Insular Alzheimer’s disease pathology as a cause of “age-related” autonomic dysfunction and mortality in the non-demented elderly

Abstract

Only a few brain structures have been implicated in the autonomic control of blood pressure and heart rate. Among them are heteromodal association areas in the cortex, especially the insular cortex. Ischemic insular lesions have been associated with both cardiac arrhythmias and mortality. However, stroke may not be the only insular pathology with the potential to disrupt autonomic function. Alzheimer's disease (AD) is associated with both insular pathology and autonomic dysfunction. Alzheimer's dementia is merely the final stage of a pathological process that spans decades. Recent studies have demonstrated a hierarchichal sequence of AD pathology that includes the insular cortex. This may explain why AD has effects on BP and central autonomic cardio-regulatory functions. However, AD reaches the insular cortex at a "preclinical" stage in its development (i.e., before "dementia" can be diagnosed). Thus, AD pathology should also be considered as a possible explanation for autonomic morbidity and mortality in non-demented elderly persons. We hypothesize that autonomic dyscontrol, commonly seen in non-demented well elderly persons without significant cardiovascular disease (CVD), reflects subclinical stages of AD pathology affecting the insular cortex. If true, then preclinical AD pathology should be considered as a possible explanation for arrhythmia/fall related morbidity and mortality in non-demented elderly persons.