The present review on HIV-associated neurocognitive disorders (HAND) provides a worldwide overview of studies that have investigated the rate and neuropsychological (NP) profile of HAND research since the inception of the 2007 HAND diagnostic nomenclature. In the first part, the review highlights some of the current controversies around HAND prevalence rates. In the second part, the review critically assesses some solutions to move the field forward. In the third part, we present the cross-sectional NP profile in non-Western HIV+ cohorts and in relation to Western cohorts’ findings. The adopted global perspective highlights the successful expansion of NP studies in HIV infection to culturally diverse low- to medium-income countries with high HIV burden. These studies have produced interestingly similar rates of HAND whether patients were naïve or treated and/or virally suppressed compared to the rich income countries where the NP research in NeuroHIV has originated. The perspective also demonstrates that globally, the group which is the most representative of the HIV epidemic, and thus at risk for HAND are persons with chronic HIV infection and survivors of past immunosuppression, while in relative terms, those who have been treated early with long-term viral suppression represent a minority. In the last part, we present a review of the naturalistic longitudinal NP global studies in HIV+cohorts, discuss the role of longitudinal design in solving issues around the question of asymptomatic neurocognitive impairment, and the question of biomarker discovery. Finally, we conclude by calling for greater methods and data harmonization at a global level. (JINS, 2017, 23, 860–869)

Early stages of affective or psychotic disorders may be accompanied by neuropsychological changes that help to predict risk of developing more severe disorders. A comprehensive set of neuropsychological measures was collected in 109 help-seeking young people (16 to 30 years; 54 females), recently diagnosed with an affective or psychotic disorder and presenting with current depression. Hierarchical cluster analysis determined three clusters: one deemed to have a “poor memory” profile (n = 40); another with a “poor mental flexibility” profile (n = 38) and a third with widespread difficulties plus “impaired attention and memory” (n = 31). In general, the three clusters were comparable in demographic, functional and clinical factors suggesting some unique role for neurocognitive impairments. A discriminant function analysis confirmed that the clusters were best characterized by performance in “attentional” versus “learning/memory” measures. Furthermore, profiles of independent neuropsychological variables validated the original solution for two of the clusters, distinguishing all cluster-groups on an attentional measure. The findings of this study suggest that despite presenting with very similar levels of current depressive symptomatology, young help-seeking individuals in the early stages of illness have underlying neuropsychological heterogeneity. Distinct neuropsychological profiling may help to predict later psychiatric outcomes and enhance individually-tailored early intervention strategies. (JINS, 2011, 17, 267–276)

Type 2 diabetes mellitus (DM2) is a common metabolic disorder. DM2 is associated with cognitive impairments, and with depressive symptoms, which occur in about one third of patients. In the current study we compared the cognitive profile and psychological well-being of 119 patients with DM2 (mean age: 66 ± 6; mean duration: 9 ± 6 years) with 55 age and education matched-control participants. Groups were compared on cognitive performance in five major cognitive domains, psychological wellbeing [assessed by Symptom Checklist (SCL)-90-R and the Beck Depression Inventory (BDI-II)] and abnormalities on brain MRI. We hypothesized an interrelationship between cognition, MRI abnormalities, and psychological well-being. DM2 patients performed significantly worse than controls on cognitive tasks, especially on tasks that required more mental efficiency, although the differences were modest (effect sizes Cohen d < .6). We speculate that DM2 patients have a diminished ability to efficiently process unstructured information. Patients with DM2 had significantly higher scores on the SCL-90-R (p < .001) and on the BDI-II (p < .001) and worse MRI ratings than controls, but psychological distress did not correlate with cognition, MRI ratings or biomedical characteristics. Contrary to our hypothesis, cognitive disturbances and psychological distress thus seem independent symptoms of the same disease. (JINS, 2007, 13, 288–297.)

It has been hypothesized that exposure to repetitive head trauma from contact sports over a long-playing career may eventuate in an increased risk of late-life cognitive impairment. There are currently two competing hypotheses about the possible mechanism underlying such impairment. One is the presence of a unique neurodegenerative disorder known as “chronic traumatic encephalopathy” (CTE). The other is diminished cerebral reserve leading to the earlier clinical expression of age-related neurodegenerative diseases such as mild cognitive impairment (MCI) and Alzheimer's disease (AD). The present study examined informant AD8 inventory data in a sample of 513 retired National Football League (NFL) players. These data were indicative of possible cognitive impairment in 35.1% of this relatively young sample. A comparison of neurocognitive profiles in a subsample of this group to a clinical sample of patients with a diagnosis of MCI due to AD revealed a highly similar profile of impairments. Overall, the data suggest that there may be an increased prevalence of late-life cognitive impairment in retired NFL players, which may reflect diminished cerebral reserve. The findings are considered preliminary, but emphasize the need for larger, controlled studies on this issue. (JINS, 2013, 19, 1–8)

Objectives: Parkinson’s disease (PD) results in a range of non-motor deficits that can affect mood, cognition, and language, and many of these issues are unresponsive to pharmacological intervention. Aerobic exercise can improve mood and cognition in healthy older adults, although only a few studies have examined exercise effects on these domains in PD. The current study assesses the effects of aerobic exercise on aspects of cognition, mood, and language production in people with PD. Methods: This study compares the effects of aerobic exercise to stretch-balance training and a no-contact control group in participants with idiopathic PD. The aerobic and stretch-balance groups trained three times a week for 16 weeks, while controls continued normal activities. Outcome measures included disease severity, mood, cognition (speed of processing, memory, and executive function), and language production (picture descriptions). Cognition and language were assessed in single and dual task conditions. Results: Depressive symptoms increased only in the control group (p<.02). Executive function improved in the aerobic exercise group only in the single task (p=.007) and declined in controls in the dual task. Completeness of picture descriptions improved significantly more in the aerobic group than in the stretch-balance group (p<.02). Conclusions: Aerobic exercise is a viable intervention for PD that can be protective against increased depressive symptoms, and can improve several non-motor domains, including executive dysfunction and related aspects of language production. (JINS, 2016, 22, 878–889)

We examined the sensitivity of the Rey Auditory Verbal Learning Test (AVLT), California Verbal Learning Test (CVLT), Boston Naming Test (BNT), and Multilingual Aphasia Examination Visual Naming subtest (MAE VN) to lateralized temporal lobe epilepsy (TLE) in patients who subsequently underwent anterior temporal lobectomy. For the AVLT (n = 189), left TLE patients performed more poorly than their right TLE counterparts [left TLE = 42.9 (10.6), right TLE = 47.7 (9.9); p < .002 (Cohen's d = .47)]. Although statistically significant, the CVLT group difference (n = 212) was of a smaller magnitude [left LTE = 40.7 (11.1), right TLE = 43.8 (9.9); (p < .03, Cohen's d = .29)] than the AVLT. Group differences were also present for both measures of confrontation naming ability [BNT: left LTE = 43.1 (8.9), right TLE = 48.1 (8.9); p < .001 (Cohen's d = .56); MAE VN: left TLE = 42.2, right TLE = 45.6, p = .02 (Cohen's d = .36)]. When these data were modeled in independent logistic regression analyses, the AVLT and BNT both significantly predicted side of seizure focus, although the positive likelihood ratios were modest. In the subset of 108 patients receiving both BNT and AVLT, the AVLT was the only significant predictor of seizure laterality, suggesting individual patient variability regarding whether naming or memory testing may be more sensitive to lateralized TLE. (JINS, 2008, 14, 394–400.)

Age and gender effects on verbal episodic memory are well established. However, the possibility of interactions between age and gender has been raised by studies linking estrogen and verbal memory performance, and by research suggesting gender differences in age-related cortical atrophy. We evaluated whether age by gender interactions in verbal memory were present. Subjects within three years of the median age of menopause were excluded from a large cohort of normal subjects, resulting in a younger sample (16–47 years) of 288 men and 285 women, and an older sample (55–89 years) of 201 men and 245 women. All subjects were administered the CVLT-2, a multiple-trial list-learning task. Verbal memory was negatively correlated with age for younger men, older men, and older women, but not for younger women. Multivariate analyses indicated age by gender interactions on memory for the younger group but not the older group. Results indicate that verbal memory declines with age for younger men but not younger women, whereas both older men and older women show age-related declines. These findings are consistent with hypotheses linking estrogen and verbal memory performance, and with imaging data suggesting that age-related hippocampal atrophy is found in younger men but not younger women. The role of estrogen on cognition in normal aging warrants further study. (JINS, 2003, 9, 97–102.)

Using randomized control trial methodology, we evaluated the effectiveness of a 5-week cognitive–motor dual-tasking training program developed to improve performance of a group of people with dual-tasking difficulties arising from acquired brain injury. Training involved twice-daily practice on exercises involving walking being combined with tasks which increased in cognitive demand over the course of the intervention. A treatment group (n = 10) was compared with a control group (n = 9). The primary outcome measure was a task requiring participants to walk and carry out a spoken sentence verification task simultaneously. Secondary outcome measures were measures of dual-tasking involving either two motor tasks or two cognitive tasks. A questionnaire measure relating to activities of daily living requiring dual-tasking was also completed. Compliance with the training program was good. We found evidence of improvement in performance on the primary outcome measure, but little evidence of generalization to other measures. There was some evidence that participants believed that their dual-tasking performance in everyday life was improved after the intervention. The study was limited in terms of sample size, was not blinded and did not control fully for therapist contact time, but has produced valuable data relating to effect sizes associated with this form of intervention. (JINS, 2009, 15, 112–120.)

Neuropsychological studies of temporal lobe epilepsy have focused heavily on the nature and extent of memory dysfunction and its relationship to the neuropathological status of the hippocampus and related mesial temporal lobe structures. In this study, we examined whole brain and lobar quantitative MRI volumes and comprehensive neuropsychological performance in 58 patients with temporal lobe epilepsy and 62 healthy controls in order to determine (1) the nature and degree of extratemporal structural abnormalities in localization-related temporal lobe epilepsy; (2) the nature and degree of cognitive abnormalities outside of anterograde memory function; and (3) the relationship of volumetric abnormalities to neuropsychological status. Temporal lobe epilepsy patients exhibited significant reduction in the volume of adjusted (age, gender, height) total cerebral tissue (−5.8%), more evident in white (−9.8%) compared to gray matter (−3.0%) tissue volumes. Significant volumetric reductions were evident across frontal, temporal and parietal but not occipital lobe regions. Subarachnoid but not total ventricular CSF was significantly increased in epilepsy patients. Neuropsychological abnormality was generalized in nature, consistent with the generalized nature of the morphometric abnormalities, and reductions in cerebral tissue volumes were directly associated with poorer cognitive performance. In summary, patients with temporal lobe epilepsy exhibited clinically significant structural and functional abnormalities that extended outside the epileptogenic temporal lobe. The degree to which these structural and cognitive abnormalities are due to factors that cause the epilepsy, as opposed to reflecting the consequences of chronic epilepsy (e.g., duration and severity of epilepsy), remain to be determined. (JINS, 2003, 9, 353–362.)

Objectives: Prospective memory (PM), the ability to execute delayed intentions, has received increasing attention in neuropsychology and gerontology. Most of this research is motivated by the claim that PM is critical for maintaining functional independence; yet, there is a dearth of empirical evidence to back up the claims. Thus, the present study tested whether PM predicts functional independence in older adults using validated behavioral performance measures for both PM and functional independence. Methods: Fifty-eight healthy older adults performed a computerized PM paradigm, the Virtual Week task, as well as a timed version of an instrumental activities of daily living (TIADL) task. Furthermore, we assessed vocabulary, processing speed, and self-reported prospective remembering. Results: TIADL scores correlated significantly with performance in the Virtual Week task, vocabulary, and processing speed. Hierarchical linear regressions revealed that vocabulary and Virtual Week performance were significant predictors for TIADL. However, self-reported PM scores did not predict everyday functioning. Conclusions: The findings indicate that PM is an important cognitive ability for successful and independent everyday life beyond vocabulary. Moreover, the results show a substantial incremental contribution of intact PM performance for the prediction of everyday functioning by using objective PM measures. (JINS, 2018, 24, 640–645)

The recently developed Everyday Cognition scales (ECog) measure multiple cognitively relevant functional domains (e.g., Everyday Memory, Everyday Language, Everyday Visuospatial abilities, and three everyday executive domains). The present study further evaluated the validity of the ECog by examining its relationship with objective measures of neuropsychological function, and neurobiological markers of disease as reflected by structural neuroimaging. Participants included 474 older adults (244 normals, 142 with MCI, 88 with dementia). The neuropsychological domains measured were episodic memory, semantic memory, spatial ability, and executive functioning. Brain MRI volumes included total brain (BV), hippocampus (HC) and dorsolateral prefrontal cortex (DLPFC). Neuropsychological measures of episodic memory and executive function were most consistently related to the ECog domains; spatial abilities had a specific relationship to the Everyday Visuospatial ECog domain. HC and BV volumes were related to most ECog domains, while DLPFC volume was independently related to two everyday executive domains (Everyday Planning and Everyday Organization). The pattern of associations varied somewhat as a function of diagnosis. Episodic memory and HC had more consistent associations with the ECog domains in older adults with MCI/dementia than in cognitively normal elderly. (JINS, 2013, 19, 1–12)

The goal of the present study was to evaluate the diagnostic discriminability of three different global scores for the German version of the Consortium to Establish a Registry on Alzheimer’s Disease-Neuropsychological Assessment Battery (CERAD-NAB). The CERAD-NAB was administered to 1100 healthy control participants [NC; Mini-Mental State Examination (MMSE) mean = 28.9] and 352 patients with very mild Alzheimer’s disease (AD; MMSE mean = 26.1) at baseline and subsets of participants at follow-up an average of 2.4 (NC) and 1.2 (AD) years later. We calculated the following global scores: Chandler et al.’s (2005) score (summed raw scores), logistic regression on principal components analysis scores (PCA-LR), and logistic regression on demographically corrected CERAD-NAB variables (LR). Correct classification rates (CCR) were compared with areas under the receiver operating characteristics curves (AUC). The CCR of the LR score (AUC = .976) exceeded that of the PCA-LR, while the PCA-LR (AUC = .968) and Chandler (AUC = .968) scores performed comparably. Retest data improved the CCR of the PCA-LR and Chandler (trend) scores. Thus, for the German CERAD-NAB, Chandler et al.’s total score provided an effective global measure of cognitive functioning, whereby the inclusion of retest data tended to improve correct classification of individual cases. (JINS, 2010, 16, 910–920.)

The theory of cognitive reserve attempts to explain why some individuals are more resilient to age-related brain pathology. Efforts to explore reserve have been hindered by measurement difficulties. Reed et al. (2010) proposed quantifying reserve as residual variance in episodic memory performance that remains after accounting for demographic factors and brain pathology (whole brain, hippocampal, and white matter hyperintensity volumes). This residual variance represents the discrepancy between an individual's predicted and actual memory performance. The goals of the present study were to extend these methods to a larger, community-based sample and to investigate whether the residual reserve variable is explained by age, predicts longitudinal changes in language, and predicts dementia conversion independent of age. Results support this operational measure of reserve. The residual reserve variable was associated with higher reading ability, lower likelihood of meeting criteria for mild cognitive impairment, lower odds of dementia conversion independent of age, and less decline in language abilities over 3 years. Finally, the residual reserve variable moderated the negative impact of memory variance explained by brain pathology on language decline. This method has the potential to facilitate research on the mechanisms of cognitive reserve and the efficacy of interventions designed to impart reserve. (JINS, 2013, 19, 1–9)

Relationships between cortical brain structure and neurocognitive functioning have been reported in schizophrenia, but findings are inconclusive, and only a few studies in bipolar disorder have addressed this issue. This is the first study to directly compare relationships between cortical thickness and surface area with neurocognitive functioning in patients with schizophrenia (n = 117) and bipolar disorder (n = 121) and healthy controls (n = 192). MRI scans were obtained, and regional cortical thickness and surface area measurements were analyzed for relationships with test scores from 6 neurocognitive domains. In the combined sample, cortical thickness in the right rostral anterior cingulate was inversely related to working memory, and cortical surface area in four frontal and temporal regions were positively related to neurocognitive functioning. A positive relationship between left transverse temporal thickness and processing speed was specific to schizophrenia. A negative relationship between right temporal pole thickness and working memory was specific to bipolar disorder. In conclusion, significant cortical structure/function relationships were found in a large sample of healthy controls and patients with schizophrenia or bipolar disorder. The differences that were found between schizophrenia and bipolar may indicate differential relationship patterns in the two disorders, which may be of relevance for understanding the underlying pathophysiology. (JINS, 2011, 17, 1080–1093)

The strength and nature of the association between IQ and performance on other cognitive tests has both practical and conceptual significance for clinical neuropsychology. In this study, 28 measures derived from 16 cognitive tests were analyzed as a function of IQ in 221 adults. Participants were grouped by their IQ scores as having below average (BA), average (A), or above average (AA) intelligence. Planned comparisons revealed that A adults performed significantly better than BA adults on 25 of the 28 cognitive measures, and that AA adults performed significantly better than A adults on 19 of 28 measures. Effect sizes averaged .74 for BA–A comparisons and .41 for A–AA comparisons. Linear, quadratic, and cubic functions described the relationships between IQ and cognitive test performance equally well for most individual test measures and for a composite index of test performance, whereas quadratic and cubic functions explained the proportion of abnormal performances better than a linear function. These findings confirm that IQ predicts concurrent neuropsychological performance across the entire spectrum of intelligence, but more so among persons of average IQ or less than among those with above average IQ. (JINS, 2004, 10, 82–90.)

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 traumatic brain injury (TBI) patients and 13 controls over a 4-year period. Patients were scanned at 2 months, 1 year, and 4 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. (JINS, 2012, 18, 1–13)

The ability to generate words from phonemic (i.e., words beginning with ‘F,’ ‘A,’ and ‘S’) and semantic (i.e., animals, fruits, and vegetables) categories was assessed longitudinally in patients with Alzheimer's disease (AD; N = 59) and normal controls (NC; N = 59). Patients with AD performed worse than NC participants on both tasks at each of 4 annual evaluations and exhibited greater impairment relative to controls on the semantic-category task than on the phonemic-category task. In addition, the performance of the patients with AD declined over time on both tasks, but the rate of decline was faster on the semantic-category than on the phonemic-category task. Examination of individual responses across the annual evaluations revealed that patients with AD were more consistent than NC participants in failing to generate previously produced semantic-category, but not phonemic-category, items in all years following the 1st year in which the item was not produced. These results are consistent with the notion that patients with AD suffer a gradual deterioration of the organization and content of semantic memory as the disease progresses. (JINS, 1999, 5, 692–703.)

Virtual reality (VR) assessment paradigms have the potential to address the limited ecological validity of pen and paper measures of executive function (EF) and the pragmatic and reliability issues associated with functional measures. To investigate the ecological validity and construct validity of a newly developed VR measure of EF, the Virtual Library Task (VLT); a real life analogous task—the Real Library Task (RLT); and five neuropsychological measures of EF were administered to 30 patients with traumatic brain injury (TBI) and 30 healthy Controls. Significant others for each participant also completed the Dysexecutive Questionnaire (DEX), which is a behavioral rating scale of everyday EF. Performances on the VLT and the RLT were significantly positively correlated indicating that VR performance is similar to real world performance. The TBI group performed significantly worse than the Control group on the VLT and the Modified Six Elements Test (MSET) but the other four neuropsychological measures of EF failed to differentiate the groups. Both the MSET and the VLT significantly predicted everyday EF suggesting that they are both ecologically valid tools for the assessment of EF. The VLT has the advantage over the MSET of providing objective measurement of individual components of EF. (JINS, 2012, 18, 440–450)

The primary aims of this study were to examine post-injury cognitive development in young children with traumatic brain injury (TBI) and to investigate the role of the proximal family environment in predicting cognitive outcomes. Age at injury was 3–6 years, and TBI was classified as severe (n = 23), moderate (n = 21), and complicated mild (n = 43). A comparison group of children who sustained orthopedic injuries (OI, n = 117) was also recruited. Child cognitive assessments were administered at a post-acute baseline evaluation and repeated at 6, 12, and 18 months post-injury. Assessment of the family environment consisted of baseline measures of learning support and stimulation in the home and of parenting characteristics observed during videotaped parent–child interactions. Relative to the OI group, children with severe TBI group had generalized cognitive deficiencies and those with less severe TBI had weaknesses in visual memory and executive function. Although deficits persisted or emerged across follow-up, more optimal family environments were associated with higher scores for all injury groups. The findings confirm other reports of poor recovery of cognitive skills following early childhood TBI and suggest environmental influences on outcomes. (JINS, 2010, 16, 157–168.)

The present study examined the influence of African American acculturation on the performance of neuropsychological tests following traumatic brain injury (TBI). Seventy one participants already enrolled in a larger-scale study assessing the impact of TBI (i.e., the South Eastern Michigan Traumatic Brain Injury Model Systems project) completed a self-report measure of African American acculturation (African American Acculturation Scale–Short Form; Landrine & Klonoff, 1995) in addition to a standardized battery of neuropsychological tests. Hierarchical regression analyses were conducted to evaluate the relationship between level of acculturation and test performance after controlling for injury-related (initial Glasgow Coma Scale score, time since injury) and demographic variables (age, sex, years of education, and socioeconomic status). Lower levels of acculturation were associated with significantly poorer performances on the Galveston Orientation & Amnesia Test, MAE Tokens test, WAIS–R Block Design, Rey Auditory Verbal Learning Test, and Symbol Digit Modalities Test. Decreased levels of acculturation were also significantly related to lower scores on a composite indicator of overall neuropsychological test performance. In addition, the examiner's ethnicity (Black or White) was related with scores on a few of the tests (i.e., Block Design, Trail Making Test), but was not significantly associated with the overall neuropsychological test performance. Overall, these findings suggest that differences in cultural experience may be an important factor in the neuropsychological assessment of African Americans following TBI, and provide additional support for the hypothesis that cultural factors may partially account for the differences among ethnic/cultural groups on neuropsychological tests. (JINS, 2004, 10, 566–577.)