TY - JOUR
T1 - Cognitive gene risk profile for the prediction of cognitive decline in presymptomatic Alzheimer's disease
AU - Porter, Tenielle
AU - Villemagne, Victor L.
AU - Savage, Greg
AU - Milicic, Lidija
AU - Ying Lim, Yen
AU - Maruff, Paul
AU - Masters, Colin L.
AU - Ames, David
AU - Bush, Ashley I.
AU - Martins, Ralph N.
AU - Rainey-Smith, Stephanie
AU - Rowe, Christopher C.
AU - Taddei, Kevin
AU - Groth, David
AU - Verdile, Giuseppe
AU - Burnham, Samantha C.
AU - Laws, Simon M.
AU - The AIBL Research Group
AU - Ward, Larry
AU - Fripp, Jurgen
AU - Fowler, Christopher
AU - Brown, Belinda
AU - Grenfell, Rob
PY - 2018/3
Y1 - 2018/3
N2 - Introduction: In cognitively normal (CN) older adults, high levels of Aβ-amyloid are associated with significant decline in cognition, especially episodic memory. Several genes have previously been associated with cognition, including APOE, KIBRA, KLOTHO, BDNF, COMT, SPON1 and CSMD1. While some of this variation has been attributed to some of these genes individually, the combined effects of these genes on rates of cognitive decline, particularly in preclinical Alzheimer's Disease remain largely unknown. Methods: To elucidate if risk alleles within these genes can be suitably combined to predict cognitive decline 127 CN older adults with elevated PET-ascertained Aβ-amyloid were included in a decision tree analysis to define a “Cognitive Gene Risk Profile” for decline in a verbal episodic memory composite. Results: The episodic memory-derived Cognitive Gene Risk Profile defined four groups: APOE ε4+ Risk, ε4+ Resilient, ε4− Risk, ε4− Resilient, with the ε4+ Risk group declining significantly faster than all other groups (ε4+ Resilient, p = 0.0008; ε4− Risk, p = 0.025; ε4− Resilient, p = 0.0006). The ε4+ Risk group also declined significantly faster than all other groups on Global, Clinical Progression and Pre-Alzheimer's cognitive composites. Discussion: The defined Cognitive Gene Risk Profile has potential utility in participant selection/stratification for preclinical AD trials that incorporate Aβ-amyloid and where decline in cognition is essential to determine therapeutic effectiveness.
AB - Introduction: In cognitively normal (CN) older adults, high levels of Aβ-amyloid are associated with significant decline in cognition, especially episodic memory. Several genes have previously been associated with cognition, including APOE, KIBRA, KLOTHO, BDNF, COMT, SPON1 and CSMD1. While some of this variation has been attributed to some of these genes individually, the combined effects of these genes on rates of cognitive decline, particularly in preclinical Alzheimer's Disease remain largely unknown. Methods: To elucidate if risk alleles within these genes can be suitably combined to predict cognitive decline 127 CN older adults with elevated PET-ascertained Aβ-amyloid were included in a decision tree analysis to define a “Cognitive Gene Risk Profile” for decline in a verbal episodic memory composite. Results: The episodic memory-derived Cognitive Gene Risk Profile defined four groups: APOE ε4+ Risk, ε4+ Resilient, ε4− Risk, ε4− Resilient, with the ε4+ Risk group declining significantly faster than all other groups (ε4+ Resilient, p = 0.0008; ε4− Risk, p = 0.025; ε4− Resilient, p = 0.0006). The ε4+ Risk group also declined significantly faster than all other groups on Global, Clinical Progression and Pre-Alzheimer's cognitive composites. Discussion: The defined Cognitive Gene Risk Profile has potential utility in participant selection/stratification for preclinical AD trials that incorporate Aβ-amyloid and where decline in cognition is essential to determine therapeutic effectiveness.
KW - genetic risk profiles
KW - cognitive decline
KW - alzheimer's disease
KW - episodic memory
KW - Aβ-amyloid
UR - http://www.scopus.com/inward/record.url?scp=85065204448&partnerID=8YFLogxK
U2 - 10.1016/j.pmip.2018.03.001
DO - 10.1016/j.pmip.2018.03.001
M3 - Article
AN - SCOPUS:85065204448
SN - 2468-1717
VL - 7-8
SP - 14
EP - 20
JO - Personalized Medicine in Psychiatry
JF - Personalized Medicine in Psychiatry
ER -