Alzheimer disease neuropathology:understanding autonomic dysfunction

Abstract Alzheimer's disease is a widely studied disorder with research focusing on cognitive and functional impairments, behavioral and psychological symptoms, and on abnormal motor manifestations. Despite the importance of autonomic dysfunctions they have received less attention in systematic studies. The underlying neurodegenerative process of AD, mainly affecting cortical areas, has been studied for more than one century. However, autonomic-related structures have not been studied neuropathologically with the same intensity. The autonomic nervous system governs normal visceral functions, and its activity is expressed in relation to homeostatic needs of the organism's current physical and mental activities. The disease process leads to autonomic dysfunction or dysautonomy possibly linked to increased rates of morbidity and mortality. Objective: The aim of this review was to analyze the cortical, subcortical, and more caudal autonomic-related regions, and the specific neurodegenerative process in Alzheimer's disease that affects these structures. Methods: A search for papers addressing autonomic related-structures affected by Alzheimer's degeneration, and under normal condition was performed through MedLine, PsycInfo and Lilacs, on the bibliographical references of papers of interest, together with a manual search for classic studies in older journals and books, spanning over a century of publications. Results: The main central autonomic-related structures are described, including cortical areas, subcortical structures (amygdala, thalamus, hypothalamus, brainstem, cerebellum) and spinal cord. They constitute autonomic neural networks that underpin vital functions. These same structures, affected by specific Alzheimer's disease neurodegeneration, were also described in detail. The autonomic-related structures present variable neurodegenerative changes that develop progressively according to the degenerative stages described by Braak and Braak. Conclusion: The neural networks constituted by the central autonomic-related structures, when damaged by progressive neurodegeneration, represent the neuropathological substrate of autonomic dysfunction. The presence of this dysfunction and its possible relationship with higher rates of morbidity, and perhaps of mortality, in affected subjects must be kept in mind when managing Alzheimer's patients