Disease Progression and Longitudinal Clinical Outcomes of Lewy Body Dementia in the NACC Database

Abstract

Introduction: As the identification of Lewy body dementia (LBD) is often confirmed postmortem, there is a paucity of evidence on the progression of disease antemortem. This study aimed to comprehensively assess the course of LBD over time across cognitive, functional, and neuropsychiatric outcomes using real-world data. Methods: Adults with at least one visit to an Alzheimer's Disease Center with a diagnosis of mild cognitive impairment/dementia (index date), indication of LBD, and at least one follow-up visit were identified in the National Alzheimer's Coordinating Center database (September 2005-June 2020). Participant characteristics, medication use, comorbidities, and changes in outcomes were assessed over a 5-year follow-up period and stratified by disease severity based on the Clinical Dementia Rating (CDRÒ) Dementia Staging Instrument-Sum of Boxes (CDR-SB) score at index. Results: A total of 2052 participants with LBD (mean age at index 73.4 years) were included (mild, 219; moderate, 988; severe, 845). Mean annualized increase over 5 years was 0.9 points for CDR-Global Score, 5.6 points for CDR-SB, 10.4 points for the Functional Activities Questionnaire, and 2.0 points for the Neuropsychiatric Inventory-Questionnaire. Disease progression was greater among participants with moderate and severe LBD at index compared with those with mild LBD. Conclusion: Participants with LBD experienced decline across all outcomes over time, and impairment increased with disease severity. Findings highlight the substantial clinical burden associated with LBD and the importance of earlier diagnosis and effective treatment. Further research is needed to understand the predictors of cognitive and functional decline in LBD which may help inform clinical trials.

Phase 2A Learnings Incorporated into RewinD-LB, a Phase 2B Clinical Trial of Neflamapimod in Dementia with Lewy Bodies

“…Further supporting the use of these endpoints to assess effects on the underlying disease process, in longitudinal studies progression of cortical atrophy by MRI has been correlated to the CDR-SB in patients with DLB ( 24 ), and progression of basal forebrain atrophy to gait dysfunction in PD ( 25 ). In addition, clinical disease progression was well captured by the CDR-SB in a large longitudinal cohort ( 26 ). Finally, the CDR-SB through being primarily dependent on caregiver report and based on assessment of cognition and function over the two prior to assessment (i.e., intended to provide an assessment integrated over two weeks), should be less impacted by the cognitive fluctuations that are common in DLB.…”

Kinetic parameters of alpha-synuclein seed amplification assay correlate with cognitive impairment in patients with Lewy body disorders

“…2 A) and the average MoCA of patients with DLB was lower than for patients with PD (Table 1 ). Nonlinear properties of the MoCA score have been reported [ 38 , 39 ], but longitudinal studies will be required to resolve the origin of this observation. Thus, our cross-sectional dataset suggests that SAA could be suited to report quantitative differences in cognitive performance during the early phases of cognitive decline (MoCA 20-30).…”

The Importance of Dopamine Deficiency Evaluation in Non-Alzheimer Disease Dementias

“…Lewy body dementia is an umbrella term that encompasses the clinical conditions of dementia with Lewy bodies (DLB) and Parkinson disease with dementia (PDD). These conditions are characterized by the accumulation of aggregated α-synuclein into Lewy bodies and Lewy neurites in neurons and neuronal processes [ 1 – 3 ]. The diagnosis and management of DLB is often a challenge because cognitive impairment and hallucinations can also occur in Alzheimer disease (AD) and PDD.…”

“…The diagnosis and management of DLB is often a challenge because cognitive impairment and hallucinations can also occur in Alzheimer disease (AD) and PDD. Often there is significant amyloid or tau deposition with co-pathology of AD in patients with DLB and PDD and hence acetylcholinesterase inhibitors may be beneficial [ 1 – 3 ]. However, unlike AD, patients with DLB and PDD suffer from severe neuroleptic sensitivity [ 1 , 2 ], and this sensitivity to antipsychotics can complicate the management of hallucinations.…”

“…Often there is significant amyloid or tau deposition with co-pathology of AD in patients with DLB and PDD and hence acetylcholinesterase inhibitors may be beneficial [ 1 – 3 ]. However, unlike AD, patients with DLB and PDD suffer from severe neuroleptic sensitivity [ 1 , 2 ], and this sensitivity to antipsychotics can complicate the management of hallucinations. In differentially diagnosing these conditions, it is also important to establish a dopamine deficient state so that therapy with either dopa-mine precursors, dopamine agonists, or anticonvulsants might be used to ameliorate the symptomatology of Parkinson disease.…”