Longitudinal biomarkers in Dementia with Lewy bodies: A systematic review and meta‐analysis

Abstract

AbstractBackgroundDementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia after Alzheimer’s disease (AD). DLB is a clinically and biologically heterogeneous disease, and little is known about longitudinal trajectories of patients with DLB. Disease progression can be measured with biomarkers capturing structural, functional, and pathological processes, aiding in understanding disease mechanism and discovering potential drug targets. We aimed to perform a systematic review to explore longitudinal patterns of biomarkers in DLB.MethodsSearches were conducted within five different databases, including cohort studies and case series on DLB patients with repeated measures of fluid or imaging biomarkers, and at least six months follow‐up. Fourteen studies were included (Figure 1), reporting data on longitudinal MRI, DaT‐Scan, PiB and flortaucipir‐PET, plasma p‐tau, and HMPAO SPECT, with up to 2,5 years of follow‐up (Table 1). No data on cerebrospinal fluid biomarkers were available. We could only perform a meta‐analysis on annualized brain atrophy rates, with a random effect model and standardized mean differences (SMD).ResultsProgressive putaminal atrophy is seen in DLB patients, even when DaT‐scans are initially normal. In the meta‐analysis, brain atrophy rates were not significantly higher in pure DLB compared to cognitively unimpaired controls, with the exception of accelerated ventricular expansion rates (SMD 0.57 [0.03‐1.10], p = 0.04, 2 studies, 58 patients). Autopsy‐confirmed AD copathology resulted in greater global atrophy rates compared to pure DLB (SMD 0.72 [0.21‐1.31], p = 0.006, Figure 2), similar to AD. AD copathology accelerates temporal lobe and striatal atrophy rates. In one study, brain amyloid accumulation in DLB initially accelerated and then decelerated, similar to AD and cognitively unimpaired subjects, with absolute SUVr lower than AD. In another study, brain tau accumulation rate correlated with brain atrophy rates in the middle temporal pole in DLB patients.ConclusionsOnly a few studies reported longitudinal data on biomarkers in DLB. DLB patients do not have significantly higher brain atrophy rates compared to controls, while the presence of AD copathology accelerates global and regional atrophy. Future studies with longer follow‐ups and multimodal biomarkers are needed to further characterize disease progression and elucidate clinical and biological heterogeneity.