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symptoms are lacking. In light of the current evidence suggesting that WMH are associated with compromised PFC function, careful examination of subject inclusion for normal aging studies is necessary in order to dif- ferentiate the potential pathological influence of WMH from true age-related changes.


In summary, we found that disruption of white matter integrity may be one mechanism for PFC dysfunction commonly seen in elderly individuals. Available evidence suggests that WMH are associated with behavioral defi- cits in executive function and may selectively decrease frontal lobe function. Accordingly, our data show that increasing WMH volume was associated with decreased PFC recruitment during episodic and working memory tasks in cognitively normal elderly individuals. This has several important implications for the field of aging. Moreover, WMH are associated with cerebrovascular disease, which is both preventable and amenable to intervention by changes in lifestyle or medications. It is therefore possible that some age-related cognitive decline could be treated or even prevented.


This project was supported by NIH grants P30 AG10129, MH59352, and R01 AG021028 and in part by funding from the NIMH predoctoral National Research Service Award MH-065082 awarded to CWN.

Reprint requests should be sent to Christine Wu Nordahl, University of California-Davis, 2805 50th Street, Sacramento, CA 95817, or via e-mail: crswu@ucdavis.edu.

The data reported in this experiment have been deposited in the fMRI Data Center (www.fmridc.org). The accession number is 2-2005-120FQ.


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