Young and nondemented older adults were tested on a continuous recognition memory task requiring visual pattern separation. During the task, some objects were repeated across trials and some objects, referred to as lures, were presented that were similar to previously presented objects. The lures resulted in increased interference and an increased need for pattern separation. For each object, the participant was asked to indicate whether (1) this was the first time the object was seen (new), (2) the object was seen previously (old), or (3) the object was similar to a previous object (similar). Older adults were able to correctly identify objects as old or new as well as young adults; however, older adults were impaired when identifying lures as similar. Therefore, pattern separation may be less efficient in older adults resulting in poorer recognition memory performance when interference is increased.A primary region of the brain affected by normal aging is the hippocampus in humans (Good et al. 2001;Allen et al. 2005;Driscoll and Sutherland 2005;Raz et al. 2005;Walhovd et al. 2005) and animal models (Rosenzweig and Barnes 2003;Driscoll et al. 2006). However, the subregions of the hippocampus may be differentially affected by normal aging (Small et al. 2002(Small et al. , 2004. The dentate gyrus (DG) subregion may be particularly susceptible to age-related changes in both humans (Small et al. 2002) and animal models (Small et al. 2004;Patrylo and Williamson 2007), whereas aging may have less of an impact on pyramidal cells in the CA subregions (Small et al. 2002(Small et al. , 2004. In contrast, the CA subregions of the hippocampus may be more vulnerable to pathological aging associated with Alzheimer's disease (Braak and Braak 1996;Price et al. 2001;West et al. 2001). Therefore, tasks sensitive to dysfunction in particular subregions of the hippocampus may help to differentiate cognitive impairment associated with normal aging from pathological changes associated with Alzheimer's disease. Although hippocampal-dependent tasks are highly sensitive to age-related changes in the brain (for review, see Rosenzweig and Barnes 2003), behavioral studies in humans have not examined the performance of nondemented older adults on tasks shown to be particularly sensitive to DG function. As described in detail below, a key function of the DG may be to support pattern separation. Age-related changes in the DG may impair the ability to reduce similarity among new input patterns, resulting in decreased pattern separation (Wilson et al. 2006). Therefore, decreased efficiency in pattern separation may be a critical, but relatively unexamined, processing deficit in nondemented older humans.Pattern separation is described as a mechanism for separating partially overlapping patterns of activation so that one pattern may be retrieved as separate from other patterns (Gilbert et al. 2001;Gilbert and Kesner 2006;Kirwan and Stark 2007). The operation of a pattern separation mechanism is critical for reducing potential interference among ...
Young and nondemented older adults completed a visual object continuous recognition memory task in which some stimuli (lures) were similar but not identical to previously presented objects. The lures were hypothesized to result in increased interference and increased pattern separation demand. To examine variability in object pattern separation deficits, older adults were divided into impaired and unimpaired groups based on performance on a standardized serial list-learning task. Impaired older adults showed intact recognition memory, but were impaired relative to young and unimpaired older adults when identifying similar lure stimuli, demonstrating that object pattern separation varies in older adults.
Two experiments tested the effect of temporal interference on order memory for fixed and random sequences in young adults and nondemented older adults. The results demonstrate that temporal order memory for fixed and random sequences is impaired in nondemented older adults, particularly when temporal interference is high. However, temporal order memory for fixed sequences is comparable between older adults and young adults when temporal interference is minimized. The results suggest that temporal order memory is less efficient and more susceptible to interference in older adults, possibly due to impaired temporal pattern separation.
We examined performance of healthy older and younger adults and individuals with Alzheimer’s disease (AD) and Parkinson’s disease (PD) on digit cancellation, a task putatively sensitive to cognitive impairment but possibly affected by visual impairment, particularly in contrast sensitivity. Critical contrast thresholds were established to create custom stimulus arrays that were proximally matched across individuals. Age- and PD-related differences in search were fully accounted for by the sensory deficit. Increased contrast benefited AD patients but could not override cognitive impairment. We conclude that visually-fair neuropsychological testing can effectively compensate for normal age- and PD-related visual changes that affect cognitive performance.
Signal detection requires ratings reliability throughout a clinical trial. The confirmation of site-based rater scores by a second, independent and blinded rater is a reasonable metric of ratings reliability. We used audio-digital pens to record site-based interviews of the Montgomery-Asberg Depression Rating Scale (MADRS) in a double-blind, placebo controlled trial of a novel antidepressant in treatment resistant depressed patients. Blinded, site-independent raters generated "dual" scores that revealed high correlations between site-based and site-independent raters (r=0.940 for all ratings) and high sensitivity, specificity, predictive values, and kappa coefficients for treatment response and non-response outcomes using the site-based rater scores as the standard. The blinded raters achieved an 89.4% overall accuracy and 0.786 kappa for matching the treatment response or non-response outcomes of the site-based raters. A limitation of this method is that independent ratings depend on the quality of site-based interviews and patient responses to the site-based interviewers. Nonetheless, this quality assurance strategy may have broad applicability for studies that use subjective measures and wherever ratings reliability is a concern. "Dual" scoring of recorded site-based ratings can be a relatively unobtrusive surveillance strategy to confirm scores and to identify and remediate rater "outliers" during a study.
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