewer with American College of Radiology.

Clinical Predictors of Survival in Probable Dementia with Lewy Bodies (P13-6.006)

Clinical Predictors of Survival in Probable Dementia with Lewy Bodies (P13-6.006)

Motor Symptoms in Dementia With Lewy Bodies: Literature Review and Evidence-Based Management

Dementia with Lewy bodies (DLB) is a neurodegenerative disorder typified by symptoms in cognitive, behavioral, and motor domains. Management of these manifestations involves a delicate balance between targeting relief in some symptoms while avoiding exacerbations in others. This is often clinically challenging as the tradeoffs are intrinsic to the pathophysiologic processes for which we lack approved targeted interventions. Even for motor symptoms, the application of therapeutic strategies used in Parkinson's disease to DLB is fraught with nuance. This review delves into the distinguishing characteristics of motor symptoms in DLB, the nature of the tradeoffs vis-à-vis management of cognitive and behavioral manifestations, and the current evidence supporting available treatments. It concludes by surveying disease-modifying pharmacotherapies on the horizon and providing practical management considerations. [ Psychiatr Ann. 2022;52(10):415–422.]

Diagnosis and Treatment of Cognitive and Neuropsychiatric Symptoms in Parkinson Disease and Dementia With Lewy Bodies.

This article summarizes the underlying biology and current diagnostic and treatment strategies for the cognitive and neuropsychiatric features of Parkinson disease (PD) and dementia with Lewy bodies (DLB). Cognitive impairment and neuropsychiatric symptoms have been increasingly recognized in PD and DLB, leading to improved diagnosis and treatment strategies. While PD is most associated with and diagnosed by the presence of motor symptoms, nonmotor symptoms can often be the most debilitating for patients. Neuropsychiatric symptoms are highly prevalent nonmotor features and include cognitive impairment, depression, anxiety, psychosis, impulse control disorders, and apathy. Neuropsychiatric symptoms can be difficult to recognize and diagnose in patients with PD, in part because of comorbidity and symptom overlap with core PD features. Treatment strategies are a combination of pharmacologic and nonpharmacologic interventions used in the general population and those specific to PD. DLB is a clinical dementia syndrome, often with similar cognitive, behavioral, autonomic, and motor features as PD. Moreover, DLB has shared underlying pathophysiology with PD, as both are associated with postmortem findings of α-synuclein neuropathology at autopsy and have shared genetic risk and prodromal symptoms. DLB is clinically differentiated from PD by the presenting features of cognitive impairment in DLB, compared with the variable onset of cognitive impairment occurring 1 year or more after established motor onset in PD. Thus, diagnosis and treatment of cognitive impairment and neuropsychiatric symptoms in DLB are similar to that of PD and have important implications for maintaining patient independence and providing support for caregivers because motor, cognitive, and neuropsychiatric symptoms have an additive effect on patient functional disability. A careful history and physical examination are often needed to accurately diagnose and treat the heterogeneous cognitive and behavioral symptoms of PD and DLB. Accurate diagnosis and treatment of neuropsychiatric symptoms and cognitive impairment in PD and DLB are important, as these are a considerable source of patient disability and caregiver burden.

The presence and co-incidence of geriatric syndromes in older patients with mild-moderate Lewy body dementia

IntroductionGeriatric symptoms are common in dementia cases, while few studies have focused on these symptoms in Lewy body dementia (LBD). The purpose of this study is to investigate the distributions of Apolipoprotein E (APOE) ε4 and geriatric symptoms, and explore their associaitons in Dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD).MethodsA retrospective study with 185 mild-moderate probable DLB (n = 93) and PDD (n = 92) patients was assigned. Demographic and clinical characteristics, neuropsychological assessments, and APOE genotypes were recorded. Description, correlation and logistic regression models were used to analyze the presence of geriatric symptom complaints and their associations with APOE ε4.ResultsDLB patients displayed more frequency of fluctuating cognition, visual hallucination, rapid eye movement sleep behavior disorder, delusion, depression, anxiety, apathy, and loss of appetite, whereas the PDD cases had constipation, fear of falling, and insomnia more frequently. The APOE ε4 allele was more common in DLB than PDD (29.9% vs. 7.0%, p < 0.001), and the patients with DLB + APOE ε4 (+) were presented more delusions (p = 0.005) and apathy (p = 0.007) than patients with PDD + APOE ε4 (+). We also found that the APOE ε4 allele was significantly associated with hyperhidrosis (OR = 3.472, 95%CI: 1.082–11.144, p = 0.036) and depression (OR = 3.002, 95%CI: 1.079–8.353, p = 0.035) in DLB patients, while there were no significant associations between APOE ε4 allele and the age at visit, the age at onset, scores of MDS-UPDRS III, H&Y stage, ADL, MMSE, MOCA and NPI, as well as the presences of fluctuating cognition, VH, parkinsonism and RBD in both groups.ConclusionThe presence and co-incidence of geriatric symptoms are common in patients with mild-moderate LBD. The presence of APOE ε4 allele is associated with hyperhidrosis and depression, but not global cognition, activitives of daily life, motor function and other neuropsychitric symptoms in DLB. These findings improve the awareness of geriatric symptoms, and contribute to the healthcare management of mild-moderate DLB and PDD.

Prodromal characteristics of dementia with Lewy bodies: baseline results of the MEMENTO memory clinics nationwide cohort

BackgroundIsolated subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) are the prodromal phases of dementia with Lewy bodies (DLB). MEMENTO is a nationwide study of patients with SCI and MCI with clinic, neuropsychology, biology, and brain imaging data. We aimed to compare SCI and MCI patients with symptoms of prodromal DLB to others in this study at baseline.MethodsParticipants of the French MEMENTO cohort study were recruited for either SCI or MCI. Among them, 892 were included in the Lewy sub-study, designed to search specifically for symptoms of DLB. Probable prodromal DLB diagnosis (pro-DLB group) was done using a two-criteria cutoff score among the four core clinical features of DLB. This Pro-DLB group was compared to two other groups at baseline: one without any core symptoms (NS group) and the one with one core symptom (1S group). A comprehensive cognitive battery, questionnaires on behavior, neurovegetative and neurosensory symptoms, brain 3D volumetric MRI, CSF, FDG PET, and amyloid PET were done.ResultsThe pro-DLB group comprised 148 patients (16.6%). This group showed more multidomain (59.8%) MCI with slower processing speed and a higher proportion of patients with depression, anxiety, apathy, constipation, rhinorrhea, sicca syndrome, and photophobia, compared to the NS group. The pro-DLB group had isolated lower P-Tau in the CSF (not significant after adjustments for confounders) and on brain MRI widening of sulci including fronto-insular, occipital, and olfactory sulci (FDR corrected), when compared to the NS group. Evolution to dementia was not different between the three groups over a median follow-up of 2.6 years.ConclusionsPatients with symptoms of prodromal DLB are cognitively slower, with more behavioral disorders, autonomic symptoms, and photophobia. The occipital, fronto-insular, and olfactory bulb involvement on brain MRI was consistent with symptoms and known neuropathology. The next step will be to study the clinical, biological, and imaging evolution of these patients.Trial registrationClinicaltrials.gov, NCT01926249

Zonisamide improves axial symptoms in dementia with Lewy bodies with parkinsonism: Post hoc analysis of clinical trials.

Patients with dementia with Lewy bodies (DLB) experience worsening axial symptoms with disease progression, which can negatively affect quality of life. Previous phase 2 and 3 clinical trials conducted in Japan showed that zonisamide improved parkinsonism in patients with DLB. In the present study, we performed a post hoc analysis of pooled data from the previous phase 2 and 3 trials to examine the effect of zonisamide on axial symptoms in this patient group. In our pooled analysis, the primary outcome was the change from baseline to 12 weeks in axial symptom score, measured as the sum of Unified Parkinson's Disease Rating Scale Part III items relevant to gait/balance/midline function. A total of 498 patients were included in this analysis. Zonisamide 25 mg and 50 mg significantly reduced the axial symptom score at week 12 compared with placebo (p < 0.01 and p < 0.001, respectively, by mixed model of repeated measures). Our findings indicate that zonisamide may improve axial symptoms in DLB with parkinsonism and, thus, may potentially reduce the risk of falls and improve quality of life in this vulnerable patient population.

Psychotic Features Among Patients in the Prodromal Stage of Dementia with Lewy Bodies During Longitudinal Observation.

Many cases of dementia with Lewy bodies (DLB) present with various psychotic features, including hallucinations, depression, catatonia, and delusions before the onset of cognitive impairment. However, the characteristic features of these psychotic symptoms in prodromal DLB have not been sufficiently described. To clarify and describe the psychotic features of prodromal DLB before overt cognitive impairment. The authors analyzed the characteristic psychotic features of prodromal DLB in 21 subjects who developed severe psychotic symptoms without dementia and were diagnosed as DLB after the longitudinal observation period. They were then confirmed to have DLB through indicative and supportive biomarkers of scintigraphy. The psychotic features included a wide variety of symptoms, but convergent to three principal categories: catatonia, delusions-hallucinations, and depression and/or mania. Catatonia was observed in nine cases, five were delusional-hallucinatory, and seven were manic and/or depressive. Seven of the 21 cases exhibited delirium during longitudinal observation. A psychotic state repeatedly appeared without any trigger in 20 of the 21 patients. All subjects developed cognitive impairment at 9.1±4.6 (mean±SD) years after the initial appearance of psychotic symptoms, and subsequently diagnosed with DLB at 71.3±6.1 (mean±SD) years. Elderly patients with psychotic symptoms, such as catatonia, delusion-hallucination, manic and/or depressive features, and delirium without dementia, could indicate symptomatic psychosis or a prodromal stage of any neurocognitive disorder such as DLB. Therefore, further extensive workout (e.g., radioisotope neuroimaging) is required to avoid misdiagnosis.

419 - Effect of Transcranial Direct Current Stimulation (tDCS) in Dementia with Lewy Bodies

AbstractIntroduction:Dementia with Lewy Bodies (DLB), this second most common form of degenerative dementia, presents more functional disability, more potentially fatal complication, more impaired quality of life than Alzheimer’s dementia. There is no FDA-proved medication can slow, stop or improve the progression of cognitive declines in DLB. Identifying effective treatments is a critical issue for DLB. In neuropathology, extracelluar α-syn oligomers interfere with the expression of long-term potentiation, and influence memory and learning. Transcranial direct current stimulation (tDCS) has been proposed to affect long-term synaptic plasticity through LTP and LTD, thereby improving cognitive ability. So far, only two researches assess the effect of tDCS in DLB. In this pilot study, we investigate the effects of tDCS in DLB.Method:Using a double-blind, randomized, sham- controlled and crossover trial design, 11 DLB aged 55-90 years (mean age 77.8) were included in the study. DLB diagnostics is according to DSM-5 criteria. The CDR ratings of DLB participants ranged from 0.5 to 2. The active tDCS (or sham) process includes consecutive daily sessions of active tDCS (or sham) for 10 days. The anodal electrode was over the left dorsal lateral prefrontal cortex (DLPFC) and the cathodal electrode on the right supraorbital area. In each session, we applied a current intensity of 2 mA and an electrode size of 25 cm2 for 30 min in the active group. All subjects received a series of neuropsychological tests, which included CDR, MMSE, CASI, NPI and WCST, before and after these treatment sessions. Chi-square tests, Wilcoxon signed rank tests and Mann-Whitney U tests were used to assess the differences in participant demographic characteristics and to compare the differences among groups.Results:On CASI, MMSE, NPI and WCST, there were no statistically significant differences between pre- and post the 10-session course for the active and the sham groups. No side effects reported during or immediately after active tDCS stimulation.Conclusion:These results suggest that left DLPFC anodal, and right deltoid cathodal tDCS, do not improve cognition, behavioral and psychological symptoms in DLB. Larger-scale trials are needed to confirm the effect of tDCS in DLB.

Locus Coeruleus Malfunction Is Linked to Psychopathology in Prodromal Dementia With Lewy Bodies.

Background: The locus coeruleus (LC) is a nucleus in the human brainstem with a variety of noradrenaline-driven functions involved in cognition, emotions, and perception. Dementia with Lewy bodies (DLB) constitutes a neurodegenerative disease involving deposits of alpha-synuclein, first appearing in the brainstem. The goal of this narrative review is to delineate the relationship between the expression of psychiatric symptoms as an early-onset of DLB and the degeneration of the LC's noradrenaline system.Methods: We searched in PubMed for relevant articles concerning LC degeneration and psychiatric symptoms in prodromal DLB in this narrative review. We rely on the McKeith criteria for prodromal psychiatric DLB.Results: We found four studies that document neuronal loss, deposits of Lewy bodies and other hints for neurodegeneration in the LC in patients with DLB. Furthermore, we reviewed theories and studies on how the degenerated noradrenaline LC system contributes to psychiatric DLB's phenotype. We hypothesized how anxiety, hallucinations, delusions, and depressive symptoms might occur in DLB patients due to degenerated noradrenergic neurons entailing consecutive altered noradrenergic transmission in the LC's projection areas.Conclusions: LC degeneration in prodromal DLB might cause psychiatric symptoms as the first and non-motor manifestation of DLB, as the LC is affected earlier by degeneration than are dopaminergic structures such as the substantia nigra, which are impaired later in the disease course.