Progressive loss of independence in neuronal representations predicts cognitive decline

Intelligent behavior depends on the brain's ability to represent multiple features of the environment simultaneously while keeping those representations independent^1,2. Patients with Alzheimer's disease often mix up objects, people, and events^3-7, raising the possibility that disease mixes up the way that information is represented in the brain. Here we show that the independence of visual representations progressively breaks down during early stages of disease progression in a rhesus macaque model of Alzheimer's disease and related dementias^8-10. In visual area V4, representations of different visual features become progressively less independent, such that the representation of one feature is increasingly influenced by the value of another. We term this loss of independence neuronal feature confusion. This neuronal change predicts a specific behavioral consequence: because feature representations become less independent, preferences associated with one visual feature increasingly influence visually guided choices associated with other, independent features. Using an analogous image-selection task, we found the same behavioral signature in people with mild cognitive impairment, distinguishing them from age-matched controls. These results identify a specific and measurable alteration in neuronal population representations that predicts a behavioral change observed across species. More broadly, these findings demonstrate that neuronal population representations can guide the development of sensitive, non-invasive behavioral methods for early detection of functional changes associated with Alzheimer's disease.