A novel approach to assessing memory at the population level: vulnerability to semantic interference.

One of the most challenging tasks in the cognitive assessment of older adults is the differentiation of normal from pathological cognitive aging. Mild cognitive impairment (MCI) with deficits reported in one or more cognitive domains, including episodic memory, executive functions, verbal abilities, visuospatial skills, attention, and perceptual speed is often found to reflect preclinical Alzheimer’s disease (AD) and other dementias (Backman et al., 2005; Masur et al., 1994). However, there is growing interest in identifying novel cognitive paradigms that might help detect preclinical dementia even earlier, particularly as new, potentially disease-modifying treatments, appear on the horizon for AD. In addition to episodic memory, it has been postulated that AD is also associated with altered structure of semantic memory, an individual’s concept-based knowledge of the world (Hodges et al., 1992). Buschke et al. (Buschke et al., 1997) has argued that early AD is characterized by specific deficits that prevent effective use of semantic cues. On tests requiring recall of remembered words, mildly impaired AD patients are specifically prone to semantic intrusions that suggest incomplete processing of the target (Loewenstein et al., 1991). Semantic intrusions include substituting the target item for a semantically similar exemplar (e.g., “lighter” for “matches”) or for the superordinate semantic category to which the target belonged (e.g., “jewelry” for “ring”). These intrusions reflect an underlying deficit in inhibiting the activation of competing semantic exemplars within a general semantic category (e.g., “objects that start a fire” in the case of the first example). Therefore the use of an interference paradigm, in which semantically similar objects compete for expression in memory, may further highlight the specific information processing deficits associated with AD. This line of work has shown remarkable potential for distinguishing between individuals with normal cognition and mild dementia in case-control studies of specialty clinical samples of AD patients and research volunteers (Loewenstein et al., 2007; Loewenstein et al., 2004). However, it has yet to be determined how broadly this experience will generalize to dementia in the community at large. The Semantic Interference Test (SIT) is a selective reminding task that employs two semantically related groups of household objects. It is based on a modification of the Fuld Object Memory Evaluation (OME) (Fuld, 1981) and involves actual common objects as stimuli which are tactually, visually and aurally encoded. Unlike the original OME which had five learning trials, the SIT paradigm presents the initial group of OME objects for three learning trials, followed by presentation of a new group of objects semantically related to the first group (e.g., cup is semantically related to bowl; key to lock; playing card to domino), and followed by an immediate recall and then a delayed recall of the initial list of objects. In addition to semantic intrusions from one list to another, this paradigm allows for evaluation of interference effects: proactive interference, in which new learning is inhibited by the competing effects of old learning, and retroactive interference, in which recall of previously learned material is impeded by competing intervening information. Loewenstein and colleagues found that a SIT composite measure of vulnerability to semantic interference was highly sensitive (84.6%) and specific (96.2%) in differentiating mild AD patients from healthy older adults. Vulnerability to proactive interference, specifically, was most discriminative between patients with mild cognitive impairment (MCI) and healthy control participants (Loewenstein et al., 2004). Further work showed that vulnerability to proactive interference on the SIT was highly predictive of progression to dementia within three years among older adults with MCI, more so than traditional neuropsychological measures of delayed recall (Loewenstein et al., 2007). Here we report the performance of this novel memory paradigm, which examines vulnerability to semantic interference, in a population-based epidemiologic study of older adults. Specifically, we examined associations between scores the SIT (Loewenstein et al., 2003) and demographic characteristics, hypothesizing that better test performance would be associated with younger age and higher education. Further, we hypothesized that SIT performance would be associated with level of decline in cognitively driven everyday functioning, as independently measured by the Clinical Dementia Rating (CDR) scale (Hughes et al., 1982). Additionally, we provide normative data for the SIT stratified by age level in 5-year bands that can be used by clinician or researchers in future investigations.