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ObjectiveTo directly examine the relationship between magnetic resonance imaging (MRI) abnormalities and neuropathologic changes in the brains of patients with the acquired immunodeficiency syndrome.DesignA total of 17 brains from patients with acquired immunodeficiency syndrome for which postmortem MRI scans were available were used in this study. Volumes of cortical gray matter, deep gray matter, and abnormal white matter were estimated from the MRIs of the left hemispheres of the formalin-fixed brains from patients with acquired immunodeficiency syndrome using quantitative morphometric techniques. Quantitative estimates of human immunodeficiency virus, gliosis, and neocortical synaptic and dendritic density were obtained from the corresponding right hemispheres. Quantification of human immunodeficiency virus and gliosis was performed on all 17 specimens, while quantification of synaptic and dendritic density was performed on 10 of the 17 specimens.SettingAll specimens were obtained from patients with the acquired immunodeficiency syndrome who underwent autopsy between 1990 and 1992 at the University of California-San Diego Medical Center and the San Diego (Calif) Department of Veterans Affairs Hospital.ResultsNo association was found between MRI volumes and gliosis, a nonspecific marker of central nervous system damage. Significant and regionally specific relationships were obtained, however, between the severity of central nervous system human immunodeficiency virus infection and the MRI volume estimates of gray matter and abnormal white matter. In addition, a significant association was observed between cortical gray matter volumes and cortical synaptic density.ConclusionThese findings indicate that the quantitative morphometric analysis of MRIs in patients may provide sensitive in vivo markers of neuropathologic changes associated with human immunodeficiency virus infection of the brain.

Objective: The Hick-Hyman law states that response time (RT) increases linearly with increasing information uncertainty. The effects of aging on uncertainty representations in choice RT paradigms remain unclear, including whether aging differentially affects processes mediating externally cued versus internally driven uncertainty. This study sought to characterize age-related differences in uncertainty representations using a card-sorting task., Method: The task separately manipulated internally driven uncertainty (i.e., probability of each stimulus type with fixed number of response piles) and externally cued uncertainty (i.e., number of response piles with fixed probability of each stimulus type)., Results: Older adults (OA) showed greater RT slowing than younger adults in response to uncertainty load, an effect that was stronger in the externally cued than internally driven condition. While both age groups showed lower accuracy and greater RTs in response to unexpected (surprising) stimuli in the internally driven condition at low uncertainty loads, OA were unable to distinguish between expected and nonexpected stimuli at higher uncertainty loads when the probability of each stimulus type was close to equal. Among OA, better performance on the internally driven, but not externally cued, condition was associated with better global cognitive performance and verbal fluency., Conclusions: Collectively, these findings provide behavioral evidence of age-related disruptions to bottom-up (externally cued) and top-down (supporting internally driven mental representations) resources to process uncertainty and coordinate task-relevant action. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Our ability to remember past events requires not only storing enduring engrams or memory traces of these events, but also successfully reactivating these latent traces in response to appropriate cues at the time of retrieval-a process that has been termed ecphory. However, relatively little is known about the processes that facilitate the dynamic interactions between retrieval cues and stored memory traces that are critical for successful recognition and recollection. Recently, an intriguing link between pupil dilation and recognition memory has been identified, with studied items eliciting greater pupil dilation than unstudied items during retrieval. However, the processes contributing to this "pupillary old/new effect" remain unresolved, with current explanations suggesting that it reflects the strength of the underlying memory trace. Here, we explore the novel hypothesis that the pupillary old/new effect does not index memory strength alone, but rather reflects the facilitation of cue-trace interactions during episodic memory retrieval that may be supported by activity within the pupil-linked locus coeruleus-noradrenergic (LC-NA) arousal system. First, we show that the magnitude of pupil dilation is influenced by the degree of overlap between cue and trace information. Second, we find that the magnitude of pupil dilation reflects the amount of study contextual information reinstated during retrieval. These findings provide a novel framework for understanding the pupillary old/new effect, and identify a potential role for the LC-NA system in recognition memory retrieval., (© 2023 Society for Psychophysiological Research.)

Many daily activities require performance of multiple tasks integrating cognitive and motor processes. While the fact that both processes go through deterioration and changes with aging has been generally accepted, not much is known about how aging interacts with stages of motor skill acquisition under a cognitively demanding situation. To address this question, we combined a visuomotor adaptation task with a secondary cognitive task. We made two primary findings beyond the expected age-related performance deterioration. First, while young adults showed classical dual-task cost in the early motor learning phase dominated by explicit processes, older adults instead strikingly displayed enhanced performance in the later stage, dominated by implicit processes. For older adults, the secondary task may have facilitated a shift to their relatively intact implicit learning processes that reduced reliance on their already-deficient explicit processes during visuomotor adaptation. Second, we demonstrated that consistently performing the secondary task in learning and re-learning phases can operate as an internal task-context and facilitate visuomotor memory retrieval later regardless of age groups. Therefore, our study demonstrated age-related similarities and differences in integrating concurrent cognitive load with motor skill acquisition which, may in turn, contributes to the understanding of a shift in balance across multiple systems., (© 2022. The Author(s).)

When recognizing objects in our environments, we rely on both what we see and what we know. While older adults often display increased sensitivity to top-down influences of contextual information during object recognition, the locus of this increased sensitivity remains unresolved. To examine the effects of aging on the neural dynamics of bottom-up and top-down visual processing during rapid object recognition, we probed the differential effects of object perceptual ambiguity and scene context congruity on specific EEG event-related potential components indexing dissociable processes along the visual processing stream. Older adults displayed larger behavioral scene congruity effects than young adults. Older adults' larger visual P2 amplitudes to object perceptual ambiguity (as opposed to the scene congruity P2 effects in young adults) suggest continued resolution of perceptual ambiguity that interfered with scene congruity processing, while post-perceptual semantic integration (as indexed by N400) remained largely intact. These findings suggest that compromised bottom-up perceptual processing in healthy aging leads to an increased involvement of top-down processes to resolve greater perceptual ambiguity during object recognition., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Accessing semantic representations of real-world objects requires integration of multimodal perceptual features that are represented across relevant neocortical areas. Early Alzheimer's disease (AD) neuropathology, including neurofibrillary tangles in the perirhinal cortex as well as disrupted cortico-cortical connectivity, would be expected to disrupt the integration of object features. This integration deficit may underlie AD patients' semantic memory deficits and would be predicted to be more prominent for living objects, which tend to be more defined by sensory features compared with nonliving objects., Method: Two experiments were conducted to assess feature integration in cognitively healthy older adults and patients with amnestic mild cognitive impairment (MCI). In both experiments, pictures of real-world objects were presented in congruent or incongruent colors. Participants were instructed to make a speeded color congruency judgment (Experiment 1) or name the presented surface color (Experiment 2)., Results: Across experiments, MCI patients showed a selective integration deficit for living, but not nonliving, objects across both experimental paradigms that was consistent with a deterioration in semantic structural representations rather than a deficit in controlled semantic retrieval. Planned secondary analyses with a subset of patients (Experiment 1) for whom PET imaging was available indicated that the degree of impairment was associated with the magnitude of cortical amyloid burden., Conclusions: These findings suggest that early AD pathology leads to impaired integration of distributed semantic object representations. The development of integration tasks as sensitive markers of early AD pathology may lead to more effective diagnostic tools for early detection and intervention. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Enhanced processing following a warning cue is thought to be mediated by a phasic alerting response involving the locus coeruleus-noradrenergic (LC-NA) system. We examined the effect of aging on phasic alerting using pupil dilation as a marker of LC-NA activity in conjunction with a novel assessment of task-evoked pupil dilation. While both young and older adults displayed behavioral and pupillary alerting effects, reflected in decreased RT and increased pupillary response under high (tone) versus low (no tone) alerting conditions, older adults displayed a weaker pupillary response that benefited more from the alerting tone. The strong association between dilation and speed displayed by older adults in both alerting conditions was reduced in young adults in the high alerting condition, suggesting that in young (but not older) adults the tone conferred relatively little behavioral benefit beyond that provided by the alerting effect elicited by the target. These findings suggest a functioning but deficient LC-NA alerting system in older adults, and help reconcile previous results concerning the effects of aging on phasic alerting., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction : During the clinical assessment of episodic memory, encoding ability is typically inferred from immediate recall performance. This dependency on effortful retrieval may not be optimal for estimating encoding, particularly in the presence of executive dysfunction. We examined whether a test of immediate recognition memory could meaningfully supplement recall in estimating encoding and provide unique information about memory retention. Method : Fifty older adult outpatients were administered a neuropsychological test battery including original and revised versions of the Hopkins Verbal Learning Test; the former (HVLT) assesses recognition memory immediately after learning trials, while the latter (HVLT-R) assesses only delayed recognition. Hierarchical regressions evaluated the incremental value of immediate recognition in predicting both delayed verbal and visual recognition. ANCOVA was performed on subgroups defined by the number of impaired performances on executive functioning tests (EF-intact, EF-1, EF-2) to examine the influence of executive impairment on measures of immediate recall and recognition. Recall- and recognition-based estimates of verbal memory retention were also compared across groups to determine whether they yield distinct patterns of memory consolidation. Results : Immediate verbal recognition accounted for significant variance in both delayed verbal and visual recognition beyond immediate recall, age, and education. Although subgroups were demographically similar, EF-1 and EF-2 performed significantly worse than EF-intact across verbal and visual memory recall. Contrastingly, there were no group differences in immediate recognition. Subgroups attained similar scores on a conventional, recall-based memory retention measure, but EF-2 showed relatively greater forgetting on a recognition-based retention measure. Conclusions : Immediate verbal recognition is an independent determinant of delayed memory performance but is not captured in current test paradigms. Study results provide proof-of-concept that recognition testing at learning can provide a more comprehensive index of encoding ability than recall alone, may facilitate disentangling memory functions from executive deficits, and could have important downstream implications for estimating memory consolidation.

Visual selective attention (VSA) improves across childhood. Conjunction search tasks require integrating multiple visual features in order to find a target among distractors and are often used to measure VSA. Motivated by the visual system's architecture and developmental changes in neural connectivity, we predicted that feature integration across separate visual pathways (e.g., color and motion) should develop later than feature integration within the same visual pathways (e.g., luminance and motion). A total of 89 4- to 10-year-old children completed a visual search task that manipulated whether feature integration was between separate parallel visual pathways or within the same visual pathway. We first examined whether color-motion integration was associated with a performance cost relative to luminance-motion integration across childhood. We found that color-motion integration was worse than luminance-motion integration in early childhood but that this difference decreased with age. We also examined whether luminance-motion and color-motion visual search performance developed differently across childhood. Reaction time (RT) visual search slopes for the luminance-motion condition were both stable across childhood and steeper overall than those for the color-motion condition. In contrast, RT search slopes for the color-motion condition became steeperincrease across childhood. Finally, we found that age-related improvements in color-motion integration, relative to luminance-motion integration, were associated with longer color-motion search rates across childhood. These data suggest that age-related improvements in color-motion feature integration may increase competition between color-motion targets and distractors, thereby increasing the amount of time needed to process distractors as nontargets during the selection process., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Previous studies in young adults have demonstrated strong functional links between phasic alerting and exogenous orienting. The present study examined changes in the dynamic interaction between these attentional networks in healthy aging and in amnestic mild cognitive impairment., Method: Healthy young adults, healthy older adults, and patients with amnestic mild cognitive impairment (MCI) were asked to identify as quickly as possible the color of a target stimulus that appeared within one of 2 peripheral boxes. Orienting was manipulated by a brief flashing of the same (valid cue) or opposite (invalid cue) box in which the target subsequently appeared. Alerting was manipulated by presenting an auditory white noise burst simultaneously with the visual orienting cue on half of the trials., Results: All 3 groups displayed significant alerting and orienting effects but differed in the nature of the interaction between alerting and orienting. As expected, young adults displayed increased orienting under high alerting conditions through a selective enhancement of validly cued targets. While older adults displayed a greater effect of alerting on orienting compared to young adults, MCI patients did not display a significant interaction between attentional networks., Conclusions: Results provide support for the presence of increased compensatory interactions between attentional networks in healthy aging that may be no longer effective with the emergence of clinical symptoms in MCI. The demonstration of qualitatively distinct effects of healthy aging and MCI suggests that behavioral tests of attentional network interactions may serve as cognitive markers in individuals at increased risk for developing AD. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Background: Previous epidemiologic studies have reported adverse neurodevelopmental sequelae following prenatal infectious exposure, yet long-term effects estimated from these observational studies are often subject to biases due to confounding and loss to follow-up., Objectives: We demonstrate the joint use of inverse probability (IP) treatment and censoring weights when evaluating neurotoxic effects of prenatal bacterial infection., Methods: We applied IP weighting for both treatment and censoring to estimate the effects of maternal bacterial infection during pregnancy on mean intelligence quotient (IQ) scores measured at age 7 using the Wechsler Intelligence Scale for Children. Participants were members of a population-based pregnancy cohort recruited in the Boston and Providence sites of the Collaborative Perinatal Project between 1959 and 1966 (n = 11 984). We calculated average treatment effects (ATE) and average treatment effects on the treated (ATT) using IP weights estimated via generalized boosted models., Results: ATE- and ATT-weighted mean IQ scores were lowest among offspring exposed to multi-systemic bacterial infection during pregnancy and highest for those unexposed. The effects of prenatal bacterial infection were greater among male offspring, particularly on performance IQ scores. Offspring who were exposed to multi-systemic bacterial infection in the third trimester displayed the largest reduction in mean full-scale, verbal, and performance IQ scores at age 7 compared to those unexposed or exposed in earlier trimesters., Conclusions: We find that prenatal bacterial infection is associated with cognitive impairments at age 7. Associations are strongest for more severe infections, that occur in the third trimester, and among males. Public health intervention targeting bacterial infection in pregnant women may help enhance the cognitive development of offspring., (© 2019 John Wiley & Sons Ltd.)

The Hick-Hyman law states that choice response time (RT) increases linearly with increasing information uncertainty. Neuroimaging studies suggest that the representation of uncertainty in support of response generation is mediated by the cognitive control network (CCN), which is disrupted in Alzheimer's disease (AD). Thus, we predicted that patients with AD would be sensitive to increased uncertainty particularly under conditions that place demands on the internal representation of uncertainty, and that choice RT performance under these conditions would be associated with performance on tests of executive function. Cognitively normal older adults (CN) and patients with AD completed card-sorting tasks that separately manipulated either externally cued uncertainty (i.e., number of sorting piles with a fixed probability of each stimulus type) or more internally driven uncertainty (i.e., the probability of each stimulus type with a fixed number of sorting piles). Consistent with our predictions, AD patients were impaired relative to CN particularly on the internally driven uncertainty task, and RT in this task was associated with performance on neuropsychological measures of executive functioning but not episodic memory. We suggest that this pattern of findings is consistent with presumed disruptions to the CCN in AD and provides neuropsychological evidence in support of the role of the CCN in the representation of uncertainty.

Objectives: Patients with Alzheimer's disease (AD) demonstrate deficits in cross-cortical feature binding distinct from age-related changes in selective attention. This may have consequences for driving performance given its demands on multisensory integration. We examined the relationship of visuospatial search and binding to driving in patients with early AD and elderly controls (EC)., Methods: Participants (42 AD; 37 EC) completed search tasks requiring either luminance-motion (L-M) or color-motion (C-M) binding, analogs of within and across visual processing stream binding, respectively. Standardized road test (RIRT) and naturalistic driving data (CDAS) were collected alongside clinical screening measures., Results: Patients performed worse than controls on most cognitive and driving indices. Visual search and clinical measures were differentially related to driving behavior across groups. L-M search and Trail Making Test (TMT-B) were associated with RIRT performance in controls, while C-M binding, TMT-B errors, and Clock Drawing correlated with CDAS performance in patients. After controlling for demographic and clinical predictors, L-M reaction time significantly predicted RIRT performance in controls. In patients, C-M binding made significant contributions to CDAS above and beyond demographic and clinical predictors. RIRT and C-M binding measures accounted for 51% of variance in CDAS performance in patients., Conclusions: Whereas selective attention is associated with driving behavior in EC, cross-cortical binding appears most sensitive to driving in AD. This latter relationship may emerge only in naturalistic settings, which better reflect patients' driving behavior. Visual integration may offer distinct insights into driving behavior, and thus has important implications for assessing driving competency in early AD. (JINS, 2018, 24, 486-497).

Introduction: We conducted a 27-month longitudinal study of mid-life adults with preclinical Alzheimer's disease (AD), using spectral domain optical coherence tomography to compare changes in volume and thickness in all retinal neuronal layers to those of age-matched healthy control subjects., Methods: Fifty-six older adults (mean age = 65.36 years) with multiple risk factors for AD completed spectral domain optical coherence tomography retinal imaging and cognitive testing at baseline. Twenty-seven months later, they completed the same examinations and an 18 F-florbetapir positron emission tomography imaging study., Results: Compared to healthy control subjects, those in the preclinical stage of AD showed a significant decrease in macular retinal nerve fiber layer (mRNFL) volume, over a 27-month follow-up interval period, as well as a decrease in outer nuclear layer and inner plexiform layer volumes and thickness in the inferior quadrant. However, only the mRNFL volume was linearly related to neocortical positron emission tomography amyloid standardized uptake value ratio after controlling for any main effects of age ( R 2  = 0.103; ρ = 0.017). Furthermore, the magnitude of mRNFL volume reduction was significantly correlated with performance on a task of participants' abilities to efficiently integrate visual and auditory speech information (McGurk effect)., Discussion: We observed a decrease in mRNFL, outer nuclear layer, and inner plexiform layer volumes, in preclinical AD relative to controls. Moreover, the largely myelinated axonal loss in the RNFL is related to increased neocortical amyloid-β accumulation after controlling for age. Volume loss in the RNFL, during the preclinical stage, is not related to performance on measures of episodic memory or problem solving. However, this retinal change does appear to be modestly related to relative decrements in performance on a measure of audiovisual integration efficiency that has been recently advanced as a possible early cognitive marker of mild cognitive impairment.

Effective audiovisual sensory integration involves dynamic changes in functional connectivity between superior temporal sulcus and primary sensory areas. This study examined whether disrupted connectivity in early Alzheimer's disease (AD) produces impaired audiovisual integration under conditions requiring greater corticocortical interactions. Audiovisual speech integration was examined in healthy young adult controls (YC), healthy elderly controls (EC), and patients with amnestic mild cognitive impairment (MCI) using McGurk-type stimuli (providing either congruent or incongruent audiovisual speech information) under conditions differing in the strength of bottom-up support and the degree of top-down lexical asymmetry. All groups accurately identified auditory speech under congruent audiovisual conditions, and displayed high levels of visual bias under strong bottom-up incongruent conditions. Under weak bottom-up incongruent conditions, however, EC and amnestic MCI groups displayed opposite patterns of performance, with enhanced visual bias in the EC group and reduced visual bias in the MCI group relative to the YC group. Moreover, there was no overlap between the EC and MCI groups in individual visual bias scores reflecting the change in audiovisual integration from the strong to the weak stimulus conditions. Top-down lexicality influences on visual biasing were observed only in the MCI patients under weaker bottom-up conditions. Results support a deficit in bottom-up audiovisual integration in early AD attributable to disruptions in corticocortical connectivity. Given that this deficit is not simply an exacerbation of changes associated with healthy aging, tests of audiovisual speech integration may serve as sensitive and specific markers of the earliest cognitive change associated with AD.

Visual search is an aspect of visual cognition that may be more impaired in Dementia with Lewy Bodies (DLB) than Alzheimer's disease (AD). To assess this possibility, the present study compared patients with DLB (n = 17), AD (n = 30), or Parkinson's disease with dementia (PDD; n = 10) to non-demented patients with PD (n = 18) and normal control (NC) participants (n = 13) on single-feature and feature-conjunction visual search tasks. In the single-feature task participants had to determine if a target stimulus (i.e., a black dot) was present among 3, 6, or 12 distractor stimuli (i.e., white dots) that differed in one salient feature. In the feature-conjunction task participants had to determine if a target stimulus (i.e., a black circle) was present among 3, 6, or 12 distractor stimuli (i.e., white dots and black squares) that shared either of the target's salient features. Results showed that target detection time in the single-feature task was not influenced by the number of distractors (i.e., "pop-out" effect) for any of the groups. In contrast, target detection time increased as the number of distractors increased in the feature-conjunction task for all groups, but more so for patients with AD or DLB than for any of the other groups. These results suggest that the single-feature search "pop-out" effect is preserved in DLB and AD patients, whereas ability to perform the feature-conjunction search is impaired. This pattern of preserved single-feature search with impaired feature-conjunction search is consistent with a deficit in feature binding that may be mediated by abnormalities in networks involving the dorsal occipito-parietal cortex., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: Visual processing abilities of patients with dementia with Lewy bodies (DLB) or Alzheimer disease (AD) dementia were assessed psychophysically using a simple horizontal motion discrimination task that engages the dorsal visual processing stream., Methods: Participants included patients with mild dementia with DLB, AD dementia or Parkinson disease (PD) with dementia (PDD), without dementia with PD, and normal controls. Participants indicated the left or right direction of coherently moving dots that were embedded within dynamic visual noise provided by randomly moving dots. The proportion of coherently moving dots was increased or decreased across trials to determine a threshold at which participants could correctly indicate their direction with greater than 80% accuracy., Results: Motion discrimination thresholds of patients with DLB and PDD were comparable and significantly higher (i.e., worse) than those of patients with AD dementia. The thresholds of patients with AD dementia and patients with PD were normal. These results were confirmed in subgroups of patients with DLB/PDD and AD dementia with autopsy-confirmed disease. A motion discrimination threshold greater than 0.23 distinguished between DLB/PDD and AD dementia with 67% sensitivity and 85% specificity., Conclusions: Differential deficits in detecting direction of simple horizontal motion suggest that dorsal processing stream dysfunction is greater in DLB and PDD than in AD dementia. Therefore, impaired performance on simple visual motion discrimination tasks that specifically engage occipitoparietal brain regions suggests the presence of Lewy body pathology., (© 2015 American Academy of Neurology.)

Evidence from patients with amnesia suggests that recognition memory span tasks engage both long-term memory (i.e., secondary memory) processes mediated by the diencephalic-medial temporal lobe memory system and working memory processes mediated by fronto-striatal systems. Thus, the recognition memory span task may be particularly effective for detecting memory deficits in disorders that disrupt both memory systems. The presence of unique pathology in fronto-striatal circuits in Dementia with Lewy Bodies (DLB) compared to AD suggests that performance on the recognition memory span task might be differentially affected in the two disorders even though they have quantitatively similar deficits in secondary memory. In the present study, patients with autopsy-confirmed DLB or AD, and Normal Control (NC) participants, were tested on separate recognition memory span tasks that required them to retain increasing amounts of verbal, spatial, or visual object (i.e., faces) information across trials. Results showed that recognition memory spans for verbal and spatial stimuli, but not face stimuli, were lower in patients with DLB than in those with AD, and more impaired relative to NC performance. This was despite similar deficits in the two patient groups on independent measures of secondary memory such as the total number of words recalled from long-term storage on the Buschke Selective Reminding Test. The disproportionate vulnerability of recognition memory span task performance in DLB compared to AD may be due to greater fronto-striatal involvement in DLB and a corresponding decrement in cooperative interaction between working memory and secondary memory processes. Assessment of recognition memory span may contribute to the ability to distinguish between DLB and AD relatively early in the course of disease., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Repetition priming refers to a form of implicit memory in which prior exposure to a stimulus facilitates the subsequent processing of the same or a related stimulus. One frequently used repetition priming task is word-stem completion priming. In this task, participants complete a series of beginning word stems with the first word that comes to mind after having viewed, in an unrelated context, words that can complete some of the stems. Patients with Alzheimer's disease (AD) exhibit a significant deficit in word-stem completion priming, but the neural mechanisms underlying this deficit have yet to be identified. The present study examined the possibility that the word-stem completion priming deficit in AD is due to disruption of ascending neuromodulatory systems that mediate cortical arousal by comparing word-stem completion priming and behavioral measures of spatial orienting and phasic alerting. Results showed that in healthy elderly controls higher levels of phasic alerting were associated with a sharpening of the temporal dynamics of priming across two delay intervals: those with higher levels of alerting showed more immediate priming but less delayed priming than those with lesser levels of alerting. In patients with AD, priming was impaired despite intact levels of phasic alerting and spatial orienting, and group status rather than individual levels of alerting or orienting predicted the magnitude of their stem-completion priming. Furthermore, the change in priming across delays they displayed was not related to level of alerting or orienting. These findings support the role of the noradrenergic projection system in modulating the level of steady-state cortical activation (or "cortical tonus") underlying both phasic alerting and the temporal dynamics of repetition priming. However, impaired priming in patients with AD does not appear to be due to disruption of this neuromodulatory system., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Recent neuroimaging studies suggest that prototype learning may be mediated by at least two dissociable memory systems depending on the mode of acquisition, with A/Not-A prototype learning dependent upon a perceptual representation system located within posterior visual cortex and A/B prototype learning dependent upon a declarative memory system associated with medial temporal and frontal regions. The degree to which patients with Alzheimer's disease (AD) can acquire new categorical information may therefore critically depend upon the mode of acquisition. The present study examined A/Not-A and A/B prototype learning in AD patients using procedures that allowed direct comparison of learning across tasks. Despite impaired explicit recall of category features in all tasks, patients showed differential patterns of category acquisition across tasks. First, AD patients demonstrated impaired prototype induction along with intact exemplar classification under incidental A/Not-A conditions, suggesting that the loss of functional connectivity within visual cortical areas disrupted the integration processes supporting prototype induction within the perceptual representation system. Second, AD patients demonstrated intact prototype induction but impaired exemplar classification during A/B learning under observational conditions, suggesting that this form of prototype learning is dependent on a declarative memory system that is disrupted in AD. Third, the surprisingly intact classification of both prototypes and exemplars during A/B learning under trial-and-error feedback conditions suggests that AD patients shifted control from their deficient declarative memory system to a feedback-dependent procedural memory system when training conditions allowed. Taken together, these findings serve to not only increase our understanding of category learning in AD, but to also provide new insights into the ways in which different memory systems interact to support the acquisition of categorical knowledge., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objectives: To examine the sensitivity and specificity of the Assessment of Driving-Related Skills (ADReS), a clinical tool recommended by the American Medical Association for identifying potentially unsafe older drivers that includes tests of vision, motor function, and cognition., Design: Cross-sectional observation study., Setting: Memory assessment outpatient clinic of a university hospital., Participants: Drivers with normal cognition (n = 47) and cognitive impairment (n = 75)., Measurements: A neurologist completed the ADReS during an office visit. Additional cognitive tests of executive, visuospatial, and visuomotor function were also performed. On a separate day, participants completed a standardized on-road test, assessed by a professional driving instructor using a global safety rating and a quantitative driving score., Results: In this sample of currently active older drivers with and without cognitive impairment, measures of cognition-particularly the Trail-Making Test Part B-were more highly correlated with driving scores than other measures of function. Using recommended scoring procedures, the ADReS had a sensitivity of 0.81 for detecting impaired driving on the road test, with a specificity of 0.32 and an area under the receiver operating characteristic curve (AUC) of 0.57. A logistic regression model that incorporated computerized maze task and Mini-Mental State Examination scores improved overall classification accuracy, yielding a sensitivity of 0.61, a specificity of 0.84, and an AUC of 0.80., Conclusion: In its present form, the ADReS has limited utility as an office screen for individuals who should undergo formal driving assessment. Improved scoring methods and screening tests with greater diagnostic accuracy than the ADReS are needed for general office practice., (© 2013, Copyright the Authors Journal compilation © 2013, The American Geriatrics Society.)

Previous findings that older drivers engage in strategic self-regulatory behaviors to minimize perceived safety risks are primarily based on survey reports rather than actual behavior. This study analyzed in-car video recording of naturalistic driving of 18 patients with Alzheimer disease (AD) and 20 age-matched controls in order to (1) characterize self-regulatory behaviors engaged by older drivers and (2) assess how behaviors change with cognitive impairment. Only participants who were rated "safe" on a prior standardized road test were selected for this study. Both groups drove primarily in environments that minimized the demands on driving skill and that incurred the least risk for involvement in major crashes. Patients with AD displayed further restrictions of driving behavior beyond those of healthy elderly individuals, suggesting additional regulation on the basis of cognitive status. These data provide critical empirical support for findings from previous survey studies indicating an overall reduction in driving mobility among older drivers with cognitive impairment.

Objectives: To relate the standardized road test to video recordings of naturalistic driving in older adults with a range of cognitive impairment., Design: Cross-sectional observational study., Setting: Academic medical center memory disorders clinic., Participants: One hundred three older drivers (44 healthy, 59 with cognitive impairment) who passed a road test., Measurements: Error rate and global ratings of safety (pass with and without recommendations, marginal with restrictions or training, or fail) made by a professional driving instructor., Results: There was fair agreement between global ratings on the road test and naturalistic driving. More errors were detected in the naturalistic environment, but this did not affect global ratings. Error scores between settings were significantly correlated, and the types of errors made were similar. History of crashes corrected for miles driven per week was related to road test error scores but not naturalistic driving error scores. Global cognition (Mini-Mental State Examination) was correlated with road test and naturalistic driving errors. In healthy older adults, younger age was correlated with fewer errors on the road test and more errors in naturalistic driving., Conclusion: Road test performance is a reasonable proxy for estimating fitness to drive in older individuals' typical driving environments, but differences between performance assessed using these two methods remain poorly understood and deserve further study., (© 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.)

Given previous demonstrations of both selective and divided attention deficits in Alzheimer's disease (AD) patients, understanding how declines in the integrity of component processes of selective attention in these patients interact with impairments to executive processes mediating dual-task performance has both theoretical and practical relevance. To address this issue, healthy elderly and AD patients performed computerized tasks of spatial orienting, Simon response interference, and visual search both in isolation and while simultaneously engaged in a visuomotor tracking task (i.e., maintaining car position within a simulated driving environment). Results from the single-task conditions confirmed previous demonstrations of selective attention deficits in AD. Dual-task conditions produced in AD patients (but not healthy elderly) a change in the efficiency of the selective attention mechanisms themselves, as reflected in differential effects on cue or display conditions within each task. Rather than exacerbating the selective attention deficits observed under single-task conditions, however, dual-task conditions produced an apparent diminution of these deficits. We suggest this diminution is due to the combination of deficient top-down inhibitory processes along with a decrease in the attention-capturing properties of cue information under dual-task conditions in AD patients. These findings not only increase our understanding of the nature of the attentional deficits in AD patients, but also have implications for understanding the processes mediating attention in neurologically intact individuals., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Objective: We conducted a combined observational cohort and case-control study in patients with Alzheimer disease (AD) to assess the effects of acetylcholinesterase inhibitor (ChEI) treatment on cognitive functions important for driving., Methods: Performance of 24 outpatients with newly diagnosed (untreated) early-stage AD was compared before beginning ChEI (pre-ChEI) and after 3 months of therapy (post-ChEI) on a set of computerized tests of visual attention and executive function administered under both single-task and dual-task conditions. To address the limitation of a lack of an untreated control group in this observational cohort study, performance of 35 outpatients with newly diagnosed (untreated) early-stage AD (ChEI nonusers) were also compared with a demographically matched group of AD patients treated with stable doses of a ChEI (ChEI users) on these tasks., Results: Performance was consistently worse under dual-task than single-task conditions regardless of ChEI treatment status. However, ChEI treatment consistently affected specific components of attention within each test across both sets of comparisons: ChEI treatment enhanced simulated driving accuracy and was associated with significantly better visual search target detection accuracy and response time in both pre-ChEI-post-ChEI and users-nonusers treatment comparisons. Cholinesterase inhibitor treatment also improved overall time to complete a set of mazes while not affecting accuracy of completion., Conclusions: Cholinesterase inhibitor treatment was associated with improvements in tests of executive function and visual attention. These findings could have important implications for patients who continue to drive in the early stages of AD.

Objective: The goal of this study was to define the natural progression of driving impairment in persons who initially have very mild to mild dementia., Methods: We studied 128 older drivers, including 84 with early Alzheimer disease (AD) and 44 age-matched control subjects without cognitive impairment. Subjects underwent repeated assessments of their cognitive, neurologic, visual, and physical function over 3 years. Self-reports of driving accidents and traffic violations were supplemented by reports from family informants and state records. Within 2 weeks of the office evaluation, subjects were examined by a professional driving instructor on a standardized road test., Results: At baseline, subjects with AD had experienced more accidents and performed more poorly on the road test, compared to controls. Over time, both groups declined in driving performance on the road test, with subjects with AD declining more than controls. Survival analysis indicated that while the majority of subjects with AD passed the examination at baseline, greater severity of dementia, increased age, and lower education were associated with higher rates of failure and marginal performance., Conclusions: This study confirms previous reports of potentially hazardous driving in persons with early Alzheimer disease, but also indicates that some individuals with very mild dementia can continue to drive safely for extended periods of time. Regular follow-up assessments, however, are warranted in those individuals.

This study examined the ability of computerized maze test performance to predict the road test performance of cognitively impaired and normal older drivers. The authors examined 133 older drivers, including 65 with probable Alzheimer disease, 23 with possible Alzheimer disease, and 45 control subjects without cognitive impairment. Subjects completed 5 computerized maze tasks employing a touch screen and pointer as well as a battery of standard neuropsychological tests. Parameters measured for mazes included errors, planning time, drawing time, and total time. Within 2 weeks, subjects were examined by a professional driving instructor on a standardized road test modeled after the Washington University Road Test. Road test total score was significantly correlated with total time across the 5 mazes. This maze score was significant for both Alzheimer disease subjects and control subjects. One maze in particular, requiring less than 2 minutes to complete, was highly correlated with driving performance. For the standard neuropsychological tests, highest correlations were seen with Trail Making A (TrailsA) and the Hopkins Verbal Learning Tests Trial 1 (HVLT1). Multiple regression models for road test score using stepwise subtraction of maze and neuropsychological test variables revealed significant independent contributions for total maze time, HVLT1, and TrailsA for the entire group; total maze time and HVLT1 for Alzheimer disease subjects; and TrailsA for normal subjects. As a visual analog of driving, a brief computerized test of maze navigation time compares well to standard neuropsychological tests of psychomotor speed, scanning, attention, and working memory as a predictor of driving performance by persons with early Alzheimer disease and normal elders. Measurement of maze task performance appears to be useful in the assessment of older drivers at risk for hazardous driving.

Although deterioration of higher-order visual information processing abilities occurs in Alzheimer's disease (AD), few cross-sectional or longitudinal studies have systematically examined this deficit. The performance of 135 patients with probable AD and 97 matched normal control (NC) participants were compared on a structured test of perceptual organization ability, the Hooper Visual Organization Test (VOT). Both the standard VOT score and a derived score that corrected for anomia were significantly lower for AD patients than for NC participants, but neither score was particularly effective at distinguishing between the groups. The derived VOT score proved to be a more effective measure of visuospatial functioning than the standard VOT score as it loaded with other visuospatial tests in a principal components analysis while the standard score loaded with language tests. The VOT was sensitive to severity of dementia in the AD patients. Longitudinal assessment of 37 of the AD patients and 46 NC participants revealed significant decline over one year in the VOT scores of AD patients, but not in those of NC participants. These results indicate that higher-order visual information processing is impaired in patients with AD and gradually deteriorates with disease progression. This deficit may not be a particularly salient early marker of the disease, but it may be useful in tracking disease course.

A. Tales, R. J. Snowden, M. Brown, and G. Wilcock (2006) have questioned the authors' view of a possible interdependence between attentional systems mediating exogenous spatial orienting and phasic alerting as well as the authors' suggestion that phasic alerting deficits in patients with Alzheimer's disease (AD) may be influencing their performance on tests of spatial orienting. Consistent with this possibility, both laboratories have previously demonstrated increased spatial orienting and decreased phasic alerting in patients with AD. In Tales et al.'s current study, however, they have instead suggested that their results provide evidence for functional independence between these attentional systems in AD. In this commentary, the authors address the misinterpretations of their study and evaluate the degree to which Tales et al.'s study addresses the issues that they raise. Given Tales et al.'s difficulty performing analyses on response time data because of variance issues, the presence of a reduced (although not significant) alerting effect in Tales et al.'s AD group (consistent with the authors' previous findings), and a potential floor effect in their measure of alerting, the authors question the validity of Tales et al.'s conclusions and reaffirm their position that not considering interactions among attentional systems can lead to inaccurate characterizations of the mechanisms by which they operate.

The present study assessed frontostriatal mediated memory functions in children with ADHD (N=12) and healthy control participants (N=12) using two tests of conditional associative learning (i.e., object and spatial) that shared similar stimulus-response association structures but that differed in terms of the demands placed upon strategic processes. Children with ADHD displayed normal performance on the object learning task but were impaired on the spatial learning task that placed greater demands on internally derived strategic processes. Secondary analyses further indicated that this strategic processing impairment cannot be attributed specifically to perseverative or working memory errors but rather appears to be related to a more general inability to maintain a high degree of consistency in responding across trials. Although the results of this study must be interpreted in light of the small sample sizes, they suggest that ADHD does not produce a basic deficit in acquiring stimulus-response associations previously shown to be associated with basal ganglia dysfunction. Rather, these findings suggest that the impaired conditional associative learning performance of children with ADHD is attributable to deficits in strategic processes previously been found to be dependent upon the integrity of the prefrontal cortex.

The cortical pathology in Alzheimer's disease (AD) should lead to the loss of effective interaction between distinct neocortical areas. This study compared 2 conditions within a single sensory integration task that differed in the demands placed on effective cross-cortical interaction. AD patients were impaired in their ability to bind distinct visual features of a stimulus when this binding placed greater demands on cross-cortical interaction (i.e., motion and color) but were not impaired when this binding placed lesser demands on such interaction (i.e., motion and luminance). In contrast, neurologically intact individuals and patients with Huntington's disease were able to effectively bind features under both conditions. These results provide psychophysical support for the presence of functional disconnectivity in AD and demonstrate the utility of AD for investigating the neurocognitive substrates of sensory integration., (Copyright (c) 2005 APA, all rights reserved.)

Neuropsychological and motor deficits in Parkinson's disease that may contribute to driving impairment were examined in a cohort study comparing patients with Parkinson's disease (PD) to patients with Alzheimer's disease (AD) and to healthy elderly controls. Nondemented individuals with Parkinson's disease [Hoehn & Yahr (H&Y) stage I-III], patients with Alzheimer's disease [Clinical Demetia Rating scale (CDR) range 0-1], and elderly controls, who were actively driving, completed a neuropsychological battery and a standardized road test administered by a professional driving instructor. On-road driving ability was rated on number of driving errors and a global rating of safe, marginal, or unsafe. Overall, Alzheimer's patients were more impaired drivers than Parkinson's patients. Parkinson's patients distinguished themselves from other drivers by a head-turning deficiency. Drivers with neuropsychological impairment were more likely to be unsafe drivers in both disease groups compared to controls. Compared to controls, unsafe drivers with Alzheimer's disease were impaired across all neuropsychological measures except finger tapping. Driving performance in Parkinson's patients was related to disease severity (H&Y), neuropsychological measures [Rey Osterreith Complex Figure (ROCF), Trails B, Hopkins Verbal List Learning Test (HVLT)-delay], and specific motor symptoms (axial rigidity, postural instability), but not to the Unified Parkinson Disease Rating Scale (UPDRS) motor score. Multifactorial measures (ROCF, Trails B) were useful in distinguishing safe from unsafe drivers in both patient groups.

Objective: To investigate the behavioral and neural effects of rule-based knowledge on motor sequence learning., Methods: The authors developed a novel 2-dimensional variant of the serial reaction time (SRT) task to test the effect of prior, verbalizable rule knowledge on motor learning behavior. To examine neurophysiological effects, they also performed functional magnetic resonance imaging on a small cohort of subjects while performing the same task., Results: Behavioral data demonstrated that instruction on sequence-governing rules enhanced behavioral performance in both learning magnitudes and rates. The neuroimaging data revealed substantially different, but partially overlapping, learning-related activation patterns with and without prior rule instruction. Direct comparison of these 2 conditions revealed significantly different involvement of bilateral superior and anterior prefrontal cortex (Brodmann areas 8 and 10, respectively), right superior temporal cortex (BA 38/21), and left cerebellum., Conclusions: These behavioral findings demonstrate an advantage of teaching governing rules prior to 2D-SRT task performance. While these neuroimaging findings remain to be replicated in a larger cohort of subjects, results suggest that substantially different-though partially overlapping-brain regions subserve learning in these 2 rehabilitation-relevant conditions. Thus, appropriate choice of pretraining may benefit, for example, rehabilitation populations, at least in motor skill acquisition that requires sequencing.

The effects of aging and Alzheimer's disease (AD) on phasic alerting and exogenous spatial orienting were examined within a single precuing task. Phasic alerting decreased with normal aging and was completely eliminated with AD. AD patients also demonstrated an increased spatial orienting effect, attributable to an increased benefit from spatial orienting that was associated with a decreased benefit from nonselective alerting. These results suggest that performance within the precuing paradigm reflects the product of an interaction between nonselective alerting processes and spatially selective orienting processes. The results also highlight the importance of simultaneously assessing alerting and orienting within the same task, because changes attributable to alerting may otherwise be attributed incorrectly to changes in 1 or more processes associated with spatial orienting.

A battery of standard neuropsychological tests examining various features of executive function, attention, and visual perception was administered to 27 subjects with questionable to mild dementia and compared to a 4-point caregiver rating scale of driving ability. Based on the results of this study, a computerized maze task, employing 10 mazes, was administered to a second sample of 40 normal elders and questionable to moderately demented drivers. Comparison was made to the same caregiver rating scale as well as to crash frequency. In the first study of neuropsychological tests, errors on Porteus Mazes emerged as the only significant predictor of driving ability in a stepwise regression analysis. In the follow-up study employing the computerized mazes, all 10 mazes were significantly related to driving ability ratings. Computerized tests of maze performance offer promise as a screening tool to identify potential driving impairment among cognitively impaired elderly and demented drivers.

Objective: To define the pathophysiologic substrate of gender differences in cognition and behavior in Alzheimer's disease (AD)., Design: Hemispheric regional cerebral blood flow (rCBF) was studied in a consecutive series of dementia patients using single photon emission computed tomography (SPECT)., Participants: Subjects included 300 outpatients who were studied with SPECT as part of a diagnostic evaluation for degenerative dementia or memory disorder., Method: Based on qualitative descriptions by a radiologist, subjects were classified as having unilateral left, unilateral right, bilateral, or no perfusion defects. Semiquantitative analysis of SPECT images was also performed using region of interest radionuclide counts normalized to the cerebellum., Results: Among 174 females and 126 males, unilateral left hemisphere defects were found more commonly in women than men (24% vs 10%; chi 2 = 9.4; P = .009). This observation was most significant for the 103 females and 62 males regarded as having probable AD (26% vs 8%; chi 2 = 9.3; P = .01). In a multiple regression model of clinical variables, shorter duration of disease and female gender were significant independent predictors of the unilateral left hemisphere pattern among those with probable AD. Age, family history, education, handedness, and severity of cognitive impairment were not significant contributors., Conclusions: Women with AD exhibit greater heterogeneity in rCBF than men. Asymmetry in rCBF occurs more often in women. In some cases, this is related to relative preservation of right hemisphere function in women.

Single-photon emission computed tomography (SPECT) was used in this study to examine the neurophysiologic basis of driving impairment in 79 subjects with dementia. Driving impairment, as measured by caregiver ratings, was significantly related to regional reduction of right hemisphere cortical perfusion on SPECT, particularly in the temporo-occipital area. With increased severity of driving impairment, frontal cortical perfusion was also reduced. Clock drawing was more significantly related to driving impairment than the Mini-Mental State Examination (MMSE). Driving impairment in Alzheimer's disease is related to changes in cortical function which vary according to the severity of the disease. Cognitive tests of visuoperceptual and executive functions may be more useful screening tools for identifying those at greatest risk for driving problems than examinations like the MMSE that are weighted toward left-hemisphere-based verbal tasks., (Copyright 2000 S. Karger AG, Basel)

The ability to generate words from phonemic (i.e., words beginning with 'F,' 'A,' and 'S') and semantic (i.e., animals, fruits, and vegetables) categories was assessed longitudinally in patients with Alzheimer's disease (AD; N = 59) and normal controls (NC; N = 59). Patients with AD performed worse than NC participants on both tasks at each of 4 annual evaluations and exhibited greater impairment relative to controls on the semantic-category task than on the phonemic-category task. In addition, the performance of the patients with AD declined over time on both tasks, but the rate of decline was faster on the semantic-category than on the phonemic-category task. Examination of individual responses across the annual evaluations revealed that patients with AD were more consistent than NC participants in failing to generate previously produced semantic-category, but not phonemic-category, items in all years following the 1st year in which the item was not produced. These results are consistent with the notion that patients with AD suffer a gradual deterioration of the organization and content of semantic memory as the disease progresses.

Perceptual repetition priming was examined in patients with dementia of the Alzheimer type (DAT) and normal control (NC) participants using a task involving the discrimination of geometric designs that had either a continuous ("closed") or discontinuous ("open") perimeter. With the open stimuli, the groups displayed significant and equivalent levels of priming after immediate repetition of the stimuli, whereas only the NC group primed significantly over a delay of three intervening items. Neither group demonstrated significant priming with the closed stimuli. Results indicate that under some conditions DAT patients can exhibit normal repetition priming with stimuli that do not have preexisting representations but that (due possibly to a deficiency in the level of steady-state cortical activation) this priming dissipates more rapidly in DAT patients than in NC participants.

A word-fragment completion task was used to assess long-term, non-associative lexical priming in patients with probable Alzheimer's disease (AD) and age- and education-matched elderly normal control (NC) subjects. Despite equivalent baseline performance, the AD patients exhibited less facilitation in their ability to complete word fragments from having previously read the intact words than did the NC subjects. The AD patients were also impaired relative to NC subjects on an explicit recognition memory task, but there was no relationship between explicit memory performance and priming for either group. These results are consistent with previous demonstrations of impaired semantically-based priming in patients with AD and extend the domain of their impairment to priming that is predominantly based on lexical activation.

Objective: To examine the relationship between gender and specific types of behavior problems that occur in patients with Alzheimer's disease., Design: This was an observational study using the Dementia Behavior Disturbance Scale to quantify and define behavioral problems encountered by caregivers. Multiple regressions were used to control for the possible influence of dementia severity as measured by the Mini-Mental State Examination and the duration of dementia., Setting: Patients were sampled from the outpatient dementia clinics of Roger Williams Hospital and Miriam Hospital in Providence, Rhode Island., Participants: A total of 125 patients with probable Alzheimer's disease, defined by NINCDS-ADRDA diagnostic criteria, were included in the study. There were 75 women and 50 men., Main Outcome Measures: Caregivers rated the presence and frequency of 28 different behavior problems from the Dementia Behavior Disturbance Scale. Domains of behavior disturbance were then defined by a factor analysis of the data., Results: Male and female groups were comparable for the demographic variables of age, education, and duration of dementia, as well as severity of depression, degree of cognitive impairment and overall severity of behavior disturbance. Among the six behavior factors that were defined, two were significantly related to gender. One factor, which included apathy and vegetative signs, was related to male gender; a second factor, which included reclusiveness and emotional lability, was related to female gender., Conclusions: Although overall severity of behavior disturbance in Alzheimer's disease may be related primarily to severity in dementia, significant differences in the types of behaviors manifested exist between males and females with the disease.

HIV infection has been associated with decline in a number of cognitive functions that are components of 'working memory'. Thus, tests of working memory that require the interaction of these components may be particularly sensitive to cognitive dysfunction that arises from HIV infection. To assess this possibility, working memory was examined in 147 HIV-seropositive (HIV+) and 38 HIV-seronegative (HIV-) males using the Reading Span Test and the Digit Span subtest from the Wechsler Memory Scale-Revised (WMS-R). Speed of information processing, a component of some working memory tasks, was assessed with a version of the Sternberg Memory Scanning task. Results indicated that symptomatic HIV+ subjects were impaired relative to HIV- control subjects on the Reading Span and Digit Span tests. Asymptomatic and mildly symptomatic HIV+ groups exhibited a trend toward impairment on these tests, and on the whole, a greater proportion of HIV+ subjects than HIV- subjects were impaired. The groups did not differ significantly in information processing speed. These results indicate that deficits in working memory are apparent in at least a subset of HIV-infected individuals. These deficits are most apparent in symptomatic HIV+ individuals, but the decline may begin during the asymptomatic phase of infection.

This experiment investigated the effects of verbal labels on recognition memory for ambiguous visual figures in patients with Alzheimer's disease (AD), patients with Huntington's disease (HD), and matched normal control subjects. The study employed ambiguous figures that could be interpreted in two different ways. During the study phase each figure was presented together with a verbal label that corresponded to one interpretation of the figure. After a 30-min retention interval a recognition memory test was given during which the study figures and distractor figures were presented one at a time without verbal labels. For each study figure two distractor figures were employed, each corresponding to a different interpretation of the study figure. The patients' overall recognition memory performance was severely impaired compared to control subjects. However, all subject groups tended to produce responses and response latencies to distractor items that were consistent with the verbal labels presented during the study phase. This bias effect occurred in the AD patients despite the fact that their recognition memory performance was at chance level. Indeed, there was no significant difference in the bias evidenced by the AD and HD patients and their respective matched control subjects. The bias effects were obtained in an explicit memory task, and the findings are discussed in terms of unconscious influences on explicit memory processes.

Individuals infected with Human Immunodeficiency Virus (HIV) and having cognitive impairment have been described as having slow mentation. Data supporting this proposition come from a variety of sources, including Sternberg's (1966) item recognition memory task. The procedure nominally provides an index of speed of mental operations, independent from input/output demands. However, since the original use of this procedure in the 1960s, advances in cognitive psychology have revealed many of its limitations. The purpose of the present study was to examine the psychometric characteristics of this task. Each participant performed the Sternberg item recognition task twice, 6 mo apart. The stability of the estimate of the slope of regression equations and for zero intercept ranged from excellent (r = .87) to poor (r = .30), and the data from many individual subjects could not be reliably modelled using multiple linear regression techniques. These data, as well as those from previous research, demonstrate the limited practical use of this task in clinical samples. Furthermore, as cognitive psychological theory has advanced in the past 30 yr, the conceptual underpinnings of the procedure have essentially evaporated.

Objective: To directly examine the relationship between magnetic resonance imaging (MRI) abnormalities and neuropathologic changes in the brains of patients with the acquired immunodeficiency syndrome., Design: A total of 17 brains from patients with acquired immunodeficiency syndrome for which postmortem MRI scans were available were used in this study. Volumes of cortical gray matter, deep gray matter, and abnormal white matter were estimated from the MRIs of the left hemispheres of the formalin-fixed brains from patients with acquired immunodeficiency syndrome using quantitative morphometric techniques. Quantitative estimates of human immunodeficiency virus, gliosis, and neocortical synaptic and dendritic density were obtained from the corresponding right hemispheres. Quantification of human immunodeficiency virus and gliosis was performed on all 17 specimens, while quantification of synaptic and dendritic density was performed on 10 of the 17 specimens., Setting: All specimens were obtained from patients with the acquired immunodeficiency syndrome who underwent autopsy between 1990 and 1992 at the University of California-San Diego Medical Center and the San Diego (Calif) Department of Veterans Affairs Hospital., Results: No association was found between MRI volumes and gliosis, a nonspecific marker of central nervous system damage. Significant and regionally specific relationships were obtained, however, between the severity of central nervous system human immunodeficiency virus infection and the MRI volume estimates of gray matter and abnormal white matter. In addition, a significant association was observed between cortical gray matter volumes and cortical synaptic density., Conclusion: These findings indicate that the quantitative morphometric analysis of MRIs in patients may provide sensitive in vivo markers of neuropathologic changes associated with human immunodeficiency virus infection of the brain.