Researchers searching for better ways to assess the early progression towards clinical Alzheimer’s disease have established what looks like a decent way to measure loss of learning capability, a decline that occurs well before loss of memory function. This sort of approach compares poorly with a hypothetical blood biomarker or other non-invasive, low-cost assay, but while there are a few promising inroads towards the development of such a test, none have yet emerged into clinical practice.

As amyloid-β (Aβ) accumulates in a person’s brain during the long preclinical stage of Alzheimer’s disease, deficits in learning emerge prior to impairments in episodic memory, according to a new study. Cognitively normal people who tested positive for brain amyloid learned fewer Chinese characters over a six-day period than their amyloid-negative peers. Their learning deficit was more pronounced than any form of memory impairment, and it correlated with smaller hippocampi.

In public parlance, memory loss has become almost synonymous with AD. Alas, during the disease’s preclinical stage-which scientists are trying to target for intervention – memory loss creeps up slowly and varies from person to person. Hence trials enrolling people at those stages struggle to assess clinical efficacy of the drug under investigation. New tests are sorely needed.

The new study tested 80 cognitively normal participants – 42 amyloid-negative, 38 amyloid-positive – and included other cognitive and neuroimaging measures. As had been seen in the previous cohort, amyloid-negative participants learned the meaning of Chinese characters faster, with accuracy differences between the groups emerging on day one and growing in each session. The two groups’ average rate of learning over the entire six days differed by more than two standard deviations. In contrast, the groups barely differed on their most recent scores on any test of episodic memory. Among Aβ-positive participants only, those who learned the Chinese characters more slowly had smaller hippocampi and larger brain ventricles, suggesting less gray-matter volume.