Abstract
Background
Paired associative learning (PAL) is highly sensitive to disruption to brain areas that subserve memory in the early stages of Alzheimer's disease (AD). This is characterised by reduction in learning from repeated exposure to stimulus pairs. PAL requires that a set of associations be learned over several trials, where the objective is to increase accuracy. In cognitively normal (CN) older adults, high beta-amyloid (Aβ+) levels indicates the onset of preclinical AD. While these individuals show no cognitive impairment at baseline, they show cognitive decline, hippocampal volume loss, and progression to prodromal AD when followed over 12+ months. We administered a demanding experimental PAL repeatedly over 6 days, to determine Aβ+ related cognitive dysfunction in CN adults.
Methods
CN older adults (n = 44; aged 65-85) underwent PET neuroimaging to determine Aβ levels (Aβ+ = 16, Aβ- = 28) and hippocampal volume, as well as neuropsychological assessment of verbal memory (California Verbal Learning Test, 2nd Edition; CVLT-II) and general cognition (Mini Mental State Examination; MMSE). Participants also completed an online repeated cognitive assessment (ORCA; orcabattery.org.au) task that required participants implicitly learn 50 audio-visual associations (spoken English paired with written Chinese). Participants completed two 10-minute sessions per day for six consecutive days.
Results
Aβ- and Aβ+ individuals did not differ on other measures of cognitive function, or hippocampal volume. A significant interaction between group x day was found, F(5,210) = 3.74, p <.001. A quadratic trend was significant for both groups (both p’s <.01). Figure 1 shows group performance over 6 days. Aβ- individuals performed significantly better than Aβ+ individuals from day 2 onwards. The magnitude of the difference between groups at day 1 was moderate (Cohen's d = 0.31), increasing to large by day 3 (Cohen's d = 0.78), and very large by day 6 (Cohen's d = 1.24).
Conclusions
Results indicate that in CN adults, Aβ+ is associated with impairments in learning novel information over days. These results suggest that Aβ+ related cognitive dysfunction can be detected much earlier than 12 months, when using a demanding cognitive task designed to measure the ability to acquire novel information.