Retinal Degeneration as a Biomarker to Diagnose and Prognose Alzheimer s Disease
Abstract
Alzheimer’s disease (AD) affects more than 5.4 million Americans, with numbers projected to be more than 13.8 million by 2050. The prevalence among U.S. Veterans is almost 600,000 individuals (more than 7 percent of Veterans by age 65) and is expected to increase dramatically in the coming decades. Increasing incidence of traumatic brain injury (TBI) and post-traumatic stress disorder are significant risk factors for developing AD and dementia. For example, TBI is associated with a 60% greater risk for AD in aging Veterans and, similar to AD, is associated with multiple visual dysfunctions impacting personal autonomy and quality of life. AD is also linked to significantly increased healthcare expenses for Veterans. The aggregate cost of care for adult individuals affected by AD and other dementia is estimated to be approximately $221 billion in direct and indirect expenses with another $34 billion for out-of-pocket expenses. Symptoms affecting the visual system may be among the earliest signs of AD and dementia, while brain scans can detect AD only after the disease is well beyond a treatable phase. The most common visual symptoms in Veteran patients with AD are impairment of spatial contrast sensitivity, motion perception, color discrimination, and visual loss. Other reported visual abnormalities include ocular motility, reduced pupillary light reflex, and circadian abnormalities with associated sleep disturbances. These deficits are associated with retinal abnormalities including decreased blood circulation, and degeneration of the retina, the optic nerve and the nerve fiber layer that forms the optic nerve before it exits the retina, as observed in postmortem retinas and more recently by imaging and electrophysiological studies. With increasingly advanced techniques, retinal changes can be visualized at a very fine level, making ocular and visual examinations in Veteran patients less invasive and more cost-effective than currently used techniques. Development of diagnostic criteria at the earliest signs and during progression of visual complaints by AD patients has many benefits but first, a better understanding of pre-AD and early-onset retinal degeneration and visual deficits is needed to guide clinicians’ use of appropriate tests. Our preliminary data in an animal model of AD are in agreement with the retinal degeneration observed in postmortem tissue from AD patients. Our immediate objective is to establish the pathological changes and their time course that define AD retinal degeneration and associated visual dysfunction. Our long-term objective is to provide a foundation for parallel human studies on diagnostic and prognostic vision biomarkers that will identify a window of opportunity for clinical interventional studies in early disease. Our approach using two animal models of AD with human AD postmortem retinas couples analysis of degeneration-associated structural changes in the retina and optic nerve with functional vision-guided behavioral alterations representing the visual deficits experienced by Veteran patients with AD. Supporting development of these diagnostic biomarkers should provide several advantages to the military for their personnel and Veterans at risk for or with AD by providing guidance for parallel patient studies that will ultimately (1) identify appropriate non-invasive tests for early detection; (2) improve diagnostic accuracy; (3) allow timely treatment; and (4) improve health, autonomy, quality of life, and financial outcomes.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210294
Entities
People
- Luis Pérez De Sevilla Müller
Organizations
- United States Army
- University of California, Los Angeles