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: email@example.com.
The data reported in this experiment have been deposited in the fMRI Data Center (www.fmridc.org). The accession number is 2-2005-120FQ.
Breteler, M. M., van Amerongen, N. M., van Swieten, J. C., Claus, J. J., Grobbee, D. E., van Gijn, J., Hofman, A., & van Harskamp, F. (1994). Cognitive correlates of ventricular enlargement and cerebral white matter lesions on magnetic resonance imaging. The Rotterdam Study. Stroke, 25, 1109–1115. Breteler, M. M., van Swieten, J. C., Bots, M. L., Grobbee, D. E., Claus, J. J., van den Hout, J. H., van Harskamp, F., Tanghe, H. L., de Jong, P. T., & van Gijn, J. (1994). Cerebral white matter lesions, vascular risk factors, and cognitive function in a population-based study: The Rotterdam Study. Neurology, 44, 1246–1252. Bronge, L. (2002). Magnetic resonance imaging in dementia. A study of brain white matter changes. Acta Radiologica, Supplementum, 43, 1–32. Buckner, R. L., & Wheeler, M. E. (2001). The cognitive neuroscience of remembering. Nature Reviews Neuroscience, 2, 624–634. Bunge, S. A., Burrows, B., & Wagner, A. D. (2004). Prefrontal and hippocampal contributions to visual associative
Journal of Cognitive Neuroscience
recognition: Interactions between cognitive control and episodic retrieval. Brain and Cognition, 56, 141–152. Cabeza, R. (2002). Hemispheric asymmetry reduction in older adults: The HAROLD model. Psychology and Aging, 17, 85–100. Cabeza, R., & Nyberg, L. (2000). Imaging cognition II: An empirical review of 275 PET and fMRI studies. Journal of Cognitive Neuroscience, 12, 1–47. Carter, C. S., Botvinick, M. M., & Cohen, J. D. (1999). The contribution of the anterior cingulate cortex to executive processes in cognition. Reviews in the Neurosciences, 10, 49–57. Chafee, M. V., & Goldman-Rakic, P. S. (2000). Inactivation of parietal and prefrontal cortex reveals interdependence of neural activity during memory-guided saccades. Journal of Neurophysiology, 83, 1550–1566. Craik, F. I., Morris, L. W., Morris, R. G., & Loewen, E. R. (1990). Relations between source amnesia and frontal lobe functioning in older adults. Psychology and Aging, 5, 148–151. de Leeuw, F. E., de Groot, J. C., Achten, E., Oudkerk, M., Ramos, L. M., Heijboer, R., Hofman, A., Jolles, J., van Gijn, J., & Breteler, M. M. (2001). Prevalence of cerebral white matter lesions in elderly people: A population based magnetic resonance imaging study. The Rotterdam Scan Study. Journal of Neurology, Neurosurgery, and Psychiatry, 70, 9–14. DeCarli, C., Maisog, J., Murphy, D. G., Teichberg, D., Rapoport, S. I., & Horwitz, B. (1992). Method for quantification of brain, ventricular, and subarachnoid CSF volumes from MR images. Journal of Computer Assisted Tomography, 16, 274–284. DeCarli, C., Murphy, D. G., Teichberg, D., Campbell, G., & Sobering, G. S. (1996). Local histogram correction of MRI spatially dependent image pixel intensity nonuniformity. Journal of Magnetic Resonance Imaging, 6, 519–528. DeCarli, C., Murphy, D. G., Tranh, M., Grady, C. L., Haxby, J. V., Gillette, J. A., Salerno, J. A., Gonzales-Aviles, A., Horwitz, B., & Rapoport, S. I. (1995). The effect of white matter hyperintensity volume on brain structure, cognitive performance, and cerebral metabolism of glucose in 51 healthy adults. Neurology, 45, 2077–2084. Desjardins, A. E., Kiehl, K. A., & Liddle, P. F. (2001). Removal of confounding effects of global signal in functional MRI analyses. Neuroimage, 13, 751–758. Good, C. D., Johnsrude, I. S., Ashburner, J., Henson, R. N., Friston, K. J., & Frackowiak, R. S. (2001). A voxel-based morphometric study of ageing in 465 normal adult human brains. Neuroimage, 14, 21–36. Grady, C. L. (2000). Functional brain imaging and age-related changes in cognition. Biological Psychology, 54, 259–281. Grady, C. L., & Craik, F. I. (2000). Changes in memory processing with age. Current Opinion in Neurobiology, 10, 224–231. Grady, C. L., McIntosh, A. R., & Craik, F. I. (2003). Age-related differences in the functional connectivity of the hippocampus during memory encoding. Hippocampus, 13, 572–586. Gunning-Dixon, F. M., & Raz, N. (2000). The cognitive correlates of white matter abnormalities in normal aging: A quantitative review. Neuropsychology, 14, 224–232. Head, D., Buckner, R. L., Shimony, J. S., Williams, L. E., Akbudak, E., Conturo, T. E., McAvoy, M., Morris, J. C., & Snyder, A. Z. (2004). Differential vulnerability of anterior white matter in nondemented aging with minimal acceleration in dementia of the Alzheimer type:
Volume 18, Number 3