We tested the hypothesis that maternal worm infections in pregnancy affect infant motor and neurocognitive development, and that anthelminthic treatment during pregnancy can reverse these effects. We used measures which examine infant motor, cognitive and executive function, including inhibition. We assessed 983 Ugandan infants aged 15 months, using locally appropriate measures within the Entebbe Mother and Baby Study, a trial of anthelminthic treatment during pregnancy. Key exposures were maternal worm infections and anthelminthic treatment during pregnancy. Effects of other health and social factors were controlled for statistically. Of the five major worm species found in the pregnant women, two had influences on the developmental measures: Maternal Mansonella perstans and Strongyloides stercoralis infections showed negative associations with the A-not B-task, and Language, respectively. Performance on other psychomotor and cognitive measures was associated with illnesses during infancy and infants’ behavior during assessment, but not with maternal worm infections. There were no positive effects of maternal anthelminthic treatment on infant abilities. Mansonella perstans and Strongyloides stercoralis infection during pregnancy seem associated with impaired early executive function and language, respectively, but single-dose anthelminthic treatment during pregnancy was not beneficial. The biological mechanisms that could underlie these neurocognitive effects are discussed. (JINS, 2012, 18, 1019–1030)

Huntington's disease (HD) is a genetic neurodegenerative disorder affecting the basal ganglia. These subcortical structures are particularly important for motor functions, response selection and implicit learning. In the current study, we have assessed prodromal and symptomatic HD participants with an implicit contextual learning task that is not based on motor learning, but on a purely visual implicit learning mechanism. We used an implicit contextual learning task in which subjects need to locate a target among several distractors. In half of the trials, the positions of the distractors and target stimuli were repeated. By memorizing this contextual information, attention can be guided faster to the target stimulus. Nine symptomatic HD participants, 16 prodromal HD participants and 22 control subjects were included. We found that the responses of the control subjects were faster for the repeated trials than for the new trials, indicating that their visual search was facilitated when repeated contextual information was present. In contrast, no difference in response times between the repeated and new trials was found for the symptomatic and prodromal HD participants. The results of the current study indicate that both prodromal and symptomatic HD participants are impaired on an implicit contextual learning task. (JINS, 2012, 18, 1–8)

This study explored Closing-in behavior (CIB), the tendency in figure copying to draw very close to or on top of the model, in mild cognitive impairment (MCI). The files of 154 people diagnosed with MCI were reviewed and CIB was identified in 21% of cases. Two approaches were used to explore CIB. First, we capitalized on the diverse cognitive profiles within MCI, subdividing the overall sample into people with and without memory deficits. The frequency of CIB was significantly higher in multidomain non-amnestic MCI than in multidomain amnestic MCI, suggesting that CIB is not associated with specific memory impairment. Second, we assessed the cognitive correlates of CIB, by selecting patients with MCI who completed a battery of executive, visuo-constructional and memory tasks. Sub-groups of patients with and without CIB showed a similar overall severity of cognitive decline and comparable performance in visuo-constructional and memory tasks, but those with CIB were slightly but significantly more impaired on executive function tasks. The study provides evidence against memory-based accounts of CIB, and supports recent suggestions that executive impairments are the dominant cognitive correlate of this clinical sign. (JINS, 2012, 18, 269–276)

Studies in adults with multiple sclerosis (MS) have associated regional brain abnormalities with memory impairment. While memory problems in children with MS are often reported, little is known about the neural correlates that may contribute to these difficulties. We measured verbal and nonverbal memory using the Test of Memory and Learning (TOMAL-2) in 32 children and adolescents with MS and 26 age- and sex-matched healthy controls. Memory performance was correlated with volumetric measures of the whole brain, hippocampus, amygdala, and thalamus. Brain volumes were normalized for age and sex using magnetic resonance imaging (MRI) data from the National Institutes of Health MRI Study of Normal Brain development. With the exception of story recall, performance on memory tests was similar to that of the control group. Relative to controls, patient with MS showed reduced volume in the whole brain (p < .001), amygdala (p < .005), and thalamus (p < .001), but not the hippocampus. In the patient group, word-list learning correlated with whole brain volume (r = .53) and hippocampal volume (r = .43), whereas visual recognition memory correlated with thalamic volume (r = .48). Findings are consistent with the well-established role of the hippocampus in learning and consolidation and also highlight the importance of diffuse brain pathology on memory function. (JINS, 2012, 18, 471–480)

The Montreal Cognitive Assessment (MoCA) is a brief instrument developed for the screening of milder forms of cognitive impairment, having surpassed the well-known limitations of the MMSE. The aim of the present study was to validate the MoCA as well as its short version, which was proposed by the NINDS-CSN VCI Harmonization Standards for screening Vascular Dementia (VaD) patients. The results, based on a homogeneous sample of 34 VaD patients, indicate that the MoCA is a psychometrically valid and reliable instrument for cognitive screening in VaD patients, showing excellent discriminant validity. Both the full and short versions of the MoCA had excellent diagnostic accuracy in discriminating VaD patients, exhibiting an area under curve (AUC) higher than the MMSE [AUC(MoCA full version) = .950; 95% IC = .868–.988; AUC(MoCA short version) = .936; 95% IC = .849–.981; AUC(MMSE) = .860; 95% IC = .754–.932]. With a cutoff below 17 on the MoCA full version and 8 on the short version, the results for sensitivity, specificity, positive and negative predictive values, and classification accuracy were superior compared to the MMSE. In conclusion, both versions of the MoCA are valid, reliable, sensitive and accurate screening instruments for VaD patients. (JINS, 2012, 18, 1–10)

The association of cerebral white matter lesions (WMLs) with cognitive status is not well understood in middle-aged individuals. Our aim was to determine the specific contribution of periventricular hyperintensities (PVHs) and deep white matter hyperintensities (DWMHs) to cognitive function in a community sample of asymptomatic participants aged 50 to 65 years. One hundred stroke- and dementia-free adults completed a comprehensive neuropsychological battery and brain MRI protocol. Participants were classified according to PVH and DWMH scores (Fazekas scale). We dichotomized our sample into low grade WMLs (participants without or with mild lesions) and high grade WMLs (participants with moderate or severe lesions). Analyses were performed separately in PVH and DWMH groups. High grade DWMHs were associated with significantly lower scores in executive functioning (−0.45 standard deviations [SD]), attention (−0.42 SD), verbal fluency (−0.68 SD), visual memory (−0.52 SD), visuospatial skills (−0.79 SD), and psychomotor speed (−0.46 SD). Further analyses revealed that high grade DWMHs were also associated with a three- to fourfold increased risk of impaired scores (i.e.,<1.5 SD) in executive functioning, verbal fluency, visuospatial skills, and psychomotor speed. Our findings suggest that only DWMHs, not PVHs, are related to diminished cognitive function in middle-aged individuals. (JINS, 2012, 18, 1–12)

Identifying factors that improve the assessment of athletes’ psychological functioning is imperative to make proper return-to-play decisions following concussion. Prior research indicates that an individual's affect is related to symptom reporting. The present study examines two novel methods of affect assessment in college athletes at baseline participating in a sports-concussion management program. A total of 256 athletes completed a neuropsychological baseline battery with measurements of psychological symptoms (BDI-Fast Screen, Post-Concussion Symptom Scale, and ImPact Total Symptom Score) and a measure of affective memory bias (the Affective Verbal Learning Test; AVLT). Examiners completed an observation-based rating of affect. Multivariate analysis of variance and χ2 analyses were conducted to examine the effect of affect on symptom reports. Examiners’ Affect Ratings were predictive of broad symptom reporting, while the performance based index of affect (Affective Verbal Learning Test, AVLT) was more predictive of depressive symptoms. These findings suggest that performance on the AVLT may be a useful indicator of self-reported depression in a collegiate athlete sample. Additionally, these results demonstrate that examiners’ behavioral assessments of affect are important in the assessment of psychological functioning in athletes. Continued work should focus on developing objective measures that are sensitive and valid for the evaluation of outcomes from concussion. (JINS, 2012, 18, 101–107)

Prospective memory (PM) is the ability to remember to perform a future action at a specified later time, which is investigated through the use of event-based and time-based tasks. Prior investigations have found that PM is impaired following traumatic brain injury (TBI). However, there is limited information regarding the cognitive functions that mediate TBI and PM performance. Thus, this study investigated time-based PM in TBI patients, and the relationship among time-based PM, time perception, and executive functions. To accomplish this objective, 18 severe TBI patients and 18 healthy matched controls performed a time-based PM task, a time reproduction task, and two executive functions (Stroop and n-back) tasks. While both groups increased their monitoring frequency close to the target time, TBI patients monitored more and were less accurate than healthy controls at the target time confirming the time-based PM dysfunction in these patients. Importantly, executive functions, particularly inhibition and updating abilities, were strongly related to time-based PM performance; both time perception and executive functions are involved in time-based prospective memory in controls, whereas, only executive functions appear to be involved in TBI time-based prospective memory performance. (JINS, 2012, 18, 1–9)

The earliest cognitive deficits observed in amnestic mild cognitive impairment (aMCI) appear to center on memory tasks that require relational memory (RM), the ability to link or integrate unrelated pieces of information. RM impairments in aMCI likely reflect neural changes in the medial temporal lobe (MTL) and posterior parietal cortex (PPC). We tested the hypothesis that individuals with aMCI, as compared to cognitively normal (CN) controls, would recruit neural regions outside of the MTL and PPC to support relational memory. To this end, we directly compared the neural underpinnings of successful relational retrieval in aMCI and CN groups, using event-related functional magnetic resonance imaging (fMRI), holding constant the stimuli and encoding task. The fMRI data showed that the CN, compared to the aMCI, group activated left precuneus, left angular gyrus, right posterior cingulate, and right parahippocampal cortex during relational retrieval, while the aMCI group, relative to the CN group, activated superior temporal gyrus and supramarginal gyrus for this comparison. Such findings indicate an early shift in the functional neural architecture of relational retrieval in aMCI, and may prove useful in future studies aimed at capitalizing on functionally intact neural regions as targets for treatment and slowing of the disease course. (JINS, 2012, 18, 1–12)

Prospective memory (PM) is the ability to remember to execute delayed intentions. Previous studies indicate that PM is impaired in persons with mild cognitive impairment (MCI) and dementia, but the extent, nature, and cognitive correlates are unclear. A meta-analytic review was, therefore, performed (literature search 1990 to July 2011) on case-control studies on PM in dementia (10 studies, 336 patients, 505 controls) and MCI (7 studies, 225 patients, 253 controls). Differences between event-based and time-based PM and between measures of prospective and retrospective memory were examined, as well as correlations with other cognitive functions. Results showed that patients with dementia or MCI exhibit large deficits in PM (Hedges’ d −1.62 [95% confidence interval −1.98 to −1.27; p < .0001] for dementia; −1.24 [−1.51 to −0.995; p < .0001] for MCI; difference dementia vs. MCI: QM = 1.94, p = .16). Impairments were comparable in size for event-based and time-based PM (p > .05), as well as for prospective and retrospective memory (p > .05). PM showed modest correlations with measures of retrospective memory (median r = 0.27) and executive functioning (median r = 0.30). PM appears a valid construct in neuropsychological assessment in patients with dementia or MCI, but more insight is needed in the optimal characteristics of PM tasks to be used in clinical practice. (JINS, 2012, 18, 1–11)

There is limited research on the association between participation in cognitively stimulating activity and cognitive function in older Hispanics. The main purpose of the present study was to explore whether frequency of cognitive activity and its association with cognitive function in Hispanics is comparable to that of non-Hispanics. In a multiethnic cohort of 1571 non-demented older adults, we assessed past and current cognitive activity, availability of cognitive resources in the home in childhood and middle age, and five domains of cognitive function. The measures of cognitive activity and cognitive resources had adequate reliability and validity in our subset of Hispanic participants (n = 81). Hispanics reported lower levels of education, lower frequency of cognitive activity and less cognitive resources than non-Hispanic White (n = 1102) and non-Hispanic Black (n = 388) participants. Despite these differences the strength of the association between cognitive activity and cognitive function was comparable across ethnic groups. Because Hispanics have lower frequency of cognitive activity, the benefit of cognitive activity to late life cognitive function may be potentially larger in this segment of the population. Thus, interventions aimed at increasing frequency of participation in cognitively stimulating activity may offer a potential target to reduce cognitive impairment in Hispanics. (JINS, 2012, 18, 1–11)

Obstructive sleep apnea (OSA) is a nocturnal respiratory disorder associated with cognitive and behavioral sequelae, including impairments in executive functioning (EF). Previous literature has focused on “cool” EF, meaning abilities such as working memory and planning that do not involve affective control requirements. Little is known about the impact OSA may have on “hot” EF that involves regulation of affect and risk-related decision-making, and that may be particularly salient during adolescence, when these skills are rapidly developing. This study examined performance on the Iowa Gambling Task (IGT), a task believed to assess aspects of “hot” EF, in overweight adolescents at risk for OSA. Consistent with hypotheses, individuals without OSA made more beneficial decisions on the IGT over time, but participants with OSA did not benefit from feedback and continued to make choices associated with higher initial rewards, but greater long-term losses. The relationship between developmental level and IGT performance was moderated by OSA status. Individuals with OSA did not demonstrate the expected developmental gains in performance during the IGT. This finding suggests that OSA may impact the development of critical aspects of EF, or at least the expression of these skills during the developmentally important period of adolescence. (JINS, 2012, 18, 481–489)

In healthy individuals and those with insomnia, poor sleep quality is associated with decrements in performance on tests of cognition, especially executive function. Sleep disturbances and cognitive deficits are both prevalent in Parkinson's disease (PD). Sleep problems occur in over 75% of patients, with sleep fragmentation and decreased sleep efficiency being the most common sleep complaints, but their relation to cognition is unknown. We examined the association between sleep quality and cognition in PD. In 35 non-demented individuals with PD and 18 normal control adults (NC), sleep was measured using 24-hr wrist actigraphy over 7 days. Cognitive domains tested included attention and executive function, memory and psychomotor function. In both groups, poor sleep was associated with worse performance on tests of attention/executive function but not memory or psychomotor function. In the PD group, attention/executive function was predicted by sleep efficiency, whereas memory and psychomotor function were not predicted by sleep quality. Psychomotor and memory function were predicted by motor symptom severity. This study is the first to demonstrate that sleep quality in PD is significantly correlated with cognition and that it differentially impacts attention and executive function, thereby furthering our understanding of the link between sleep and cognition. (JINS, 2012, 18, 108–117)

The effect of race on cognitive test performance in the evaluation of Alzheimer's disease (AD) remains controversial. One factor that may contribute substantially to differences in cognitive test performance in diverse populations is education. The current study examined the extent to which quality of education, even after controlling for formal years of education, accounts for differences in cognitive performance between African Americans and White Non-Hispanics (WNHs). The retrospective cohort included 244 patients diagnosed with AD who self-identified as African Americans (n = 51) or WNHs (n = 193). The Wechsler Test of Adult Reading (WTAR) was used as an estimate of quality of education. In an analysis that controlled for traditional demographics, including age, sex, and years of formal education, African Americans scored significantly lower than WNHs on the Mini-Mental State Examination, as well as on neuropsychological tests of memory, attention, and language. However, after also adjusting for reading level, all previously observed differences were significantly attenuated. The attenuating effect remained even after controlling for disease severity, indicating that reading scores are not confounded by severity of dementia. These findings suggest that quality, and not just quantity, of education needs to be taken into account when assessing cognitive performance in African Americans with AD. (JINS, 2012, 18, 277–285)

Decline in executive function has been noted in the prodromal stage of Alzheimer's disease (AD) and may presage more global cognitive declines. In this prospective longitudinal study, five measures of executive function were used to predict subsequent global cognitive decline in initially nondemented older adults. Of 71 participants, 15 demonstrated significant decline over a 1-year period on the Dementia Rating Scale (Mattis, 1988) and the remaining participants remained stable. In the year before decline, the decline group performed significantly worse than the no-decline group on two measures of executive function: the Color-Word Interference Test (CWIT; inhibition/switching condition) and Verbal Fluency (VF; switching condition). In contrast, decliners and non-decliners performed similarly on measures of spatial fluency (Design Fluency switching condition), spatial planning (Tower Test), and number-letter switching (Trail Making Test switching condition). Furthermore, the CWIT inhibition-switching measure significantly improved the prediction of decline and no-decline group classification beyond that of learning and memory measures. These findings suggest that some executive function measures requiring inhibition and switching provide predictive utility of subsequent global cognitive decline independent of episodic memory and may further facilitate early detection of dementia. (JINS, 2012, 18, 118–127)

This study examined whether participation in a variety of lifestyle activities was comparable to frequent participation in cognitively challenging activities in mitigating impairments in cognitive abilities susceptible to aging in healthy, community-dwelling older women. Frequencies of participation in various lifestyle activities on the Lifestyle Activities Questionnaire (LAQ) were divided according to high (e.g., reading), moderate (e.g., discussing politics), and low (e.g., watching television) cognitive demand. We also considered the utility of participation in a variety of lifestyle activities regardless of cognitive challenge. Immediate and delayed verbal recall, psychomotor speed, and executive function were each measured at baseline and at five successive exams, spanning a 9.5-year interval. Greater variety of participation in activities, regardless of cognitive challenge, was associated with an 8 to 11% reduction in the risk of impairment in verbal memory and global cognitive outcomes. Participation in a variety of lifestyle activities was more predictive than frequency or level of cognitive challenge for significant reductions in risk of incident impairment on measures sensitive to cognitive aging and risk for dementia. Our findings offer new perspectives in promoting a diverse repertoire of activities to mitigate age-related cognitive declines. (JINS, 2012, 18, 286–294)

Antipsychotic medications can contribute to neurocognitive and motor impairments, but specific links to individualized pharmacological treatment regimens are unclear. In 68 participants with stabilized first-episode psychosis (FEP), we investigated the links between neuropsychological functions and an established anticholinergic potency index and a new D2 antagonist potency index developed in our lab. Each participant's psychiatric medication regimen was converted into estimated receptor antagonist loads based upon specific medication dosage(s) and reported in vitro brain muscarinic cholinergic and D2 receptor antagonism. In addition to the global neuropsychological impairments of FEP participants, the findings supported the hypothesized links between receptor antagonist loads and specific deficits. Higher anticholinergic load was associated with poorer delayed verbal memory but was not related to motor functioning. In contrast, higher D2 load was associated with poorer motor functioning but not verbal memory. These selective antagonist load associations explained 19% of the variance in motor functioning and 17% of the variance in delayed verbal memory. Evidently, some of the neuropsychological impairments found in persons with FEP are selectively related to the specific pharmacodynamics and the dosing of their medication regimens. Moreover, these effects can be readily estimated from practical and inexpensive indices. (JINS, 2012, 18, 1–11)

While distal sensory polyneuropathy (DSP) is the most common neurological condition associated with HIV, causing nerve damage in upper and lower extremities, its impact on neuropsychological test performance is unclear. In this study, we analyzed baseline data for 278 HIV-infected participants with comprehensive neurological and neurocognitive evaluations to examine the contribution of DSP and anatomic distribution of neuropathic signs (upper extremity or lower extremity) on standardized domain scores. We found that participants with DSP performed significantly worse in multiple domains containing timed psychomotor tests (i.e., motor, information processing speed and executive functioning). With regard to executive functioning, differences were limited to a test with a motor component (Trail Making Test, Part B). The group with clinically detectable neuropathic signs in the upper extremities and the group with signs limited to the lower extremities both performed worse in the motor domain than the group without DSP. Participants with DSP demonstrated a unique pattern of impairment limited to neuropsychological domains with timed psychomotor tests. These results suggest that caution should be used in interpretation of neuropsychological tests in patients with DSP, as some abnormalities may be exacerbated by peripheral nervous system pathology. (JINS, 2012, 19, 1–10)

Whereas patients with Alzheimer's disease (AD) experience difficulties forming and retrieving memories, their memory impairments may also partially reflect an unrecognized dysfunction in sleep-dependent consolidation that normally stabilizes declarative memory storage across cortical areas. Patients with amnestic mild cognitive impairment (aMCI) exhibit circumscribed declarative memory deficits, and many eventually progress to an AD diagnosis. Whether sleep is disrupted in aMCI and whether sleep disruptions contribute to memory impairment is unknown. We measured sleep physiology and memory for two nights and found that aMCI patients had fewer stage-2 spindles than age-matched healthy adults. Furthermore, aMCI patients spent less time in slow-wave sleep and showed lower delta and theta power during sleep compared to controls. Slow-wave and theta activity during sleep appear to reflect important aspects of memory processing, as evening-to-morning change in declarative memory correlated with delta and theta power during intervening sleep in both groups. These results suggest that sleep changes in aMCI patients contribute to memory impairments by interfering with sleep-dependent memory consolidation. (JINS, 2012, 18, 490–500)

The current study examined whether healthy older adults (OA) and individuals at the earliest stages of dementia of the Alzheimer's type (DAT) differ from younger adults (YA) and from each other on a simple, extended continuous tapping task using intervals (500 ms, 1000 ms, and 1500 ms) thought to differentially engage attentional control systems. OA groups sped up their tapping at the slowest target rate compared to the YA; this pattern was magnified in the early stage DAT groups. Performance variability appeared especially sensitive to DAT-related changes, as reliable differences between healthy OA and very mild DAT individuals emerged for multiple tap rates. These differences are proposed to result from breakdowns in attentional control that disrupt error-correction processes and the ability to resolve discrepancies between internally-generated temporal expectancies and the external temporal demands of the repetitive timing task. (JINS, 2012, 18, 1–12)