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

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).

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.

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.

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.