Increased functional brain response during word retrieval in cognitively intact older adults at genetic risk for Alzheimer's disease

Recent language studies in aging and dementia provide two complementary lines of evidence that: (1) measures of semantic knowledge and word-finding ability show declines comparable to those of episodic memory, and greater impairment than executive function measures, during the prodromal period of Alzheimer's disease and (2) cognitively intact older adult carriers of the apolipoprotein E (APOE) ε4 allele also demonstrate poorer object naming than their low-risk peers. Given that possible changes in the neural substrates of word retrieval (e.g., Broca's area and fusiform gyrus) in at-risk adults may signal impending cognitive decline and serve as a prodromal marker of AD, we examined whether APOE ε4 carriers exhibit changes in brain response in regions subserving word retrieval and semantic knowledge. Eleven cognitively intact APOE ε4 older adults and 11 age, education, and family history of AD-matched APOE ε3 adults named aloud photographs of animals, tools, and vehicles during event-related fMRI. Results showed that, in the face of equivalent naming accuracy, APOE ε4 adults demonstrated more widespread brain response with greater signal change in the left fusiform gyrus, bilateral medial prefrontal cortex, and right perisylvian cortex. Findings are discussed in the context of possible compensatory mechanisms invoked to maintain performance in those at genetic risk for AD.