Linda K. Langley

Nicotine patches in Alzheimer's disease : pilot study on learning, memory, and safety

In view of the cholinergic deficits present in patients with Alzheimers disease (AD), a widely investigated treatment strategy for the cognitive deficits in AD is cholinergic stimulation. Although nicotinic cholinergic receptor binding has been demonstrated to be deficient in the AD brain, the predominant theoretical and therapeutic focus to date has been on muscarinic cholinergic receptors and systems. The purpose of the present study was to evaluate the effects of sustained nicotine administration on behavior, cognition, and physiology. A double-blind placebo-controlled trial was conducted in which six patients with probable AD were exposed to 7, 8, and 7 days of placebo, nicotine, and washout, respectively. Daily sessions evaluating learning, memory, and behavior were conducted. Global cognitive functioning, rest and activity levels, cardiac activity, and blood levels were also measured. Findings included improved learning during the nicotine condition, which persisted throughout washout. Memory, behavior, and global cognition were not significantly affected. Sustained administration of nicotine appeared to be safe, although sleep showed a significant decrease.

Inhibition and habituation : Preserved mechanisms of attentional selection in aging and Alzheimer's disease

Are inhibition and habituation, processes that contribute to selective attention, impaired by aging or Alzheimers disease (AD)? Younger adults, older adults, and adults with AD read lists of letters presented either alone or paired with distractor letters. Slower reading times for lists containing distractors relative to lists without distractors indexed concurrent interference (distraction). Slower reading times for lists in which distractors subsequently became targets relative to lists in which distractors and targets were unrelated indexed negative priming (inhibition). Faster reading times when distractors were constant in identity or location rather than random indexed repeated distractor effects (habituation). Distraction increased with aging and AD, whereas inhibition and habituation showed no age- or AD-related decline, suggesting that inhibition and habituation still function to aid attentional selection in older adults and adults with AD.

Aging and Attentional Guidance During Visual Search: Functional Neuroanatomy by Positron Emission Tomography

Positron emission tomography (PET) was used to examine adult age differences in neural activation during visual search. Target detection was less accurate for older adults than for younger adults, but both age groups were successful in using color to guide attention to a subset of display items. Increasing perceptual difficulty led to greater activation of occipitotemporal cortex for younger adults than for older adults, apparently as the result of older adults maintaining higher levels of activation within the easier task conditions. The results suggest that compensation for age-related decline in the efficiency of occipitotemporal cortical functioning was implemented by changes in the relative level of activation within this visual processing pathway, rather than by the recruitment of other cortical regions.

Functional neuroimaging of memory: Implications for cognitive aging

Our understanding of the ways in which changes in specific neural systems mediate adult age differences in memory is rapidly increasing, due in no small part to the advent of functional neuroimaging techniques. This article reviews age‐related changes in memory performance obtained with behavioral measures, describes models of the neural mechanisms of memory, and derives predictions from these models regarding age‐related changes in brain activation patterns. The neuroimaging findings obtained to date support models emphasizing the role of prefrontal cortex in age‐related changes in memory functioning, especially for episodic memory retrieval. In general, neural activation associated with episodic memory encoding is regionally similar for younger and older adults but relatively lower in magnitude for older adults. During retrieval, activation that is restricted to the right prefrontal cortex for younger adults is more likely to be bilateral for older adults. Prefrontal activation exhibits an age‐related increase when working memory tasks require simple storage and an age‐related decrease when working memory requires higher‐level executive processes. Although the evidence is limited, behavioral performance and activation patterns appear to be similar among younger and older adults on tests of semantic (context‐independent) and implicit memory. We conclude that several methodological issues, such as defining the relation between brain structure and function, and determining the relationship between performance and activation, are particularly important for understanding age‐related changes. Future directions for aging research include further investigation of the relation between encoding and retrieval and the identification of both spared and impaired neural systems. Microsc. Res. Tech. 51:75–84, 2000.

Inhibition of return in aging and Alzheimer's disease: performance as a function of task demands and stimulus timing.

Inhibition of return (IOR) is a phenomenon of spatial attention that biases attention toward novel events in the environment. Recent evidence suggests that the magnitude and timing of IOR varies as a function of task conditions (e.g., detection vs. discrimination tasks, short vs. long cue-target intervals, intrinsic vs. extrinsic cues). Although IOR appears relatively preserved with both normal aging and Alzheimers disease (AD), it has been tested under relatively simple task conditions. To test whether IOR is resistant to age and/or AD when cognitive demands are increased, we employed a double-cue IOR paradigm that required categorization as well as detection responses. The stimulus onset asynchrony (SOA) between the cue and target events was varied to determine whether group differences existed in IOR effects over time. Younger normal adults and older normal adults exhibited significant IOR effects on both the detection task and the categorization task at a short cue-target SOA (950 ms). In contrast, AD patients exhibited significant IOR effects at the short SOA on the detection task but not on the categorization task. From the short to the long SOA (3500 ms), IOR effects exhibited by younger normal adults declined significantly during both the detection and the categorization tasks, suggesting that inhibition resolved over time. In contrast, neither older normal adults nor AD patients exhibited SOA-related IOR reductions on the detection task. These results suggest that IOR may show differential age- and AD-related vulnerabilities depending on task conditions and timing characteristics.

Age-Related Changes in Selective Attention and Perceptual Load During Visual Search

Three visual search experiments were conducted to test the hypothesis that age differences in selective attention vary as a function of perceptual load (E. A. Maylor & N. Lavie, 1998). Under resource-limited conditions (Experiments 1 and 2), the distraction from irrelevant display items generally decreased as display size (perceptual load) increased. This perceptual load effect was similar for younger and older adults, contrary to the findings of Maylor and Lavie. Distraction at low perceptual loads appeared to reflect both general and specific inhibitory mechanisms. Under more data-limited conditions (Experiment 3), an age-related decline in selective attention was evident, but the age difference was not attributable to capacity limitations as predicted by the perceptual load theory.

The emotional blink: adult age differences in visual attention to emotional information.

To assess age differences in attention-emotion interactions, the authors asked young adults (ages 18-33 years) and older adults (ages 60-80 years) to identify target words in a rapid serial visual presentation (RSVP) task. The second of two target words was neutral or emotional in content (positive in Experiment 1, negative in Experiment 2). In general, the ability to identify targets from a word stream declined with age. Age differences specific to the attentional blink were greatly reduced when baseline detection accuracy was equated between groups. With regard to emotion effects, older adults showed enhanced identification of both positive and negative words relative to neutral words, whereas young adults showed enhanced identification of positive words and reduced identification of negative words. Together these findings suggest that the nature of attention-emotion interactions changes with age, but there was little support for a motivational shift consistent with emotional regulation goals at an early stage of cognitive processing.

Common-sense beliefs about the prevention of Alzheimer's disease.

Objectives: Common-sense illness beliefs are important because they influence actions that people take to prevent and treat disease. This research (1) asked younger and older adults about their illness representations of Alzheimers disease (AD) and (2) manipulated beliefs about AD preventability to determine causal relationships in the data. Method: In Study 1, the beliefs of younger (age 18–38; n = 82) and older (age 58–89; n = 57) adults about the causes of and ways to prevent AD were compared. In Study 2, younger adults were randomly assigned to read information stating either that AD can be prevented or not. Results: Compared to younger adults, older adults saw themselves as less at risk, t(137) = 3.03, p = 0.003, d = 0.52, were more likely to believe that AD is preventable, t(137) = 5.01, p < 0.001, d = 0.87 and were more likely to report engaging in behaviors to prevent AD, χ 2(1, 139) = 19.01, p < 0.001, r = 0.37. Manipulating beliefs in Study 2 caused those told that AD was preventable to see themselves as less at risk, report more prevention behaviors, and hold those with the disease more responsible for their fate. Conclusion: These findings highlight the association of illness representations with reports of behavior and show a disconnect between beliefs and what we currently know about AD.

Interrater and Test–Retest Reliability of a Fixed Condition Design Fluency Test

Despite its potential as a unique neuropsychological test, the emergence of a psychometrically sound research foundation for Jones-Gotman and Milners (1977) Design Fluency Test (DFT) has been constrained by the lack of consistent administration and scoring practices and limited information about its reliability. Here we describe an approach to administering and scoring the fixed condition DFT that is modeled on Jones-Gotman and Milners original method and that clarifies procedural ambiguities. Results include interrater and long-term test-retest reliability analyses using this approach. First, based on five raters who scored 50 DFT protocols, good to excellent intra-class correlation coefficients were obtained for all DFT scores. Second, in a broadly representative sample of 87 healthy adults who were tested twice over an average of 5½ years, the test–retest reliabilities for total and novel design scores ranged from good to excellent. This study demonstrates that the fixed condition DFT can be scored reliably using these procedures and that the reliability coefficients for DFT total and novel designs scores are comparable to those of other commonly used neuropsychological tests.

Interaction of Blood Pressure and Adult Age in Memory Search and Visual Search Performance

According to one model of the interaction between blood pressure and adult age, chronically elevated blood pressure accelerates age-related decline in fluid intelligence. To test this model, 48 unmedicated individuals with high blood pressure (HBP) and 48 individuals with normal blood pressure (NBP), comprising three categories of adult age (20–39, 40–59, and 60–79 years), performed memory search and visual search tasks. In contrast to the prediction, performance slowing related to HBP was evident for middle-aged adults, but not for the older adults, perhaps as a result of survival and selective attrition effects. There were specific age-related changes associated with memory search and visual search, in addition to generalized slowing, whereas the HBP-related changes were not task-specific.