Longitudinal biomarkers in dementia with Lewy bodies: A systematic review and meta-analysis

Dementia with Lewy bodies (DLB) is the second most prevalent neurodegenerative dementia. It is clinically and biologically heterogeneous, yet longitudinal biomarker studies assessing different aspects of neuropathological processes in DLB are scarce. We systematically reviewed the literature to identify biomarkers suitable for tracking disease progression in DLB and to evaluate potential outcome measures for clinical trials by examining which biomarkers show longitudinal changes correlating with clinical progression.

Following PRISMA guidelines, we searched CENTRAL, MEDLINE, Embase, Scopus, and Web of Science for longitudinal biomarker studies in DLB (sample size ≥10, follow-up duration ≥6 months). We conducted meta-analysis of three structural MRI-studies assessing whole-brain atrophy.

Of 9162 titles screened, 17 studies met selection criteria including ±460 patients with MCI-LB/DLB. 15 studies included imaging biomarkers (MRI, SPECT, PET) and two studies included fluid biomarkers (plasma, CSF). Except for DAT-SPECT, most studies addressed non-DLB specific neurodegeneration or Alzheimer's disease (AD) pathology. Structural MRI-studies showed greater longitudinal atrophy in AD and mixed DLB + AD versus DLB and controls. Meta-analysis confirmed that DLB-patients were comparable to controls (p = 0.37), but showed lower atrophy rates than AD (p = 0.01). Amyloid-PET and biofluid studies suggested that amyloid accumulation follows typical progression, even in non-AD diagnoses. DAT-SPECT and FDG-PET demonstrated longitudinal changes correlating with clinical progression, showing promise as monitoring biomarkers.

No single biomarker currently suffices to track disease progression in DLB. DAT-SPECT and FDG-PET showed promise, but further research is warranted on these and alternative, more disease-specific, accessible and feasible modalities to improve disease monitoring in future clinical trials.