In the Baltimore Longitudinal Study of Aging (BLSA), we examined the temporal unfolding of declining performance on tests of episodic memory (Free Recall on the Free and Cued Selective Reminding Test), executive function (Category Fluency, Letter Fluency, and Trails), and Verbal Intelligence (Nelson, 1982; American Version of the Nelson Adult Reading Test [AMNART]) before the diagnosis of dementia in 92 subjects with incident Alzheimer's disease (AD) followed for up to 15 years before diagnosis. To examine the preclinical onset of cognitive decline, we aligned subjects at the time of initial AD diagnosis and examined the cognitive course preceding diagnosis. We found that declines in performance on tests of episodic memory accelerated 7 years before diagnosis. Declining performance on tests of executive function accelerated 2–3 years before diagnosis, and verbal intelligence declined in close proximity to diagnosis. This cognitive profile is compatible with pathologic data suggesting that structures which mediate memory are affected earlier than frontal structures during the preclinical onset of AD. It also supports the view that VIQ as estimated by the AMNART does not decline during the preclinical onset of AD. (JINS, 2008, 14, 266–278.)Supported in part by grants AG017854, AG08325, AG03949, and AG16573 from the National Institutes of Health, and by the National Institute on Aging Intramural Research Program of the National Institutes of Health.

Disturbances of visual perception frequently accompany neurodegenerative disorders but have been little studied in Huntington's disease (HD) gene carriers. We used psychophysical tests to assess visual perception among individuals in the prediagnostic and early stages of HD. The sample comprised four groups, which included 201 nongene carriers (NG), 32 prediagnostic gene carriers with minimal neurological abnormalities (PD1); 20 prediagnostic gene carriers with moderate neurological abnormalities (PD2), and 36 gene carriers with diagnosed HD. Contrast sensitivity for stationary and moving sinusoidal gratings, and tests of form and motion discrimination, were used to probe different visual pathways. Patients with HD showed impaired contrast sensitivity for moving gratings. For one of the three contrast sensitivity tests, the prediagnostic gene carriers with greater neurological abnormality (PD2) also had impaired performance as compared with NG. These findings suggest that early stage HD disrupts visual functions associated with the magnocellular pathway. However, these changes are only observed in individuals diagnosed with HD or who are in the more symptomatic stages of prediagnostic HD. (JINS, 2008, 14, 446–453.)

The reason people read from top to bottom is unknown, but could be related to brain-mediated directional biases or environmental factors. To learn if there is a brain-mediated directional bias responsible for top–down reading direction, we evaluated the directional scanning in the vertical dimension by using directional letter and face cancellation tasks. Twenty participants were instructed to cancel either target letters or faces using either an up–down or down–up direction, with the stimuli located in left, right, and center hemispace. The results indicated significant differences in completion time between the search direction (up vs. down) and spatial position for the letter cancellation task, with a faster completion time for the bottom–up scan in right space and top–down in left space. Because the left hemisphere primarily attends to contralateral right hemispace our results suggest that, when attending to letter stimuli, the left hemisphere is biased to scan in a proximal to distal (upward) direction. Although the reasons why this is reversed in left hemispace and why we did not see directional biases in the face condition remains unclear, these results do suggest that the direction in which we learn to read is inconsistent with the brain's intrinsic directional bias. (JINS, 2008, 14, 102–109.)

The present study was aimed at investigating the effect of acute levodopa administration on the performance of a group of individuals with Parkinson's disease (PD) on a time-based prospective memory task. Twenty PD patients and 15 healthy controls were administered a task that required executing three actions after 10 min had elapsed in three consecutive trials. Scores were computed for correct recall of the intention to perform the actions and for correct execution of the actions. PD participants were evaluated after a 12-hr drug wash-out in two conditions: (1) after levodopa administration (“on”); (2) without drug administration (“off”). In the “on” condition, PD patients were significantly more accurate in retrieving the intention to perform the actions than in the “off” condition and their performance was actually comparable to that of healthy controls. The increased accuracy in complying with the prospective memory task following levodopa medication supports the idea that dopamine depletion plays a role in the prospective memory deficits observed in PD patients. (JINS, 2008, 14, 601–610.)

Cognitive impairments in information processing speed, attention and executive functioning are widely reported in patients with multiple sclerosis (MS). Several studies have identified impaired performance on the Stroop test in people with MS, yet uncertainty remains over the cause of this phenomenon. In this study, 25 patients with MS were assessed with a neuropsychological test battery including a computerized Stroop test and a computerized test of information processing speed, the Graded Conditional Discrimination Tasks (GCDT). The patient group was compared with an individually age, sex and estimated premorbid IQ-matched healthy control group. The patients' reaction times (RTs) were significantly longer than those of the controls on all Stroop test trials and there was a significantly enhanced absolute (RTincongruent-RTneutral) and relative (100·[RTincongruent-RTneutral]/RTneutral) Stroop interference effect for the MS group. The linear function relating RT to stimulus complexity in the GCDT was significantly steeper in the patient group, indicating slowed information processing. The results are discussed with reference to the difference engine model, a theory of diversity in speeded cognition. It is concluded that, in the assessment of people with MS, great caution must be used in the interpretation of performance on neuropsychological tests which rely on RT as the primary measure. (JINS, 2008, 14, 805–814.)

Social cognition and learning potential have been proposed as mediating variables between neurocognition and functional outcome in schizophrenia. The present study examined this relation in a schizophrenia group (N = 26) with normal IQ. Neurocognition was measured with a composite score from tests of verbal learning, psychomotor speed, and executive functioning. Functional outcome was defined as social problem-solving skills and assessed with a role-play test. Social cognition was indexed by tests of visual and auditory emotion perception; and learning potential by estimating a gain score using a triple administration of the WCST. Neurocognition was confirmed to be a strong predictor of social problem-solving, and emotion perception was related to both neurocognition and social problem-solving. When controlling for emotion perception, the association between neurocognition and social problem-solving was weakened, implying a mediating role of emotion perception. Learning potential was not significantly related to neurocognition or social problem-solving, and thus not found to mediate the studied relation. In conclusion, our study indicates that emotion perception is a mediator between neurocognition and functional outcome as assessed with a social problem-solving task and thus a key factor in understanding functional outcome of schizophrenia. (JINS, 2008, 14, 279–288.)

Deficits in inhibitory abilities are frequently observed in normal aging. However, few studies have explored the generality of these deficits in a single group of participants. Here, we used an adaptation of the Simon task to differentially assess perceptual and motor inhibition using the same stimuli and task design and to determine whether these processes use separate or shared cognitive resources. We were interested in determining whether (1) normal aging is associated with the use of separate (as previously evidenced in young participants) or similar cognitive resources to perform perceptual and motor inhibition tasks; (2) older participants present a specific impairment in one of these two processes. Analyses of reaction times indicated that motor and perceptual inhibitory processes share some cognitive resources and both are impaired in normal aging. These results can be interpreted by considering that a dedifferentiation process is responsible for the inhibitory deficits presented by older participants. (JINS, 2008, 14, 1014–1021.)

There is evidence in the literature that cognitive functions in schizophrenia (SC) may be improved by atypical neuroleptics (NLPs) in contrast to typical medication, but there is still controversy regarding this apparent superiority of atypical drugs. In this study, we assessed the differential effects of risperidone and haloperidol on verbal memory, attention, and psychiatric symptoms in SC. The performance of 28 SC participants, randomly assigned to risperidone (2–6 mg/day) or haloperidol (2–40 mg/day), was compared with that of healthy controls. The California Verbal Learning Test (CVLT), the d2 Cancellation Test, and the Positive and Negative Symptoms Scale were administered at baseline and 3, 6, and 12 months. Relative to controls, all SC participants showed markedly impaired verbal memory and processing speed at each assessment period. There was no differential effect between the two NLPs on CVLT and d2 performance. However, risperidone was more effective than haloperidol in reducing psychiatric symptoms. Improvement in symptom severity was not associated with improvement in neurocognitive performance on these specific tests. Neither conventional nor atypical neuroleptic medications improved neurocognitive functioning over a 12-month follow-up, suggesting that psychopathological improvement under risperidone is independent of cognitive function. (JINS, 2008, 14, 110–118.)

The involvement of the left temporal lobe in semantics and object naming has been repeatedly demonstrated in the context of language comprehension; however, its role in the mechanisms and time course for the retrieval of an integrated object memory from its constituent features have not been well delineated. In this study, 19 young adults were presented with two features of an object (e.g., “desert” and “humps”) and asked to determine whether these two features were congruent to form a retrieval of a specific object (“camel”) or incongruent and formed no retrieval while event-related potentials (ERP) were recorded. Beginning around 750 ms the ERP retrieval and nonretrieval waveforms over the left anterior fronto-temporal region show significance differences, indicating distinct processes for retrievals and nonretrievals. In addition to providing further data implicating the left frontal-anterior temporal region in object memory/retrieval, the results provide insight into the time course of semantic processing related to object memory retrieval in this region. The likely semantic process at 750 ms in this task would be coactivation of feature representations common to the same object. The consistency of this finding suggests that the process is stable across individuals. The potential clinical applications are discussed. (JINS, 2008, 14, 815–822.)

Children with prenatal alcohol exposure (PAE) show deficits in verbal learning and spatial memory, as well as abnormal hippocampal development. The relationship between their memory and neuroanatomic impairments, however, has not been directly explored. Given that the hippocampus is integral for the synthesis and retrieval of learned information and is particularly vulnerable to the teratogenic effects of alcohol, we assessed whether reduced learning and recall abilities in children with fetal alcohol spectrum disorders (FASDs) are associated with abnormal hippocampal volumes. Nineteen children with FASDs and 18 typically developing controls aged 9 to 15 years were assessed for verbal learning and verbal and spatial recall and underwent structural magnetic resonance imaging. Images were analyzed for total intracranial volume and for right and left hippocampal volumes. Results revealed smaller left hippocampi and poorer verbal learning and verbal and spatial recall performance in children with FASDs than controls, as well as positive correlations between selective memory indices and hippocampal volumes only in the FASD group. Additionally, hippocampal volumes increased significantly with age in controls only, suggesting that PAE may be associated with long-term abnormalities in hippocampal development that may contribute to impaired verbal learning and verbal and spatial recall. (JINS, 2008, 14, 1022–1033.)

We investigated whether MCI patients with hippocampal atrophy or multiple subcortical infarcts demonstrate neuropsychological patterns and markers considered typical of Alzheimer's disease (AD) and of vascular dementia (VD), respectively. An extensive neuropsychological battery, including tests of memory, visual-spatial and executive functions, language, attention, praxis and psychomotor speed, was administered to 36 mild cognitive impairment (MCI) patients with hippocampal atrophy and 41 MCI patients with multiple subcortical infarcts. Both groups of MCI patients were very mildly impaired and well matched in terms of MMSE scores. A clear, disproportionately severe, episodic memory disorder was observed in MCI patients with hippocampal atrophy. A less specific neuropsychological profile, consisting of impairment on an Action Naming task that is sensitive to frontal lobe lesions, was observed in MCI patients with multiple subcortical infarcts. In MCI patients, a disproportionately severe episodic memory impairment strongly points to an Alzheimer's type brain pathology, whereas the prevalence of executive deficits and other frontal lobe symptoms are a much weaker diagnostic marker of small vessel subcortical disease. (JINS, 2008, 14, 611–619.)

Although most neuropsychological batteries used with multiple sclerosis (MS) patients now exclude tests that require significant motor writing or manual manipulation speed, many of the most sensitive commonly used cognitive tests nonetheless require some type of rapid oral motor response. The aim of this study is to examine the extent to which primary oral motor articulation speed problems of individuals with MS contribute to performance and group differences on neuropsychological tasks requiring a rapid spoken response. Fifty MS patients and 50 healthy controls were administered the PASAT, COWAT, Animal Naming, and SDMT tests, in addition to a measure of rudimentary oral motor speed known as the maximum repetition rate of syllables and multisyllabic combinations (MRR) task. Regression analyses revealed that the amount of variance accounted for by the group (MS-Control) variable was reduced the following amounts for the tasks when the MRR was entered before the group variable: SDMT, 10% to 6%; PASAT, 4% to 2%; COWAT, 5% to 2%; Animal Naming, 11% to 7%. Our data suggest that rudimentary oral motor speed is slowed in MS patients and makes an important contribution to group differences in performance on commonly used neuropsychological tasks requiring a rapid spoken response. (JINS, 2008, 14, 454–462.)

This study examines: (a) the impact of traumatic brain injury (TBI) on emotional empathy, (b) the relationship between emotional empathy and neuropsychological ability, and (c) the influence of low emotional empathy on measures of affect. Eighty-nine patients completed the Balanced Emotional Empathy Scale (BEES), a number of neuropsychological tests, some of which were ecologically valid tests of executive ability, plus two measures of affect, the Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI). The TBI cohort showed a high frequency (60.7%) of low emotional empathy scores compared to the control group (31%). There was no relationship between injury severity and the ability to empathize, or between emotional empathy and neuropsychological performance. There was no evidence to suggest that low scores on affective measures influenced emotional empathy scores. A high proportion of TBI patients lack the ability to empathize, but the deficit does not appear related to any specific cognitive impairment and cannot be predicted by measures of affect. (JINS, 2008, 14, 289–296.)

The psychometric criterion of mild cognitive impairment (MCI) generally involves having an unusually low score on memory testing (i.e., −1.5 SDs). However, healthy older adults can obtain low scores, particularly when multiple memory measures are administered. In turn, there is a substantial risk of psychometrically misclassifying MCI in healthy older adults. This study examined the base rates of low memory scores in older adults (55–87 years; n = 550) from the Wechsler Memory Scale–Third Edition (WMS-III; Wechsler, 1997b) standardization sample. The WMS-III consists of four co-normed episodic memory tests (i.e., Logical Memory, Faces, Verbal Paired Associates, and Family Pictures) that yield eight age- and demographically-adjusted standard scores (Auditory Recognition and Working Memory tests not included). When the eight age-adjusted scores were examined simultaneously, 26% of older adults had one or more scores at or below the 5th percentile (i.e., −1.5 SDs). On the eight demographically- adjusted scores, 39% had at least one score at or below the 5th percentile. There was an inverse relationship between intellectual abilities and prevalence of low memory scores, particularly with the age-adjusted WMS-III scores. Understanding the base rates of low scores can reduce the overinterpretation of low memory scores and minimize false-positive misclassification.Drs. Brooks, Iverson, and Feldman have no known, perceived, or actual conflict of interest with this research. Dr. Holdnack is the Senior Research Director with The Psychological Corporation. (JINS, 2008, 14, 463–478.)

This study investigated the role of visuospatial tasks in identifying cognitive decline in patients with Alzheimer's disease (AD), by correlating neuropsychological performance with cerebral perfusion measures. There were 157 participants: 29 neurologically healthy controls (age: 70.3 ± 6.6, MMSE ≥ 27), 86 patients with mild AD (age: 69.18 ± 8.28, MMSE ≥ 21) and 42 patients moderate/severe AD (age: 68.86 ± 10.69, MMSE 8–20). Single Photon Emission Computerized Tomography (SPECT) was used to derive regional perfusion ratios, and correlated using partial least squares (PLS) with neuropsychological test scores from the Benton Line Orientation (BLO) and the Rey-Osterrieth Complex Figure (RO). Cross-sectional analysis demonstrated that mean scores differed in accordance with disease status: control group (BLO 25.5, RO 33.3); mild AD (BLO 20.1, RO 25.5); moderate/severe AD (BLO 10.7, RO 16). Correlations were observed between BLO/RO and right parietal SPECT regions in the AD groups. Visuospatial performance, often undersampled in cognitive batteries for AD, is clearly impaired even in mild AD and correlates with functional deficits as indexed by cerebral perfusion ratios on SPECT implicating right hemisphere circuits. Furthermore, PLS reveals that usual spatial tasks probe a distributed brain network in both hemispheres including many areas targeted by early AD pathology. (JINS, 2008, 14, 1034–1045.)

Previous studies have established that prospective memory is commonly affected following traumatic brain injury (TBI). This study examines whether demographic factors, injury severity and site, executive function, and metacognitive factors predict prospective memory performance in adults with TBI, using a cross-sectional multivariate correlational model. Prospective memory of 44 adults (mean age = 30 years) with severe TBI was measured by the Cambridge Prospective Memory Test (CAMPROMPT) time-based and event-based scores. Using stepwise multiple regression, the time-based score was predicted by the Controlled Oral Word Association Test (COWAT) Animals subtest score, length of post-traumatic amnesia (PTA) and use of note-taking on the CAMPROMPT. The event-based score was predicted by length of PTA and COWAT Animals score. Therefore, patients with longer periods of PTA and executive function impairment may be expected to display poorer prospective memory. Note-taking was associated with improved performance on time-based prospective memory tasks. (JINS, 2008, 14, 823–831.)

Semantic and episodic memory networks function as highly interconnected systems, both relying on the hippocampal/medial temporal lobe complex (HC/MTL). Episodic memory encoding triggers the retrieval of semantic information, serving to incorporate contextual relationships between the newly acquired memory and existing semantic representations. While emotional material augments episodic memory encoding at the time of stimulus presentation, interactions between emotion and semantic memory that contribute to subsequent episodic recall are not well understood. Using a modified oddball task, we examined the modulatory effects of negative emotion on semantic interactions with episodic memory by measuring the free-recall of serially presented neutral or negative words varying in semantic relatedness. We found increased free-recall for words related to and preceding emotionally negative oddballs, suggesting that negative emotion can indirectly facilitate episodic free-recall by enhancing semantic contributions during encoding. Our findings demonstrate the ability of emotion and semantic memory to interact to mutually enhance free-recall. (JINS, 2008, 14, 620–628.)

Children with either fetal alcohol spectrum disorder (FASD) or attention-deficit/hyperactivity disorder (ADHD) display deficits in attention and executive function (EF) and differential diagnosis of these two clinical groups may be difficult, especially when information about prenatal alcohol exposure is unavailable. The current study compared EF performance of three groups: children with heavy prenatal alcohol exposure (ALC); nonexposed children with attention-deficit/hyperactivity disorder (ADHD); and typically developing controls (CON). Both clinical groups met diagnostic criteria for ADHD. The EF tasks used were the Wisconsin Card Sorting Test (WCST), the Controlled Oral Word Association Test (COWAT), and the Trail Making Test (TMT). Results indicated different patterns of deficit; both clinical groups displayed deficits on the WCST and a relative weakness on letter versus category fluency. Only the ALC group displayed overall deficits on letter fluency and a relative weakness on TMT-B versus TMT-A. In addition, WCST performance was significantly lower than expected based on IQ in the ADHD group and significantly higher than expected in the ALC group. These results, which indicate that, although EF deficits occurred in both clinical groups, the degree and pattern of deficit differed between the ALC and ADHD groups, may improve differential diagnosis. (JINS, 2008, 14, 119–129.)

This study investigated cognitive predictors of medical decision-making capacity (MDC) in patients with amnestic mild cognitive impairment (MCI). A total of 56 healthy controls, 60 patients with MCI, and 31 patients with mild Alzheimer's disease (AD) were administered the Capacity to Consent to Treatment Instrument (CCTI) and a neuropsychological test battery. The CCTI assesses MDC across four established treatment consent standards—S1 (expressing choice), S3 (appreciation), S4 (reasoning), and S5 (understanding)—and one experimental standard [S2] (reasonable choice). Scores on neuropsychological measures were correlated with scores on each CCTI standard. Significant bivariate correlates were subsequently entered into stepwise regression analyses to identity group-specific multivariable predictors of MDC across CCTI standards. Different multivariable cognitive models emerged across groups and consent standards. For the MCI group, measures of short-term verbal memory were key predictors of MDC for each of the three clinically relevant standards (S3, S4, and S5). Secondary predictors were measures of executive function. In contrast, in the mild AD group, measures tapping executive function and processing speed were primary predictors of S3, S4, and S5. MDC in patients with MCI is supported primarily by short-term verbal memory. The findings demonstrate the impact of amnestic deficits on MDC in patients with MCI. (JINS, 2008, 14, 297–308.)Disclosure: The capacity outcome measure used in the study is owned by the UAB Research Foundation (UABRF). Dr. Marson and Dr. Harrell receive royalty income through UABRF. Statistical analyses were carried out by Mr. Okonkwo, and statistical consultation was provided by Dr. Raman.

We report the adaptation of the Aachen Aphasia Test (AAT) to the Portuguese language (PAAT) and the results of its standardization in 125 persons with aphasia and 153 healthy controls. Patients with aphasia had a previous syndromic diagnosis, obtained through a Portuguese aphasia battery, which served as a reference. The control group was stratified by age and educational level. Hierarchical cluster analyses showed good construct validity. The increasing degree of difficulty and complexity throughout the item sets comprising subtests was confirmed. The discriminatory power of the PAAT for the selection of aphasic from non-aphasic persons proved to be as high as for the AAT versions in other languages. Classification of standard aphasic syndromes by means of discriminant analyses was good. Internal consistency, measured by means of Cronbach's alpha coefficient, was high to very high for the different PAAT subtests. Performance differences caused by age or educational level among the healthy control persons emphasized the need for correction factors. In conclusion, the PAAT showed robust psychometrical properties, comparable to the original German and to adaptations to other languages. It constitutes a useful tool for cross-linguistic and multicenter studies. (JINS, 2008, 14, 1046–1056.)