TY - JOUR
T1 - Aβ-related memory decline in APOE ϵ4 noncarriers
T2 - Implications for Alzheimer disease
AU - Lim, Yen Ying
AU - Laws, Simon M.
AU - Villemagne, Victor L.
AU - Pietrzak, Robert H.
AU - Porter, Tenielle
AU - Ames, David
AU - Fowler, Christopher
AU - Rainey-Smith, Stephanie
AU - Snyder, Peter J.
AU - Martins, Ralph N.
AU - Salvado, Olivier
AU - Bourgeat, Pierrick
AU - Rowe, Christopher C.
AU - Masters, Colin L.
AU - Maruff, Paul
PY - 2016/4/26
Y1 - 2016/4/26
N2 - Objective: As the absence of Aβ-related memory decline in APOE ϵ4 noncarriers may be due to the relative brevity of previous studies, we aimed to characterize Aβ-related cognitive decline over 72 months in APOE ϵ4 carriers and noncarriers who were cognitively normal (CN). Methods: CN older adults (n 423) underwent Aβ imaging and APOE genotyping. Participants completed comprehensive neuropsychological testing at baseline 18-, 36-, 54-, and 72-month assessments. Results: Relative to Aβ- CN ϵ4 noncarriers, both Aβ+ CN ϵ4 carriers and noncarriers showed significantly increased decline in measures of memory, language, and executive function as well as higher rates of progression to a clinical classification of mild cognitive impairment. Memory decline was greater in Aβ+ CN ϵ4 carriers than in Aβ+ CN ϵ4 noncarriers. No cognitive decline was evident in Aβ- CN ϵ4 carriers. Conclusions: In CN older adults, Aβ+ is associated with memory decline in ϵ4 noncarriers; however, the rate of this decline is much slower than that observed in ϵ4 carriers. These data indicate that the processes by which ϵ4 carriage increases the rate of Aβ-related cognitive decline occur in the preclinical stage of Alzheimer disease.
AB - Objective: As the absence of Aβ-related memory decline in APOE ϵ4 noncarriers may be due to the relative brevity of previous studies, we aimed to characterize Aβ-related cognitive decline over 72 months in APOE ϵ4 carriers and noncarriers who were cognitively normal (CN). Methods: CN older adults (n 423) underwent Aβ imaging and APOE genotyping. Participants completed comprehensive neuropsychological testing at baseline 18-, 36-, 54-, and 72-month assessments. Results: Relative to Aβ- CN ϵ4 noncarriers, both Aβ+ CN ϵ4 carriers and noncarriers showed significantly increased decline in measures of memory, language, and executive function as well as higher rates of progression to a clinical classification of mild cognitive impairment. Memory decline was greater in Aβ+ CN ϵ4 carriers than in Aβ+ CN ϵ4 noncarriers. No cognitive decline was evident in Aβ- CN ϵ4 carriers. Conclusions: In CN older adults, Aβ+ is associated with memory decline in ϵ4 noncarriers; however, the rate of this decline is much slower than that observed in ϵ4 carriers. These data indicate that the processes by which ϵ4 carriage increases the rate of Aβ-related cognitive decline occur in the preclinical stage of Alzheimer disease.
UR - http://www.scopus.com/inward/record.url?scp=84964861819&partnerID=8YFLogxK
U2 - 10.1212/WNL.0000000000002604
DO - 10.1212/WNL.0000000000002604
M3 - Article
C2 - 27029632
AN - SCOPUS:84964861819
SN - 0028-3878
VL - 86
SP - 1635
EP - 1642
JO - Neurology
JF - Neurology
IS - 17
ER -