Cardiovascular and Retinal Vascular Changes in Preclinical Alzheimer's Disease
One in three adults over 85 years old suffer from Alzheimer’s disease (AD) or other forms of dementia. This already widespread condition is expected to increase further in both incidence and prevalence in coming years. As a result, the need to understand the etiology and pathogenesis of dementia becomes ever more urgent. AD, in addition to its steep cost of care, is the most common form of dementia and the sixth leading cause of death in the United States. It is a complex disease and its mechanisms are poorly understood. The more we learn about AD, the more questions are raised about our current conceptual models of disease. Despite the rapid advancement of medical technology, reliable and sensitive diagnostic markers to identify individuals at risk to AD prior onset of clinical symptoms remain in the developmental phase resulting in inefficient diagnostic procedures. Diagnosis is further hampered by the heterogeneity of behavioral presentations, cognitive impairments, and functional statuses observed in AD, all of which may be the result of varying etiologies. Furthermore, older AD patients often suffer from comorbid medical conditions that further complicate accurate disease monitoring. ^ In the absence of an effective AD treatment, it is prudent to apply our current knowledge of the intersection between AD, cardiovascular disease (CVD), and cerebrovascular disease to foster efforts to delay the onset of dementia more generally. The purpose of MANUSCRIPT I is to review our current understanding of the epidemiology, genetics, and pathophysiology of AD as well as the intersection between AD and vascular causes of dementia. The epidemiology and shared risk factors and etiologies for these three disease “clusters” are explored, including shared genetic contributions and lifestyle, behavioral and environmental risk factors. In this first publication, we also explore possible mechanistic pathways of AD and the shared pathophysiology and neuropathological substrates of these three disease clusters. ^ CVD and cerebrovascular pathology is present for most individuals with AD, although the converse is not necessarily true. Given this relationship, it is important to address how early in the disease course those vascular changes can be observed. Such research is needed to enable early interventions to maintain quality of life in premorbid AD and reduce the burden of disease. To determine whether there is cardiovascular alteration in the early stages of AD, MANUSCRIPT II evaluated electrocardiologic measures of vagal tone for 63 adults (ages 55-75) at rest, during cognitive testing, and then again at rest. All subjects had multiple risk factors for AD, and all completed amyloid PET scans (18F-Florbetapir) to determine amyloid positivity (A?+). Cardiac autonomic dysfunction, specifically, an increase in sympathetic activity and a decrease in parasympathetic activity often referred to as vagal withdrawal, is prevalent among individuals with AD and is indicative of impaired autonomic function. Preclinical AD participants (Florbetapir amyloid PET SUVr ? 1.1) did not consistently show changes in vagal ratio or Respiratory Sinus Arrhythmia (RSA) at any point during the experiment and they failed to demonstrate the expected response to the modest stress they experienced during cognitive task performance. Both changes are directly modulated by both muscarinic and nicotinic cholinergic autonomic neurotransmission. Because the earliest stages of AD are marked, in part, by altered function of the basal forebrain cholinergic system, with eventual degenerative changes including neuronal loss, this result suggests a link between A? aggregation and impaired autonomic cardiovascular function, even in the preclinical stage of AD. (Abstract shortened by ProQuest.) ^
Claudia Yang Santos,
"Cardiovascular and Retinal Vascular Changes in Preclinical Alzheimer's Disease"
Dissertations and Master's Theses (Campus Access).