Neurochemical markers do not correlate with cognitive decline in the Lewy body variant of Alzheimer disease

Background: Reductions in neocortical synapses and cholinergic function occur in patients with Alzheimer disease (AD) and in patients with the Lewy body variant of AD (LBV). The relation between these losses and cognitive decline has been reported frequently in patients with AD but remains unclear for patients with LBV. Objectives: To investigate the relation between clinical markers of disease progression and choline acetyltransferase activity or synaptic density, measured by synaptophysin (Syn) level, in patients with LBV, and to investigate the relation of these neurochemical markers with one another. Methods: Brain specimens of 41 patients with autopsy-confirmed (National Institute on Aging criteria for AD) LBV were examined. The last Mini-Mental State Examination and Blessed Information-Memory-Concentration test scores before death were reviewed. Midfrontal synapse counts were quantified by a dot-immunobinding assay for Syn. Choline acetyltransferase activity of the midfrontal cortex was assayed by established protocols. Results: The last Mini-Mental State Examination score before death did not correlate significantly with Syn level (n = 25, r = 0.25, P = .24); however, there was a trend toward significance for the relation between last Mini-Mental State Examination score and choline acetyltransferase activity (n = 39, r = 0.31, P = .05). The last Blessed Information-Memory-Concentration test score did not correlate with either Syn level (n = 24, r = -0.17, P = .44) or choline acetyltransferase activity (n = 39, r = -0.16, P = .33). Finally, there was only a modest correlation between Syn level and choline acetyltransferase activity (n = 25, r = 0.38, P = .06), which did not reach statistical significance. Conclusion: Unlike AD, neurochemical markers do not appear to correlate well with cognitive decline in LBV.