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

From the Geriatric Medicine Unit (Drs. Starr and Abousleiman), University of Edinburgh, Divisions of Informatics (Dr. Goddard, B. Loeffler) and Clinical Neuroscience (Dr. Wardlaw), and Departments of Psychiatry (Dr. Simonotto) and Medical Physics (Dr. Marshall), University of Edinburgh, UK.

Address correspondence and reprint requests to Dr Starr, Royal Victoria Hospital, Craigleith Road, Edinburgh, UK EH4 2DN; e-mail: John.Starr{at}ed.ac.uk

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.

Supported by a grant from the Scottish Higher Education Funding Council. The SHEFC Brain Imaging Research Centre for Scotland (Division of Clinical Neurosciences, Edinburgh, UK) was established with a Joint Research Equipment Initiative Grant from the Scottish Higher Education Funding Council and Medical Research Council (www.dcn.ed.ac.uk/bic).

Received May 1, 2004. Accepted in final form April 7, 2005.

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