Outcome Measures for Dementia With Lewy Body Clinical Trials

Patel, Bhavana; Irwin, David J.; Kaufer, Daniel I.; Boeve, Bradley F.; Taylor, Angela; Armstrong, Melissa J.

doi:10.1097/wad.0000000000000473

Cited by 10 publications

(6 citation statements)

References 73 publications

(141 reference statements)

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“…Therefore, establishing robust outcome measures is crucial to permit the evaluation of symptomatic treatments and DMTs in DLB. To date, no specific DLB outcome measures have been validated for use in clinical trials, which have typically relied on scales developed for AD and PD [ 5 ] (Table 1 ). Previously, regulatory authorities have emphasized the need for outcome measures that address functional, cognitive, and global domains in AD, but guidance is lacking in DLB [ 6 – 8 ].…”

Section: Introductionmentioning

confidence: 99%

Clinical outcome measures in dementia with Lewy bodies trials: critique and recommendations

Rodríguez‐Porcel

Wyman‐Chick

Ruiz

et al. 2022

Transl Neurodegener

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The selection of appropriate outcome measures is fundamental to the design of any successful clinical trial. Although dementia with Lewy bodies (DLB) is one of the most common neurodegenerative conditions, assessment of therapeutic benefit in clinical trials often relies on tools developed for other conditions, such as Alzheimer’s or Parkinson’s disease. These may not be sufficiently valid or sensitive to treatment changes in DLB, decreasing their utility. In this review, we discuss the limitations and strengths of selected available tools used to measure DLB-associated outcomes in clinical trials and highlight the potential roles for more specific objective measures. We emphasize that the existing outcome measures require validation in the DLB population and that DLB-specific outcomes need to be developed. Finally, we highlight how the selection of outcome measures may vary between symptomatic and disease-modifying therapy trials.

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Section: Introductionmentioning

confidence: 99%

Clinical outcome measures in dementia with Lewy bodies trials: critique and recommendations

Rodríguez‐Porcel

Wyman‐Chick

Ruiz

et al. 2022

Transl Neurodegener

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“…Our findings of gait related changes driving motor progression in DLB+ suggest differential weight of some extrapyramidal features. This should be considered carefully when determining important primary outcomes in future clinical trials 41 and composite scores. 42 Unlike some studies, 43 severity of resting tremor score or frequency was similar between PDD and DLB+ in this study.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal motor decline in dementia with Lewy bodies, Parkinson disease dementia, and Alzheimer's dementia in a community autopsy cohort

Choudhury

Zhang

Adler

et al. 2023

Alzheimer's & Dementia

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

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“…Prior research has examined cognitive impairment in the context of medical prediction, diagnosis, and treatment (10)(11)(12)(13)(14). For example, the relative severity of cognitive impairment can be used to characterize and predict treatment response in dementia (13,15,16), and it has been linked to poor health outcomes in diabetes (5,17,18). Recent research also posits cognitive variability as an early-emerging marker of cognitive and physical decline (6,19).…”

Section: Characterizing Momentary Cognition: Historical Challenges An...mentioning

confidence: 99%

Dynamic associations between glucose and ecological momentary cognition in Type 1 Diabetes

Hawks¹,

Beck²,

Jung³

et al. 2023

Preprint

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Type 1 diabetes (T1D) is a chronic condition characterized by glucose variability due to autoimmune destruction of insulin-secreting pancreatic beta-cells. Prior research (linking greater glucose variability to cognitive impairment and adverse health outcomes) and recent technological innovations (continuous glucose monitoring [CGM], cognitive ecological momentary assessment [EMA]) laid a foundation for the current study, which aimed to advance understanding of between- and within-person influences on physiological and cognitive processes relevant to health in T1D. We obtained intensive longitudinal, naturalistic measurements of cognition (EMA) and glucose (CGM) in N=199 adults with T1D. Given reduced cognitive performance during periods of low (hypo) and high (hyper) glycemia, our analyses focused on the strength of within-person quadratic associations between glucose and cognition—operationalized as the rate of change in the slope of the glucose-cognition relationship, hereafter, glucose acceleration. First, we used multilevel modeling to obtain group (i.e., aggregated across participants) and individual (i.e., specific to each participant) estimates of glucose acceleration. Next, we used machine learning to identify between-person predictors of individual estimates of glucose acceleration. Finally, we built personalized models to contextualize individual estimates of glucose acceleration in relation to time-varying processes. Group estimates of glucose acceleration were significant for processing speed but not sustained attention. Specifically, processing speed was fastest at glucose concentrations slightly above individuals’ means, regardless of absolute levels of the means. Between individuals, estimates of glucose acceleration varied in relation to several clinical and demographic variables, including age, microvascular complications, and percent time in hypoglycemia (< 70 mg/dL). Within individuals, fluctuations in glucose and processing speed were related to prior night’s sleep duration, self-reported assessment context (e.g., noise), and self-reported stress. Results generate testable insights about shared (across individuals) factors that impact cognitive fluctuations. They also highlight opportunities to support personalized medicine by increasing understanding about unique (person-specific) influences on cognitive fluctuations in T1D.

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Outcome Measures for Dementia With Lewy Body Clinical Trials

Cited by 10 publications

References 73 publications

Clinical outcome measures in dementia with Lewy bodies trials: critique and recommendations

Clinical outcome measures in dementia with Lewy bodies trials: critique and recommendations

Longitudinal motor decline in dementia with Lewy bodies, Parkinson disease dementia, and Alzheimer's dementia in a community autopsy cohort

Dynamic associations between glucose and ecological momentary cognition in Type 1 Diabetes

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