Performance on complex memory tests is associated with β-amyloid in individuals at risk of developing Alzheimer's disease

Abstract

The pathophysiological development of Alzheimer's disease (AD) begins in the brain years before the onset of clinical symptoms. The accumulation of beta-amyloid (Aβ) is thought to be the first cortical pathology to occur. Carrying one apolipoprotein E (APOE) ε4 allele increases the risk of developing AD at least 2-3 times and is associated with earlier Aβ accumulation. Although it is difficult to identify Aβ-related cognitive impairment in early AD with standard cognitive tests, more sensitive memory tests may be able to do this. We sought to examine associations between Aβ and performance on three tests within three subdomains of memory, verbal, visual, and associative memory, to elucidate which of these tests were sensitive to Aβ-related cognitive impairment in at-risk subjects. 55 APOE ε4 carriers underwent MRI, ¹¹ C-Pittsburgh Compound B (PiB) PET, and cognitive testing. A composite cortical PiB SUVR cut-off score of 1.5 was used to categorise subjects as either APOE ε4 Aβ+ or APOE ε4 Aβ-. Correlations were carried out using cortical surface analysis. In the whole APOE ε4 group, we found significant correlations between Aβ load and performance on verbal, visual, and associative memory tests in widespread cortical areas, the strongest association being with performance on associative memory tests. In the APOE ε4 Aβ+ group, we found significant correlations between Aβ load and performance of verbal and associative, but not visual, memory in localised cortical areas. Performance on verbal and associative memory tests provides sensitive markers of early Aβ-related cognitive impairment in at-risk subjects.

Keywords: APOE4; amyloid imaging; memory; neuropsychological testing; preclinical Alzheimer's disease.