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From the Department of Neurology (Drs. Mungas, Reed, and DeCarli), School of Medicine, University of California, Davis; Veterans Administration Northern California Health Care System (Drs. Mungas and Reed), Sacramento; School of Public Health and Helen Wills Neuroscience Institute (Drs. Harvey and Jagust), University of California, Berkeley; Division of Biostatistics (Dr. Beckett), Department of Public Health Sciences, School of Medicine, University of California, Davis; Department of Preventive Medicine (Dr. Mack), School of Medicine, University of Southern California; Departments of Psychiatry (Drs. Kramer and Weiner) and Radiology (Drs. Weiner and Schuff), School of Medicine, University of California, San Francisco; Magnetic Resonance Unit (Dr. Schuff), Department of Veterans Affairs Medical Center, San Francisco; Department of Neurology (Dr. Chui), School of Medicine, University of Southern California.
Address correspondence and reprint requests to Dr. Dan Mungas, Department of Neurology, School of Medicine, University of California, Davis, 4860 Y Street, Suite 3700, Sacramento, CA 95817; e-mail: dmmungas{at}ucdavis.edu
Objective: To examine how baseline and change of volumetric MRI relate to cognitive decline in older individuals.
Background: Memory is associated with hippocampal integrity, whereas executive function has been linked to impaired frontal lobe function. Previous studies have shown that hippocampal and cortical atrophy are more strongly related to cognition than are measures of subcortical cerebrovascular disease (CVD). The authors hypothesized that memory (MEM) decline would be related to change in hippocampal volume (HC), whereas decline in executive function (EXEC) would be related to change of cortical gray matter volume (CGM) and measures of subcortical CVD.
Methods: Subjects from a multicenter study (n = 103) included cognitively normal, mildly impaired, and demented cases with and without subcortical lacunes. All had longitudinal cognitive evaluation (mean = 4.8 years) and two or more MRI scans at least one year apart (mean = 3.4 years). MRI measures included HC, CGM, total lacune volume (LAC), and white matter hyperintensity volume (WMH). Random effects modeling of longitudinal data assessed effects of MRI baseline and MRI change on baseline and change of psychometrically matched measures of MEM and EXEC.
Results: Change in MEM was related to HC baseline and HC change. Change in EXEC was related to baseline CGM and to change in CGM, HC, and LAC. Results were unchanged when demented cases were excluded. WMH was not associated with change in MEM or EXEC independent of HC, CGM, and LAC.
Conclusion: Hippocampal volume was the primary determinant of memory decline, whereas executive function (EXEC) decline was related to multiple brain components. Results support a hypothesis that MEM decline is strongly influenced by Alzheimer disease (AD), whereas EXEC decline may be complexly determined by cerebrovascular disease and AD.
Supported in part by grants AG123435, AG10129 from the National Institute on Aging, Bethesda, MD, and by the California Department of Health Services Alzheimer’s Disease Program, contracts 94-20354, 94-20355, 98-14970, and 98-14971.
Disclosure: The authors report no conflicts of interest.
Received May 14, 2004. Accepted in final form April 27, 2005.
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