DOPAMINE RESPONSIVE FEATURES IN ALZHEIMER'S DISEASE, ALZHEIMER'S DISEASE WITH LEWY BODIES (LB), AND PURE LB DISEASE

Abstract

The degree to which Alzheimer disease (“pure AD”), AD with concurrent Lewy body (LB) pathology (“AD w/LBs”), and pure LB disease (“pure LBP”) represent a continuum or distinct disorders is not clear. Parkinsonian symptoms can be disabling in these conditions, are variably responsive to dopaminergic replacement therapy and their characteristics might reflect the nature of the underlying neuropathology. In the current study we looked at the association of dopaminergic-responsive and non-responsive signs and dopaminergic medication use during life in persons with no neuropathologic findings at autopsy (NCs, n = 62), pathologically-proven pure AD (n = 634), AD w/LBs (n = 175), and pure LBP (n = 52) using the National Alzheimer Coordinating Center database (total = 923). We identified such cases that had full Unified Parkinson Disease Rating Scale (UPDRS) scores at their first visit such that dopamine replacement-responsive signs (Levy A scores, 0-80) and non-responsive signs (Levy B scores, 0-20) could be calculated. We performed ANOVA's and two-sided t-tests to compare these scores across groups and compared the use of dopaminergic replacement therapy between groups using chi-square analyses for all subjects for whom such data was available (n= 1,125). At their first visit, 4% of NCs, 3% of persons with pure AD, 8% of persons with AD w/LBs, and 38% of persons with pure LBP were on dopaminergic replacement therapy. Mean Levy A scores were 1.8, 4.4, 6.4, and 12.7 and Levy B scores were 1.6, 2.2, 2.8, and 5.0, respectively (p's < 0.001). Differences in mean Levy A and B scores were significantly different among all groups except for Levy B scores between persons with normal brains and those with pure AD. Despite an increasing prevalence of treatment with dopamine replacement therapy, progressively worse Levy A and B scores predict progressively more pure LB pathology. Dopamine-responsive signs more clearly differentiated the groups. Further analysis of UPDRS sub-items in relation to pathologic diagnosis will be of utility in creating scales to better differentiate these groups and predict medication response during life.