Cynthia Owsley - US grants

The aim of the proposed research is to examine possible neural mechanisms underlying the spatial vision of older humans. Previous research has indicated that many older adults in their 60's to 80's have an impaired ability to see small and intermediate sized objects. This is true even of older people who are free from ocular diseases, suggesting that these visual deficits are a part of the normal aging process. Although there has been much research concerned with describing older people's visual deficits, there has been little research focused on the neural mechanisms underlying these age-related losses. Th experiments proposed here use psychophysical techniques to examine neural mechanisms which may play a role in the vision problems of the elderly. The long-term objectives of this research are three-fold. First, more than pinpointing what visual capacities change in old age, scientists must identify what underlying neural processes are vulnerable to aging. Psychophysical studies are particularly useful in addressing this issue. Second, if we more thoroughly understand mechanisms behind age-related vision problems, we can better predict and identify circumstances in which older people may experience difficulty. Third, it is important to separate, as much as possible, those visual changes that are expected on the basis of aging alone, from those that are symptomatic of ocular disease.

Previous research has indicated that many older adults tend to have serious deficits in spatial (pattern) vision, despite the fact that they are considered to be in good ocular health. Although the field has made great strides in describing these disorders, we are still unclear as to what factors, both optical and neural, underlie this aging-related decline in older adults' spatial sensitivity. The proposed studies are designed to continue our research elucidating these underlying mechanisms, using non- invasive, psychophysical (behavioral) measurement techniques. As in our earlier work, we will be focusing on spatial vision in older adults who are free from identifiable ocular disease. We recognize, however, that there is a fine line between what is called "normal" biological aging vs. specific disease processes that tend to occur in the elderly. Yet it is necessary to understand impairments in visual function that can occur in later life even in those individuals considered to be in good ocular health. Experiments will examine three specific questions: (1) To what extent are optical changes in the aged eye responsible or spatial contrast sensitivity losses in older adults? (2) To what extent are changes in the spatial tuning of neural mechanisms underlying spatial vision responsible for decreases in spatio-temporal sensitivity in later life? (3) The third question we will address involves patients with intraocular lenses (IOLs), today the most common treatment for elderly patients after cataract extraction. We will examine how differences in the modulation transfer function of the IOL vs. the normal aged crystalline lens relates to spatial contrast sensitivity differences in these patients. The long-term objective of this research is to achieve a better understanding of the optical and neural factors underlying older adults' deficits in spatial vision, so that improved treatments and solutions can be developed to minimize and eliminate these visual deficits.

The specific goal of this application is to present a scientific symposium on the visual and cognitive predictors of poor driving performance in older adults, at an international transportation meeting in Sweden in September, 1991. This meeting is co-sponsored by the Transportation Research Board of the National Research Council in the U.S., and the Swedish Road and Traffic Research Institute. The older driver problem can be summarized briefly by the fact that older drivers have more traffic convictions and accidents and incur more fatalities per miles dhven than any other age group. This symposium is designed to present information to the international community about recent empirical and conceptual developments in understanding what visual and cognitive factors place an older driver at fisk for crash involvement. The symposium participants have been selected so that a number of perspectives are represented, including vision and cognitive science, in normals and in those with Alzheimers disease; human factors psychology; transportation research; and gerontology. The symposium has international research representation as well. The aim of this symposium is to promote discussion between our panel and the international audience, so that future research efforts take into consideration international advances in the gerontology and transportation fields. This symposium could serve as a catalyst for fostering communication among scientists, so that the quality of older driver research is enhanced both in the U.S. and abroad, which will ultimately promote both the safety and the mobility of older individuals.

Many older adults have significant visual impairments in spatial contrast sensitivity, acuity, and visual sensitivity, even when they are believed to be in good eye health. Since these impairments cannot be attributed to the presence of ocular or neurological disease, they are believed to reflect the biological aging of the visual system. Visual deficits in the elderly can severely hamper their performance of routine daily activities. With the increase in the older adult population in our society, there is a pressing need to better understand the visual functional problems of the elderly, and to ultimately identify ways in which the quality of visual performance can be maintained despite advancing age. Toward this eventual goal, we will use two different approaches to examine factors which underlie loss of spatial vision in older adults. In Part 1 of this Research Plan we will use psychophysical (behavioral) techniques to examine why spatial contrast sensitivity deficits in the elderly are greatly accentuated at lower light levels. Experiments using laser interferometric techniques will address the contribution of neural vs. optical factors to their sensitivity loss. Additional experiments will examine the roles of spatial summation, internal neural noise, and stimulus uncertainty in producing the exacerbated loss at lower luminance. Older adults' performance in these studies will be compared to that of young adults in good eye health. In Part 2 we will make use of a unique opportunity to measure visual function and retinal topography on the same eyes from a relatively large sample of adults of various ages. These individuals are candidates for orbital exenterations (i.e., eye removal) because of craniofacial cancer. Prior to eye removal, psychophysical studies of spatial resolution and visual sensitivity at various eccentricities will be performed on each patient. Following surgery, retinal topography studies will be carried out which will provide estimates of photoreceptor and ganglion cell densities. Earlier studies attempting to link visual function and retinal topography were based on cross-species or cross-individual comparisons, using very small samples. Our approach, which will be within-species and within-individual, and which will use human subjects, has clear advantages over the previous approach, and will have immediate relevance for understanding visual processing in humans throughout adulthood. Information provided by Parts 1 and 2 of this Research Plan will assist in identifying the mechanisms underlying older adults' loss in spatial vision, which is a crucial first step toward developing interventions to minimize the visual functional problems the elderly face in everyday life.

DESCRIPTION: The long-term goal of this research is the prevention of unintentional injuries due to vehicle crashes by older drivers, through risk factor identification and the development and evaluation of interventions to minimize risk. The objective of the proposed study is to identify performance limitations which place older drivers at risk for crashes in which the older driver is injured. Special attention will be directed at visual and cognitive (including attentional) performance since these skills are critical for vehicle control, tend to decline with age yet are under certain circumstances reversible, and have been associated with unsafe driving among the elderly in prior research. This objective will be addressed by a multiple cohort follow-up study utilizing polled analysis techniques, on an aggregate sample of 3,839 older drivers brought together through the University of Alabama at Birmingham's Center for Research in Applied Gerontology. Visual, cognitive, and medical data are already being collected on these drivers through other studies and is thus financially underwritten by other projects. A major advantage of the research design is that the high cost of collecting functional data on almost 4,000 older drivers does not have to be covered by this project. In addition, the cost of procuring crash data (including the detailed accident report) is also financially underwritten by five or six cohort sites. Injury information will be collected from medical records from the treatment facility, using state-of-the-art injury coding schemes. The cohorts proposed for study will have up to 9 years of follow-up. An interdiscliplinary research team has been assembled to carry out this study, including researchers expert in vision and cognitive sciences, older driver research, injury epidemiology, medicine, gerontology, and biostatistics. The main hypothesis to be tested is that the visual/cognitive impairments that place older drivers at risk for crashes, also place them at risk for injury. However, crashes that lead to injury may be more strongly related to more severe forms of visual/cognitive impairment, than crashes that do not lead to injury. Older drivers in poor health are more likely to incur crashes than those in good health, where poor health is defined as the existence of co-morbid medical conditions. Data analysis will center around developing predictive models of injurious crashes based on visual and cognitive function and medical conditions.

The Pilot Project Program module of the UAB Roybal Center is designed to foster and facilitate the development and execution and execution of pilot projects which contribute to the overall research mission of the Center. Pilot studies should contribute toward the Center's ultimate goals, namely intervention development and evaluation in order to enhance mobility in the elderly and to minimize or eliminate the adverse consequence of mobility problems. The Pilot Project Program will be administered through the Management Core of the UAB Roybal Center, and will be directed on a day-to-day basis by the Co-Director of the Center (Dr.Cynthia Owsley). Three to four pilot projects will be funded each year. A call for proposal through campus mail, the campus newspaper, and electronic mail. Proposals will be reviewed be relevant experts for scientific merit and programmatic relevance to the Center. A Selection Committee of representatives from the Center's Management Core and individual research projects and chaired by the module director will examine reviews and make recommendations to the Center Director. At least one project per year will be devoted to addressing mobility problems in African American older adults, given the importance of studying under-served populations and also given the demographics of our geographic area. The Pilot Project Program will be systematically evaluated by examining the extent to which each project contributes to the scientific literature generates data useful in the design and funding of future research studies, and leads to the eventual transfer of research findings in the previous five, and with this sound track record, we expect the Pilot Project Program described herein to be critical aspect of the UAB Roybal Center.

behavioral /social science research tag

Older adults rely heavily on the automobile to maintain their mobility, and thus driving is tied to quality of life, personal independence, and self esteem. Cognitive impairment has been identified in prior work as a risk factor for unsafe driving and crash involvement in older adults. While most experts agree that driving is unsafe and therefore unwarranted in the moderate to severe stages of AD, there is a great deal of controversy about whether those with the mild form of this condition should be behind the wheel. Rather than stereotyping older drivers with presumed mild 'AD as having a high crash risk, an increasing number of experts are arguing that the functional evaluation of driving skills is the only fair way to decide for or against licensure in an individual driver, because age or medical diagnosis alone have proven to be unreliable as criteria. In this project, we propose a prospective study to examine the relationship between cognitive impairment and driving performance in older adults with mild Alzheimer's disease (AD) and in age-matched controls who do not have AD. Subjects will be made available to the project through the ADRC Clinical Core. Cognitive abilities will be assessed by a comprehensive battery of tests covering cognitive and other functional domains believed to be important to safe driving. These tests will be carried out by the ADRC Neuropsychology Core, and supplemented by additional tests on the day of driving assessment. Driving performance will be assessed in a driving simulator which provides several measures of driving ability under various task demands. The driving simulator facility is already in place at UAB and is made available as a research resource by the NIA-funded Roybal Center for Research in Applied Gerontology. Any associations found between cognitive impairment and driving simulator performance will be adjusted for potential confounders such as age, vision impairment, and other chronic medical and functional problems known to impact driving ability in older adults. The major goal of this project is determine how cognitive impairment in persons with AD is related to impaired driving performance, so that a functional test battery can be ultimately developed to screen older persons with AD for fitness to drive.

DESCRIPTION (Adapted from Applicant's abstract): A ubiquitous problem of growing old is difficulty seeing at night and under low illumination. Poor vision under reduced light levels in the elderly hinders their performance of daily activities, and has been linked to the occurrence of motor vehicle collisions and falls, which result in injury and elevated mortality risk. Even for those older adults who are free of significant eye disease there can be scotopic dysfunction, suggesting that these impairments are due to a biological aging of the visual system. Optical changes in the aged eye cannot account for the severity of night/low luminance vision problems, suggesting that they have a neural origin. Older adults with early age-related macular degeneration (AMD) exhibit similar night/low luminance vision problems, but theirs are typically more severe. Our long-term goal is to identify the causes of scoptic deficits in older adults and in those with early AMD so that treatment interventions to minimize or reverse these deficits can be developed thus enhancing older adults' quality of life. Studies will focus on retinal mechanisms that may underlie these impairments. The specific aims of this research plan are: (1) to identify mechanisms of scotopic sensitivity impairment and dark adaptation delays in aging and early AMD using flash electroretinography and dark adaptometry; (2) to develop a questionnaire instrument for measuring health-related quality of life that is targeted at nighttime/low luminance vision problems; and (3) to evaluate the impact of vitamin A in reversing or minimizing scotopic sensitivity and delays in dark adaptation and in enhancing vision-targeted health-related quality of life in aging and early AMD.

DESCRIPTION: (Applicant's Abstract) Clinical vision research is a high priority at the University of Alabama at Birmingham (UAB). This priority has been tangibly realized through the establishment of the Clinical Research Unit in the Department of Ophthalmology and the appointment of Cynthia Owsley, PhD, MSPH as its Director. The primary goal of this R21 application is to increase the patient-oriented research capability at UAB in the area of eye disease and vision impairment. This area of research has been a largely untapped, but very promising reservoir of opportunity at UAB for public health scientists. The Clinical Research Unit will provide the research resources and infrastructure to facilitate clinical and epidemiological research projects of the highest quality among participating faculty. These resources will consist of personnel who will provide collaboration and consultation on: (1) biostatistics and study methodology, (2)database design and data acquisition systems, (3) project management, (4) "grantsmanship", such as identifying grants programs relevant to faculty interests, developing ideas into tangible proposals, and constructing budgets, and (5) facilitating faculty training through encouraging enrollment into existing clinical research training programs on the UAB campus and/or through NIH's clinical scientist training program (K-awards). The UAB community represents a unique venue for clinical vision research. First, the clinical vision research faculty at UAB represents all three types of degree professionals in vision: MDs, ODs, and PhDs, who already work collaboratively. This type of professional interaction is not possible at many institutions where only one or two of the three types of professionals are on the faculty, but not all three. Second, NIH and DHHS have called for scientists to meet the challenge of eliminating health disparities in the U.S. population. The focus of most of our faculty research projects will be on subpopulations that have a higher prevalence of eye disease, vision impairment and decrements in health-related quality of life as compared to the general population (e.g., African Americans, older adults, nursing home residents, persons with low vision). Furthermore, UAB has already established many community relations and research infrastructure contacts with these subpopulations that will immediately facilitate our research efforts.

[unreadable] DESCRIPTION (provided by applicant): Sound scientific evidence about the effectiveness of low vision rehabilitation services as provided today in the U.S. remains unavailable despite the high prevalence of visual impairment in this country, the widespread availability of services, and increased public awareness about low vision. Information about the effectiveness of these services is needed in order to: (1) Provide an evidence-base demonstrating the effectiveness of low vision services on vision-targeted health-related quality of life and performance of visual tasks so clients are offered realistic information about potential personal benefits. (2) Provide information about what types or levels of services have effectiveness on vision-targeted health-related quality of life and performance of visual tasks. (3) Provide information that could assist the Center for Medicare and Medicaid Services (CMS) in formulating policy on coverage of these services. The long-term goal of this program of research is to conduct a randomized clinical trial on the effectiveness of low vision rehabilitation services as they are carried out in the U.S. for adult clients who seek them. Before such a randomized clinical trial can be reasonably designed, there are several issues that first must be addressed. This Planning Grant affords us a mechanism by which we can carry out these essential preliminary activities. The specific aims of this planning phase are to answer these questions. (1) What is usual care? How should the low vision rehabilitation services available to adults in the U.S. be characterized? What is the range of services offered? (2) Is a recently developed vision-targeted health related quality of life questionnaire responsive to low vision rehabilitation? (3) What are valid, reliable, and responsive visual performance task measurements that could be used as outcome measures in the clinical trial? (4) Using this information, we will design a multi-center randomized clinical trial for submission to the National Eye Institute, develop a manual of procedures, and design an electronic database. [unreadable] [unreadable] [unreadable]

The Pilot Project Core of the UAB Roybal Center is designed to foster and facilitate the development and execution of pilot projects which will contribute to the overall theme of the Center "Translational Research on Aging and Mobility." Specifically, these projects are will consist of preliminary studies, with the long-range goal of applying the theories, paradigms, and methodology of the behavioral and social sciences to solve the mobility problems of older adults. Pilot projects are expected to lead to the development of more highly developed research projects (e.g., NIH R01s, R03s, K-awards etc., VA Merit awards; private sector support) with the primary aim of obtaining information that can be translated into real solutions for the mobility challenges of the elderly. Pilot projects can assume a variety of formats, such as pilot studies on a preliminary hypothesis, descriptive studies to explore associations between functional impairments and adverse mobility outcomes, and feasibility studies to establish the credibility of a research approach or a methodology. Even though pilot projects represent the earliest steps in developing a research idea, they should be consistent with the Roybal Center's emphasis on research translation from basic research to practical positive outcome for older adults' health and well-being. The Pilot Project Core will be directed by the Co-Director of the Center, Dr. Cynthia Owsley. Two to five pilot projects will be selected for funding each year. A call for applications will be issued through campus mail, the campus newspaper, and electronic mail, and other dissemination outlets. Applications will be reviewed by relevant experts for scientific merit and programmatic relevance to the Center. The Pilot Project Core will be systematically evaluated by examining the extent to which each project contributes to the scientific literature, generates data useful in the design and funding of future research studies, and leads to the eventual transfer of research findings to solving a mobility problem of the elderly.

DESCRIPTION (provided by applicant): Driving of the personal vehicle is the primary and preferred mode of travel for older adults in the US. More than fulfilling the critically important getting around or mobility function, driving in older adults profoundly impacts health status and thus has direct public health relevance. Being a driver has been linked to increased quality of life, reduced likelihood of depression and social isolation, and increased accessibility to healthcare. Therefore policies defining the vision standards for licensure as applied to the elderly population must be rational, i.e., evidence-based. This research is designed to take critical steps toward establishing this evidence-basis by making use of unique opportunities and resources available in Alabama. Alabama is a state with no visual acuity re-screening after initial licensure. Such a situation represents an opportunity to conduct a study would overcome methodological problems of earlier studies purporting to examine the association between visual acuity and crash involvement and the safety benefit of visual acuity re-screening of senior drivers. The distribution of visual acuity values in a study carried out on drivers licensed in Alabama will not be limited to those with good visual acuity, since drivers with visual acuity impairment are not detected and removed from the road by a re-screening law as they would be in most other states. Toward this end, a prospective study on older drivers ages = 70 years will be carried out, where certain visual and cognitive functional screening tests will be administered at baseline, followed by tracking of the samples' crash data for the subsequent three years. This research program is translational in that it involves the translation of basic research findings on what factors elevate the risk of older driver crash involvement to the practical issue of how these known risk factors can guide screening for re-licensure in this population. The practical question to be addressed is what screening tests and cutpoints should motor vehicle licensing offices be using when older drivers present for license renewal in order to optimize older driver safety in the subsequent years? Using the data from this prospective study, we will be able to determine the number of at-fault crashes for the cohort that would have been prevented had various screening criteria for license removal been implemented at baseline. This will allow us to characterize the public safety benefit of the various, alternative screening criteria for licensure of older drivers, information that will be useful to state agencies in designing driver re-screening policies to optimize public safety.

DESCRIPTION (provided by applicant): Age-related maculopathy (ARM) is the leading cause of irreversible vision impairment in older adults in the industrialized world. ARM is a complex, multi-factorial disease in which central retinal photoreceptors are lost, either by an atrophic process, the most common disease express, or by a neovascular event, the most destructive form causing severe vision impairment. Of the 14 million Americans with ARM, the vast majority of these individuals, 12 million, have early disease. At present, physicians have nothing to offer them in terms of proven treatments to arrest the progression of early ARM, nor do they have proven strategies for preventing the disease altogether. Fortunately, recent discoveries have stimulated research toward developing preventative therapies and strategies that arrest early disease progression. An increasing body of evidence suggests that inflammation and lipids (cholesterol) play important roles in pathogenesis. Scientists are already working to translate basic research discoveries in these areas to experimental therapies for ARM prevention, whose efficacy must be demonstrated in clinical trials. The primary outcome measures used in clinical trials on advanced ARM visual acuity and grading of stereo fundus photos are not well suited as primary endpoints in clinical trials on early ARM because they are insensitive to disease progression in the early phases of ARM. Previous research indicates that rod-mediated dark adaptation may be an alternative outcome for consideration, for several reasons. First, rod photoreceptors are vulnerable to degeneration and dysfunction in the earliest phases of ARM. Second, kinetic measures of scotopic function (i.e., those that reflect the recovery of sensitivity over time) are more sensitive than static measures in detecting early ARM. Third, rod- mediated dark adaptation taps into the retinoid cycle, which is likely disrupted in ARM by lesions in the RPE/Bruch's membrane complex which disrupt nutritional transport to rod photoreceptors. A critical question that remains unaddressed is whether rod-mediated dark adaptation impairment precedes the development of early ARM as defined by the gold standard of fundus appearance. This is an important question because if rod- mediated dark adaptation delays precede the clinical signs of the disease, this functional assay would have potential as a diagnostic marker for the disease and/or as an outcome measure in clinical trials and epidemiological studies of early ARM. A prospective study is proposed to address this and related questions.

The Pilot Project Core of the UAB Roybal Center is designed to foster and facilitate the development and execution of pilot projects which will contribute to the overall theme of the Center "Translational Research on Aging and Mobility." Specifically, these projects are will consit of preliminary studies, with the long-range goal of applying the theories, paradigms, and methodology of the behavioral and social sciences to solve the mobility problems of older adults. Pilot projects are expected to lead to the develoment of more highly developed research projects (e.g., NIH ROIs, R03s, K-awards etc., VA Merit awards;private sector support) with the primary aim of obtaining information that can be translated into real solutions for the mobility challenges of the elderiy. Pilot projects can assume a variety of formats, such as pilot studies on a preliminary hypothesis, descriptive studies to explore associations between functional impairments and adverse mobility outcomes, and feasibility studies to establish the credibility of a research approach or a methodology. Even though pilot projects represent the eariiest steps in developing a research idea, they should be consistent with the Roybal Center's emphasis on research translation from basic research to practical positive outcome for older adults'health and well-being. The Pilot Project Core will be directed by the Co-Director of the Center, Dr. Cynthia Owsley. Two to five pilot projects will be selected for funding each year. A call for applications will be issued through campus mail, the campus newspaper, and electronic mail, and other dissemination outlets. Applications will be reviewed by relevant experts for scientific merit and programmatic relevance to the Center. The Pilot Project Core will be systematically evaluate by examining the extent to which each project contributes to the scientific literature, generates data useful in the design and funding of future research studies, and leads to the eventual transfer of research findings to solving a mobility problem of the elderly.

DESCRIPTION (provided by applicant): The focus of our TRC network center is on a high-risk yet underserved segment of the e 40 years old population, namely African Americans residing in Jefferson County, Alabama, many of who are uninsured. Rates of vision impairment and eye disease among African Americans are two times higher than those of older whites, especially glaucoma and diabetic retinopathy. The public health challenge is that if these eye problems had been detected early, much of this disease and vision impairment would be reversible and preventable with currently available ophthalmic treatments. Previous research has suggested that African Americans adults are less likely to receive routine, comprehensive eye care, when newly emerging eye conditions could be detected and treated in a timely fashion. The personal burden of eye disease and vision impairment is heavy. Vision impairment causes difficulties in maintaining a high quality of life and hampers reading, mobility, financial management, and engagement in social activities. Persons with vision impairment are at increased risk for depression, transportation challenges, being unemployed, placement into long-term care, injury, and mortality. As a society, the economic burden of vision impairment is staggering. The annual cost of adult vision problems in the U.S. has been estimated to be about $51.4 billion. Many barriers to care likely underlie the exacerbated vision impairment rates in African Americans, including cost, lack of health insurance, communication, trust, and their having an inadequate understanding of how eye diseases can be prevented. Characteristics of the healthcare system itself undoubtedly contribute, such as a shortage of eye care providers who work in geographic areas with high-risk populations, a shortage of clinics that accept patients who are uninsured, insufficient funds to staff these clinics, and associated challenges in following preferred practice patterns to improving outcomes. We have a unique resource here in Alabama to address these pressing issues, through a partnership between the University of Alabama at Birmingham (UAB) and the Cooper Green Hospital/Jefferson Health System (CGH/JHS). CGH/JHS serves all residents of Jefferson County regardless of their ability to pay. About 80% percent of adult patients seen at the CHS/JHS clinics are African American and about 70% have no health insurance whatsoever. Over 60% have been diagnosed with glaucoma or have diabetes or both. Using the CGH/JHS administrative database and our ability to study individual patients in the clinics, our research center will provide information on how to improve access to and the quality of eye care for this underserved population. Studies will focus on primary open angle glaucoma, diabetic eye care, and visually impaired persons in need of rehabilitation services. Our center will also participate in TRC network-wide studies to be designed collaboratively with the other network centers and CDC.

DESCRIPTION (provided by applicant): The objective of this research is to identify how visual impairment impacts the safety and performance of older drivers. Driving cessation in older adults is tied to many negative health indicators including increased risk for depression, reduced access to healthcare services, and increased likelihood of placement into long-term-care. The societal significance of research on older drivers is dramatically apparent when we recognize that vision impairment is common in the older adult population, and that older drivers have among the highest rates of motor vehicle collisions compared to other age groups. A critical scientific challenge is to identify what aspects of vision are required for safe driving by older adults. Previous research on older driver safety and performance has focused on the study of police accident reports, brief driving evaluations, or driving simulator studies. These techniques have serious scientific limitations; crash studies do not provide information about what lead up to the collision; in on-road studies research personnel are in the vehicle potentially biasing how the driver behaves; simulator studies present artificial, cartoon-like scenarios that over-simplify the roadway environment. All these issues undermine the ability to understand the actual visual factors underlying driver performance and safety. Naturalistic driving methods overcome these limitations by unobtrusively placing multiple sensors and video cameras in the vehicle that record vehicle kinematics, driver behaviors (e.g., gaze behavior), and roadway environment. They allow driving to be studied in an objective way over lengthy time periods (months) in the driver's own vehicle where the driver chooses the route during the course of everyday life. In this research we will use naturalistic driving techniques to examine the relationships between vision and older driver safety and performance. We focus on older drivers with normal vision and those with contrast sensitivity deficits and slowed visual processing speed, since these problems are the strongest and most consistently identified visual risk factors for driving problems in the older adult population. Analyses will focus on the relationship between vision and critical safety events (crashes, near-crashes), lane-keeping, turning at intersections, driving under secondary tasks demands, and when a co-pilot (passenger) is present. These relationships will be examined in light of other driver characteristics, environmental factors, and vehicle factors. Driving performance as measured by naturalistic driving methods will also be compared to driving ratings provided by a driving rehabilitation specialist on a standardized driving route, which is currently the clinical gold standard. This research will stimulate the development of interventions to enhance driving mobility in visually impaired older adults and thus improve quality of life.

Driving is inarguably a highly visual task. A large body of work has found that drivers with visual sensory impairments (e.g. impaired contrast sensitivity, visual field defects) and/or higher order visual- cognitive processing deficits (e.g. slowed visual processing speed, impaired divided attention) are at increased risk for collision involvement as indicated by accident reports obtained from state licensing agencies. Essential to a comprehensive understanding of the role of vision in driver safety is how the driver's visual capacities ? both visual sensory and visual-cognitive skills ? impact vehicle control and behaviors before and during a vehicle crash. While accident reports provide a wealth of information about the circumstances of a crash (e.g., place, weather conditions, vehicles involved), they tell us little to nothing about the visual mechanisms underlying the occurrence of a crash. In this research plan we implement an innovative approach to study vision and driver safety -- using naturalistic driving data, which avoids the methodological pitfalls associated with accident reports. Naturalistic driving data are generated by participants driving their own vehicles in the course of their everyday life for a year or greater. Their vehicles are unobtrusively equipped with sensors and video cameras, which record vehicle kinematics, GPS location, presence of near-by objects, driver behavior, and the roadway environment. Naturalistic data provide an unprecedented level of objective detail on safety critical events such as crashes and near-crashes including pre- and peri-crash information about driver behavior and contextual factors. We propose to use an existing data source, the Strategic Highway Research Program 2 (SHRP2) Naturalistic Driving Study. SHRP2 collected naturalistic driving data on 3,541 drivers aged 16-98 years old containing 35 million vehicle miles of travel. Specific aims in our research plan will examine associations between crash and near-crash involvement and both visual sensory function and visual- cognitive function, adjusted for age, mileage, and other potential confounders. We will further examine how associations between visual function and crash and near-crash events are modified by the driver's involvement in potentially distracting secondary tasks, risk-taking characteristics, age, and situational on- road characteristics. This research plan will contribute to our knowledge of how visual impairment and distracting behaviors while driving contribute to actual on-road safety and motor vehicle collisions. This information will be invaluable in designing interventions and countermeasures to enhance driver safety in the US and worldwide by elucidating modifiable factors that are associated with increased collision risk.

Project Summary Age-related macular degeneration (AMD), the leading cause of irreversible vision impairment in the US and third globally, is a disease of the photoreceptor support system involving the retinal pigment epithelium (RPE), Bruch's membrane, and the choriocapillaris, ultimately leading to photoreceptor demise and eventual vision loss. Our research with that of others has clearly documented the selective vulnerability of rod photoreceptors and rod-mediated (scotopic) vision, including delayed rod-mediated dark adaptation (RMDA) and impaired rod-mediated light sensitivity, in aging and early AMD. RMDA is not only more likely to be slower in eyes with early AMD compared to eyes in normal macular health, but also delayed RMDA is a functional biomarker (i.e., risk factor) for incident early AMD. The next frontier is to establish the structural basis of rod-mediated dysfunction in older adults at-risk for AMD and those already converted to early AMD. Our unifying hypothesis across all aims is: Early AMD is a disease of micronutrient deficiency and vascular insufficiency, due to detectable structural changes in the retinoid re-supply route from the choriocapillaris to the photoreceptors, manifest functionally as delayed rod- mediated dark adaptation. These structural disturbances will occur in specific chorioretinal layers and regions reflecting the spatial distribution of disease in the photoreceptor support system. Our multidisciplinary team has expertise in visual psychophysics, epidemiology, histopathology, digital image analysis and interpretation for retinal disease, study design, and biostatistics. Toward our goals, we will execute the 3 specific aims in an exceptionally well phenotyped cohort at aging-early AMD transition, staged by the AREDS 9-step scale, with 3 years of longitudinal follow-up: (1) To examine the abundance and extent of AMD's pathognomonic deposits (drusen and newly recognized subretinal drusenoid deposits) in relationship to scotopic dysfunction via optical coherence tomography (OCT); (2) To examine RPE cell bodies as structural correlates of scotopic dysfunction via quantitative fundus autofluorescence and layer thicknesses via OCT; (3) To measure vascular density (coverage of macular Bruch's membrane by choriocapillaris), a measure of exchange capacity for outer retinal cells, using OCT angiography. An accurate map and timeline of structure-function relationships in aging and early AMD gained from our research, especially the critical transition from aging to disease, will help define major effects that can be developed into future treatments and preventative measures. Our data will help define new endpoints for clinical trials for drugs to treat early AMD, the absence of which has impeded translational research on this prevalent cause of legal blindness. Endpoints are needed more than ever, because causal treatments targeting lipids in drusen and BrM can be pressed forward, thanks to clinical and pre-clinical proof- of-concept studies.

Project Summary Mild cognitive impairment (MCI) is often viewed as a transitional state leading to Alzheimer's disease. Drivers with MCI have decreased driving performance as well as steeper declines in driving exposure and driving difficulty. While driving is clearly contraindicated as dementia advances, it is critical to examine to what extent safe driving skills can be maintained in MCI. This is because driving cessation is linked to incident depression, reduced physical activity and healthcare access, and greater risk for long term care placement and mortality. Policies and procedures for detecting at-risk older drivers are either non-existent or remain controversial due to a lack of an evidence-basis. Interventions to aid in maintaining driving fitness are lacking. The Applying Programs to Preserve Skills Study (APPS) was previously funded by NIH (R01AG045154) with data collection complete as of October 2019. APPS is a single-masked randomized clinical trial to evaluate processing speed training on on-road driving skills in persons with MCI as evaluated by a certified driving rehabilitation specialist (CDRS) and backseat evaluator. The vehicle for driving performance was instrumented with a data acquisition system which recorded vehicle kinematics and 5-channel video of the roadway environment and driver. The impact of the APPS visual processing speed training intervention on objectively measured driving performance and behaviors was not an aim in the APPS R01, nor was the collection and analysis of this objective driving data included in the APPS budget. We collected this data in anticipation of applying for funding to specifically analyze these complex, valuable data after the APPS study was complete. Vehicle instrumentation to measure objective on-road and behind the wheel events is a major methodological step forward in understanding declining cognitive abilities and driving. Our research plan has the following aims. Aim 1: To examine cross-sectional and longitudinal associations between cognitive function in older drivers with MCI and on-road driving performance (e.g., speed maintenance, steer steadiness, lane control, turning). Aim 2: To examine the impact of a visual processing speed training intervention on driving performance and behaviors (as described in Aim 1) based on vehicle kinematics and driver behaviors among older drivers with MCI. Aim 3: To examine the association between driving performance in older drivers with MCI (as described in Aim 1) and driving performance ratings by a CDRS, currently the clinical gold standard. All aims will consider the roles of potentially confounding factors. This research will identify potentially aberrant driving maneuvers associated with cognitive impairment in MCI, contributing to the eventual development of a clinical tool to identify older drivers at high-risk for unsafe driving.