Physical aggression is associated with preservation of substantia nigra pars compacta in Alzheimer disease

Objective: To investigate specific neuropathologic correlates of agitation and Design: Neuronal counts in the nucleus basalis, locus ceruleus, and substantia nigra were compared in the brains of patients with pathologically definite AD with or without histories of agitation or interpersonal violence. Setting: Alzheimer disease center of a university department of neurology. Main Outcome Measures: Neuron densities in the nucleus basalis and absolute neuron counts in the locus ceruleus and substantia nigra pars compacta. Results: The patients with AD who had histories of unequivocal interpersonal violence had significantly greater neuron counts in the substantia nigra pars compacta than did the nonviolent patients with AD. This finding remained significant after multiple clinical and neuropathologic variables were adjusted for. Neuropathologic findings in the nucleus basalis and locus ceruleus were not different between violent and nonviolent patients. Conclusion: Preservation of pigmented substantia nigra neurons may be a risk factor for physical aggression in AD.