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. Author manuscript; available in PMC: 2014 Mar 15.
Published in final edited form as: Annu Rev Clin Psychol. 2013 Jan 7;9:621–648. doi: 10.1146/annurev-clinpsy-050212-185535

Figure 6.

Figure 6

Modulation of biomarker curves by genetics [apolipoprotein E (APOE) genotype] and cognitive reserve. Factors such as genetic variations and cognitive reserve may shift the hypothetical biomarker curves relative to age and disease stage. Genetic variation in the APOE gene may shift the amyloid-beta (Aβ) and neurodegeneration curves, with (a) individuals positive for APOE ε4 showing a leftward shift (pathology occurring at an earlier age) and/or (b) individuals negative for APOE ε4 showing a rightward shift (pathology occurring at a later age). (c) Other cognitive and/or health and lifestyle factors may also shift these hypothetical curves, particularly the curve representing changes in cognition. Those with low cognitive reserve and/or with a high number of medical comorbidities (C−) may show a leftward shift of the cognition curve, whereas those with high cognitive reserve and/or few medical comorbidities (C*) may show a rightward shift, relative to the initially hypothesized cognition curve (Co). Reprinted from The Lancet Neurology, Volume 9(1), Jack CR Jr et al., Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade, 119–28, copyright 2010, with permission from Elsevier. MRI, magnetic resonance imaging.