Very mild Alzheimer׳s disease is characterized by increased sensitivity to mnemonic interference

Early pathology and tissue loss in Alzheimer׳s disease (AD) occurs in the hippocampus, a brain region that has recently been implicated in relational processing irrespective of delay. Thus, tasks that involve relational processing will especially tax the hippocampal memory system, and should be sensitive to even mild dysfunction typical of early AD. Here we used a short-lag, short-delay memory task previously shown to be sensitive to hippocampal integrity in an effort to discriminate cognitive changes due to healthy aging from those associated with very mild AD. Young adults, healthy older adults, and individuals with very mild AD (N=30 for each group) participated in our investigation, which entailed attempting to find an exact match to a previously presented target among a series of stimuli that varied in perceptual similarity to the target stimulus. Older adults with very mild AD were less accurate than healthy older adults, who, in turn, were impaired relative to young adults. Older adults with very mild AD were also particularly susceptible to interference from intervening lure stimuli. A measure based on this finding was able to explain additional variance in differentiating those in the very mild stage of AD from healthy older adults after accounting for episodic memory and global cognition composite scores in logistic regression models. Our findings suggest that cognitive changes in early stage AD reflect aging along with an additional factor potentially centered on sensitivity to interference, thereby supporting multifactorial models of aging.