Biomarkers in dementia with Lewy bodies

Abstract

Dementia with Lewy bodies (DLB) is the second commonest type of neurodegenerative dementia, but accurate antemortem diagnosis remains challenging, especially at the earliest (prodromal) disease stages and in the presence of mixed (Alzheimer) pathology. To investigate this we undertook two studies, an investigation of 123I-FP-CIT imaging as a possible biomarker of prodromal DLB (at the mild cognitive impairment (MCI) stage), and a study of the effect of amyloid deposition measured by 18F-Florbetapir PET on clinical phenotype in established DLB. Methods Prodromal DLB Study: 53 subjects with MCI and symptoms suggestive of Lewy body disease underwent comprehensive clinical and cognitive assessment and 123I-FP-CIT SPECT imaging. Amyloid Imaging Study: 22 DLB, 10 Alzheimer’s disease (AD) and 15 control subjects underwent comprehensive clinical and cognitive assessment, MRI and 18F-Florbetapir PET amyloid imaging. Results Prodromal DLB Study: An abnormal 123I-FP-CIT scan was associated with increased rates of parkinsonism and RBD, but was not associated with a specific pattern of cognitive impairment. The pattern of 123I-FP-CIT binding loss was symmetrical. Males were more likely to have an abnormal scan than females. Amyloid Imaging Study: AD subjects displayed greater amyloid binding than DLB in frontal, temporal, cingulate and striatal regions. There were no significant differences between DLB and controls, but binding in DLB was intermediate between AD and controls in all regions. Frontal:Occipital binding ratio differentiated AD from DLB and controls. There were no consistent effects of amyloid on the phenotype of DLB subjects. ii Conclusions 123I-FP-CIT SPECT appears to be a marker of Lewy body disease in the prodromal stage. Longitudinal analysis is needed to determine its sensitivity and specificity. Amyloid deposition is present in a proportion of DLB subjects, but is not associated with a clear difference in clinical phenotype. Longitudinal follow-up will determine whether it is associated with a difference in disease progression.