Objectives: Children and adolescents who were born very preterm (≤32 weeks’ gestation) are vulnerable to experiencing cognitive problems, including in executive function. However, it remains to be established whether cognitive deficits are evident in adulthood and whether these exert a significant effect on an individual’s real-lifeachievement. Methods: Using a cross-sectional design, we tested a range of neurocognitive abilities, with a focus on executive function, in a sample of 122 very preterm individuals and 89 term-born controls born between 1979 and 1984. Associations between executive function and a range of achievement measures, indicative of a successful transition to adulthood, were examined. Results: Very preterm adults performed worse compared to controls on measures of intellectual ability and executive function with moderate to large effect sizes. They also demonstrated significantly lower achievement levels in terms of years spent in education, employment status, and on a measure of functioning in work and social domains. Results of regression analysis indicated a stronger positive association between executive function and real-life achievement in the very preterm group compared to controls. Conclusions: Very preterm born adults demonstrate executive function impairments compared to full-term controls, and these are associated with lower achievement in several real-life domains. (JINS, 2017, 23, 381–389)

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system, resulting in physical, cognitive and affective disturbances, with notable declines in the ability to learn and retain new information. In this study, we examined if higher levels of physical activity in MS individuals were associated with an increased resting-state connectivity of the hippocampus and cortex, resulting in better performance on a task of episodic memory. Forty-five individuals with a clinically definite diagnosis of MS were recruited for the study. Consistent with previous reports, hippocampus was functionally connected to the posteromedial cortex, parahippocampal gyrus, superior frontal gyrus, and the medial frontal cortex. Higher levels of physical activity in MS patients were associated with an increased coherence between the hippocampus and the posteromedial cortex (PMC). The increased connectivity between these two regions, in turn, was predictive of better relational memory, such that MS patients who showed an increased coherence between the left (not right) hippocampus and the PMC also showed better relational memory. Results of the study are interpreted in light of the challenge of disentangling effects of physical activity from effects of disease severity and its neuropathological correlates. (JINS, 2011, 17, 986–997)

A formula for the reliability of difference scores was used to estimate the reliability of Delis-Kaplan Executive Function System (D-KEFS; Delis et al., 2001) contrast measures from the reliabilities and correlations of their components. In turn these reliabilities were used to calculate standard errors of measurement. The majority of contrast measures had low reliabilities: of the 51 reliability coefficients calculated in the present study, none exceeded 0.7 and hence all failed to meet any of the criteria for acceptable reliability proposed by various experts in psychological measurement. The mean reliability of the contrast scores was 0.27, the median reliability was 0.30. The standard errors of measurement were large and, in many cases, equaled or were only marginally smaller than the contrast scores' standard deviations. The results suggest that, at present, D-KEFS contrast measures should not be used in neuropsychological decision making. (JINS, 2008, 14, 1069–1073.)

We examined the possible role of autonomic activity in Huntington's disease (HD) during a risky decision making task. Skin conductance responses (SCRs) of 15 HD participants and 16 healthy controls were measured while they performed a computerized version of the Simulated Gambling Task (SGT). The results replicated our previous finding of a performance decrement in HD, and showed that HD was associated with an altered pattern of SCRs during the risky decision task. Specifically, the healthy controls produced increased SCRs following selections from the disadvantageous decks and following losing selections. In contrast, the SCRs of the HD group did not differentiate between wins and losses. These findings indicate a reduced impact of loss on decision-making processes under risky conditions in HD. (JINS, 2004, 10, 239–245.)

The ability to detect dementia of the Alzheimer type (DAT) in a community-dwelling sample of elderly individuals on the basis of neuropsychological test performance was examined. Three hundred sixty community-dwelling individuals were identified by neurological examination as having probable or possible Alzheimer’s disease, being at risk for Alzheimer’s disease, or having no cognitive impairment. A logistic model comprised of tests of verbal and nonverbal memory, mental flexibility, and confrontation naming correctly classified 82% of DAT subjects and 98% of normal elderly subjects. The logistic model classified 77% of subjects who were diagnosed as at risk for Alzheimer's disease as being cognitively normal. A cross-validation with a clinically based sample of subjects correctly classified 89% of DAT patients and 100% of normal control subjects. The results suggest that psychometric discrimination of dementia may be less accurate in community-dwelling populations than in clinically based samples. (JINS, 1995, I, 252–260.)

This study aimed at comparing neuropsychological test scores in 83 cardiologists and nurses (exposed group, EG) working in the cardiac catheterization laboratory, and 83 control participants (non exposed group, nEG), to explore possible cognitive impairments. The neuropsychological assessment was carried out by means of a battery called “Esame Neuropsicologico Breve.” EG participants showed significantly lower scores on the delayed recall, visual short-term memory, and semantic lexical access ability than the nEG ones. No dose response could be detected. EG participants showed lower memory and verbal fluency performances, as compared with nEG. These reduced skills suggest alterations of some left hemisphere structures that are more exposed to IR in interventional cardiology staff. On the basis of these findings, therefore, head protection would be a mandatory good practice to reduce effects of head exposure to ionizing radiation among invasive cardiology personnel (and among other exposed professionals). (JINS, 2015, 21, 670–676)

Memory for object locations, as part of spatial memory function, has rarely been studied in patients with Alzheimer dementia (AD), while studies in patients with Mild Cognitive Impairment (MCI) patients are lacking altogether. The present study examined categorical spatial memory function using the Location Learning Test (LLT) in MCI patients (n = 30), AD patients (n = 30), and healthy controls (n = 40). Two scoring methods were compared, aimed at disentangling positional recall (location irrespective of object identity) and object-location binding. The results showed that AD patients performed worse than the MCI patients on the LLT, both on recall of positional information and on recall of the locations of different objects. In addition, both measures could validly discriminate between AD and MCI patients. These findings are in agreement with the notion that visual cued-recall tests may have better diagnostic value than traditional (verbal) free-recall tests in the assessment of patients with suspected MCI or AD. (JINS, 2010, 16, 200–204.)

This study investigated the specific patient factors that predict responsiveness to a cognitive rehabilitation program. The program has previously been demonstrated to be successful at the group level in patients with gliomas, but it is unclear which patient characteristics optimized the effect of the intervention at the individual level. Four categories of possible predictors of improvement were selected for evaluation: sociodemographic and clinical variables, self-reported cognitive symptoms, and objective neuropsychological test performance. Hierarchical logistic regression analyses were conducted, beginning with the most accessible (sociodemographic) variables and ending with the most difficult (baseline neuropsychological) to identify in clinical practice. Nearly 60% of the participants of the intervention were classified as reliably improved. Reliable improvement was predicted by age (p = .003) and education (p = .011). Additional results suggested that younger patients were more likely to benefit specifically from the cognitive rehabilitation program (p = .001), and that higher education was also associated with improvement in the control group (p = .024). The findings are discussed in light of brain reserve theory. A practical implication is that cognitive rehabilitation programs should take the patients’ age into account and, if possible, adapt programs to increase the likelihood of improvement among older participants. (JINS, 2011, 17, 256–266)

We studied how moderate to severe childhood traumatic brain injury (TBI) affects vocational outcome with time. This is the second follow-up of patients who were injured as preschoolers in traffic accidents. In the first follow-up the mean age was 23 years and in the present study the average age of the 27-patient cohort was 40 years. Twenty-two patients were assessed clinically by a neuropsychologist, neurologist and a social worker. Five patients, although not able or willing to participate in the clinical study, were contacted by telephone and interviewed on their vocational outcome. Compared to the first follow-up, 20/27 patients in total had no change in their vocational status. Nine out of the 27 patients were working full-time, two had subsidized jobs and 16 were not working. Twenty-four of 27 patients were independent in daily living. In the neuropsychological tests of executive functions, preserved flexibility associated with full-time work status. In conclusion, 1/3 of the patients were still employed full-time over 30 years after the TBI. This suggests that favorable vocational outcome, reached by young adulthood, is maintained at least until middle age. (JINS, 2004, 10, 719–723.)

The paced auditory serial addition task (PASAT), in which subjects hear a number-string and add the two most-recently heard numbers, is a neuropsychological test sensitive to cerebral dysfunction. We mapped the brain regions activated by the PASAT using positron emission tomography (PET) and 15O-water to measure cerebral blood flow. We parsed the PASAT by mapping sites activated by immediate repetition of numbers and by repetition of the prior number after the presentation of the next number in the series. The PASAT activated dispersed non-contiguous foci in the superior temporal gyri, bifrontal and biparietal sites, the anterior cingulate and bilateral cerebellar sites. These sites are consistent with the elements of the task that include auditory perception and processing, speech production, working memory, and attention. Sites mediating addition were not identified. The extent of the sites activated during the performance of the PASAT accounts for the sensitivity of this test and justifies its use in a variety of seemingly disparate conditions. (JINS, 2004, 10, 26–34.)

To investigate the effects of dopamine on the dynamics of semantic activation, 39 healthy volunteers were randomly assigned to ingest either a placebo (n = 24) or a levodopa (n = 16) capsule. Participants then performed a lexical decision task that implemented a masked priming paradigm. Direct and indirect semantic priming was measured across stimulus onset asynchronies (SOAs) of 250, 500 and 1200 ms. The results revealed significant direct and indirect semantic priming effects for the placebo group at SOAs of 250 ms and 500 ms, but no significant direct or indirect priming effects at the 1200 ms SOA. In contrast, the levodopa group showed significant direct and indirect semantic priming effects at the 250 ms SOA, while no significant direct or indirect priming effects were evident at the SOAs of 500 ms or 1200 ms. These results suggest that dopamine has a role in modulating both automatic and attentional aspects of semantic activation according to a specific time course. The implications of these results for current theories of dopaminergic modulation of semantic activation are discussed. (JINS, 2004, 10, 15–25.)

Controversy surrounds the differences of the cognitive profile between mild cognitive impairment resulting from cerebral small vessel disease (MCI-SVD) and mild cognitive impairment associated with prodromal Alzheimer’s disease (MCI-AD). The aim of this study was to explore and compare the cognitive features of MCI-SVD and MCI-AD. MCI-SVD patients (n = 56), MCI-AD patients (n = 30), and normal control subjects (n = 80) were comprehensively evaluated with neuropsychological tests covering five cognitive domains. The performance was compared between groups. Tests that discriminated between MCI-SVD and MCI-AD were identified. Multiple cognitive domains were impaired in MCI-SVD group, while memory and executive function were mainly impaired in MCI-AD group. Compared with MCI-SVD, MCI-AD patients performed relatively worse on memory tasks, but better on processing speed measures. The AVLT Long Delay Free Recall, Digit Symbol Test, and Stroop Test Part A (performance time) in combination categorized 91.1% of MCI-SVD patients and 86.7% of MCI-AD patients correctly. Current study suggested a nonspecific neuropsychological profile for MCI-SVD and a more specific cognitive pattern in MCI-AD. MCI-AD patients demonstrated greater memory impairment with relatively preserved mental processing speed compared with MCI-SVD patients. Tests tapping these two domains might be potentially useful for differentiating MCI-SVD and MCI-AD patients. (JINS, 2009, 15, 898–905.)

We investigated the psychometric properties of the random number generation (RNG) task in four studies using a mixed sample of young adults (n = 306), middle-aged adults (n = 40), and patients diagnosed with schizophrenia (n = 26). Data in study 1 were best accounted for by a three-factor solution representing inhibition of stereotypical schemas (seriation), output inhibition (repetition), and monitoring of previous output (cycling). Modest test-retest correlations were found, with the seriation factor showing acceptable stability across time (study 2). In study 3, RNG task performance was related to scores on concurrent neurocognitive tasks to establish construct validity. RNG scores correlated with healthy controls' performance on the Stroop color-word test and patients diagnosed with schizophrenia with executive dysfunctions. Patients diagnosed with schizophrenia performed poorer on the seriation factor of the RNG than healthy control participants (study 4). Our results indicate that the RNG task has modest to acceptable psychometric properties. It primarily taps executive subfunctions (i.e., inhibition, updating, and monitoring), which are affected by psychopathological or neurological deficits. (JINS, 2007, 13, 626–634.)

Accurate neuropsychological assessment of older individuals from heterogeneous backgrounds is a major challenge. Education, ethnicity, language, and age are associated with scale level differences in test scores, but item level bias might contribute to these differences. We evaluated several strategies for dealing with item and scale level demographic influences on a measure of executive abilities defined by working memory and fluency tasks. We determined the impact of differential item functioning (DIF). We compared composite scoring strategies on the basis of their relationships with volumetric magnetic resonance imaging (MRI) measures of brain structure. Participants were 791 Hispanic, white, and African American older adults. DIF had a salient impact on test scores for 9% of the sample. MRI data were available on a subset of 153 participants. Validity in comparison with structural MRI was higher after scale level adjustment for education, ethnicity/language, and gender, but item level adjustment did not have a major impact on validity. Age adjustment at the scale level had a negative impact on relationships with MRI, most likely because age adjustment removes variance related to age-associated diseases. (JINS, 2008, 14, 746–759.)

In addition to deficits in delayed recall, recent research suggests that participants with amnestic mild cognitive impairment (aMCI) demonstrate diminished use of strategic encoding strategies during learning. Few studies have explored the cognitive mechanisms underlying this deficit. The aim of this study was to investigate in aMCI whether components of working memory (executive attention – attention set-shifting, dividing and focusing attention; and episodic buffer functions – strategic retrieval and manipulation of information) predict strategic encoding strategies during learning (semantic clustering). Thirty-three participants with aMCI and 33 healthy older adults (HOA) were administered neuropsychological tests assessing word-list learning and working memory. The aMCI group demonstrated significant impairment in acquisition, retrieval of information, and decreased use of semantic clustering strategies. Use of semantic clustering in the aMCI group was not predicted by measures of executive attention or phonemic verbal fluency, but was predicted by semantic verbal fluency performance. In the HOA group, semantic clustering was strongly related to semantic verbal fluency. These findings suggest that in aMCI, diminished strategic encoding strategies during learning (semantic clustering) is selectively related to the strategic function of the episodic buffer, but only when in interaction with the manipulation and retrieval of semantic associations. (JINS, 2010, 16, 342–351.)

Alcoholic Korsakoff's syndrome (KS) is marked by remote memory impairment together with characteristic profound anterograde memory deficits. Despite previous studies of memory processes in KS, questions remain regarding the nature and severity of these impairments and identification of brain systems that underlie these different memory impairments. This study examined remote and anterograde memory function in 5 KS patients in comparison with 8 patients with Alzheimer's disease (AD) and 24 normal control subjects (NC). In addition, relationships between memory performance and regional brain volumes were examined in the KS group. Overall, the KS group showed severe impairment on both remote and anterograde memory measures, performing at the level of the AD group on most measures. Differences were observed on the pattern of temporal gradient for verbal recognition, with KS exhibiting a more steeply graded rate of decline over the most recent period examined. Severity of the remote memory deficit in KS was not associated with severity of anterograde memory deficit. Examination of brain structure–function relationships in the KS subjects revealed that photo naming of remote historical information was related to posterior cortical white matter volumes but not hippocampal volumes; sequencing was related to prefrontal but not hippocampal volumes. By contrast, a measure of anterograde memory for nonverbal visual material showed a relationship to hippocampal but not regional cortical white matter volumes. This set of dissociations, which parallels that observed in our earlier study of AD, is now documented in KS and provides further evidence that these separate cortical and limbic brain systems are principal neural substrates of the remote and anterograde memory and sequencing deficits in KS. (JINS, 2004, 10, 427–441.)

There is continuing debate about long-term effects of brain injury. We examined a range of traumatic brain injury (TBI) variables (TBI history, severity, frequency, and age of injury) as predictors of cognitive outcome over 8 years in an adult population, and interactions with apolipoprotein E (APOE) genotype, sex, and age cohorts. Three randomly sampled age cohorts (20–24, 40–44, 60–64 years at baseline; N = 6333) were each evaluated three times over 8 years. TBI variables, based on self-report, were separately modeled as predictors of cognitive performance using linear mixed effects models. TBI predicted longitudinal cognitive decline in all three age groups. APOE ε4+ genotypes in the young and middle-aged groups predicted lower baseline cognitive performance in the context of TBI. Baseline cognitive performance was better for young females than males but this pattern reversed in middle age and old age. The findings suggest TBI history is associated with long-term cognitive impairment and decline across the adult lifespan. A role for APOE genotype was apparent in the younger cohorts but there was no evidence that it is associated with impairment in early old age. The effect of sex and TBI on cognition varied with age cohort, consistent with a proposed neuroprotective role for estrogen. (JINS, 2014, 20, 444–454)

Neuropsychological studies have shown that patients with Frontotemporal dementia (FTD) perform worse than patients with Alzheimer's disease (AD) on tests of conceptualization and verbal fluency, but better on tests of memory and visuospatial functions. However, it is not known if these distinct cognitive profiles are robust enough to be detected using a relatively brief dementia screening instrument such as the Mattis Dementia Rating Scale (MDRS). To address this issue, the MDRS subscale profiles of patients with autopsy-confirmed FTD (n = 17) or AD (n = 34) were compared. Results showed distinct cognitive profiles in which FTD patients performed worse than AD patients on the Initiation/Perseveration and Conceptualization subscales while performing better on the Memory and Construction subscales. The distinct subscale profiles correctly classified 85% of AD patients and 76% of FTD patients. Profiles were maintained in a subset of mildly-to-moderately demented patients (MDRS ≥ 105) and correctly classified 89% of these patients. In addition, FTD patients (mean = 30.0 points/year) declined faster than AD patients (mean = 14.8 points/year) on MDRS total and specific subscale scores. These results suggest that the MDRS may be a useful adjunct to other clinical measures for distinguishing FTD from AD and tracking the progression of the disorder. (JINS, 2008, 14, 373–383.)

Objectives: Decrements in cognitive function may already be evident in young children with type 1 diabetes (T1D). Here we report prospectively acquired cognitive results over 18 months in a large cohort of young children with and without T1D. Methods: A total of 144 children with T1D (mean HbA1c: 7.9%) and 70 age-matched healthy controls (mean age both groups 8.5 years; median diabetes duration 3.9 years; mean age of onset 4.1 years) underwent neuropsychological testing at baseline and after 18-months of follow-up. We hypothesized that group differences observed at baseline would be more pronounced after 18 months, particularly in those T1D patients with greatest exposure to glycemic extremes. Results: Cognitive domain scores did not differ between groups at the 18 month testing session and did not change differently between groups over the follow-up period. However, within the T1D group, a history of diabetic ketoacidosis (DKA) was correlated with lower Verbal IQ and greater hyperglycemia exposure (HbA1c area under the curve) was inversely correlated to executive functions test performance. In addition, those with a history of both types of exposure performed most poorly on measures of executive function. Conclusions: The subtle cognitive differences between T1D children and nondiabetic controls observed at baseline were not observed 18 months later. Within the T1D group, as at baseline, relationships between cognition (Verbal IQ and executive functions) and glycemic variables (chronic hyperglycemia and DKA history) were evident. Continued longitudinal study of this T1D cohort and their carefully matched healthy comparison group is planned. (JINS, 2016, 21, 293–302)

Reading and writing were studied in 31 young adults with spina bifida and hydrocephalus (SBH). Like children with this condition, young adults with SBH had better word decoding than reading comprehension, and, compared to population means, had lower scores on a test of writing fluency. Reading comprehension was predicted by word decoding and listening comprehension. Writing was predicted by fine motor finger function, verbal intelligence, and short-term and working memory. These findings are consistent with cognitive models of reading and writing. Writing, but not reading, was related to highest level of education achieved and writing fluency predicted several aspects of functional independence. Reading comprehension and writing remain deficient in adults with SBH and have consequences for educational attainments and functional independence. (JINS, 2004, 10, 655–663.)