Lewy Body Dementia Research Articles

Neuropsychological Determinants of Impairment in Activities of Daily Living in Patients With Lewy Body Dementia.

Background Understanding the specific cognitive domains associated with activities of daily living (ADLs) impairment in Lewy body dementia (LBD) may help identify which targeted therapeutic interventions to pursue in future research. This study aimed to investigate the neuropsychological determinants of impairment in ADLs in LBD patients. Methods We conducted a cross-sectional study of LBD patients referred for a clinical neuropsychological evaluation within the Parkinson's Disease and Movement Disorders Center at Virginia Commonwealth University. The presence or absence of impairment in eight ADLs and neuropsychological test performances were collected and analyzed. Cluster analysis and hierarchical analysis were used to define ADL impairment into mild, moderate, and severe ADL impairment groups. We then compared cognitive performance between the ADL groups. Results This study included 193 LBD patients. Compared to LBD patients with mild and moderate ADL impairment, those with severe ADL impairment had worse scores in global cognition as measured by the Dementia Rating Scale-2 (DRS-2) (p=0.002), speeded visuospatial processing as measured by the Trail Making Test A (p=0.001), speeded executive functioning as measured by the Trail Making Test B (p=0.006), and psychomotor processing speed (p<0.001). Impairments in driving and self-care were associated with worse performances on Trail Making Test A, Trail Making Test B, and psychomotor processing speed (all p<0.05). Conclusions In patients with LBD, impaired speeded tasks of visual processing and executive functioning are associated with impaired ADLs, particularly driving and self-care. In order to improve ADLs in LBD, future studies should focus on identifying therapies that improve processing speed performance.

Psychopathology of Lewy body disease: the clinical benefits of early detection

Despite its high prevalence among neurodegenerative diseases, Lewy body disease (LBD), or Lewy body dementia (LBD), because of its clinical proximity to Alzheimer's and Parkinson's diseases, is often undiagnosed or misdiagnosed. Better identification of this condition, in order to provide better care for sufferers and their carers, is a health objective on which progress is desirable.

A Case of Lewy Body Dementia with Sensitivity to Arpipiprazole Responded to Amisulpride

A 65 year old subject presented to us symptoms suggestive of Lewy Body Dementia. On treatment with aripiprazole the symptoms worsened but was treated successfully with amisulpride. Such presentation and treatment response is not that common in clinical practice making it an unique scenario.

Functional connectivity and cerebral cortex activation during the resting state and verbal fluency tasks for patients with mild cognitive impairment, Lewy body dementia, and Alzheimer's disease: A multi-channel fNIRS study

ObjectiveTo explore changes in cerebral cortex activation and functional connectivity during resting-state and verbal fluency tasks in patients with different types of dementia. MethodsWe recorded oxygenated hemoglobin concentration (HbO) signals detected by functional near-infrared spectroscopy (fNIRS) from the prefrontal cortex, partial parietal cortex, and cortex of the temporal lobe in four groups of participants: mild cognitive impairment (MCI), Lewy body dementia (LBD), Alzheimer's disease (AD), and cognitively normal (CN). ResultsThe study recruited 120 older adults with MCI (n = 30), LBD (n = 28), AD (n = 30), or CN (n = 32). The mean functional connectivity of the frontal and temporal lobe in resting state was significantly less in the AD (0.19 ± 0.11) group than in the MCI (0.23 ± 0.11), LBD (0.29 ± 0.12), and CN (0.40 ± 0.11) groups (p < 0.001). Further, the mean HbO concentrations in the brain regions and channels were significantly lower in the AD group than in the LBD and MCI groups (p < 0.001). Cognitive levels correlated significantly with the mean HbO concentrations in the resting state and verbal fluency task conditions. ConclusionThe fNIRS HbO signals significantly differed in the cerebral cortex regions in participants with different types of dementia. These findings suggest that fNIRS can effectively enhance the differential diagnosis and assessment of dementia.

Identification of Potential Causal Genes for Neurodegenerative Diseases by Mitochondria-Related Genome-Wide Mendelian Randomization.

Current research lacks comprehensive investigations into the potential causal link between mitochondrial-related genes and the risk of neurodegenerative diseases (NDDs). We aimed to identify potential causative genes for five NDDs through an examination of mitochondrial-related gene expression levels. Through the integration of summary statistics from expression quantitative trait loci (eQTL) datasets (human blood and brain tissue), mitochondrial DNA copy number (mtDNA-CN), and genome-wide association studies (GWAS) datasets of five NDDs from European ancestry, we conducted a Mendelian randomization (MR) analysis to explore the potential causal relationship between mitochondrial-related genes and Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Lewy body dementia (LBD). Sensitivity analysis and Bayesian colocalization were employed to validate this causal relationship. Through MR analysis, we have identified potential causal relationships between 12 mitochondria-related genes and AD, PD, ALS, and FTD overlapping with motor neuron disease (FTD_MND) in human blood or brain tissue. Bayesian colocalization analysis further confirms 9 causal genes, including NDUFS2, EARS2, and MRPL41 for AD; NDUFAF2, MALSU1, and METTL8 for PD; MYO19 and MRM1 for ALS; and FASTKD1 for FTD_MND. Importantly, in both human blood and brain tissue, NDUFS2 exhibits a significant pathogenic effect on AD, while NDUFAF2 demonstrates a robust protective effect on PD. Additionally, the mtDNA-CN plays a protected role in LBD (OR = 0.62, p = 0.031). This study presents evidence establishing a causal relationship between mitochondrial dysfunction and NDDs. Furthermore, the identified candidate genes may serve as potential targets for drug development aimed at preventing NDDs.

SENSE-Cog Lewy: Investigating the Impact of Sensory Loss on the Diagnosis, Clinical Features and Prognosis of Lewy Body Dementia

Abstract Background Lewy Body Dementia (LBD) accounts for 20% of the nearly 65,000 people with dementia in Ireland, but fewer than 5% of those affected receive a formal diagnosis. LBD includes both Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB) and can be characterised by fluctuating and progressive cognitive difficulties, vivid visual hallucinations and REM sleep behaviour disturbances. Sensory function such hearing, vision and olfactory function declines with age—but increasing evidence shows that abnormal patterns of sensory dysfunction can be one of the earliest clinical signs and predictors of progression of neurodegenerative diseases such as Lewy body dementia and Parkinson’s disease dementia. Methods A scoping review was undertaken using Embase, CINAHL, PsychINFO and PubMed. Only reports on people with LBD (DLB and PDD) from any stage, prodromal to late stage were considered. Papers primarily addressing other forms of neurocognitive disorders were excluded. Sensory loss was conceptualised as the loss of smell, vision and hearing. Two reviewers independently assessed each study for inclusion, and disagreements were resolved by a third reviewer. Results Reports on sensory loss in LBD were very few and most often were comparing sensory loss across different dementia types. Strong associations were observed between olfactory loss and particular visual impairment patterns and the severity of both cognitive and non-cognitive DLB symptoms. Olfactory impairment is a potential early biomarker of DLB and PDD and severity of olfactory dysfunction can predict cognitive decline. Visual hallucinations, for example, were found to be closely linked to visual impairment patterns such as pareidolia. Conclusion This study highlights a knowledge gap regarding the patterns of sensory loss in LBD and their relationship with cognitive and non-cognitive LBD symptoms. Sensory assessments represent potentially valuable diagnostic and prognosis tool in LBD, with further research required to understand the aetiological mechanisms underlying sensory impairment in LBD and other dementias.

Exploring the causal effects of serum lipids and lipidomes on lewy body dementia: a Mendelian randomization study.

Lewy body dementia (LBD) is a neurodegenerative disorder characterized by the accumulation of Lewy bodies, which primarily composed of misfolded alpha-synuclein (αS). The development of LBD and APOE4 subtypes is thought to be associated with disorders of lipid metabolism. In this study, we investigated the causal relationship between serum lipids, liposomes and LBD using a two-sample Mendelian randomization (TSMR) method. A TSMR analysis of genome-wide association study (GWAS) data for 8 serum lipids, 179 lipidomes components, LBD and its subtypes was performed, using inverse variance weighted as the primary outcome. To ensure robustness, the sensitivity analyses including MR Pleiotropy RESidual Sum and Outlier, Cochran's test, leave-one-out method and funnel plots were performed. In this study, we found that low-density lipoprotein cholesterol (LDL-C) (OR=1.45, 95% CI=1.19-1.77, P<0.001) and remnant cholesterol (RC) (OR=2.64, 95% CI=1.64-4.28, P<0.001) had significant positive causal effects on LBD, and RC also had a positive effect on LBD in carriers of the APOE4 gene. The results of lipidome analysis showed that phosphatidylcholine (PC) (O-16:0_20:4) levels (OR=0.86, 95% CI=0.75-0.98, P=0.02) and PC (O-18:1_20:4) levels (OR=0.76, 95% CI=0.65-0.89, P <0.001) had negative causal effects on LBD, whereas phosphatidylinositol (PI) (18:1_20:4) levels had a positive causal effect on LBD (OR=1.19, 95% CI=1.02-1.39, P=0.03). For LBD with APOE4 carriers, high levels of PC (16:1_18:0) and PC (O-18:2_18:1) had a significant positive effect, while high levels of PC (O-16:1_18:0), phosphatidylethanolamine (PE) (O-18:2_18:1), sphingomyelin (SM) (d38:2), and triacylglycerol (TAG) (56:5) significantly reduced the risk. No heterogeneity and horizontal pleiotropy were observed in sensitivity analysis. Elevated LDL-C and RC levels are significant risk factors for LBD, with RC also impacting APOE4-carrying LBD. Glycerophospholipids play a crucial role in the pathogenesis of LBD, but the specific components that play a role differ from those with the APOE4 carries. These findings highlight the importance of lipid metabolism in LBD and APOE4 subtypes.

Alpha-synuclein modulates the repair of genomic DNA double-strand breaks in a DNA-PKcs-regulated manner

α-synuclein (αSyn) is a presynaptic and nuclear protein that aggregates in important neurodegenerative diseases such as Parkinson's Disease (PD), Parkinson's Disease Dementia (PDD) and Lewy Body Dementia (LBD). Our past work suggests that nuclear αSyn may regulate forms of DNA double-strand break (DSB) repair in HAP1 cells after DNA damage induction with the chemotherapeutic agent bleomycin1. Here, we report that genetic deletion of αSyn specifically impairs the non-homologous end-joining (NHEJ) pathway of DSB repair using an extrachromosomal plasmid-based repair assay in HAP1 cells. Notably, induction of a single DSB at a precise genomic location using a CRISPR/Cas9 lentiviral approach also showed the importance of αSyn in regulating NHEJ in HAP1 cells and primary mouse cortical neuron cultures. This modulation of DSB repair is regulated by the activity of the DNA damage response signaling kinase DNA-PKcs, since the effect of αSyn loss-of-function is reversed by DNA-PKcs inhibition. Together, these findings suggest that αSyn plays an important physiologic role in regulating DSB repair in both a transformed cell line and in primary cortical neurons. Loss of this nuclear function may contribute to the neuronal genomic instability detected in PD, PDD and LBD and points to DNA-PKcs as a potential therapeutic target.

A - 124 A Case of Lewy Body Dementia and Charles Bonnet Syndrome in a Patient with Bilateral Enucleation

Abstract Objective The patient presented with a history of blindness due to bilateral enucleation (age 10 and 23) and visual hallucinations for approximately 2 years. Approximately 30% of visually impaired individuals are affected by Charles Bonnet syndrome, characterized by complex visual hallucinations in visually challenged patients, possibly stemming from the brain’s attempt to fill the visual void. Additionally, she was diagnosed with Lewy Body dementia (LBD) 2 years prior by her neurologist, and she reported challenges with completing instrumental activities of daily living (IADLs). Method The patient was a left-handed 83-year-old woman, with a history of total blindness and bilateral enucleation, who presented with progressive memory loss 3–4 years prior, along with balance/gait disturbances for 1–1.5 years. The patient and her family sought neuropsychological testing to clarify her cognitive functioning in light of her physical and neurologic symptoms. Results Premorbid functioning was estimated in the low average range, with 11 years of education. Due to her total vision loss, neuropsychological evaluation was limited. Her cognitive profile was marked by impairments in immediate memory, delayed memory, recognition, executive functioning, and language. Conclusions In light of the patient’s marked cognitive deficits in memory, attention, and executive functioning, along with visual hallucinations (although also attributed to possible Charles Bonnet syndrome), balance/gait disturbances, fluctuating awareness, autonomic dysfunction (i.e., bladder/bowel control), and sleep changes (i.e., acting out dreams), her presentation is consistent with LBD, in the moderate stage of severity. Given the symptomatology, it raises the possibility the patient may be experiencing Charles Bonnet syndrome along with LBD.

Causal relationships between dyslexia and the risk of eight dementias

Observational and genetic studies have reported the relationship between dyslexia and Alzheimer’s disease (AD). Until now, the causal effect of dyslexia on AD risk has remained unclear. We conducted a two-sample univariable Mendelian randomization (MR) analysis to determine the causal association between dyslexia and the risk of AD, vascular dementia (VD), Lewy body dementia (LBD), and frontotemporal dementia (FTD) and its four subtypes. First, we selected 42 dyslexia genetic variants from a large-scale genome-wide association studies (GWAS) dataset and extracted their corresponding GWAS summary statistics from AD, VD, LBD, and FTD. Second, we selected four MR methods, including inverse-variance weighted (IVW), weighted median, MR-Egger, and MR-PRESSO. Heterogeneity, horizontal pleiotropy, and leave-one-out sensitivity analysis were then used to evaluate the reliability of all causal estimates. We also conducted multivariable MR (MVMR) and mediation analysis to assess the potential mediating role of cognitive performance (CP) or educational achievement (EA) on the causal association between dyslexia and AD. Two MVMR methods, including MV IVW and MV-Egger, and two-step MR were used to perform the analysis. Using IVW, we found a significant causal association between increased dyslexia and increased risk of AD (OR = 1.15, 95% CI: 1.04–1.28, P = 0.006), but not VD, LBD, FTD, or its four subtypes. MR-PRESSO further supported the statistically significant association between dyslexia and AD (OR = 1.15, 95% CI: 1.05–1.27, P = 0.006). All sensitivity analyses confirmed the reliability of causal estimates. Using MV IVW and mediation analysis, we found no causal relationship between dyslexia and AD after adjusting for CP but not EA, CP mediated the total effect of dyslexia on AD with a proportion of 46.32%. We provide genetic evidence to support a causal effect of increased dyslexia on increased risk of AD, which was largely mediated by CP. Reading activity may be a potential intervention strategy for AD by improving cognitive function.

B - 3 The Role of Artificial Intelligence: Utilization of the Meyers Battery for Diagnostically Differentiating a Complex Neuropsychological Case

Abstract Objectives As medical technology progresses, artificial intelligence (AI) is becoming a common method for providing diagnostic information to patients. In neuropsychology, the Meyers Neuropsychological Battery (MNB) provides impartial data through artificial intelligence. The following case illustrates how AI provided diagnostic clarity and aided in treatment planning. Method A 65-year-old female was referred by her neurosurgeon due to cognitive decline, delusions and hallucinations, and episodes of aggression toward her caretaker. A full, comprehensive neuropsychological examination was administered. Her medical history was remarkable for hypertension, hypercholesterolemia, thyroid cancer, two cerebrovascular accidents, traumatic brain injury, and multiple ischemic strokes. The patient’s most recent imaging was remarkable for chronic encephalomalacia involving the R basal ganglia, mild chronic small vessel ischemic changes, a ventricular shunt within the anterior horn of the R lateral ventricle, and post-coil embolization of a right supraclinoid artery. Results The patient was administered the MNB along with psychological measures. Results were consistent with diffuse and lateralized (RCH &amp;gt; LCH) neuropsychological impairment. Employing the MNB algorithms and AI, this patient’s data matched statistically with Multi-Infarct Dementia, Hydrocephalus, and Lewy Body Dementia. Conclusion These independent applications and AI enable neuropsychologists to respond beyond the “referral question” and provide an objective perspective unique to the patient’s neuropsychological profile. AI is not applied as the only diagnostic approach but rather provides the patient’s medical team with an alternative perspective regarding the entire neuropsychological picture. MNB’s AI not only aids in “matching” neurological conditions to the patient’s profile but also excludes proposed diagnoses in question and underscores a realistic treatment plan.

Associations between concussion and more severe TBIs, mild cognitive impairment, and early-onset dementia among military retirees over 40 years.

As the population of U.S. service members (SMs) who have sustained concussions and more severe traumatic brain injuries (TBIs) during military service ages, understanding the long-term outcomes associated with such injuries will provide critical information that may promote long-term assessment, support, and rehabilitation following military service. The objective of this research was to examine whether concussion and more severe TBIs are associated with greater risk of precursors to dementia (i.e., mild cognitive impairment, memory loss), early-onset dementia, and any dementia. This study used a retrospective cohort design wherein archival medical and career records from 1980 to 2020 identified U.S. military personnel who retired from military service and their corresponding Tricare-reimbursable medical encounters in inpatient and/or outpatient settings in military treatment facilities and/or purchased care settings both before and after retirement. All military personnel who served on active duty between 1980 and 2020 and were at least 45 years of age by 2020 were eligible for inclusion (N = 6,092,432). Those who were discharged from military service with a retirement designation, and were thus eligible for Tricare for Life, were included in the analytic sample (N = 1,211,972). Diagnoses of concussion and more severe TBI during active duty service recorded in inpatient settings between 1980 and 2020 and in outpatient settings from 2001 to 2020 were identified. Focal outcomes of interest included memory loss, mild cognitive impairment, Alzheimer's, Lewy Body dementia, frontotemporal dementia, and vascular dementia. Dementia diagnoses before age 65 were labeled early-onset. Those with (vs. without) concussion diagnoses during military service were significantly more likely to be diagnosed with memory loss and mild cognitive impairment and any of the dementias examined. However, they were not at greater risk of being diagnosed with early-onset dementia. Military SMs diagnosed with concussion may be at elevated risk for long-term neurodegenerative outcomes including memory loss, mild cognitive impairment, and dementia. As the population of SMs who sustained TBI during the Global War on Terror continue to age, the prevalence of dementia will increase and may bring a unique burden to the VHA.

A rare case of early onset lewy body dementia with parkinsonism associated with chronic exposure to copper contaminated drinking water.

There is a well-recognized relationship between a person's body burden of essential trace elements such as copper and their neurological function in which both deficiencies and exposures to excessive concentrations are associated with adverse clinical outcomes. Preclinical studies indicate chronic excess copper exposure is associated with altered motor function, dopaminergic neuronal loss, astrocytosis, and microgliosis. Copper also promotes oligomerization and fibrilization of α-synuclein suggesting it may hasten the course of an α-synucleinopathy. Here we report a rare case of early onset Lewy Body Dementia with Parkinsonism in a 53-year-old Caucasian woman exposed to copper contaminated drinking water for more than 10 years. Her hair and that of her daughter had streaks of blue-green discoloration as did the porcelain sinks in their home. Testing confirmed copper contamination of the drinking water. A neurologist diagnosed her with Lewy Body Dementia with Parkinsonism. Skin biopsy for phosphorylated α was consistent with a diagnosis of an α-synucleinopathy. These findings suggest chronic exposure to excessive copper may act as disease modifying factor in Lewy Body Dementia with Parkinsonism. It has previously been recommended that individuals at risk of Alzheimer's disease (AD) avoid excessive intake of copper. Genetic studies indicate that Lewy Body Dementia shares risk factors and pathways with AD. Based on the observations in this patient we recommend that individuals at risk for an α-synucleinopathy based on a positive family history, genetic testing, and/or positive results on a skin biopsy for phosphorylated α-synuclein avoid exposure to excess copper.

Bugs and Brains: The Microbiome &amp; Dementia

Interest in the microbiome and its correlation with different neurological diseases has grown significantly over the past decade. The gut microbiome contains a vast array of diverse organisms living in the gastrointestinal (GI) tract. Predominantly composed of bacteria, the gut microbiome helps regulate homeostasis and metabolism in the host, aiding in immune system development as well as vitamin and nutrient absorption. Studies suggest that, in addition to providing humans with these physiological benefits, the gut microbiome is also linked to and communicates with the brain via the gut-brain axis (GBA). Long-standing research on the GBA has demonstrated that the GI tract and the central nervous system are interconnected through both neurological and immunological signaling pathways. Recent research is expanding our understanding of the microbiome and the GBA, revealing correlations between the microbiome impact on the GBA and neurological conditions such as Alzheimer’s dementia and Lewy body dementia, going as far as to identify and highlight specific microbial species that may serve as risk or protective factors for various forms of dementia. This letter aims to highlight the current findings and recommend the use of tools such as microbial cell-free DNA testing to gain a better understanding of the role of gut dysbiosis in dementia patients.

Associations Between Neuropsychiatric Symptoms and Inflammation in Neurodegenerative Dementia: A Systematic Review.

Neuropsychiatric symptoms are common in dementia and linked to adverse outcomes. Inflammation is increasingly recognized as playing a role as a driver of early disease progression in Alzheimer's disease (AD) and related dementias. Inflammation has also been linked to primary psychiatric disorders, however its association with neuropsychiatric symptoms in neurodegenerative dementias remains uncertain. We conducted a systematic literature review investigating associations between inflammation and neuropsychiatric symptoms in neurodegenerative dementias, including AD, Lewy body, Frontotemporal, Parkinson's (PD) and Huntington's disease dementias. Ninety-nine studies met our inclusion criteria, and the majority (n = 59) investigated AD and/or mild cognitive impairment (MCI). Thirty-five studies included PD, and only 6 investigated non-AD dementias. Inflammation was measured in blood, CSF, by genotype, brain tissue and PET imaging. Overall, studies exhibited considerable heterogeneity and evidence for specific inflammatory markers was inconsistent, with lack of replication and few longitudinal studies with repeat biomarkers. Depression was the most frequently investigated symptom. In AD, some studies reported increases in peripheral IL-6, TNF-a associated with depressive symptoms. Preliminary investigations using PET measures of microglial activation found an association with agitation. In PD, studies reported positive associations between TNF-a, IL-6, CRP, MCP-1, IL-10 and depression. Central and peripheral inflammation may play a role in neuropsychiatric symptoms in neurodegenerative dementias; however, the evidence is inconsistent. There is a need for multi-site longitudinal studies with detailed assessments of neuropsychiatric symptoms combined with replicable peripheral and central markers of inflammation.

Correlation between dopaminergic and metabolic asymmetry in Lewy body disease – A dual-imaging study

IntroductionThe a-Synuclein Origin and Connectome (SOC) model of Lewy body diseases postulates that a-syuclein will be asymmetrically distributed in some patients with Lewy body diseases, potentially leading to asymmetric neuronal dysfunction and symptoms. MethodsWe included two patient groups: 19 non-demented Parkinson's disease (nPD) patients with [18F]FDG PET and motor symptoms assessed by UPDRS-III, and 65 Lewy body dementia (LBD) patients with [18F]FDG PET and dopamine radioisotope imaging. Asymmetry indices were calculated for [18F]FDG PET by including the cortex for each hemisphere, for dopamine radioisotope imaging by including the putamen and caudate separately, and for motor symptoms by using the difference between right-left UPDRS-III score. Correlations between these asymmetry indices were explored to test the predictions of the SOC model. To identify cases with a more typical LBD imaging profile, we calculated a Cingulate Island Sign (CIS) index on the [18F]FDG PET image. ResultsWe found a significant correlation between cortical interhemispheric [18F]FDG asymmetry and motor-symptom asymmetry in nPD patients (r = 0.62, P = 0.004). In patients with LBD, we found a significant correlation between cortical interhemispheric [18F]FDG asymmetry and dopamine transporter asymmetry in the caudate (r = 0.37, P = 0.0019), but not in the putamen (r = 0.15, P = 0.22). We observed that the correlation in the caudate was stronger in LBD subjects with the highest CIS index, i.e., with more typical LBD imaging profiles. ConclusionOur study partly supports the SOC model, but further investigations are needed – ideally of de novo, non-demented PD patients.

Novel C. elegans models of Lewy body disease reveal pathological protein interactions and widespread miRNA dysregulation

Lewy body diseases (LBD) comprise a group of complex neurodegenerative conditions originating from accumulation of misfolded alpha-synuclein (α-syn) in the form of Lewy bodies. LBD pathologies are characterized by α-syn deposition in association with other proteins such as Amyloid β (Aβ), Tau, and TAR-DNA-binding protein. To investigate the complex interactions of these proteins, we constructed 2 novel transgenic overexpressing (OE) C. elegans strains (α-synA53T;Taupro-agg (OE) and α-synA53T;Aβ1-42;Taupro-agg (OE)) and compared them with previously established Parkinson’s, Alzheimer’s, and Lewy Body Dementia disease models. The LBD models presented here demonstrate impairments including uncoordinated movement, egg-laying deficits, altered serotonergic and cholinergic signaling, memory and posture deficits, as well as dopaminergic neuron damage and loss. Expression levels of total and prone to aggregation α-syn protein were increased in α-synA53T;Aβ1-42 but decreased in α-synA53T;Taupro-agg animals when compared to α-synA53T animals suggesting protein interactions. These alterations were also observed at the mRNA level suggesting a pre-transcriptional mechanism. miRNA-seq revealed that cel-miR-1018 was upregulated in LBD models α-synA53T, α-synA53T;Aβ1-42, and α-synA53T;Taupro-agg compared with WT. cel-miR-58c was upregulated in α-synA53T;Taupro-agg but downregulated in α-synA53T and α-synA53T;Aβ1-42 compared with WT. cel-miR-41-3p and cel-miR-355-5p were significantly downregulated in 3 LBD models. Our results obtained in a model organism provide evidence of interactions between different pathological proteins and alterations in specific miRNAs that may further exacerbate or ameliorate LBD pathology.

End-of-Life Healthcare Utilization in Lewy Body Dementia.

Lewy body dementia (LBD) is the second most common neurodegenerative dementia in the US, presenting unique end-of-life challenges. This study examined healthcare utilization and care continuity in the last year of life in LBD. Medicare claims for enrollees with LBD, continuously enrolled in the year preceding death, were examined from 2011-2018. We assessed hospital stays, emergency department (ED) visits, intensive care unit (ICU) admissions, life-extending procedures, medications, and care continuity. We identified 45,762 LBD decedents, predominantly female (51.8%), White (85.9%), with average age of 84.1 years (SD 7.5). There was a median of 2 ED visits (IQR 1-5) and 1 inpatient stay (IQR 0-2). Higher age was inversely associated with ICU stays (Odds Ratio [OR] 0.96; 95% Confidence Interval [CI] 0.96-0.97) and life-extending procedures (OR 0.96; 95% CI 0.95-0.96). Black and Hispanic patients experienced higher rates of ED visits, inpatient hospitalizations, ICU admissions, life-extending procedures, and in-hospital deaths relative to White patients. On average, 15 (7.5) medications were prescribed in the last year. Enhanced care continuity correlated with reduced hospital (OR 0.72; 95% CI 0.70-0.74) and ED visits (OR 0.71; 95% CI 0.69-0.87) and fewer life-extending procedures (OR 0.71; 95% CI 0.64-0.79). This study underscored the complex healthcare needs of people with LBD during their final year, which was influenced by age and race. Care continuity may reduce hospital and ED visits and life-extending procedures.

Automatic Classification of Conclusions from Multi-Tracer Reports of PET Brain Imaging in Cognitive Impairment.

The goal of this paper is to build an automatic way to interpret conclusions from brain molecular imaging reports performed for investigation of cognitive disturbances (FDG, Amyloid and Tau PET) by comparing several traditional machine learning (ML) techniques-based text classification methods. Two purposes are defined: to identify positive or negative results in all three modalities, and to extract diagnostic impressions for Alzheimer's Disease (AD), Fronto-Temporal Dementia (FTD), Lewy Bodies Dementia (LBD) based on metabolism of perfusion patterns. A dataset was created by manual parallel annotation of 1668 conclusions of reports from the Nuclear Medicine and Molecular Imaging Division of Geneva University Hospitals. The 6 Machine Learning (ML) algorithms (Support Vector Machine (Linear and Radial Basis function), Naive Bayes, Logistic Regression, Random Forrest, and K-Nearest Neighbors) were trained and evaluated with a 5-fold cross-validation scheme to assess their performance and generalizability. The best classifier was SVM showing the following accuracies: FDG (0.97), Tau (0.94), Amyloid (0.98), Oriented Diagnostic (0.87 for a diagnosis among AD, FTD, LBD, undetermined, other), paving the way for a paradigm shift in the field of data handling in nuclear medicine research.

To What Extent Does Computational Modeling Help Understanding Dementia?

Dementia refers to a set of neurodegenerative illnesses defined by a decline in cognitive functions, such as thinking, reasoning, memory recall, and the ability to carry out daily tasks. In recent years, there have been significant advancements in dementia research. However, many aspects of dementia, including its underlying etiology, remain unknown. Thus, it is critical to use new approaches and technologies to uncover unresolved issues about these diseases. Computational modeling is used in various scientific, engineering, and problem-solving disciplines to simulate and study complex systems or events using computer algorithms and mathematical equations. It entails developing a simplified model of a real-world system to acquire insights, make predictions, test hypotheses, and optimize operations. This paper discusses recent case studies and computational models to understand how computational modeling can aid in uncovering the characteristics of visual hallucinations related to Lewy body dementia and the etiology of Alzheimer’s disease.