Memory complaints are widespread among the elderly and aging is a major risk factor for Alzheimer's disease (AD), leading to the impression that a gradual loss of memory ability, eventually culminating in dementia, may be a nearly universal consequence of getting old. Our studies explore an alternative aging trajectory by studying 80+ year olds, who have episodic memory performance that appears to have escaped age-related decline and that remains in the range that is at least normal for 50-60 year-olds and we have labelled `SuperAgers'. We enrolled a dedicated and unique cohort of SuperAgers and Controls committed to longitudinal assessment and brain donation at death. Our initial studies identified domain-specific biologic, psychosocial, and genetic features of the SuperAgers, including maintenance of cortical integrity (especially in the anterior cingulate), an abundance of anterior cingulate Von Economo neurons and sparse cortical Alzheimer pathology compared to their cognitively average peers. These features may contribute in part to maintenance of superior memory performance past the 8th decade of life. This Project plans to extend the characterization of the SuperAging phenotype through hypothesis-driven novel evaluations of functional brain network connectivity, regional distribution of gene expression, and integrity of dendritic, synaptic and axonal markers. The proposed project will allow us to expand our unique group of SuperAgers and cognitively average peers and address important questions related to the neurobiology of resilience and cognitive reserve. By identifying neurobiologic features that contribute to superior memory performance in old age, outcomes from this project will help isolate factors that promote successful cognitive aging and perhaps also prevent age- related brain diseases such as AD. The project's reliance on a cohort that has already been partially recruited, its longitudinal design, multidisciplinary structure, and collaboration-friendly organization increases the likelihood that consequential progress will be achieved.

Public Health Relevance

The proposed research will characterize, in an interdisciplinary and longitudinal manner, a cohort of 80+ year- olds who display exceptionally successful cognitive aging and whom we have termed SuperAgers. This proposal will explore the mechanisms of the unique biologic and genetic features associated with SuperAging. The identification of these factors may make it possible to help elderly maintain cognitive strengths and prevent Alzheimer's disease.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG067781-02
Application #
10150793
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Wagster, Molly V
Project Start
2020-05-01
Project End
2025-01-31
Budget Start
2021-02-01
Budget End
2022-01-31
Support Year
2
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Neurology
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611