TY - JOUR
T1 - Amyloid-related memory decline in preclinical Alzheimer's disease is dependent on APOE ε4 and is detectable over 18-months
AU - Thai, Christine
AU - Lim, Yen Ying
AU - Villemagne, Victor L.
AU - Laws, Simon M.
AU - Ames, David
AU - Ellis, Kathryn A.
AU - Rainey-Smith, Stephanie R.
AU - Martins, Ralph N.
AU - Masters, Colin L.
AU - Rowe, Christopher C.
AU - Maruff, Paul
AU - Chambers, Brian
AU - Chiu, Edmond
AU - Clarnette, Roger
AU - Darby, David
AU - Davison, Mary
AU - Drago, John
AU - Drysdale, Peter
AU - Gilbert, Jacqueline
AU - Lim, Kwang
AU - Lautenschlager, Nicola
AU - LoGiudice, Dina
AU - McCardle, Peter
AU - McFarlane, Steve
AU - Mander, Alastair
AU - Merory, John
AU - O'Connor, Daniel
AU - Scholes, Ron
AU - Samuel, Mathew
AU - Trivedi, Darshan
AU - Woodward, Michael
AU - The AIBL Research Group
N1 - Copyright the Author(s) 2015. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.
PY - 2015/10/2
Y1 - 2015/10/2
N2 - High levels of β-amyloid (Aβ) in the brain and carriage of the APOE ε4 allele have each been linked to cognitive impairment in cognitively normal (CN) older adults. However, the relationship between these two biomarkers and cognitive decline is unclear. The aim of this study was to investigate the relationship between cerebral Aβ level, APOE ε4 carrier status, and cognitive decline over 18 months, in 317 cognitively healthy (CN) older adults (47.6% males, 52.4%females) aged between 60 and 89 years (Mean = 69.9, SD = 6.8). Cognition was assessed using the Cogstate Brief Battery (CBB) and the California Verbal Learning Test, Second Edition (CVLT-II). Planned comparisons indicated that CN older adults with high Aβ who were also APOE ε4 carriers demonstrated the most pronounced decline in learning and working memory. In CN older adults who were APOE ε4 non-carriers, high Aβ was unrelated to cognitive decline in learning and working memory. Carriage of APOE ε4 in CN older adults with low Aβ was associated with a significantly increased rate of decline in learning and unexpectedly, improved cognitive performance on measures of verbal episodic memory over 18 months. These results suggest that Aβ and APOE ε4 interact to increase the rate of cognitive decline in CN older adults and provide further support for the use of Aβ and APOE ε4 as biomarkers of early Alzheimer's disease.
AB - High levels of β-amyloid (Aβ) in the brain and carriage of the APOE ε4 allele have each been linked to cognitive impairment in cognitively normal (CN) older adults. However, the relationship between these two biomarkers and cognitive decline is unclear. The aim of this study was to investigate the relationship between cerebral Aβ level, APOE ε4 carrier status, and cognitive decline over 18 months, in 317 cognitively healthy (CN) older adults (47.6% males, 52.4%females) aged between 60 and 89 years (Mean = 69.9, SD = 6.8). Cognition was assessed using the Cogstate Brief Battery (CBB) and the California Verbal Learning Test, Second Edition (CVLT-II). Planned comparisons indicated that CN older adults with high Aβ who were also APOE ε4 carriers demonstrated the most pronounced decline in learning and working memory. In CN older adults who were APOE ε4 non-carriers, high Aβ was unrelated to cognitive decline in learning and working memory. Carriage of APOE ε4 in CN older adults with low Aβ was associated with a significantly increased rate of decline in learning and unexpectedly, improved cognitive performance on measures of verbal episodic memory over 18 months. These results suggest that Aβ and APOE ε4 interact to increase the rate of cognitive decline in CN older adults and provide further support for the use of Aβ and APOE ε4 as biomarkers of early Alzheimer's disease.
UR - http://www.scopus.com/inward/record.url?scp=84947270775&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0139082
DO - 10.1371/journal.pone.0139082
M3 - Article
C2 - 26430784
AN - SCOPUS:84947270775
SN - 1932-6203
VL - 10
SP - 1
EP - 10
JO - PLoS ONE
JF - PLoS ONE
IS - 10
M1 - e0139082
ER -