Basic Mechanisms in Neurodegenerative Disease: Implications for Behavioral Pathogenesis and Treatment

Current therapies for neurodegenerative diseases focus primarily on the use of psychotropic drugs to influence their non-cognitive manifestations. In this article, we take a conceptual approach to understanding behavioral syndromes in dementing disorders, with a heuristic emphasis on Alsheimer's disease. We draw upon recent developments in research to explore the fundamental mechanisms implicated in the pathophysiology of neuropsychiatric impairments, and consider endocrine, vascular, genetic, and interpersonal factors that may modulate their expression. Emerging evidence points to dysfunction of particular neural systems within the diseased brain as the basis for neuropsychiatric syndromes, but the specificity of postulated clincal-pathologic correlations remains to be verified by research designed to test critical hypotheses. We highlight advances in clinical and experimental psychopharmacology that extend conventional concepts of the actions of psychotropic drugs, and prompt a broad approach to investigating and treating behavioral pathology in dementia.