11C-PiB PET and hippocampal volumes are complementary in distinguishing dementia with Lewy bodies and Alzheimer's disease

Abstract

The two most common neurodegenerative disorders associated with dementia in the elderly are Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). Early in the disease process, clinical differentiation between these disorders is often difficult; hence imaging markers for differential diagnosis would be useful. 11 C -Pittsburgh Compound-B (PiB) retention on PET is a surrogate marker for amyloid pathology and hippocampal volume on MRI is associated with the neurofibrillary pathology of AD. We propose that imaging markers closely associated with neurofibrillary and amyloid pathologies of AD may provide complementary information for the differential diagnosis of DLB and AD. We studied clinically diagnosed patients with AD (n = 13), DLB (n = 5), and cognitively normal subjects (n = 20) who were consecutively recruited from the Mayo Clinic Alzheimer's Disease Research Center. All subjects underwent clinical evaluation, MRI and PiB-PET within six weeks. A global cortical PiB retention summary measure was formed by combining prefrontal, orbitofrontal, parietal, temporal, anterior cingulate and posterior cingulate/precuneus values divided by the cerebellar cortical PiB retention for each subject, with equal weighting of the individual values in computing the summary measure. Hippocampal volumes were analyzed as adjusted W-scores for head size, age and gender. The global cortical PiB retention in DLB patients was on average lower than AD, but higher than cognitively normal subjects. Similarly, hippocampal W-scores of DLB patients were on average higher than AD, but lower than cognitively normal subjects. Three of the five (60%) DLB patients were “PiB positive” (global cortical PiB retention summary measure ≥1.5), and one subject was “borderline” (1.49). Hippocampal W-scores were lower than zero in three of the five (60%) DLB patients. Only one DLB patient had both hippocampal atrophy and “positive PiB.” Plotting hippocampal W-scores against global cortical PiB retention completely separated the DLB and AD subjects (Figure). MRI and PiB PET are complementary in distinguishing patients with DLB and AD, and provide insight into the pathological mechanisms underlying dementia in DLB patients. A majority of the DLB patients had PiB retention and/or hippocampal atrophy, in agreement with pathology studies showing that patients with clinically diagnosed DLB may often have some degree of additional AD pathology.