Episodic and semantic memory tasks activate different brain regions in Alzheimer disease

Objective: To compare brain activity identified by fMRI in subjects with Alzheimer disease ( AD) and older healthy controls (HCs) performing an episodic/working memory (EWM) and semantic memory (SM) task. Methods: Nine AD (mean age 73.6) and 10 HC (mean age 71.8) subjects underwent an fMRI memory paradigm. Tasks comprised 1) baseline ( recognizing a single digit presented for 1 second), 2) SM ( addition of two single digits, always producing a single digit answer), and 3) EWM ( recall of the previous single digit on the stimulus of the next digit). Each condition was presented in 2-minute blocks with a shorter and longer time interval for the first and second minute within blocks. Results: Comparing AD and HC subjects, there were no activated brain regions in common for EWM > SM, but left anterior cingulate ( Brodmann area [ BA] 24, 0, 31, 4) and left medial frontal lobe gyrus ( BA 25, -6, 23, -15) were activated by both groups for SM > EWM. Key differences were that for EWM > SM, HC subjects activated the right parahippocampal gyrus, whereas subjects with AD activated the right superior frontal gyrus and left uncus. Conclusions: Subjects with Alzheimer disease ( AD) recruited brain regions for easier episodic/working memory ( EWM) tasks used by healthy controls ( HCs) for more difficult EWM tasks. AD subjects recruited brain regions for semantic memory tasks used by HCs for more difficult EWM tasks. The authors propose a functional memory reserve model of compensatory recruitment according to task difficulty and underlying neuropathology.