Progression of clinical diagnostic features and cognitive decline in mild cognitive impairment with Lewy bodies

Abstract

Background Mild cognitive impairment with Lewy bodies (MCI-LB) may be identified prospectively based on the presence of cognitive impairment and several core clinical features (visual hallucinations, cognitive fluctuations, parkinsonism, and REM sleep behavior disorder). MCI-LB may vary in its presenting features, which may reflect differences in underlying pathological pattern, severity, or comorbidity. We aimed to assess how clinical features of MCI-LB accumulate over time, and whether this is associated with the rate of cognitive decline. Methods In this cohort study, 74 individuals seen with MCI-LB prospectively underwent repeated annual cognitive and clinical assessment up to nineyears. Relationships between clinical features (number of core features present and specific features present) and cognitive change on the Addenbrooke's Cognitive Examination-Revised (ACE-R) were examined with time-varying mixed models. The accumulation of core clinical features over time was examined with a multi-state Markov model. Results When an individual with MCI-LB endorsed more clinical features, they typically experienced a faster cognitive decline (ACE-R Score Difference β=-1.1 [-1.7 to -0.5]), specifically when experiencing visual hallucinations (β=-2.1 [-3.5 to -0.8]) or cognitive fluctuations (β=-3.4 [-4.8 to -2.1]). Individuals with MCI-LB typically acquired more clinical features with the passage of time (25.5% [20.0-32.0%] one-year probability), limiting the prognostic utility of baseline-only features. Conclusions The clinical presentation of MCI-LB may evolve over time. The accumulation of more clinical features of Lewy body disease, in particular visual hallucinations and cognitive fluctuations, may be associated with a worse prognosis in clinical settings.