Association of amyloid pathology with memory performance and cognitive complaints in cognitively normal older adults: a monozygotic twin study

Abstract

Amyloid pathology in cognitively normal older adults has been associated with low memory performance and cognitive complaints, but findings are conflicting. Using a monozygotic twin design, we further explored this relation. We investigated 199 cognitively normal older adults (96 twin pairs) and assessed cognitive performance, cognitive complaints, and amyloid pathology on positron emission tomography and in the cerebrospinal fluid (CSF). Participants were on average 70.5 (SD = 7.6) years and 114 (57%) were female. Amyloid–positron emission tomography abnormality on visual read and lower CSF amyloid-β 1-42/1-40 ratio were associated with lower Rey visuospatial memory performance (respectively, β = −0.39 [SE = 0.17], p = 0.02 and β = 0.15 [SE = 0.07], p = 0.04). Twin analyses showed that CSF amyloid-β 1-42/1-40 ratio in one twin of a pair could predict visuospatial memory performance in the cotwin (r = 0.20 [SE = 0.10], p = 0.04). Monozygotic twin discordance analyses further showed a probable effect of disease staging on face-name associative memory performance. Our results suggest amyloid aggregation to be associated with lower visuospatial and face-name–associated memory performance in cognitively normal older adults, supporting the view that amyloid pathology leads to memory dysfunction in very early stages of the disease.