Learning to PERSEVERE: A pilot study of peer mentor support and caregiver education in Lewy body dementia

Background:Lewy Body Disease (LBD) is the second most common neurodegenerative disorder. Despite high family caregiver strain and adverse patient and caregiver outcomes, few interventions exist for LBD family caregivers. Based on a successful peer mentoring pilot study in advanced Parkinson\u27s Disease, we revised the curriculum of this peer-led educational intervention incorporating LBD caregiver input. Objective:We assessed feasibility of a peer mentor-led educational intervention and its impact on LBD family caregivers\u27 knowledge, dementia attitudes, and mastery. Methods:Using community-based participatory research, we refined a 16-week peer mentoring intervention and recruited caregivers online through national foundations. Experienced LBD caregiver mentors were trained and matched with newer caregiver mentees with whom they spoke weekly for 16 weeks, supported by the intervention curriculum. We measured intervention fidelity biweekly, program satisfaction, and change in LBD knowledge, dementia attitudes, and caregiving mastery before and after the 16-week intervention. Results:Thirty mentor-mentee pairs completed a median of 15 calls (range: 8-19; 424 total calls; median 45 min each). As satisfaction indicators, participants rated 95.3% of calls as useful, and at week 16, all participants indicated they would recommend the intervention to other caregivers. Mentees\u27 knowledge and dementia attitudes improved by 13% (p \u3c 0.05) and 7% (p \u3c 0.001), respectively. Training improved mentors\u27 LBD knowledge by 32% (p \u3c 0.0001) and dementia attitudes by 2.5% (p \u3c 0.001). Neither mentor nor mentee mastery changed significantly (p = 0.36, respectively). Conclusions:This LBD caregiver-designed and -led intervention was feasible, well-received, and effective in improving knowledge and dementia attitudes in both seasoned and newer caregivers. Trial registration:https://clinicaltrials.gov/ct2/show/NCT04649164ClinicalTrials.gov Identifier: NCT04649164 ; December 2, 2020

Peer Mentoring Program for Informal Caregivers of Homebound Individuals With Advanced Parkinson Disease (Share the Care): Protocol for a Single-Center, Crossover Pilot Study

BackgroundHomebound individuals with advanced Parkinson disease (PD) require intensive caregiving, the majority of which is provided by informal, family caregivers. PD caregiver strain is an independent risk factor for institutionalization. There are currently no effective interventions to support advanced PD caregivers. Studies in other neurologic disorders, however, have demonstrated the potential for peer mentoring interventions to improve caregiver outcomes. In the context of an ongoing trial of interdisciplinary home visits, we designed and piloted a nested trial of caregiver peer mentoring for informal caregivers of individuals with advanced PD. ObjectiveThe aim of this study was to test the feasibility of peer mentoring for caregivers of homebound individuals with advanced PD and to evaluate its effects on anxiety, depression, and caregiver strain. MethodsThis was a single-center, 16-week pilot study of caregiver peer mentoring nested within a year-long controlled trial of interdisciplinary home visits. We recruited 34 experienced former or current family caregivers who completed structured mentor training. Caregivers enrolled in the larger interdisciplinary home visit trial consented to receive 16 weeks of weekly, one-to-one peer mentoring calls with a trained peer mentor. Weekly calls were guided by a curriculum on advanced PD management and caregiver support. Fidelity to and satisfaction with the intervention were gathered via biweekly study diaries. Anxiety, depression, and caregiver strain were measured pre- and postmentoring intervention at home visits 2 and 3. ResultsEnrollment and peer-mentor training began in 2018, and 65 caregivers enrolled in the overarching trial. The majority of mentors and mentees were White, female spouses or partners of individuals with PD; mentors had a mean of 8.7 (SD 6.4) years of caregiving experience, and 33 mentors were matched with at least 1 mentee. ConclusionsThis is the first study of caregiver peer mentoring in PD and may establish an adaptable and sustainable model for disease-specific caregiver interventions in PD and other neurodegenerative diseases. Trial RegistrationClinicalTrials.gov NCT03189459; http://clinicaltrials.gov/ct2/show/NCT03189459 International Registered Report Identifier (IRRID)DERR1-10.2196/3475

KICK OUT PD: Feasibility and quality of life in the pilot karate intervention to change kinematic outcomes in Parkinson's Disease.

BackgroundMultiple exercise modalities and mindfulness activities are beneficial in Parkinson's Disease (PD). Karate is a martial art that combines aerobic and large-amplitude movements, balance and core training, and mindfulness, suggesting a potential benefit for individuals with PD from multiple perspectives.ObjectiveTo evaluate the feasibility of community-based Shotokan karate classes involving physical activity and mindfulness among individuals with mild- to moderate-stage PD, and to explore the effects of karate on objective and patient-reported outcomes.MethodsWe conducted a 10-week, unblinded trial of twice weekly, PD-specific karate classes. Feasibility was assessed by: dropout rates, adherence via attendance records, adverse effects and falls, and continued participation six months post-intervention. Participants completed pre- and post-intervention assessments of disease-related quality of life (Parkinson's Disease Questionnaire-8, PDQ-8), falls, and post-intervention assessment of change in overall wellbeing (Patient Global Impression of Change, PGIC), with exploratory measures of mobility using the Timed Up and Go (TUG), mood using the Hospital Anxiety and Depression Scale (HADS), and cognition using digit span forward and backward and the Symbol Digit Modalities Test (SDMT).ResultsOf 19 enrolled participants, 15 completed the study (79%). Among completers, mean adherence was 87% during the ten weeks of intervention, and 53% maintained karate participation six months later and endorsed sustained improvement, respectively. No adverse effects or change in fall frequency were detected. Among completers, 53% were women, and mean PD duration was 6 years (range 2-20). Quality of life improved to a clinically significant degree (PDQ-8: mean 25.3 (standard deviation (SD) 20.8) versus 19.3 (SD 19.6), p = 0.01, effect size 0.83). On the PGIC, 87% endorsed feeling moderately or considerably better. Mobility did not change significantly (TUG: 9.6 seconds (SD 2.23) versus 9.0 seconds (SD 1.89), p = 0.12, effect size 0.43), nor were there changes in overall physical activity, mood, or cognition (p = 0.35-0.92).ConclusionsIn a small, 10-week, unblinded trial of community-based karate classes for individuals with mild and moderate PD, high adherence was noted. Quality of life and wellbeing improved significantly, without changes in exploratory outcomes of mobility or neuropsychological outcomes. The study was underpowered, particularly for the exploratory outcomes. Controlled and longitudinal investigation is warranted to confirm our pilot findings and explore the long-term effects and sustainability of karate in PD.Trial registrationClinicaltrials.gov: NCT03555695

Longitudinal, Interdisciplinary Home Visits Versus Usual Care for Homebound People With Advanced Parkinson Disease: Protocol for a Controlled Trial

BackgroundThe current understanding of advanced Parkinson disease (PD) and its treatment is largely based on data from outpatient visits. The most advanced and disabled individuals with PD are disconnected from both care and research. A previous pilot study among older, multimorbid patients with advanced PD demonstrated the feasibility of interdisciplinary home visits to reach the target population, improve care quality, and potentially avoid institutionalization. ObjectiveThe aim of this study protocol is to investigate whether interdisciplinary home visits can prevent a decline in quality of life of patients with PD and prevent worsening of caregiver strain. The protocol also explores whether program costs are offset by savings in health care utilization and institutionalization compared with usual care. MethodsIn this single-center, controlled trial, 65 patient-caregiver dyads affected by advanced PD (Hoehn and Yahr stages 3-5 and homebound) are recruited to receive quarterly interdisciplinary home visits over 1 year. The 1-year intervention is delivered by a nurse and a research coordinator, who travel to the home, and it is supported by a movement disorder specialist and social worker (both present by video). Each dyad is compared with age-, sex-, and Hoehn and Yahr stage–matched control dyads drawn from US participants in the longitudinal Parkinson’s Outcome Project registry. The primary outcome measure is the change in patient quality of life between baseline and 1 year. Secondary outcome measures include changes in Hoehn and Yahr stage, caregiver strain, self-reported fall frequency, emergency room visits, hospital admissions, and time to institutionalization or death. Intervention costs and changes in health care utilization will be analyzed in a budget impact analysis to explore the potential for model adaptation and dissemination. ResultsThe protocol was funded in September 2017 and approved by the Rush Institutional Review Board in October 2017. Recruitment began in May 2018 and closed in November 2019 with 65 patient-caregiver dyads enrolled. All study visits have been completed, and analysis is underway. ConclusionsTo our knowledge, this is the first controlled trial to investigate the effects of interdisciplinary home visits among homebound individuals with advanced PD and their caregivers. This study also establishes a unique cohort of patients from whom we can study the natural course of advanced PD, its treatments, and unmet needs. Trial RegistrationClinicalTrials.gov NCT03189459; http://clinicaltrials.gov/ct2/show/NCT03189459. International Registered Report Identifier (IRRID)PRR1-10.2196/3169

The complexity of DLB: U.S.‐based Dementia with Lewy Body Consortium

Background The clinical syndrome of dementia with Lewy bodies (DLB) is well defined with good positive predictive value for the presence of Lewy body pathology at autopsy. However, the presence of Lewy body pathology in dementia is not always linked to the clinical syndrome of DLB, particularly early in the clinical course (e.g., prodromal and mild cognitive impairment), and co‐pathologies are quite frequent. This clinical and pathologic complexity leads to many challenges including early recognition and diagnosis, clinical management, and development of symptomatic and disease modifying therapies. To address these issues, a number of consortia have been established to longitudinally study DLB and related Lewy body diseases, including a US based Dementia with Lewy Bodies Consortium (DLBC). Method The U.S.‐based DLBC is a multi‐centered, NIH funded, project to longitudinally and systematically study subjects with DLB and mild cognitive impairment/high likelihood DLB (MCI‐DLB). The primary goal of the DLBC is to generate biospecimens linked to clinical, imaging, and neuropathologic characterization in a longitudinally followed cohort across the participating DLBC sites. Biofluids, including blood and cerebrospinal fluid (CSF), and data generated by the DLBC will be ultimately be available to investigators through the NINDS‐funded Parkinson’s Disease Biomarker Program. Result To date, one hundred and thirteen subjects have been enrolled in the DLBC. Preliminary results from the first ninety‐two subjects note a male predominance in the sample (82 of 92, 89%). At baseline visit, mean age was 69.4 (SD 7.1 years), baseline UPDRS‐MDS Part III was 28.9 (15.7 SD) and MoCA 20.4 (SD 5.4). Neuropathologic data are limited, but suggest that an elevated CSF p‐tau may assist in clinically differentiating DLB with or without high levels of Alzheimer’s disease pathology. Imaging results including volumetric MRI, amyloid imaging and DaTscan are pending. Conclusion The development of DLB cohorts, such as the US based DLBC, is essential to understanding the complexity and pathobiologic significance of the clinical syndrome, biomarker characteristics and imaging findings in patients with underlying Lewy body disease. These results continue to emphasize the importance of further development of biomarkers in DLB and related neurodegenerative disorders

A - 63 Neuropsychiatric and Cognitive Correlates of Pareidolias in Dementia with Lewy Bodies

OBJECTIVEPareidolias represent visual illusions of meaningful objects in ambiguous stimuli. Prior research has demonstrated phenomenological similarities between pareidolias and visual hallucinations (VH) and the potential clinical utility of pareidolias in discriminating dementia with Lewy bodies (DLB) from Alzheimer's dementia (ad). Though pareidolias have been linked with VH severity in DLB, the relationships between pareidolias and other neuropsychiatric symptoms have not been explored in large DLB samples. METHODIndividuals meeting 2017 McKeith criteria for probable DLB (n = 114) were enrolled in a multi-site systematic longitudinal study of the US DLB Consortium. Study assessments included an informant-rated psychiatric inventory (NPI), Montreal Cognitive Assessment (MoCA), and Noise Pareidolia Task (NPT). Ninety-five participants completed all clinical assessments. To examine baseline relationships between pareidolias responses (NPT) and the presence of 12 neuropsychiatric symptom dimensions (NPI), we used Poisson regression models with robust standard error estimates adjusted for age, education, disease duration, cognition (MoCA), and cholinesterase inhibitor use. RESULTSContrary to expectation, the presence of VH was not associated with pareidolias in DLB (Incidence Rate Ratio = 1.37, p = 0.275). The presence of both delusions (IRR = 2.11, p = 0.01) and depression (IRR = 1.79, p = 0.015) was associated with greater pareidolias. Additionally, overall cognitive dysfunction was associated with pareidolias (IRR = 0.90, p < 0.001). CONCLUSIONSOur findings indicate that pareidolias are associated with poorer cognition and neuropsychiatric dimensions beyond VH, including depression and delusions. As pareidolias have been put forth as a surrogate marker of VH in DLB, future studies examining pareidolias in conjunction with comprehensive psychiatric/cognitive assessment and neuroimaging will further elucidate the clinical utility of pareidolia testing

Identification of Hippocampal and Amygdala Subfields Predictive of MoCA Scores in Patients with Dementia with Lewy Bodies

Abstract Background Hippocampal and amygdala subfields variably affect cognitive impairment in neurodegenerative diseases. Subfields of these regions can be well segmented using modern neuroimaging tools but their role in neurodegenerative disease is under active investigation. In this study, we identified hippocampal and amygdala subregions predictive of cognitive performance and motor symptoms severity measured by MoCA (Montreal Cognitive Assessment) and MDS‐UPDRS III, respectively, in patients with dementia with Lewy Bodies (DLB). Method We selected all participants with probable DLB (N = 48, mean age = 71±7 years, 15% female) enrolled in the Dementia with Lewy Bodies Consortium (DLBC) as of July 2022, with concurrent measures of 3D T1 MRI sequence, MoCA, and MDS‐UPDRS III scores. We performed cortical reconstruction and volumetric segmentation of hippocampal subfields and nuclei of the amygdala using FreeSurfer (v 7.2). We used combat harmonization to account for site and scanner differences. We trained and applied a bootstrapped, bidirectional stepwise regression model of 29 predictor variables comprised of sub‐fields and mean cortical thickness against MoCA and MDS‐UPDRS III, respectively, with an 80‐20 train‐test split ratio, and 5000 repetitions, corrected for age and sex. Result Subfield segmentation is shown in Figure 1A . The best fitting model for MoCA included mean cortical thickness, parasubiculum, hippocampal and amygdala transition area, corticoamygdaloid transition area, and CA3 body ( Figure 1B , adjusted R 2 = 0.51). The best fitting model for MDS‐UPDRS III included the cortical nucleus of the amygdala and CA1 body ( Figure 1C , adjusted R 2 = 0.22). This model was considered a poor fit. We considered MoCA for further analysis and closely predicted scores in our 20% partitioned test sample ( Figure 2A , R 2 = 0.38). Conclusion We report model‐based selection of hippocampal and amygdala subfields to predict MoCA scores in DLB. Atrophy in these regions has been associated with global cognitive deficit in mild cognitive impairment and Alzheimer disease cohorts. The model fit for MDS‐UPDRS III scores was poor, providing evidence that these brain regions do not serve a role in motor control

ATN cerebrospinal fluid biomarkers in dementia with Lewy bodies: Initial results from the United States Dementia with Lewy Bodies Consortium

INTRODUCTION: The National Institute on Aging - Alzheimer\u27s Association (NIA-AA) ATN research framework proposes to use biomarkers for amyloid (A), tau (T), and neurodegeneration (N) to stage individuals with AD pathological features and track changes longitudinally. The overall aim was to utilize this framework to characterize pre-mortem ATN status longitudinally in a clinically diagnosed cohort of dementia with Lewy bodies (DLB) and to correlate it with the post mortem diagnosis. METHODS: The cohort was subtyped by cerebrospinal fluid (CSF) ATN category. A subcohort had longitudinal data, and a subgroup was neuropathologically evaluated. RESULTS: We observed a significant difference in Aβ after 12 months in the A+T- group. Post mortem neuropathologic analyses indicated that most of the p-Tau 181 positive (T+) cases also had a high Braak stage. DISCUSSION: This suggests that DLB patients who are A+ but T- may need to be monitored to determine whether they remain A+ or ever progress to T positivity. HIGHLIGHTS: Some A+T- DLB subjects transition from A+ to negative after 12-months. Clinically diagnosed DLB with LBP-AD (A+T+) maintain their positivity. Clinically diagnosed DLB with LBP-AD (A+T+) maintain their positivity. Monitoring of the A+T- sub-type of DLB may be necessary

ATN cerebrospinal fluid biomarkers in dementia with Lewy bodies: Initial results from the United States Dementia with Lewy Bodies Consortium

IntroductionThe National Institute on Aging - Alzheimer's Association (NIA-AA) ATN research framework proposes to use biomarkers for amyloid (A), tau (T), and neurodegeneration (N) to stage individuals with AD pathological features and track changes longitudinally. The overall aim was to utilize this framework to characterize pre-mortem ATN status longitudinally in a clinically diagnosed cohort of dementia with Lewy bodies (DLB) and to correlate it with the post mortem diagnosis.MethodsThe cohort was subtyped by cerebrospinal fluid (CSF) ATN category. A subcohort had longitudinal data, and a subgroup was neuropathologically evaluated.ResultsWe observed a significant difference in Aβ42/40 after 12 months in the A+T- group. Post mortem neuropathologic analyses indicated that most of the p-Tau 181 positive (T+) cases also had a high Braak stage.DiscussionThis suggests that DLB patients who are A+ but T- may need to be monitored to determine whether they remain A+ or ever progress to T positivity.HighlightsSome A+T- DLB subjects transition from A+ to negative after 12-months. Clinically diagnosed DLB with LBP-AD (A+T+) maintain their positivity. Clinically diagnosed DLB with LBP-AD (A+T+) maintain their positivity. Monitoring of the A+T- sub-type of DLB may be necessary