Verbal fluency performance in amnestic MCI and older adults with cognitive complaints

Archives of Clinical Neuropsychology 23 (2008) 229–241 Verbal fluency performance in amnestic MCI and older adults with cognitive complaints Katherine E. Nutter-Upham a,b , Andrew J. Saykin a,c,∗ , Laura A. Rabin a,b , Robert M. Roth a , Heather A. Wishart a , Nadia Pare a , Laura A. Flashman a a Neuropsychology Program, Department of Psychiatry, Dartmouth Medical School/DHMC, Lebanon, NH, USA b Department of Psychology, Brooklyn College, City University of New York, Brooklyn, NY, USA c Center for Neuroimaging, Department of Radiology, Indiana University School of Medicine, Indianapolis, IN, USA Accepted 23 January 2008 Abstract Verbal fluency tests are employed regularly during neuropsychological assessments of older adults, and deficits are a common finding in patients with Alzheimer’s disease (AD). Little extant research, however, has investigated verbal fluency ability and subtypes in preclinical stages of neurodegenerative disease. We examined verbal fluency performance in 107 older adults with amnestic mild cognitive impairment (MCI, n = 37), cognitive complaints (CC, n = 37) despite intact neuropsychological functioning, and demographically matched healthy controls (HC, n = 33). Participants completed fluency tasks with letter, semantic category, and semantic switching constraints. Both phonemic and semantic fluency were statistically (but not clinically) reduced in amnestic MCI relative to cognitively intact older adults, indicating subtle changes in the quality of the semantic store and retrieval slowing. Investigation of the underlying constructs of verbal fluency yielded two factors: Switching (including switching and shifting tasks) and Production (including letter, category, and action naming tasks), and both factors discriminated MCI from HC albeit to different degrees. Correlational findings further suggested that all fluency tasks involved executive control to some degree, while those with an added executive component (i.e., switching and shifting) were less dependent on semantic knowledge. Overall, our findings highlight the importance of including multiple verbal fluency tests in assessment batteries targeting preclinical dementia populations and suggest that individual fluency tasks may tap specific cognitive processes. © 2008 National Academy of Neuropsychology. Published by Elsevier Ltd. All rights reserved. Keywords: Mild cognitive impairment; Verbal fluency; Assessment; Cognition 1. Introduction Amnestic mild cognitive impairment (MCI) is characterized by memory complaints and deficits in the absence of dementia, global cognitive decline, or significant problems with activities of daily living (ADLs) (Petersen et al., 1999). Numerous epidemiological studies have documented an accelerated rate of progression to Alzheimer’s disease (AD) in MCI patients (Tierney, Yao, Kiss, & McDowell, 2005), with annual conversion rates from about 10 to 15% per year, contrasted with the rate of 1–2% reported for healthy elderly. Over a six-year period, approximately 80% of those diagnosed with MCI will convert to AD (Petersen et al., 1999; Petersen, Doody, et al., 2001). Because the symptomatic ∗ Corresponding author at: Center for Neuroimaging, Department of Radiology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. Tel.: +1 317 278 6947. E-mail address: (A.J. Saykin). 0887-6177/$ – see front matter © 2008 National Academy of Neuropsychology. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.acn.2008.01.005 230 K.E. Nutter-Upham et al. / Archives of Clinical Neuropsychology 23 (2008) 229–241 treatments available for MCI (e.g., acetylcholinesterase inhibitors) exert the greatest utility if implemented early in the disease course (Farlow & Evans, 1998; Gauthier, Feldman, & Hecker, 2002), clinicians and researchers are increasingly examining the neuropsychological profiles of MCI patients to identify cognitive decline at its first sign. Traditionally, emphasis has been placed on episodic memory deficits, but recent research indicates that some MCI patients show subtle, non-amnestic cognitive difficulties. Changes in aspects of executive function, such as verbal fluency, have been observed in people years before the clinical diagnosis of AD (Backman, Jones, Berger, & Laukka, 2005). Verbal fluency performance has often been included in predictive conversion models, and older adults who eventually develop AD may show baseline decline in verbal fluency 3–5 years before diagnosis (Artero, Tierney, Touchab, & Ritchie, 2003; Saxton et al., 2004). Consistent with subtle executive dysfunction, neuroimaging studies of MCI have shown reduced gray matter density in frontal lobe subregions (Saykin et al., 2006) and differential activation of frontal lobe systems during executive function tasks (Rosano et al., 2005; Saykin et al., 2004). Investigation of verbal fluency in preclinical AD is therefore of diagnostic and predictive importance. Verbal fluency is typically defined as the ability to produce words under specific constraints, and within a fixed time interval (Lezak, Howieson, Loring, Hannay, & Fischer, 2004). Several forms of verbal fluency are regularly utilized in clinical neuropsychological or experimental assessments. Category fluency, which requires the ability to rapidly name words that are members of a specific category, is known to put strong demands on the hierarchical structure of semantic knowledge (Butters, Granholm, Salmon, Grant, & Wolf, 1987). Letter fluency, which requires the ability to name words that begin with a specific letter, is believed to rely less on semantic knowledge stores and more on “frontal control” regions (Bryan, Luszcz, & Crawford, 1997; Delis & Kaplan, 2001). In comparison to healthy elderly, AD patients tend to show significant deficits in verbal fluency (Butters et al., 1987; Hart, 1988; Hodges, Salmon, & Butters, 1991; Rosen, 1980; for review see Nebes, 1989), with greater impairment on semantic relative to letter fluency tasks (Chan, Butters, Salmon, & McGuire, 1993; Martin & Fedio, 1983). Investigation of the discriminative value of fluency subtypes in AD has revealed that semantic fluency (100% sensitivity, 92.5% specificity) is superior to letter fluency (89% sensitivity, 85% specificity) in predicting group membership (Monsch et al., 1992). Several explanations have been proposed to account for the discrepancy between performance on tests of semantic and letter fluency in AD. One model posits that AD patients suffer from impaired retrieval from an otherwise intact semantic memory store (Nebes & Brady, 1988; Nebes, Martin, & Horn, 1984). In this conceptualization, associations between attributes of a given semantic store (e.g., elephant attributes might include, heavy, big, wild) are intact, and deficits are entirely due to slowed retrieval. This is considered to be a non-linguistic or executive control deficit (Henry, Crawford, & Phillips, 2004). A second model attributes impaired sem (...truncated)