Disease progression in dementia with Lewy bodies: A longitudinal study on clinical symptoms, quality of life and functional impairment

Background and objectives: Dementia with Lewy Bodies (DLB) is a heterogeneous disease, with variable signs and symptoms across multiple domains. We aimed to identify associations with rate of change in cognition, everyday functioning (IADL) and quality of life (QoL).

Methods: We included 121 DLB patients (69 ± 6 yrs, 14%F, MMSE: 25 ± 3) in our prospective cohort (follow-up 2 ± 1 yrs). We described progression of symptoms and cognitive decline over time. Mixed models were used to investigate whether changes in symptoms were associated to changes in IADL (FAQ), QoL (QoL-AD) and caregiver burden (ZBI). Last, we investigated whether baseline symptoms and biomarkers predicted decline in cognition (MMSE), IADL (FAQ) and QoL (QoL-AD).

Results: Parkinsonism and RBD were most frequently present early in the disease course, while hallucinations were more likely to develop in a later stage. MMSE (annual change β ± SE = -2.06 ± 0.23), QoL-AD (-1.03 ± 0.20), and FAQ (3.04 ± 0.30) declined over time. Increasing severity of clinical symptoms was associated to increases in FAQ, QoL-AD and caregiver burden. Baseline clinical symptoms were not predictive for decline in these outcomes. By contrast, AD co-pathology (CSF pTau/Aβ42 ratio) was associated to steeper decline in MMSE (-1.23 ± 0.54). Medial temporal atrophy (-0.81 ± 0.26) and global cortical atrophy (-0.73 ± 0.36) predisposed for decline in QoL-AD.

Conclusions: Our findings imply that underlying disease processes, rather than clinical symptomatology aid in predicting decline. These findings are relevant for treatment strategies and the development of DLB specific outcome measures.