Alzheimer's disease is a major public health crisis affecting millions of Americans. The current focus for treatment development is for treatments that are administered in the earliest stages of disease, before a clinical diagnosis of Alzheimer's disease. In addition, many research projects are investigating the causes of Alzheimer's disease and the course of how the disease progresses starting from the earliest stages of disease. In order to effectively target future treatments and to properly investigate the early stages of Alzheimer's disease, non-invasive and inexpensive measures to detect early biological changes associated with Alzheimer’s disease, even before cognitive symptoms develop, are needed. These markers would be useful for clinical research, diagnosis and screening, as well as for clinical trials of potential therapeutic treatments. The goal of this project is to evaluate whether targeted markers of visual function could be used to detect biological changes associated with Alzheimer's disease in early stages. Many people forget that the retina is part of the central nervous system and has many biological and cellular properties that are similar to those seen in the brain. Therefore, we believe that measures of retinal structure and function may give us information about biological changes going on in the brain, including those that happen in the early stages of Alzheimer's disease, specifically the accumulation of the protein deposits thought to cause Alzheimer's disease (amyloid-beta plaques, tau neurofibrillary tangles). Our project will evaluate individuals at risk for Alzheimer's disease with targeted visual tests of retinal function, specifically evaluating contrast sensitivity (ability to distinguish dark shades from light shades), and retinal structure (evaluating whether certain retinal layers show degeneration). These individuals will also undergo clinical and cognitive testing and neuroimaging scans to look at brain structure and function (MRI) and to determine whether these individuals show evidence of amyloid and tau deposition in their brains (PET). Our goal is to determine whether the visual measures predict the presence of amyloid and tau in the brain, as well as changes in brain structure and function, even in individuals who don't yet have cognitive decline. If successful, we hope to establish these visual measures as useful screening tools to evaluate older adults for risk of having pathology associated with Alzheimer's disease. Ultimately, we could see these tests being done on a regular basis at an ophthalmologist office or even in a primary care setting as a screening test for Alzheimer's disease pathology. Then, in the absence of a known reason for an abnormality on the test (i.e., diagnosed eye disease), if an individual does poorly on the contrast sensitivity test and/or shows degeneration of their retina, they could then be sent for more extensive testing with a Neurologist, including perhaps MRIs and amyloid and tau PET scans (or other future tests). We hope that one day these tests could be used in clinical practice to assist with screening for Alzheimer's disease and in clinical trials of new therapeutics to screen individuals for those most at risk for having Alzheimer's related pathology. Ultimately, once an effective drug is developed, we envision using these tools to screen individuals for disease and suggest additional testing to determine whether they should be given the treatment.
Radiology and Imaging Sciences
Indiana University School of Medicine