AMYLOID DEPOSITION, CLINICAL PHENOTYPE AND IMAGING FINDINGS IN DEMENTIA WITH LEWY BODIES

Abstract

The pathological hallmarks of dementia with Lewy bodies (DLB) are Lewy bodies and Lewy neurites. Many cases also display amyloid-β deposition. The association between amyloid deposition and clinical phenotype or markers of neurodegeneration such as brain atrophy and hypoperfusion remains unclear. Positron emission tomography with 18F-Florbetapir allows the investigation of these relationships in vivo. We hypothesised that amyloid positive DLB subjects would have clinical and imaging similarities to Alzheimer's disease (AD) (such as greater memory impairment and greater medial temporal lobe atrophy and hypoperfusion) compared with amyloid negative DLB subjects. DLB (n=37), AD (n=20) and control (n=20) subjects had a thorough clinical assessment followed by 3T MRI and early and late phase PET-CT (Siemens Biograph-40) using 18F-Florbetapir (Avid (Lilly)) to assess cortical perfusion and amyloid deposition respectively. Image analysis was carried out using SPM 8 and visual assessment of late phase scans was undertaken to categorise scans as amyloid positive or negative. Amyloid positive scans were found in 54% of DLB subjects, a rate significantly greater than controls (20%; p=0.01) and significantly less than AD (85%; p=0.02). There were no significant differences between amyloid positive and amyloid negative DLB cases in age, cognitive function, degree of functional impairment or any clinical symptoms. There was a trend towards lower medial temporal lobe perfusion in the amyloid positive DLB group (0.75 v 0.80; p=0.08). Using linear regression including age and gender as independent variables, increased cortical 18F-Florbetapir binding in the DLB group was associated with lower medial temporal lobe perfusion (β=-0.52, t=-3.13, p=0.004) and a trend towards lower hippocampal volume (β=-0.29, t=-1.87, p=0.07). Significant amyloid deposition is present in over 50% of subjects with DLB, though its clinical and pathophysiological significance is unclear. Amyloid deposition was not associated with significant phenotypical differences, but it was associated with imaging evidence consistent with greater medial temporal lobe pathology. Stratification of DLB subjects on the basis of the presence of amyloid cannot be done on clinical grounds and will require direct assessment of amyloid via imaging or CSF.