Resilience and Resistance Phenotypes

Project 1 Summary
Cognitively intact centenarians as extreme outliers are likely to be an informative cohort for
discovering behavioral, environmental, and/or biological mechanisms of resistance and resilience
to AD and related dementias. Aims 1-3 of this RADCO Project 1 titled, The Cognitive Resilience
and Resistance Phenotypes Project, are 3 different approaches to gauging cognitive resilience
amongst a sample of almost 500 centenarian cognitive super agers, 600 offspring with and
without cognitive impairment, and 120 spouse controls without parental longevity. With no
cognitive impairment, particularly at their extreme age, centenarian cognitive superagers are by
definition, cognitively resilient. In the absence of neuropathologic changes associated with AD,
they would be resistant to AD. Project 1 proposes the following 3 specific aims: Specific Aim 1.
Cognitive Function-Neuroimaging Correlation. Gauge cognitive resilience in centenarian
cognitive superagers, assessing discordance between cognitive function measures and structural
and functional MRI correlates of cognitive impairment and AD. Specific Aim 2: Cognitive
Function–Biomarker Risk of AD Correlation. Gauge cognitive resilience in the RADCO sample
by assessing discordance between cognitive function measures and longitudinally assayed
biomarker indices of AD, neurodegeneration and neuroinflammation. Specific Aim 3: Cognitive
Function-Neuropathology Correlation. Gauge cognitive and brain resilience and resistance to
AD and other neuropathologies in brain donors by assessing discordance between cognitive
function measures and neuropathological measures. The conduct of these aims will differentiate
participants according to resilience endophenotypes. These endophenotypes along with
associated biosample resources including plasma and brain tissues will be passed on for use by
Project 2 investigators for the discovery of protective factors and mechanisms associated with
resilience.

Grant Number: 5U19AG073172-05
NIH Institute/Center: NIH
Principal Investigator: SUSAN BOOKHEIMER