Semantic interference deficits and the detection of mild Alzheimer’s disease and mild cognitive impairment without dementia

Impairment in delayed recall has traditionally been considered a hallmark feature of Alzheimer’s disease (AD). However, vulnerability to semantic interference may reflect early manifestations of the disorder. In this study, 26 mildly demented AD patients (mild AD), 53 patients with mild cognitive impairment without dementia (MCI), and 53 normal community-dwelling elders were first presented 10 common objects that were recalled over 3 learning trials. Subjects were then presented 10 new semantically related objects followed by recall for the original targets. After controlling for the degree of overall memory impairment, mild AD patients demonstrated greater proactive but equivalent retroactive interference relative to MCI patients. Normal elderly subjects exhibited the least amount of proactive and retroactive interference effects. Recall for targets susceptible to proactive interference correctly classified 81.3% of MCI patients and 81.3% of normal elderly subjects, outperforming measures of delayed recall and rate of forgetting. Adding recognition memory scores to the model enhanced both sensitivity (84.6%) and specificity (88.5%). A combination of proactive and retroactive interference measures yielded sensitivity of 84.6% and specificity of 96.2% in differentiating mild AD patients from normal older adults. Susceptibility to proactive semantic interference may be an early cognitive feature of MCI and AD patients presenting for clinical evaluation. (JINS, 2004, 10, 91–100.)

Introduction

Memory complaints are increasingly prevalent with advancing age and present a challenge for clinicians who must distinguish a benign condition from the early manifestations of a potentially serious and progressive illness (Celsis, 2000; Sherwin, 2000). The term mild cognitive impairment (MCI), an intermediate cognitive state between normal aging and dementia, was operationalized by Petersen and co-workers (1997, 1999) and denotes memory performance typically falling 1.5 standard deviations or more below the mean as compared to age- and education-related normative data. According to these criteria, the diagnosis ofMCIcan only be given when the individual does not have general intellectual decline or meets criteria for a dementia syndrome as evidenced by the preservation of all functional abilities required for independent living. In clinically diagnosed patients, the rate of conversion from MCI to dementia over a three-year period has ranged from20%to53%(Black, 1999; McKelvey et al., 1999; Wolf et al., 1998). Morris et al. (2001) recently reported that 60.5% of 277 patients with MCI converted to Alzheimer’s disease (AD) within 5 years and that 100% of these individuals had converted over a 9.5-year follow-up period, leading to the conclusion that MCI represents the pre-clinical stage of AD in clinic samples. Growing recognition of the importance of MCI as a diagnostic entity requires instruments that are increasingly sensitive and specific in the detection of this mild level of memory impairment. Further, these measures should have utility in monitoring progression of disease and response to newly developed pharmacological interventions (Ritchie & Touchon, 2000).

Early memory dysfunction, particularly rapid rate of forgetting and impaired delayed recall have traditionally been considered to be among the most sensitive indicators of mild AD (Ashford et al., 1989; Locasio et al., 1995; Tröster et al., 1993; Welsh et al., 1991) and to be predictive of dementia in otherwise cognitively normal community dwelling elders (Masur et al., 1994). Other investigations, however, have not found accelerated rates of forgetting in AD patients (Christensen et al., 1998; Money et al., 1992).

It has also been postulated that the primary deficits in AD might reflect impairments in the structure of semantic memory (Beatty et al., 1997; Salmon et al., 1999). Alternatively, it has been suggested that the structure of semantic memory is largely intact and that deficits in AD indicate difficulties in lexical access and information processing (Bell et al.,2000; Shenaut & Ober, 1996).

Semantic interference deficits and the detection of mild Alzheimer’s disease and mild cognitive impairment without dementia

DAVID A. LOEWENSTEIN,1,2 AMARILIS ACEVEDO,1,2 CHERYL LUIS,1,2 THOMAS CRUM,1,2 WARREN W. BARKER,1 and RANJAN DUARA1,2 1Wien Center for Alzheimer’s Disease and Memory Disorders, Mount Sinai Medical Center, Miami Beach, Florida 2Department of Psychiatry and Behavioral Sciences, University of Miami School of Medicine, Miami, Florida (Received September 27, 2002; Revised April 22, 2003; Accepted May 5, 2003)

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