Frontal Hypometabolism Does Not Explain Inhibitory Dysfunction in Alzheimer Disease *Fabienne Collette, *†Martial Van der Linden, *Gael Delrue, and ‡Eric Salmon *Neuropsychology Unit, University of Liège, Liège, Belgium; †Cognitive Psychopathology Unit, University of Geneva, Geneva, Switzerland; and ‡Cyclotron Research Center and Department of Neurology, University of Liège, Liège, Belgium Summary: A series of tasks assessing inhibitory processes was administered to pa- tients with Alzheimer disease and control subjects. Two groups of patients with Alz- heimer disease were examined: patients with hypometabolism restricted to the poste- rior (temporal and parietal) cerebral areas and patients with hypometabolism in both posterior and anterior (frontal) cerebral areas. The performances of the patients with Alzheimer disease were inferior to those of control subjects on all inhibitory tasks, but the two groups of patients obtained similar scores. These data indicate that frontal lobe hypometabolism is not necessary to produce inhibitory impairment in Alzheimer dis- ease. Consequently, inhibitory dysfunction could be the consequence of a (partial) disconnection process between posterior and anterior cerebral areas. Key Words: Inhibition—Frontal lobe—Disconnection—Cerebral metabolism. Alzheimer disease (AD) is classically characterized by a progressive accumulation of deficits affecting several cognitive domains, almost without any specific neuro- logic signs. Recent studies have nevertheless revealed the prevalence of certain types of deficits early in the course of AD, especially executive (controlled) function and episodic memory impairments (Collette et al., 2002c). The presence of executive dysfunction relatively early in AD is now well established. Indeed, several reports have demonstrated that individuals with AD are impaired on a variety of tasks that have been commonly consid- ered as measures of executive control: dual-task para- digms (Baddeley et al., 1986, 1991, 2001; Collette et al., 1999), verbal fluency tasks (Bhutani et al., 1992; Lafleche and Albert, 1995; Pasquier et al., 1995; Troyer et al., 1998), the Stroop task (Spieler et al., 1996), the negative priming paradigm (Sullivan et al., 1995; Lang- ley et al., 1998), and random number generation (Brug- ger et al., 1996). Recently, Collette et al. (1999) admin- istered a series of executive tasks (dual-task paradigm, the alpha span task, a delayed alternation task, the verbal fluency, a semantic inhibition task, and a self-ordering task) to a group of patients with AD and control subjects. As expected, the patients with AD were significantly impaired on all these tasks when compared with control subjects. More importantly, the speed of processing and severity of the disease did not appear to be significantly correlated to executive deficits in patients with AD, sug- gesting that executive impairments are not a conse- quence of deficits affecting more general factors (such as a cognitive slowing down or a global deterioration level). Altogether, these studies demonstrated the existence of impairments affecting different executive processes. Among these processes, inhibition function has been widely explored in AD (Collette and Van der Linden, 2002b). Cognitive inhibition is defined as a mechanism that actively suppresses distracting information. Differ- ent aspects of inhibitory control may be distinguished Received January 8, 2002. Accepted September 3, 2002. Supported by the Belgian Fund for Scientific Research (FNRS), the “Fondation Medicale Reine Elisabeth,” and the Interuniversity Pole of Attraction P5/04, Belgian State, Prime Minister’s Office, Federal Of- fice for Scientific, Technical and Cultural Affairs. F.C. is a Post- Doctoral researcher at the FNRS. Address correspondence and reprint requests to F. Collette, Ph.D., Service de Neuropsychologie, Boulevard du Rectorat 3 (B33), 4000 Liège (Sart-Tilman), Belgium; e-mail: f.collette@ulg.ac.be Alzheimer Disease and Associated Disorders Vol. 16, No. 4, pp. 228–238 © 2002 Lippincott Williams & Wilkins, Inc., Philadelphia 228