Prodromal Dementia With Lewy Bodies: Clinical Characterization and Predictors of Progression

Abstract

Objective: The objective of this study was to examine clinical characteristics, cognitive decline, and predictors for time to dementia in prodromal dementia with Lewy bodies with mild cognitive impairment (MCI-LB) compared with prodromal Alzheimer's disease (MCI-AD).

Methods: We included 73 MCI-LB patients (12% female; 68 ± 6 years; Mini Mental State Examination, 27 ± 2) and 124 MCI-AD patients (48% female; 68 ± 7 years; Mini Mental State Examination, 27 ± 2) from the Amsterdam Dementia Cohort. Follow-up was available for 61 MCI-LB patients and all MCI-AD patients (3 ± 2 years). We evaluated dementia with Lewy bodies core features, neuropsychiatric symptoms, caregiver burden (Zarit caregiver burden interview), MRI, apolipoprotein genotype, and cerebrospinal fluid biomarkers (tau/Aβ_1-42 ratio). Longitudinal outcome measures included cognitive slopes (memory, attention, executive functions, and language and visuospatial functions) and time to dementia.

Results: Parkinsonism was the most frequently present core feature in MCI-LB (69%). MCI-LB patients more often had neuropsychiatric symptoms and scored higher on ZARIT when compared with the MCI-AD patients. Linear mixed models showed that at baseline, MCI-LB patients performed worse on nonmemory cognitive domains, whereas memory performance was worse in MCI-AD patients. Over time, MCI-LB patients declined faster on attention, whereas MCI-AD patients declined faster on the Mini Mental State Examination and memory. Cox proportional hazards regressions showed that in the MCI-LB patients, lower attention (hazard ratio [HR] = 1.6; 95% confidence interval [CI], 1.1-2.3) and more posterior cortical atrophy (HR = 3.0; 95% CI, 1.5-5.8) predicted shorter time to dementia. In the MCI-AD patients, worse performance on memory (HR = 1.1; 95% CI, 1.0-1.2) and executive functions (HR = 1.3; 95% CI, 1.0-1.6) were independently associated with time to Alzheimer's dementia.

Conclusion: MCI-LB patients have distinct neuropsychiatric and cognitive profiles with prominent decline in attention when compared with MCI-AD patients. Our results highlight the importance of early diagnosis because symptoms already have an impact in the prodromal stages. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Keywords: Alzheimer's disease; Mild cognitive impairment (MCI); dementia with Lewy bodies (DLB).

Figure 1

The prevalence of Neuropsychiatric Inventory (NPI) symptoms in MCI‐LB (n = 57) and MCI‐AD (n = 104). *P < 0.05, χ² test. MCI‐AD, Alzheimer's disease with mild cognitive impairment; MCI‐LB, dementia with Lewy bodies with mild cognitive impairment. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 2

Estimated trajectories of cognitive domains. Regression lines represent estimated group trajectories over time in years with 95% confidence intervals based on nonimputed data. (A) MMSE score (range 0–30). (B–F) Data represent z scores based on cognitively healthy subjects. MCI‐AD, mild cognitive impairment due to Alzheimer's disease; MCI‐LB, mild cognitive impairment due to Lewy Bodies; MMSE, Mini Mental State Examination. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 3

Survival curves for predictors of progression to dementia in mild cognitive impairment due to Lewy Bodies: attention (A) and PCA (B). For attention, a z score < −2 was considered impaired. For PCA, we used the median value as a cutoff (1). PCA, posterior cortical atrophy.