Mild cognitive impairment (MCI), especially amnestic, often represents pre-dementia Alzheimer’s disease, characterized by medial temporal lobe atrophy, while white matter (WM) alterations are insufficiently described. We analyze both cortical morphometric and WM diffusivity differences in amnestic versus non-amnestic subtypes and ask if memory and WM tract affection are related independently of cortical atrophy. Forty-nine patients from a university-hospital based memory clinic with a score of 3 on the Global Deterioration Scale aged 43–77 years (45% female) were included. Two neuropsychologists have classified cases as amnestic (aMCI), non-amnestic (naMCI), or less advanced (laMCI), not satisfying criteria for aMCI/naMCI. Diffusion tensor imaging (DTI) WM tract and morphometric data of the temporal-parietal memory network were compared among patient subtypes and related to story, word list, and visual memory. WM radial and mean diffusivity (DR and MD), underlying the entorhinal cortex, were higher in aMCI compared with laMCI. WM DR and MD, underlying the entorhinal, parahippocampal, and middle temporal cortex, explained unique variance in word list and story memory, and this was not due to secondary effects of cortical thinning. DTI may thus potentially aid diagnosis in early disease stages. (JINS, 2011, 17, 000–000)

Older adults with cardiovascular disease (CVD) often complain about cognitive difficulties including reduced processing speed and attention. On cross-sectional examination, such reports relate more closely to mood than to cognitive performance; yet, in longitudinal studies, these complaints have foreshadowed cognitive decline over time. To test the hypothesis that self-reported cognitive difficulties reflect early changes in brain function, we examined cognitive complaints and depression in relation to blood oxygen level dependent (BOLD) response to a cognitive task in middle-aged adults at risk for CVD. Forty-nine adults (ages 40 to 60 years) completed a measure of perceived cognitive dysfunction (Cognitive Difficulties Scale), medical history questionnaire, neuropsychological assessment and functional magnetic resonance imaging (fMRI) during a working memory task. Increased report of cognitive difficulties was significantly associated with weaker task-related activation in the right superior frontal/ middle frontal gyrus (F(4,44) = 3.26; p = .020, CDS ß = −0.39; p = .009) and the right inferior frontal gyrus (F(4,44) = 3.14; p = .024, CDS ß = −0.45; p = .003), independent of age, education, and self-reported depressive symptoms. Lower activation intensity in the right superior frontal gyrus was related to trends toward poorer task performance. Thus, self-reported cognitive difficulties among cognitively normal middle-aged adults may provide important clinical information about early brain vulnerability that should be carefully monitored. (JINS, 2011, 17, 915–924)

Recent advances in the treatment of children with severe congenital heart defects, such as hypoplastic left heart syndrome (HLHS) and other forms of univentricular heart (UVH), have significantly improved their survival rates. However, these children are at risk for various neurodevelopmental deficits. The aim of the present study was to assess cognitive development, expressive language, and behavior in 30-month-old children with univentricular heart. The participants were 22 children with HLHS, 14 with UVH, and 41 healthy control subjects. The Bayley Scales of Infant Development II, MacArthur Communicative Development Inventories, and Child Behavior Checklist were used for assessments. The results revealed that children with HLHS exhibited a significantly lower mean mental development index, more delays in expressive language functions, and more behavioral problems than did the control children. Two children with HLHS (9%) had mental development indexes below 50, indicating significantly delayed performance. The children with UVH differed from the control children with respect to their lower mean mental development index. These findings suggest that at the age of 30 months, neurodevelopmental deficits are especially prevalent in children with HLHS. Thus, early developmental screening, intervention, and neuropsychological follow-up until school age is recommended particularly for the children with HLHS. (JINS, 2011, 17, 1094–1103)

The color word Stroop test is the most common tool used to assess selective attention in persons with traumatic brain injury (TBI). A larger Stroop effect for TBI patients, as compared to controls, is generally interpreted as reflecting a decrease in selective attention. Alternatively, it has been suggested that this increase in Stroop effects is influenced by group differences in generalized speed of processing (SOP). The current study describes an overview and meta-analysis of 10 studies, where persons with TBI (N = 324) were compared to matched controls (N = 501) on the Stroop task. The findings confirmed that Stroop interference was significantly larger for TBI groups (p = .008). However, these differences may be strongly biased by TBI-related slowdown in generalized SOP (r2 = .81 in a Brinley analysis). We also found that TBI-related changes in sensory processing may affect group differences. Mainly, a TBI-related increase in the latency difference between reading and naming the font color of a color-neutral word (r2 = .96) was linked to Stroop effects. Our results suggest that, in using Stroop, it seems prudent to control for both sensory factors and SOP to differentiate potential changes in selective attention from other changes following TBI. (JINS, 2011, 17, 354–363)

The ability to engage in self-reflective processes is a capacity that may be disrupted after neurological compromise; research to date has demonstrated that patients with traumatic brain injury (TBI) show reduced awareness of their deficits and functional ability compared to caretaker or clinician reports. Assessment of awareness of deficit, however, has been limited by the use of subjective measures (without comparison to actual performance) that are susceptible to report bias. This study used concurrent measurements from cognitive testing and confidence judgments about performance to investigate in-the-moment metacognitive experiences after moderate and severe traumatic brain injury. Deficits in metacognitive accuracy were found in adults with TBI for some but not all indices, suggesting that metacognition may not be a unitary construct. Findings also revealed that not all indices of executive functioning reliably predict metacognitive ability. (JINS, 2011, 17, 720–731)

This study investigated the correspondence between self-report and experimental measures of cognitive flexibility in individuals with anorexia nervosa (AN) and healthy controls (HCs). Ninety-four participants (45 individuals with AN and 49 HCs) completed the self-report Cognitive Flexibility Scale (CFS) and an experimental task, the Brixton Spatial Anticipation Test. The AN group performed poorly on both measures of cognitive flexibility compared with HCs. There was no significant correlation between the CFS scores and the errors on the Brixton Test for both groups. The findings suggest there is poor correspondence between the self-report measure of cognitive flexibility and performance on the flexibility test. These two assessment tools therefore cannot be used interchangeably to assess cognitive flexibility. Flexibility is an important clinical characteristic in AN. The results suggest that self-report and behavioral measures can be complementary, but cannot be used as an alternative to one another. (JINS, 2011, 17, 925–928)

We used data from two population-based longitudinal studies to estimate time of onset and rate of accelerated decline across cognitive domains before dementia diagnosis. The H70 includes an age-homogeneous sample (127 cases and 255 non-cases) initially assessed at age 70 with 12 follow-ups over 30 years. The Kungsholmen Project (KP) includes an age-heterogeneous sample (279 cases and 562 non-cases), with an average age of 82 years at initial assessment, and 4 follow-ups spanning 13 years. We fit mixed linear models to the data and determined placement of change points by a profile likelihood method. Results demonstrated onset of accelerated decline for fluid (speed, memory) versus crystallized (verbal, clock reading) abilities occurring approximately 10 and 5 years before diagnosis, respectively. Although decline before change points was greater for fluid abilities, acceleration was more pronounced for crystallized abilities after the change points. This suggests that onset and rate of acceleration vary systematically along the fluid-crystallized ability continuum. There is early onset in fluid abilities, but these changes are difficult to detect due to substantial age-related decline. Onset occurred later and acceleration was greater in crystallized abilities, suggesting that those markers may provide more valid identification of cases in later stages of the prodromal phase. (JINS, 2011, 17, 000–000)

Schizophrenia is associated with the inability to control and coordinate thoughts, actions, and perceptions. In conventional assessments of cognitive control, multiple sensory features of stimuli are concomitantly manipulated, introducing a confounding role of bottom-up perceptual information. To overcome this difficulty, we used an ambiguous visual stimulus (Necker cube), which allowed measurement of cognitive control with constant sensory input. Subjects (20 patients, 20 controls) were asked to control their perception of a transparent Necker cube by keeping a designated plane at the front or back of the stimulus, the position of which is perceptually bistable. Patients were highly deficient at controlling their perception of the cube. When a visual feature (the luminance contrast between a designated cube plane and the other planes) was systematically manipulated, an interaction was found whereby schizophrenia patients no longer under-performed on the highest contrast condition. These results show patients’ impairment of controlling perception in the absence of visual modulation and suggest the potential utility of perceptually based approaches to cognitive remediation in schizophrenia. (JINS, 2011, 551–556)

The nature of residual cognitive deficits after out of hospital cardiac arrest (OHCA) is incompletely described and has never been defined against a cardiac control (CC) group. The objective of this study is to examine neuropsychological outcomes 3 months after OHCA in patients in a “middle range” of acute severity. Thirty prospective OHCA admissions with coma >1 day and responsive but confused at 1 week, and 30 non-OHCA coronary care admissions were administered standard tests in five cognitive domains. OHCA subjects fell into two deficit profiles. One group (N = 20) had mild memory deficits and borderline psychomotor deficits compared to the CC group; 40% had returned to work. The other group (N = 10) had severe impairments in all domains. Coma duration was associated with group. Neither group had a high prevalence of depression. For most patients within the “middle range” of acute severity of OHCA, cognitive and functional outcomes at 3 months were encouraging. (JINS, 2011, 17, 364–368)

Patients often demonstrate attentional and action-intentional biases in both the transverse and coronal planes. In addition, when making forelimb movements in the transverse plane, normal participants also have spatial and magnitude asymmetries, but forelimb spatial asymmetries have not been studied in coronal space. Thus, to learn if when normal people make vertical movements they have right–left spatial and magnitude biases, seventeen healthy, blindfolded volunteers had their hands (holding pens) placed vertically in their midsagittal plane, 10 inches apart, on pieces of paper positioned above, below, and at eye-level. Participants were asked to move their hands together vertically and meet in the middle. Participants demonstrated less angular deviation in the below-eye condition than in the other spatial conditions, when moving down than up, and with their right than left hand. Movements toward eye level from upper or lower space were also more accurate than movements in the other directions. Independent of hand, lines were longer with downward than upward movements and the right hand moved more distance than the left. These attentional-intentional asymmetries may be related to gravitational force, hand-hemispheric dominance, and spatial “where” asymmetries; however, the mechanisms accounting for these asymmetries must be ascertained by future research. (JINS, 2011, 17, 732–739)

White matter alterations, leukoaraiosis (LA) on structural MRI, are associated with cognitive deficits and increased risk of dementia. LA may also impact on subjective memory complaints in otherwise healthy older adults. Little is known about the interplay between LA memory complaints and cognition. We investigated cognitive phenotypes associated with LA in 42 non-demented older adults categorized as having subjective cognitive complaints with no objective cognitive impairment—the subjective cognitive impairment group (SCI; n = 12), amnesic mild cognitive impairment (aMCI; n = 20), or healthy controls (HC; n = 11). We measured LA severity on MRI with a 40-point visual rating scale. Controlling for age and Mini-Mental State Examination (MMSE) score, analyses revealed multiple between-group differences. Follow-up linear regression models investigating the underlying contributors to each clinic group's cognitive profile indicated that LA contributed to learning slope variance (after accounting for age and MMSE) but only for the SCI group. Although the SCI group showed a significantly steeper learning slope when compared to HC and aMCI, increasing LA severity negatively impacted this group's rate of learning. This, in conjunction with the significant contribution of age on SCI learning slope performance variance suggests that greater LA burden at a younger age may contribute to subtle changes in learning for individuals with subjective cognitive complaints. (JINS, 2011, 17, 1104–1112)

Knowledge of oneself is preserved in many memory-impaired individuals with neurological damage. Therefore, cognitive strategies that capitalize on mechanisms related to the self may be particularly effective at enhancing memory in this population. The present study investigated the effect of “self-imagining,” imagining an event from a personal perspective, on short and long delayed cued recall in memory-impaired individuals with neurological damage. Sixteen patients intentionally encoded word pairs under four separate conditions: visual imagery, semantic elaboration, other person imagining, and self-imagining. The results revealed that self-imagining led to better performance than other-imagining, semantic elaboration, and visual imagery. Furthermore, the “self-imagination effect” (SIE) was preserved after a 30-min delay and was independent of memory functioning. These findings indicate that self-imagining provides a mnemonic advantage in brain-injured individuals, even those with relatively poor memory functioning, and suggest that self-imagining may tap into mnemonic mechanisms related to the self. (JINS, 2011, 17, 929–933)

Age, education, and gender are the most common covariates used to define normative standards against which neuropsychological (NP) performance is interpreted, but influences of other demographic factors have begun to be appreciated. In developing nations, urban versus rural residence may differentially affect numerous factors that could influence cognitive test performances, including quality of both formal and informal educational experiences and employment opportunities. Such disparities may necessitate corrections for urban/rural (U/R) status in NP norms. Prior investigations of the U/R effect on NP performance typically have been confounded by differences in educational attainment. We addressed in this by comparing the NP performance of large, Chinese urban (Yunnan Province, n = 201) and rural (Anhui Province, n = 141) cohorts of healthy adults, while controlling for other demographic differences. Although the groups did not differ in global NP scores, a more complex pattern was observed within specific NP ability domains and tests. Urban participants showed better performance in select measures of processing speed and executive functions, verbal fluency, and verbal learning. Self-reported daily use of academic skills was predictive of many U/R differences. Controlling for academic skill use abrogated most U/R differences but revealed rural advantages in select measures of visual reasoning and motor dexterity. (JINS, 2011, 17, 000–000)

Information processing speed is frequently cited as the primary cognitive domain impacted by multiple sclerosis (MS) and is usually evaluated with reaction time (RT) or rapid serial processing (RSP) measures. The present study compared the efficacy of RT and RSP measures to distinguish between patients with MS (N = 42) and healthy controls (N = 40). The RT measure was patterned after the Computerized Tests of Information Processing and included measures of simple, choice, and semantic RT. The RSP measures consisted of the Symbol Digit Modalities Test (SDMT) and the Stroop Test. Substantial differences in information processing speed between patients and controls were found on all tests, with slightly larger effect sizes for RSP measures than RT measures and for the SDMT than the Stroop Test. Binary logistic regression analyses showed RSP measures performed better than RT measures at distinguishing patients from controls, and likewise, the SDMT score performed better than the scores derived from the Stroop Test. Results are discussed in the context of three effects associated with common measures of processing speed: complexity, compounding, and augmentation. (JINS, 2011, 17, 1113–1121)

Script generation describes one's ability to produce complex, sequential action plans derived from mental representations of everyday activities. The aim of this study was to assess the effect of human immunodeficiency virus (HIV) infection on script generation performance. Sixty HIV+ individuals (48% of whom had HIV-associated neurocognitive disorders [HAND]) and 26 demographically comparable HIV- participants were administered a novel, standardized test of script generation, which required participants to verbally generate and organize the necessary steps for completing six daily activities. HAND participants evidenced significantly more total errors, intrusions, and script boundary errors compared to the HIV- sample, indicating difficulties inhibiting irrelevant actions and staying within the prescribed boundaries of scripts, but had adequate knowledge of the relevant actions required for each script. These findings are generally consistent with the executive dysfunction and slowing common in HAND and suggest that script generation may play a role in everyday functioning problems in HIV. (JINS, 2011, 17, 740–745)

Pituitary adenomas, even after successful treatment, are associated with cognitive impairments. It is unclear whether these deficits are a consequence of unspecific factors associated with having a chronic illness and whether the cognitive dysfunctions exceed those of other chronically ill patients. Thirty-eight patients with transsphenoidal surgery for pituitary adenomas and 38 patients undergoing L-thyroxine replacement therapy after thyroid surgery were studied neuropsychologically with established tests. Executive function was examined with the Trail-Making Test A and B, working memory with the digit span test, attention with the digit symbol test, verbal memory with the German version of the Auditory Verbal Learning and Memory Test, and general verbal intelligence by a vocabulary test. Attention (p = .007), attentional speed (p = .0004), executive control (p = .04), and working memory (p = .01), were significantly reduced in patients with pituitary adenomas compared with other chronically ill patients. In contrast, no differences were found between the groups for verbal memory (all subtests: p ≥ .06). Patients with successful surgery for pituitary adenomas show also in comparison with other chronically ill patients an increased risk for deficits in certain aspects of cognitive function, including attention and working memory, supporting the relevance of the brain lesion and its treatment for these dysfunctions. (JINS, 2011, 17, 369–375)

Subjective reports of memory functioning are often included as part of neuropsychological evaluations. However, information from subjective measures often conflicts with formal testing results. The current study explored the relationships among self-reported memory functioning and objective learning and memory measures. Sixty-four multiple sclerosis (MS) patients completed a self-report memory questionnaire (Memory Functioning Questionnaire, MFQ) and objective measures of learning and memory (California Verbal Learning Test-II, CVLT-II; Open-Trial Selective Reminding Test, OT-SRT; and Prose Memory, PM). Significant positive correlations were found between self-reported memory functioning and recall following initial exposure to material: OT-SRT Trial 1 (r = .42; p = .001); CVLT-II Trial 1 (r = .39; p = .002): PM Immediate Recall (r = .28; p = .028). Subjective memory was unrelated to recall performance on subsequent learning trials, aggregate learning scores, or delayed free recall. Results suggest that self-reported memory functioning in MS patients may be specifically related to single-trial learning. (JINS, 2011, 17, 557–561)

Learning to read and to write influences not only verbal skills but also global cognitive performance. Our study aimed to compare the visuoconstructional abilities of elderly illiterates with those of elderly literates. A total of 125 healthy subjects over 65 years old were recruited. Korean version of Mini-Mental State Examination (K-MMSE) and the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) constructional praxis examination were used. We divided subjects into three groups (educated literate n = 53, uneducated literate n = 36 and uneducated illiterate n = 36). Interlocking pentagons drawing, a part of the K-MMSE, was scored using the 6-point hierarchical scale. The uneducated-illiterate group obtained significantly lower scores than did the other two groups. Scores on the ADAS-cog constructional praxis test were highest in the educated-literate group and those in the uneducated-illiterate group obtained the lowest scores. We demonstrated that illiteracy influences not only language performance but also visuoconstructional functioning. (JINS, 2011, 17, 934–939)

A previous study reported preliminary results of enhanced processing of simple visual information in the form of faster reaction times, in female fragile X premutation carriers (fXPCs). In this study, we assessed manual and oral motor reaction times in 30 female fXPCs and 20 neurotypical (NT) controls. Participants completed two versions of the reaction time task; one version required a manual motor response and the other version required an oral motor response. Results revealed that the female fXPCs displayed faster reaction times for both manual and oral motor responses relative to NT controls. Molecular measures including CGG repeat length, FMR1 mRNA levels, and age were not associated with performance in either group. Given previously reported age and CGG repeat modulated performance on a magnitude comparison task in this same group of premutation carriers, results from the current study seem to suggest that female fXPCs may have spared basic psychomotor functionality. (JINS, 2011, 17, 746–750)

The Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene may be related to individual differences in cognition, likely via modulation of prefrontal dopamine catabolism. However, the available studies have yielded mixed results, possibly in part because they do not consistently account for other genes that affect cognition. We hypothesized that COMT Met allele homozygosity, which is associated with higher levels of prefrontal dopamine, would predict better executive function as measured using standard neuropsychological testing, and that other candidate genes might interact with COMT to modulate this effect. Participants were 95 healthy, right-handed adults who underwent genotyping and cognitive testing. COMT genotype predicted executive ability as measured by the Trail-Making Test, even after covarying for demographics and Apolipoprotein E (APOE), brain-derived neurotrophic factor (BDNF), and ankyrin repeat and kinase domain containing 1 (ANKK1) genotype. There was a COMT-ANKK1 interaction in which individuals having both the COMT Val allele and the ANKK1 T allele showed the poorest performance. This study suggests the heterogeneity in COMT effects reported in the literature may be due in part to gene–gene interactions that influence central dopaminergic systems. (JINS, 2011, 17, 1–7)