We previously reported a relationship between forearm resistance vessel function and global neuropsychological performance in patients with atherosclerotic vascular disease (AVD). This study was conducted to determine the relationships among vascular smooth muscle function, endothelial function, and initiation and processing speed in this sample. Participants were 80 individuals with AVD. Resistance vessel function was measured before and after infusion of vasoactive agents. Neuropsychological assessment included measures of estimated premorbid cognitive function, current global cognitive function, initiation, and processing speed. Vascular smooth muscle function was significantly associated with the initiation/processing speed composite score [R-Square Change = .152; F Change (1,71) = 16.61; p < .001], above and beyond the variance accounted for by age, education, premorbid cognitive function, and endothelium-dependent vascular function. This relationship remained significant when controlling for current level of global cognitive functioning and 10 vascular risk factors. Endothelium-dependent vascular function was not significantly associated with test performance. Decreased vascular smooth muscle function in forearm resistance vessels was significantly associated with relatively poor initiation and processing speed in individuals with AVD. With additional research, measures of vascular function might become useful in the early identification of those individuals at greatest risk for vascular-related cognitive dysfunction.

The meanings of several target neuropsychological variables, including measures of executive functioning, were examined using contextual analysis across a sample of English-speakers and a sample of Spanish-speakers. Results of the contextual analysis, which examined the contributions of the latent constructs of memory, psychomotor speed, visual spatial ability, and knowledge and comprehension, to the target neuropsychological variables indicate that each of the target variables likely reflects the unique contribution of several reference abilities. These findings provide evidence that the neuropsychological variables are multi-dimensional. The patterns of relations were similar across the samples of English and Spanish speakers.

Previous studies suggest that task-activated fMRI can predict future cognitive decline among healthy older adults. The present fMRI study examined the relative sensitivity of semantic memory (SM) versus episodic memory (EM) activation tasks for predicting cognitive decline. Seventy-eight cognitively intact elders underwent neuropsychological testing at entry and after an 18-month interval, with participants classified as cognitively “Stable” or “Declining” based on ≥1.0 SD decline in performance. Baseline fMRI scanning involved SM (famous name discrimination) and EM (name recognition) tasks. SM and EM fMRI activation, along with APOE ε4 status, served as predictors of cognitive outcome using a logistic regression analysis. Twenty-seven (34.6%) participants were classified as Declining and 51 (65.4%) as Stable. APOE ε4 status alone significantly predicted cognitive decline (R2 = .106; C index = .642). Addition of SM activation significantly improved prediction accuracy (R2 = .285; C index = .787), whereas the addition of EM did not (R2 = .212; C index = .711). In combination with APOE status, SM task activation predicts future cognitive decline better than EM activation. These results have implications for use of fMRI in prevention clinical trials involving the identification of persons at-risk for age-associated memory loss and Alzheimer’s disease.

The present study aimed to examine if bilingualism affects executive functions and verbal fluency in Marathi and Hindi, two major languages in India, with a considerable cognate (e.g., activity is actividad in Spanish) overlap. A total of 174 native Marathi speakers from Pune, India, with varying levels of Hindi proficiency were administered tests of executive functioning and verbal performance in Marathi. A bilingualism index was generated using self-reported Hindi and Marathi proficiency. After controlling for demographic variables, the association between bilingualism and cognitive performance was examined. Degree of bilingualism predicted better performance on the switching (Color Trails-2) and inhibition (Stroop Color-Word) components of executive functioning; but not for the abstraction component (Halstead Category Test). In the verbal domain, bilingualism was more closely associated with noun generation (where the languages share many cognates) than verb generation (which are more disparate across these languages), as predicted. However, contrary to our hypothesis that the bilingualism “disadvantage” would be attenuated on noun generation, bilingualism was associated with an advantage on these measures. These findings suggest distinct patterns of bilingualism effects on cognition for this previously unexamined language pair, and that the rate of cognates may modulate the association between bilingualism and verbal performance on neuropsychological tests.

Many neuroimaging studies interpret the commonly reported findings of age-related increases in frontal response and/or increased bilateral activation as suggestive of compensatory neural recruitment. However, it is often unclear whether differences are due to compensation or reflective of other cognitive or physiological processes. This study aimed to determine whether there are compensatory age-related changes in brain systems supporting successful associative encoding while taking into account potentially confounding factors including age-related differences in task performance, atrophy, and resting perfusion. Brain response during encoding of face-name pairs was measured using functional magnetic resonance imaging in 10 older and nine young adults and was correlated with memory performance. During successful encoding, older adults demonstrated increased frontal and decreased occipital activity as well as greater bilateral involvement relative to the young. Findings remained significant after controlling for age-related cortical atrophy and hypoperfusion. Among the older adults, greater response was associated with better memory performance. Cognitive aging may involve recruitment of compensatory mechanisms to improve performance or prevent impairment. Results extend previous findings by suggesting that age-related alterations in activation cannot be attributed to the commonly observed findings of poorer task performance, reduced resting perfusion, or cortical atrophy among older adults.

Rates of mild cognitive impairment (MCI) have varied substantially, depending on the criteria used and the samples surveyed. The present investigation used a psychometric algorithm for identifying MCI and its’ stability to determine if low cognitive functioning was related to poorer longitudinal outcomes. The Advanced Cognitive Training of Independent and Vital Elders (ACTIVE) study is a multi-site longitudinal investigation of long-term effects of cognitive training with older adults. ACTIVE exclusion criteria eliminated participants at highest risk for dementia (i.e., MMSE<23). Using composite normative for sample- and training- corrected psychometric data, 8.07% of the sample had amnestic impairment, while 25.09% had a non-amnestic impairment at baseline. Poorer baseline functional scores were observed in those with impairment at the first visit, including a higher rate of attrition, depressive symptoms, and self-reported physical functioning. Participants were then classified based upon the stability of their classification. Those who were stably impaired over the five-year interval had the worst functional outcomes (e.g., IADL performance), and inconsistency in classification over time also appeared to be associated increased risk. These findings suggest that there is prognostic value in assessing and tracking cognition to assist in identifying the critical baseline features associated with poorer outcomes.

After traumatic injury the brain undergoes a prolonged period of degenerative change that is paradoxically accompanied by cognitive recovery. The spatiotemporal pattern of atrophy and the specific relationships of atrophy to cognitive changes are ill understood. The present study used tensor based morphometry and neuropsychological testing to examine brain volume loss in 17 TBI patients and 13 controls over a four year period. Patients were scanned at two months, one year and four years post-injury. High-dimensional warping procedures were used to create change maps of each subject’s brain for each of the two intervals. TBI patients experienced volume loss in both cortical areas and white matter regions during the first interval. We also observed continuing volume loss in extensive regions of white matter during the second interval. Neuropsychological correlations indicated that cognitive tasks were associated with subsequent volume loss in task-relevant regions. The extensive volume loss in brain white matter observed well beyond the first year post-injury suggests that the injured brain remains malleable for an extended period, and the neuropsychological relationships suggest that this volume loss may be associated with subtle cognitive improvements.

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.

While neuropsychological deficits are evident among methamphetamine (meth) addicts, they are often unrelated to meth exposure parameters such as lifetime consumption and length of abstinence. The notion that some meth users develop neuropsychological impairments while others with similar drug exposure do not, suggests that there may be individual differences in vulnerability to the neurotoxic effects of meth. One source of differential vulnerability could come from genotypic variability in metabolic clearance of meth, dependent on the activity of cytochrome P450-2D6 (CYP2D6). We compared neuropsychological performance in 52 individuals with a history of meth dependence according with their CYP2D6 phenotype. All were free of HIV or hepatitis C infection and did not meet dependence criteria for other substances. Extensive metabolizers showed worse overall neuropsychological performance and were three times as likely to be cognitively impaired as intermediate/poor metabolizers. Groups did not differ in their demographic or meth use characteristics, nor did they evidence differences in mood disorder or other substance use. This preliminary study is the first to suggest that efficient meth metabolism is associated with worse neurocognitive outcomes in humans, and implicates the products of oxidative metabolism of meth as a possible source of brain injury.

Alcoholism and HIV-1 infection each affect components of selective attention and cognitive control that may contribute to deficits in emotion processing based on closely interacting fronto-parietal attention and frontal-subcortical emotion systems. Here, we investigated whether patients with alcoholism, HIV-1 infection, or both diseases have greater difficulty than healthy controls in resolving conflict from emotional words with different valences. Accordingly, patients with alcoholism (ALC, n = 20), HIV-1 infection (HIV, n = 20), ALC + HIV comorbidity (n = 22), and controls (CTL, n = 16) performed an emotional Stroop Match-to-Sample task, which assessed the contribution of emotion (happy, angry) to cognitive control (Stroop conflict processing). ALC + HIV showed greater Stroop effects than HIV, ALC, or CTL for negative (ANGRY) but not for positive (HAPPY) words, and also when the cue color did not match the Stroop stimulus color; the comorbid group performed similarly to the others when cue and word colors matched. Furthermore, emotionally salient face cues prolonged color-matching responses in all groups. HIV alone, compared with the other three groups, showed disproportionately slowed color-matching time when trials featured angry faces. The enhanced Stroop effects prominent in ALC + HIV suggest difficulty in exercising attentional top-down control on processes that consume attentional capacity, especially when cognitive effort is required to ignore negative emotions.

The current study examined regional frontal lobe volumes based on functionally relevant subdivisions in contemporaneously recruited samples of boys and girls with and without attention-deficit/hyperactivity disorder (ADHD). Forty-four boys (21 ADHD, 23 control) and 42 girls (21 ADHD, 21 control), ages 8–13 years, participated. Sulcal–gyral landmarks were used to manually delimit functionally relevant regions within the frontal lobe: primary motor cortex, anterior cingulate, deep white matter, premotor regions [supplementary motor complex (SMC), frontal eye field, lateral premotor cortex (LPM)], and prefrontal cortex (PFC) regions [medial PFC, dorsolateral PFC (DLPFC), inferior PFC, lateral orbitofrontal cortex (OFC), and medial OFC]. Compared to sex-matched controls, boys and girls with ADHD showed reduced volumes (gray and white matter) in the left SMC. Conversely, girls (but not boys) with ADHD showed reduced gray matter volume in left LPM; while boys (but not girls) with ADHD showed reduced white matter volume in left medial PFC. Reduced left SMC gray matter volumes predicted increased go/no–go commission rate in children with ADHD. Reduced left LPM gray matter volumes predicted increased go/no–go variability, but only among girls with ADHD. Results highlight different patterns of anomalous frontal lobe development among boys and girls with ADHD beyond that detected by measuring whole lobar volumes.

Moderate declines in prospective memory (PM) are common among older adults, but whether such decrements are associated with everyday functioning problems is not well established. To examine this issue, we administered the Memory for Intentions Screening Test (MIST), Prospective and Retrospective Memory Questionnaire (PRMQ), and Activities of Daily Living Questionnaire (ADLQ) to 50 healthy older Australian adults as part of a broader neuropsychological battery. In a series of hierarchical regressions controlling for demographics, medical/psychiatric factors, and other neurocognitive functions, the MIST event-based PM score and PRMQ PM scale were significantly associated with the total number of instrumental ADL (IADL) domains in which participants reported needing assistance. Extending prior findings in clinical populations, results indicate that lower PM functioning is uniquely associated with mild, concurrent IADL problems in healthy older adults. Future investigation of the potentially moderating effects of cognitive and behavioral compensatory strategies may be beneficial.

Despite the prevalence of HIV-associated episodic memory impairment and its adverse functional impact, there are no empirically-validated cognitive rehabilitation options for HIV-infected persons. The present study examined the self-generation approach, which is theorized to enhance new learning by elaborating and deepening encoding. Participants included 54 HIV-infected and 46 seronegative individuals, who learned paired word associates in both self-generated and didactic encoding experimental conditions. Results revealed main effects of HIV serostatus and encoding condition, but no interaction. Planned comparisons showed that both groups recalled significantly more words learned in the self-generation condition, and that HIV+ individuals recalled fewer words overall compared to their seronegative counterparts at delayed recall. Importantly, HIV+ participants with clinical memory impairment evidenced comparable benefits of self-generation compared to unimpaired HIV+ subjects. Self-generation strategies may improve verbal recall in individuals with HIV infection and may therefore be an appropriate and potentially effective cognitive rehabilitation tool in this population.

Septal nuclei, components of basal forebrain, are strongly and reciprocally connected with hippocampus, and have been shown in animals to play a critical role in memory. In humans, the septal forebrain has received little attention. To examine the role of human septal forebrain in memory, we acquired high-resolution magnetic resonance imaging scans from 25 healthy subjects and calculated septal forebrain volume using recently developed probabilistic cytoarchitectonic maps. We indexed memory with the California Verbal Learning Test-II. Linear regression showed that bilateral septal forebrain volume was a significant positive predictor of recognition memory accuracy. More specifically, larger septal forebrain volume was associated with the ability to recall item source/context accuracy. Results indicate specific involvement of septal forebrain in human source memory, and highlight the need for additional research into the role of septal nuclei in memory and other impairments associated with human diseases.

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.

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.

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 attention 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.

An objective in current research on children with fetal alcohol spectrum disorders (FASD) is to determine neurobehavioral profiles to identify affected individuals. Deficits observed when children with FASD are compared to typically developing controls may be confounded by lower IQ scores in the subjects with FASD. To determine if prenatal alcohol exposure is associated with neurobehavioral deficits after controlling for IQ differences, multivariate analyses were conducted to compare alcohol-exposed (ALC) subjects to a comparison group closely matched on IQ (IQC). The initial analysis included a broad neuropsychological battery with measures of language, executive function, visual–motor integration, motor ability, and academic achievement. Additional, in depth comparisons focused on visual sustained attention, verbal learning and memory and parent/guardian-reported behavior problems. Group differences (ALC < IQC) were found on verbal learning and parent-rated behavior problems. Group differences were marginally significant (measures within the broad neuropsychological comparison) or not significant (visual attention, retention of verbal material) on the remaining comparisons. Therefore, some deficits (e.g., verbal learning and behavior problems) in children with heavy prenatal alcohol exposure cannot be explained by the lower FSIQ observed in the population. These areas of relative weakness could be useful in distinguishing children with FASD from other children with lowered IQ.

Cognitive reserve is thought to reflect life experiences. Which experiences contribute to reserve and their relative importance is not understood. Subjects were 652 autopsied cases from the Rush Memory and Aging Project and the Religious Orders Study. Reserve was defined as the residual variance of the regressions of cognitive factors on brain pathology and was captured in a latent variable that was regressed on potential determinants of reserve. Neuropathology variables included Alzheimer’s disease markers, Lewy bodies, infarcts, microinfarcts, and brain weight. Cognition was measured with six cognitive domain scores. Determinants of reserve were socioeconomic status (SES), education, leisure cognitive activities at age 40 (CA40) and at study enrollment (CAbaseline) in late life. The four exogenous predictors of reserve were weakly to moderately inter-correlated. In a multivariate model, all except SES had statistically significant effects on Reserve, the strongest of which were CA40 (β= .31) and CAbaseline (β= .28). The Education effect was negative in the full model (β= −.25). Results suggest that leisure cognitive activities throughout adulthood are more important than education in determining reserve. Discrepancies between cognitive activity and education may be informative in estimating late life reserve.

Older African Americans tend to perform poorly in comparison with older Whites on episodic memory tests. Observed group differences may reflect some combination of biological differences, measurement bias, and other confounding factors that differ across groups. Cognitive reserve refers to the hypothesis that factors, such as years of education, cognitive activity, and socioeconomic status, promote brain resilience in the face of pathological threats to brain integrity in late life. Educational quality, measured by reading test performance, has been postulated as an important aspect of cognitive reserve. Previous studies have not concurrently evaluated test bias and other explanations for observed differences between older African Americans and Whites. We combined data from two studies to address this question. We analyzed data from 273 African American and 720 White older adults. We assessed DIF using an item response theory/ordinal logistic regression approach. DIF and factors associated with cognitive reserve did not explain the relationship between race, and age- and sex-adjusted episodic memory test performance. However, reading level did explain this relationship. The results reinforce the importance of considering education quality, as measured by reading level, when assessing cognition among diverse older adults.

Prior studies suggest that autism spectrum disorders (ASD) are associated with a domain-specific memory impairment for faces. The underlying cause of this problem and its relation to impaired visual scanning of faces—particularly of the eyes—remains to be determined. We recorded eye movements while 22 high-functioning ASD and 21 typically developing (TD) adolescents encoded and later recognized faces and objects from a single, nonsocial object category (electric fans). Relative to TD subjects, ASD individuals had poorer memory for faces, but not fans. Correlational analyses showed significant relationships between recognition memory and fixations. Eye tracking during encoding revealed that TD subjects made more fixations to faces than fans, whereas ASD individuals did not differ in number of fixations made to each stimulus type. Moreover, although both the TD and ASD groups showed a strong preference for fixating the eyes more than the mouth, the ASD subjects were less likely than TD subjects to scan regions of the face outside of the primary facial features (i.e., eyes, nose, and mouth). We concluded that ASD individuals have a domain-specific memory impairment for faces relative to mechanical objects and that this impairment may be related to abnormal scanning during encoding.

Our objectives were to examine cognitive outcomes for extremely preterm/extremely low birth weight (EPT/ELBW, gestational age <28 weeks and/or birth weight <1000 g) children in kindergarten and the associations of these outcomes with neonatal factors, early childhood neurodevelopmental impairment, and socioeconomic status (SES). The sample comprised a hospital-based 2001-2003 birth cohort of 148 EPT/ELBW children (mean birth weight 818 g; mean gestational age 26 weeks) and a comparison group of 111 term-born normal birth weight (NBW) classmate controls. Controlling for background factors, the EPT/ELBW group had pervasive deficits relative to the NBW group on a comprehensive test battery, with rates of cognitive deficits that were 3 to 6 times higher in the EPT/ELBW group. Deficits on a measure of response inhibition were found in 48% versus 10%, OR (95% CI) = 7.32 (3.32, 16.16), p <.001. Deficits on measures of executive function and motor and perceptual-motor abilities were found even when controlling for acquired verbal knowledge. Neonatal risk factors, early neurodevelopmental impairment, and lower SES were associated with higher rates of deficits within the EPT/ELBW group. The findings document both global and selective cognitive deficits in EPT/ELBW children at school entry and justify efforts at early identification and intervention.

The objective of this study is to investigate the relationships among frontotemporal fiber tract compromise and task-switching performance in healthy controls and patients with temporal lobe epilepsy (TLE). We performed diffusion tensor imaging (DTI) on 30 controls and 32 patients with TLE (15 left TLE). Fractional anisotropy (FA) was calculated for four fiber tracts [uncinate fasciculus (UncF), arcuate fasciculus (ArcF), dorsal cingulum (CING), and inferior fronto-occipital fasciculus (IFOF)]. Participants completed the Trail Making Test-B (TMT-B) and Verbal Fluency Category Switching (VFCS) test. Multivariate analyses of variances (MANOVAs) were performed to investigate group differences in fiber FA and set-shifting performances. Canonical correlations were used to examine the overall patterns of structural-cognitive relationships and were followed by within-group bivariate correlations. We found a significant canonical correlation between fiber FA and task-switching performance. In controls, TMT-B correlated with left IFOF, whereas VFCS correlated with FA of left ArcF and left UncF. These correlations were not significant in patients with TLE. We report significant correlations between frontotemporal fiber tract integrity and set-shifting performance in healthy controls that appear to be absent or attenuated in patients with TLE. These findings suggest a breakdown of typical structure-function relationships in TLE that may reflect aberrant developmental or degenerative processes.

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.