Armstrong, Melissa J.

AbstractBackgroundDiffusion‐weighted magnetic resonance imaging (dMRI) examines tissue microstructure integrity in vivo. Prior dementia with Lewy bodies (DLB) diffusion tensor imaging studies yielded mixed results.ObjectiveWe employed free‐water (FW) imaging to assess DLB progression and correlate with clinical decline in DLB.MethodsBaseline and follow‐up MRIs were obtained at 12 and/or 24 months for 27 individuals with DLB or mild cognitive impairment with Lewy bodies (MCI‐LB). FW was analyzed using the Mayo Clinic Adult Lifespan Template. Primary outcomes were FW differences between baseline and 12 or 24 months. To compare FW change longitudinally, we included 20 cognitively unimpaired individuals from the Alzheimer's Disease Neuroimaging Initiative.ResultsWe followed 23 participants to 12 months and 16 participants to 24 months. Both groups had worsening in Montreal Cognitive Assessment (MoCA) and Movement Disorder Society‐Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) scores. We found significant FW increases at both time points compared to baseline in the insula, amygdala, posterior cingulum, parahippocampal, entorhinal, supramarginal, fusiform, retrosplenial, and Rolandic operculum regions. At 24 months, we found more widespread microstructural changes in regions implicated in visuospatial processing, motor, and cholinergic functions. Between‐group analyses (DLB vs. controls) confirmed significant FW changes over 24 months in most of these regions. FW changes were associated with longitudinal worsening of MDS‐UPDRS and MoCA scores.ConclusionsFW increased in gray and white matter regions in DLB, likely due to neurodegenerative pathology associated with disease progression. FW change was associated with clinical decline. The findings support dMRI as a promising tool to track disease progression in DLB. © 2024 International Parkinson and Movement Disorder Society.

AbstractINTRODUCTIONLittle is known regarding quality of life (QoL) in dementia with Lewy bodies (DLB), particularly in advanced stages.METHODSDyads of individuals with moderate–advanced DLB and their primary caregivers were recruited from specialty clinics, advocacy organizations, and research registries. The study collected demographics, disease‐related measures, and measures of patient/caregiver experiences.RESULTSThe Quality of Life in Alzheimer's Disease (QoL‐AD) was completed by the person with DLB and the caregiver (proxy) in 61 dyads; 85 dyads had only a proxy‐completed QoL‐AD. Patient‐ and proxy‐reported scores were moderately correlated (r = 0.57, P < 0.0001). Worse patient‐reported QoL correlated with daytime sleepiness, autonomic symptom burden, and behavioral symptoms. Proxy ratings correlated with dementia severity, daytime sleepiness, behavioral symptoms, dependence in activities of daily living, and caregiver experience measures.DISCUSSIONPatient‐ and proxy‐reported quality of life (QoL) should be assessed separately in advanced DLB. Some symptoms associated with QoL have available therapeutic options. Research is needed regarding strategies to optimally improve QoL in DLB.Highlights Patient and proxy quality of life (QoL) ratings had moderate correlation in advanced dementia with Lewy bodies. Daytime sleepiness affected patient‐ and proxy‐reported QoL. Behavioral symptoms affected patient‐ and proxy‐reported QoL. Autonomic symptom burden affected patient‐reported QoL. Dementia severity, dependence, and caregiver experiences affected proxy ratings.

AbstractBackgroundDiffusion‐weighted MRI (dMRI) examines tissue microstructure integrity and white matter pathways in vivo. Prior dementia with Lewy bodies (DLB) studies focused on white matter or voxel‐based techniques. Less is known about longitudinal white and grey matter microstructural changes in DLB. We aimed to characterize longitudinal diffusion microstructural changes in individuals with DLB.MethoddMRI scans were collected on individuals with DLB from the Mayo Clinic Longitudinal Imaging Biomarkers of DLB Program. Demographics, clinical evaluations and MRI were collected at baseline, and 12‐ or 24‐months. Free water (FW) and FW‐corrected fractional anisotropy (FAT) were analyzed in grey and white matter using 122 bilateral template regions and tracts of interest from the Mayo Clinic Adult Lifespan Template. Primary outcomes were differences in FW and FAT between baseline and 12‐ or 24‐months.ResultWe identified 23 individuals with DLB or mild cognitive impairment with Lewy bodies (MCI‐LB) from baseline to 12‐months [mean age 69.3 years (SD 9.5); 95.8% male], and 16 individuals from baseline to 24‐months [mean age 67.5 years (SD 9.3); 100% male]. Participants at both time‐points showed worsening in Montreal Cognitive Assessment and Movement Disorders Society Unified Parkinson’s Disease Rating Scale motor scores (p<0.05). We found significant differences in FW, but not FAT, from baseline to 12‐months. Significant increases in FW at both time‐points compared to baseline were observed in the insula, putamen, parahippocampal, and rolandic operculum regions (pfdr<0.05). We found additional more widespread microstructural changes from baseline to 24‐months, with increased FW in the amygdala, entorhinal, mid and posterior cingulum, inferior frontal, hippocampal, pallidum, precuneus and retrosplenial regions (pfdr<0.05). We found decreased FAT from baseline to 24‐months in the cerebellar and superior occipital regions (pfdr<0.01).ConclusionLonger follow‐up at 24‐months identified broader networks of free water changes in individuals with DLB. Results support dMRI as a promising, non‐invasive tool to track disease progression in DLB. More investigation is needed to evaluate the relationship of microstructural changes with clinical progression in DLB.

Introduction: Lewy body dementia (LBD) is common, yet under-recognized and under-researched. To plan studies with the highest impact, engagement of the community personally affected by these conditions is essential. Methods: A web-based survey of people living with LBD and current and former caregivers of people with LBD queried research priorities through forced ranking and exploration of burden of LBD symptoms. Specific caregiving needs in LBD and perceptions of research participation were also investigated. Results: Between April 7, 2021 and July 1, 2021, 984 responses were recorded. Top research priorities included disease-modifying therapies and improved disease detection and staging. People with LBD were interested in pathophysiology and more bothered by motor symptoms; caregivers were interested in risk factors and symptomatic therapies and more bothered by neuropsychiatric symptoms. Few available LBD treatments and resources were rated as helpful, and many valuable services were never received. Previous participation in LBD research was infrequent, but interest was high. Discussion: People with LBD and caregivers highlighted the need for research across all aspects of LBD, from pathophysiology and disease modification to prognosis, education, symptomatic treatments, and caregiver support. Funders should increase support for all aspects of LBD research to target the many needs identified by individuals and families living with LBD.

AbstractBackgroundDementia with Lewy bodies (DLB) is a common neurodegenerative disorder; however, DLB can be difficult to differentiate from Alzheimer’s disease dementia (AD), particularly in the early stages. Research criteria for prodromal DLB were published in 2020 and further studies are needed to validate and refine future clinical criteria.MethodWe analyzed data from the Uniform Data Set from the National Alzheimer’s Coordinating Center (NACC database is funded by NIA/NIH U01‐AG016976). Annual visits occurred across 39 Alzheimer’s Disease Research Centers between September 2005 and September 2021. We identified non‐demented participants [i.e., normal cognition, impaired‐not mild cognitive impairment (MCI) or MCI] at baseline who subsequently received a clinical diagnosis of DLB or AD. Core clinical features (CCF) for DLB (i.e., motor features, visual hallucinations, probable REM sleep behavior disorder (pRBD), cognitive fluctuations), and supportive neuropsychiatric features (NPF; anxiety, apathy, and depression) were assessed through clinical exam and informant responses up to five years prior to dementia diagnosis.ResultThe sample consisted of 160 participants with DLB and 480 age/sex‐matched (1:3) participants with AD at first visit with dementia diagnosis. There was no significant difference in the number of visits prior to dementia diagnosis. The AD group was more racially and ethnically diverse than the DLB group. At the time of diagnosis, DLB participants demonstrated greater functional impairment. Descriptive results indicate CCF and NPF are common in DLB up to five years prior to conversion to dementia; however, motor slowing and NPF were reported in over 20% of the AD participants within the prodromal phase. The presence of 2 or more CCF yielded the greatest AUC (0.786; 95% CI: 0.743, 0.830) in distinguishing DLB from AD one year prior to dementia diagnosis. Combinations of 1 or more CCF with 1, 2, or 3 NPF resulted in significantly lower AUCs (0.725, 0.651, 0.547, respectively) due to decreased specificity.ConclusionCCF and supportive NPF are common in the prodromal phase of DLB; however, parkinsonism and NPF also occurred in the prodromal AD group. Parkinsonism may provide lower discrimination than cognitive fluctuations, visual hallucinations, or pRBD in differentiating DLB from AD in the prodromal phase.