The objective of this application is to determine how cognitive deficits in patients with age-related macular degeneration (AMD) are related to differences in functional connectivity and white matter integrity in the brain. AMD affects nearly 30% of Americans over age 75 and is associated with a two-fold increased risk of dementia. This team's previous NIH-funded work identified a strikingly prevalent cognitive deficit, even in non- demented AMD patients: poor verbal fluency. Yet there is a fundamental knowledge gap regarding the etiology of the link between AMD and cognitive deficits, and this gap impedes the development of strategies to reduce cognitive impairment in AMD. Our central hypothesis is that brain connectivity plays a critical role in understanding the link between AMD and cognitive deficits (e.g., verbal fluency). Specifically, the link may arise via two mechanisms: #1) vision changes from macular disease could have a negative effect on cognitive performance, or #2) a shared risk factor could promote damage in the brain and eye concurrently. These two mechanisms, which may both be at play, should be distinguished by different patterns of brain connectivity associated with AMD-related cognitive deficits. This will be the first study to combine longitudinal neurocognitive testing and brain imaging to better understand the extent and locus of brain changes in AMD. The study will include 120 people with AMD plus 120 age-, gender-, and education-matched adults without AMD. All participants will receive baseline and 2-year neurocognitive tests and a subset will provide structural and "resting state" functional magnetic resonance images (MRIs) at each time point.
Aim 1 uses a neurocognitive battery developed and piloted by the applicants to define AMD-related differences in cognition without using tasks that require vision.
Aims 2 &3 use measures of functional brain connectivity and region- specific white matter integrity derived from functional MRI (fMRI) and diffusion tensor imaging (DTI).
Aim 1. Characterize cognitive processes that contribute to verbal fluency deficit in AMD. We will construct regression models to test the extent to which verbal fluency performance in AMD reflects underlying cognitive deficits in semantic organization, processing speed, attention-switching, and memory.
Aim 2. Identify differences in brain connectivity associated with verbal fluency, or its cognitive contributors. We will relate measures of cognitive ability to measures of intrinsic functional and structural connectivity in the brain. We will examie whether "brain signatures" associated with cognitive deficits differ among older adults with and without AMD.
Aim 3. Identify cognitive profiles and brain signatures associated with cognitive decline in AMD patients. We will determine whether certain cognitive patterns or differences in specific neural networks, or both, predict AMD-related cognitive decline. Our working hypothesis is based on results of our pilot imaging study and favors mechanism #1: Verbal fluency deficit in AMD reflects problems in semantic organization and is related to differences in white matter tracts (primarily ventral) that support language, semantics, and vision.
People with age-related macular degeneration are more likely to develop dementia, which leads to worse disability and greater healthcare utilization. This research will yield new knowledge about the reasons for cognitive problems in patients with age-related macular degeneration and is a necessary step toward developing early detection plans, treatments, and solutions. As such, this study is relevant to the NIH's mission to reduce the burdens of human illness and disability.
|Whitson, Heather E; Duan-Porter, Wei; Schmader, Kenneth E et al. (2016) Physical Resilience in Older Adults: Systematic Review and Development of an Emerging Construct. J Gerontol A Biol Sci Med Sci 71:489-95|
|Zullig, Leah L; Whitson, Heather E; Hastings, Susan N et al. (2016) A Systematic Review of Conceptual Frameworks of Medical Complexity and New Model Development. J Gen Intern Med 31:329-37|
|Potter, Guy G; McQuoid, Douglas R; Whitson, Heather E et al. (2016) Physical frailty in late-life depression is associated with deficits in speed-dependent executive functions. Int J Geriatr Psychiatry 31:466-74|
|Liu, Phillip L; Cohen, Harvey Jay; Fillenbaum, Gerda G et al. (2016) Association of Co-Existing Impairments in Cognition and Self-Rated Vision and Hearing With Health Outcomes in Older Adults. Gerontol Geriatr Med 2:|
|Whitson, Heather E; Johnson, Kimberly S; Sloane, Richard et al. (2016) Identifying Patterns of Multimorbidity in Older Americans: Application of Latent Class Analysis. J Am Geriatr Soc 64:1668-73|
|Chen, Sunny; Whitson, Heather; QuiÃ±ones, Ana et al. (2016) Comparative health and self-rated health are equivalently associated with health indicators among older adults. J Clin Epidemiol 70:279-80|
|Berger, Miles; Nadler, Jacob W; Browndyke, Jeffrey et al. (2015) Postoperative Cognitive Dysfunction: Minding the Gaps in Our Knowledge of a Common Postoperative Complication in the Elderly. Anesthesiol Clin 33:517-50|
|Whitson, Heather E; Chou, Ying-Hui; Potter, Guy G et al. (2015) Phonemic fluency and brain connectivity in age-related macular degeneration: a pilot study. Brain Connect 5:126-35|
|Genao, Liza; Durheim, Michael T; Mi, Xiaojuan et al. (2015) Early and Long-term Outcomes of Older Adults after Acute Care Encounters for Chronic Obstructive Pulmonary Disease Exacerbation. Ann Am Thorac Soc 12:1805-12|
|Thielke, Stephen M; Diehr, Paula H; Yee, Laura M et al. (2015) Sex, Race, and Age Differences in Observed Years of Life, Healthy Life, and Able Life among Older Adults in The Cardiovascular Health Study. J Pers Med 5:440-51|
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