Asymptomatic Alzheimer disease: Defining resilience.

Hohman TJ, McLaren DG, Mormino EC, Gifford KA, Libon DJ, Jefferson AL, Alzheimer's Disease Neuroimaging Initiative
Neurology. 2016 87 (23): 2443-2450

PMID: 27815399 · PMCID: PMC5177674 · DOI:10.1212/WNL.0000000000003397

OBJECTIVE - To define robust resilience metrics by leveraging CSF biomarkers of Alzheimer disease (AD) pathology within a latent variable framework and to demonstrate the ability of such metrics to predict slower rates of cognitive decline and protection against diagnostic conversion.

METHODS - Participants with normal cognition (n = 297) and mild cognitive impairment (n = 432) were drawn from the Alzheimer's Disease Neuroimaging Initiative. Resilience metrics were defined at baseline by examining the residuals when regressing brain aging outcomes (hippocampal volume and cognition) on CSF biomarkers. A positive residual reflected better outcomes than expected for a given level of pathology (high resilience). Residuals were integrated into a latent variable model of resilience and validated by testing their ability to independently predict diagnostic conversion, cognitive decline, and the rate of ventricular dilation.

RESULTS - Latent variables of resilience predicted a decreased risk of conversion (hazard ratio < 0.54, p < 0.0001), slower cognitive decline (β > 0.02, p < 0.001), and slower rates of ventricular dilation (β < -4.7, p < 2 × 10). These results were significant even when analyses were restricted to clinically normal individuals. Furthermore, resilience metrics interacted with biomarker status such that biomarker-positive individuals with low resilience showed the greatest risk of subsequent decline.

CONCLUSIONS - Robust phenotypes of resilience calculated by leveraging AD biomarkers and baseline brain aging outcomes provide insight into which individuals are at greatest risk of short-term decline. Such comprehensive definitions of resilience are needed to further our understanding of the mechanisms that protect individuals from the clinical manifestation of AD dementia, especially among biomarker-positive individuals.

© 2016 American Academy of Neurology.

MeSH Terms (19)

Aged Alzheimer Disease Apolipoprotein E4 Biomarkers Cognitive Aging Cognitive Dysfunction Databases, Factual Disease Progression Disease Resistance Female Hippocampus Humans Least-Squares Analysis Male Memory Neuroprotection Neuropsychological Tests Organ Size Prognosis

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