Published Online
on December 20, 2007

A more recent version of this article appeared on February 1, 2008

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Submitted on April 20, 2007
Revised on June 14, 2007
Accepted on July 5, 2007

Subcortical Lacunes Are Associated With Executive Dysfunction in Cognitively Normal Elderly

Catherine L. Carey PhD^*; Joel H. Kramer PsyD; S. Andrew Josephson MD; Dan Mungas PhD; Bruce R. Reed PhD; Norbert Schuff PhD; Michael W. Weiner MD; and Helena C. Chui MD

From the Department of Psychiatry (C.L.C., J.H.K.), University of California, San Francisco Medical Center; the Department of Neurology (S.A.J.), Stroke Sciences Group, University of California, San Francisco Medical Center; the Department of Neurology (D.M., B.R.R.), University of California, Davis Medical Center; the Department of Radiology (N.S., M.W.W.), University of California, San Francisco Medical Center; and the VA Medical Center (H.C.C.), Department of Neurology Department of Neurology, University of Southern California.

^* To whom correspondence should be addressed. E-mail: ccarey{at}ucsd.edu.

Background and Purpose—The relationship between subcortical ischemic vascular disease (SIVD) and cognition in normal elderly is unclear, in part because of methodological inconsistencies across studies. To clarify this relationship, the current study investigated a well characterized cognitively normal elderly sample (55 years) with quantitative MRI and psychometrically robust neuropsychological measures within a multivariate model. Converging evidence suggests that SIVD selectively impairs frontal-executive tasks by disrupting frontal-subcortical circuits. We therefore hypothesized that MRI markers of SIVD would be selectively associated with worse executive functioning.

Methods—We studied 94 participants who were cognitively and functionally normal. Volumetric measures of white matter signal hyperintensity (WMH), subcortical lacunes, hippocampal volume, and cortical gray matter were obtained to predict performance on composite measures of executive functioning and episodic memory.

Results—Hierarchical regression demonstrated that after controlling for demographic variables, MMSE, and total intracranial volume, the total number of subcortical lacunes was the only significant predictor, with a greater number of lacunes associated with poorer executive performance. Hippocampal volume best predicted episodic memory performance.

Conclusions—Results suggest that SIVD in the form of silent lacunes corresponds to poorer executive functioning even in otherwise normal elderly, which is consistent with the hypothesis that SIVD preferentially disrupts frontal-subcortical circuits. The clinical importance of these findings is highlighted by the fact that 33% of the normal elderly participants in this study had lacunar infarcts.

Key words: cerebral lacunes • cognition • elderly • magnetic resonance imaging

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