Susan Murtha

Selective Attention Impairments in Alzheimer's Disease: Evidence for Dissociable Components

Tasks emphasizing 3 different aspects of selective attention-inhibition, visuospatial selective attention, and decision making-were administered to subjects with mild Alzheimers disease (AD) and to healthy elderly control (HEC) subjects to determine which components of selective attention were impaired in AD subjects and whether selective attention could be dissociated into different components. The tasks were administered with easy versus hard levels of difficulty to assess proportional slowing as the key variable across tasks. The results indicated that the inhibitory and visual search tasks showed greater proportional slowing in subjects with AD than in HEC subjects, and that the task involving inhibition was significantly more affected in subjects with AD. Furthermore, there were no significant intertask correlations, and the results cannot be explained simply in terms of generalized cognitive slowing. These results provide evidence that inhibition is the most strikingly affected aspect of selective attention that is observed to be impaired in early stages of AD.

The spectrum of category effects in object and action knowledge in dementia of the Alzheimer's type.

The validity and origin of category effects in the anomia demonstrated by individuals with dementia of the Alzheimers type (DAT) remains controversial. Twenty DAT subjects were tested with picture naming and semantic association judgment tests. Picture and word stimuli were drawn from biological, nonbiological, and actions-verbs categories, all of equal difficulty and previously normed on elderly controls. DAT subjects made significantly more naming and semantic judgment errors in the biological category than in the nonbiological category. They were relatively more accurate in naming and making judgments for actions-verbs when presented as words or as 5-s animations. When line drawings of actions were shown for naming, performance deteriorated significantly. Converging results from these 2 tasks provide strong evidence for a semantic memory impairment preferentially affecting biological items to a greater extent than nonbiological items or action verbs in DAT.

Functional and anatomical memory indices in patients with or at risk for Alzheimer's disease.

We investigated the sensitivity of the P300 event-related brain potential (ERP) recorded during a memory-demanding task to memory function in subjects with dementia of the Alzheimers type (DAT), those with mild cognitive impairment (MCI), and normal elderly controls. We also explored the ability of neuropsychological (delayed verbal memory), neuroanatomical (MRI-based hippocampal volume), and electrophysiological (memory search P300 amplitude) memory measures to distinguish between the three subject groups using discriminant function analyses. Fourteen patients with DAT, 16 with MCI, and 15 age- and education-matched controls were tested. P300 amplitude was reduced in DAT subjects at all levels of memory load; however, it did not differ between MCI and control subjects. Delayed verbal memory performance best discriminated DAT from MCI and control subjects, while delayed verbal memory and hippocampal volume best discriminated MCI subjects from controls. These results support the utility of neuropsychological and neuroanatomical measures in diagnosing dementia and do not support the notion that P300 amplitude is sensitive to mild memory dysfunction when measured using the current task.

Cognitive Predictors of Donepezil Therapy Response in Alzheimer Disease

Objectives: To examine whether the presence of domain-specific cognitive impairments would predict a response to donepezil medication in patients with mild-to-moderate Alzheimer disease (AD). Methods: The protocol was an open-label study of 30 AD subjects (mean age 74 years; education 11 years; Mini-Mental State Exam (MMSE) 23 of 30) beginning a 6-month course of treatment with donepezil. Global response to treatment was determined using a combination algorithm based on changes over 6 months in the ADAS-cog, MMSE and CIBIC. In addition, a set of neuropsychological and experimental cognitive tests designed to test five domains of cognition were administered before beginning therapy in order to determine which domain of testing would be predictive to response to treatment. The tests examined attention, short-term and working memory, learning and memory, visuo-spatial motor skills, and lexical-semantic knowledge. Results: Eighteen of the thirty subjects were rated as having responded (stable or improved scores on the combination algorithm) to the therapy. Responders were significantly less impaired prior to treatment on the following tests: the Clock Drawing Test, a Visual-Spatial Motor Tracking Test, and the Boston Picture Naming Test. No significant initial group differences were noted on the other neuropsychological or experimental cognitive measures. Conclusion: The tests that most reliably predicted response to donepezil in AD subjects were in the domains of visual-spatial motor abilities and lexical-semantic functioning.

The Effects of Age and Exogenous Support on Visual Search Performance

The authors investigated whether precueing a location attenuated age-related declines in selective attention and intraindividual variability on a visual search task. The cue improved response time on the single-feature search condition for both young and older adults. On the conjoined-feature search condition, only the older adults used the cue to facilitate performance, particularly when it reduced the number of searched items. The cue also mitigated intraindividual variability observed on both conditions. Not only did the cue facilitate the scaling of attention and improve search strategy, but also it decreased the waxing and waning observed in the older groups performance.

Shifting efficacy, distribution of attention and controlled processing in two subtypes of mild cognitive impairment: Response time performance and intraindividual variability on a visual search task

A visual search task was used to investigate how visual attention and intraindividual variability changes with mild cognitive impairment (MCI). Specifically, we examined the contribution of shifting efficacy, distribution of attention, and controlled processing to declines in visual attention in two groups with MCI (single-domain amnestic and multi-domain amnestic), and measured changes in intraindividual variability. Our results demonstrate that visual search performance is attenuated in multi-domain amnestic MCI, but not single-domain amnestic MCI. In addition, we found that the multi-domain amnestic MCI group was more variable than the older controls and single-domain amnestic MCI participants. These between-group differences in search efficacy and intraindividual variability increased as a function of task complexity. We attribute these decrements in performance to changes in the control of attention and shifting efficacy, but not the distribution of attention.

Visual Selective Attention in Amnestic Mild Cognitive Impairment

OBJECTIVES Subtle deficits in visual selective attention have been found in amnestic mild cognitive impairment (aMCI). However, few studies have explored performance on visual search paradigms or the Simon task, which are known to be sensitive to disease severity in Alzheimers patients. Furthermore, there is limited research investigating how deficiencies can be ameliorated with exogenous support (auditory cues). METHOD Sixteen individuals with aMCI and 14 control participants completed 3 experimental tasks that varied in demand and cue availability: visual search-alerting, visual search-orienting, and Simon task. RESULTS Visual selective attention was influenced by aMCI, auditory cues, and task characteristics. Visual search abilities were relatively consistent across groups. The aMCI participants were impaired on the Simon task when working memory was required, but conflict resolution was similar to controls. Spatially informative orienting cues improved response times, whereas spatially neutral alerting cues did not influence performance. Finally, spatially informative auditory cues benefited the aMCI group more than controls in the visual search task, specifically at the largest array size where orienting demands were greatest. DISCUSSION These findings suggest that individuals with aMCI have working memory deficits and subtle deficiencies in orienting attention and rely on exogenous information to guide attention.

Improving visual spatial working memory in younger and older adults: effects of cross-modal cues

ABSTRACT Spatially informative auditory and vibrotactile (cross-modal) cues can facilitate attention but little is known about how similar cues influence visual spatial working memory (WM) across the adult lifespan. We investigated the effects of cues (spatially informative or alerting pre-cues vs. no cues), cue modality (auditory vs. vibrotactile vs. visual), memory array size (four vs. six items), and maintenance delay (900 vs. 1800 ms) on visual spatial location WM recognition accuracy in younger adults (YA) and older adults (OA). We observed a significant interaction between spatially informative pre-cue type, array size, and delay. OA and YA benefitted equally from spatially informative pre-cues, suggesting that attentional orienting prior to WM encoding, regardless of cue modality, is preserved with age. Contrary to predictions, alerting pre-cues generally impaired performance in both age groups, suggesting that maintaining a vigilant state of arousal by facilitating the alerting attention system does not help visual spatial location WM.

Emotional valence dissociates recall performance among low- and high-span individuals

Individual variability in the control of attentional resources has been postulated as the key factor in distinguishing ‘‘low-span” participants from ‘‘high-span” participants. Control of attentional resources is an important process that allows for the rehearsal and encoding of information into short-term memory (STM). It is important to determine the interaction between external factors and individual variability on the control of attentional resources and subsequent STM processing. Despite numerous studies, emotional valence is one external factor that remains poorly understood in relation to its effect on individual differences in memory span and use of attentional resources. We examined the effects of positive (happy face icons), neutral (neutral face icons), and negative (sad face icons) emotional stimuli used as focal points on STM recall of consonants among lowand highspan individuals. Our results indicate a dissociation in performance between lowand high-span groups for positive and negative emotional stimuli. Specifically, when the consonants were presented following the positive focal point stimuli, the low-span group showed a 17% improvement in recall from baseline performance whereas the high-span group showed no change in performance. Alternatively, when the consonants were presented following the negative focal point stimuli the low-span group showed no change in recall and the high-span group showed an 18% decrease in recall from baseline performance. This dissociation has significant implications for theoretical models of the influence of emotional stimuli on cognitive processing as well as practical models of learning in the field of educational and rehabilitative psychology.

P-025: MRI atrophy in mci is specific, not sensitive, for progression to Alzheimer disease

these same brain regions. In this study, we used PET images from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (www.loni.ucla.edu ADNI) to directly compare the FDG PET images of patients with AD, patients with MCI and elderly normal controls (NC). Objective(s): To compare the pattern and magnitude of regional-to-whole brain CMRgl reductions in ADNI patients with AD and MCI. Methods: FDG PET images from 16 AD patients, 27 MCI patients and 27 NC were analyzed using SPM5. An ANOVA with pair-wise comparisons contrasted regional CMRgl in the three subject groups. A conjunction analysis characterized brain regions with significantly reduced CMRgl in both patient groups. A simple linear regression characterized the relationship between the magnitude of regional CMRgl reductions and clinical severity after assigning the NC, MCI and AD groups to clinical severity values of 0, 1 and 2, respectively. Results: In comparison with the NC, the AD and MCI groups each had lower CMRgl in posterior cingulate, precuneus, and parietotemporal regions (P 0.05 after correction for multiple comparisons), search regions implicated in a previous PET study of AD; they also had lower CMRgl in occipital cortex, the hippocampus, parahippocampal gyrus and fusiform gyrus (P 0.005, uncorrected for multiple comparisons). Based on the conjunction analysis, the AD and MCI groups each had lower CMRgl than the NC in the same posterior cingulate-precuneus and parietotemporal regions. CMRgl reductions in the posterior cingulate, precuneus and parietotemporal regions were correlated with group-related increases in clinical severity (P 0.05 after correction for multiple comparisons in the whole brain using FWE). Conclusions: This direct comparison of three subject groups confirms the similar distribution of FDG PET abnormalities in patients with AD and MCI, and its correlation with clinical severity. It also supports the comparability of measurements from different sites and scanners in the ADNI.