Building memories on prior knowledge: behavioral and fMRI evidence of impairment in early Alzheimer’s disease

Impaired memory is a hallmark of prodromal Alzheimer’s Disease (AD). Prior knowledge associated with the memoranda has proved to have a powerful effect on memory in healthy subjects. Yet, barely nothing is known about its effect in early AD. We used functional MRI to ask whether prior knowledge enhanced memory encoding in early AD and whether the nature of prior knowledge mattered. Early AD patients and healthy controls underwent a task-based fMRI experiment, being scanned while learning face-scene associations. Famous faces carried Pre-Experimental Knowledge (PEK) while unknown faces repeatedly familiarized prior to learning carried Experimental Knowledge (EK). As expected, PEK increased subsequent memory in healthy elderly. However, patients did not benefit from PEK. Partly non-overlapping brain networks supported PEK vs. EK encoding in healthy controls. Patients displayed impaired activation in a right subhippocampal region where activity predicted successful associative memory formation of PEK stimuli. These findings call for a thorough consideration of how prior knowledge impacts learning and suggest a possible underestimation of the extent of associative memory impairment in early AD.HighlightsLearning is impaired in prodromal AD, but we currently ignore whether prior knowledge available at encoding promotes learning in AD as it does in healthy controls.Patients with AD failed to benefit from pre-experimental prior knowledge (famous faces) by comparison with experimental knowledge (unknown but familiarized faces).fMRI responses at study revealed distinct networks underlying associative encoding for both pre-experimental and experimental knowledge.A subsequent memory effect found in control subjects for associations carrying pre-experimental knowledge in the right subhippocampal structures, including the perirhinal cortex, was absent in patients.Pre-experimental knowledge-based associative encoding relies on brain regions specifically targeted by early tau pathology.Using unfamiliar materials to probe memory in early AD might underestimate learning impairment.