A subtle decline in episodic memory often occurs prior to the emergence of the full dementia syndrome in nondemented older adults who develop Alzheimer's disease (AD). The APOE-ε4 genotype may engender a more virulent form of AD that hastens this decline. To examine this possibility, we compared the rate of decline in episodic memory during the preclinical phase of AD in individuals with or without at least one APOE ε4 allele. Nondemented normal control (NC; n = 84) participants, nondemented older adults who subsequently developed dementia within 1 or 2 years (i.e., preclinical AD; n = 20), and patients with mild AD (n = 53) were examined with 2 commonly employed tests of episodic memory, the Logical Memory subtest of the Wechsler Memory Scale–Revised and the California Verbal Learning Test. Results revealed a precipitous decline in verbal memory abilities 1 to 2 years prior to the onset of the dementia syndrome, but there was little effect of APOE genotype on the rate of this memory decline. The presence of an APOE-ε4 allele, however, did have a differential effect on the sensitivity of the 2 types of memory tests for tracking progression and made an independent contribution to the prediction of conversion to AD. (JINS, 2002, 8, 943–955.)

The objective of this study is to identify the clinical, neuropsychological, neuropsychiatric, and functional variables that correlate with metacognitive self-awareness (SA) in severe traumatic brain injury (TBI) outpatients and to assess the influence of the same variables on the sensory-motor, cognitive, and behavioral-affective indicators of SA. This cross-sectional observational study evaluated 37 outpatients from May 2006 to June 2007 in a neurorehabilitation hospital on the basis of the following inclusion criteria: (1) age ≥ 15 years; (2) diagnosis of severe TBI (Glasgow Coma Scale, GCS ≤ 8); (3) posttraumatic amnesia (PTA) resolution; (4) capacity to undergo formal psychometric evaluation despite cognitive and sensory-motor deficits; (5) absence of aphasia; (6) availability of informed consent. A neuropsychological battery was used to evaluate attention, memory, and executive functions. SA was assessed by the awareness questionnaire (AQ), administered to both patients and relatives. Decreased metacognitive self-awareness is significantly correlated with increased problems in some components of executive system, even when the AQ subscales were considered separately. The significant correlation found between some components of executive system and metacognitive self-awareness confirmed the importance of addressing this issue to treat SA contextually in the rehabilitation of executive functions. (JINS, 2008, 14, 862–868.)

Pathological Gambling is an impulse control disorder. Impulsivity has been investigated separately by neuropsychological tests and self-report scales. Although some studies have tried to correlate these approaches, their interaction has not been sufficiently explored among pathological gamblers (PG). In this study, we have compared 214 PG (162 with comorbidity and 52 with no comorbidity) to 82 healthy volunteers regarding the reaction time and number of errors at Go/No-go tasks, and scores on the Barratt Impulsiveness Scale (BIS). PG have committed more errors at the Go/No-go tasks and presented higher scores on the self-report scale. The neuropsychological tests and BIS composed a multinomial logistic model that discriminated PG from non-gamblers better than models having one or another type of measure. Impulsivity seems to be a multi-dimensional phenomenon, and PG a heterogeneous population in which different types of impulsivity are present. (JINS, 2006, 12, 907–912.)

Attentional–inhibitory control and social–behavioral regulation are two outcome domains commonly impaired after childhood closed head injury (CHI). We compared neuropsychological tests of attentional–inhibitory control (vigilance, selective attention, response modulation) and social discourse and intentionality (inferencing, figurative language, and speech acts) with parent ratings of attention and behavioral regulation in relation to four injury- related variables: age at CHI, time since CHI, CHI injury severity, and frontal lobe injury moderated by CHI severity. Participants were 105 school-aged children in the chronic stage of CHI, divided into mild, moderate, and severe injury severity groups, and further subdivided according to frontal lobe injury. Outcome indices were imperfectly correlated in the group as a whole, although several relations between neurocognitive tests and parent ratings were observed within CHI subgroups. Different domains of cognitive function had different predictors. For attentional–inhibitory control, age at injury and time since injury were most predictive of outcome; for social discourse, predictors were injury severity and frontal lobe injury moderated by injury severity. Variability in cognitive outcome after childhood CHI is not random, but appears related to age, time, and biological features of the injury. (JINS, 2001, 7, 683–692.)

Word-list verbal learning and memory tests with appropriate normative data can be highly sensitive to cognitive decline, but there are significant limitations of such tests available for use with older Hispanic and non-Hispanic people living in the US. The purpose of this study was to (1) create a new word-list learning and memory test in both English and Spanish and, (2) validate it with respect to sensitivity to cognitive impairment, and (3) develop statistical corrections for the effects of significant demographic variables, including ethnicity, language of administration, age, education, and gender. A community dwelling sample of 801 English- and Spanish-speaking older people was employed. Recall on learning trials and the delayed recall trial of the word-list learning test were strongly related to the Mini-Mental State Examination (MMSE), moderately related to age, and weakly related to gender and education. The relationship of word-list variables and the MMSE did not significantly differ across ethnicity/language groups. Regression coefficients for demographic variables were used in a statistical correction formula to adjust raw word-list scores, and then to develop specific percentile cut-off values. (JINS, 2001, 7, 544–555.)

Using cluster analysis Libon et al. (2010) found three verbal serial list-learning profiles involving delay memory test performance in patients with mild cognitive impairment (MCI). Amnesic MCI (aMCI) patients presented with low scores on delay free recall and recognition tests; mixed MCI (mxMCI) patients scored higher on recognition compared to delay free recall tests; and dysexecutive MCI (dMCI) patients generated relatively intact scores on both delay test conditions. The aim of the current research was to further characterize memory impairment in MCI by examining forgetting/savings, interference from a competing word list, intrusion errors/perseverations, intrusion word frequency, and recognition foils in these three statistically determined MCI groups compared to normal control (NC) participants. The aMCI patients exhibited little savings, generated more highly prototypic intrusion errors, and displayed indiscriminate responding to delayed recognition foils. The mxMCI patients exhibited higher saving scores, fewer and less prototypic intrusion errors, and selectively endorsed recognition foils from the interference list. dMCI patients also selectively endorsed recognition foils from the interference list but performed similarly compared to NC participants. These data suggest the existence of distinct memory impairments in MCI and caution against the routine use of a single memory test score to operationally define MCI. (JINS, 2011, 17, 905–914)

Children with either fetal alcohol spectrum disorder (FASD) or attention-deficit/hyperactivity disorder (ADHD) display deficits in attention and executive function (EF) and differential diagnosis of these two clinical groups may be difficult, especially when information about prenatal alcohol exposure is unavailable. The current study compared EF performance of three groups: children with heavy prenatal alcohol exposure (ALC); nonexposed children with attention-deficit/hyperactivity disorder (ADHD); and typically developing controls (CON). Both clinical groups met diagnostic criteria for ADHD. The EF tasks used were the Wisconsin Card Sorting Test (WCST), the Controlled Oral Word Association Test (COWAT), and the Trail Making Test (TMT). Results indicated different patterns of deficit; both clinical groups displayed deficits on the WCST and a relative weakness on letter versus category fluency. Only the ALC group displayed overall deficits on letter fluency and a relative weakness on TMT-B versus TMT-A. In addition, WCST performance was significantly lower than expected based on IQ in the ADHD group and significantly higher than expected in the ALC group. These results, which indicate that, although EF deficits occurred in both clinical groups, the degree and pattern of deficit differed between the ALC and ADHD groups, may improve differential diagnosis. (JINS, 2008, 14, 119–129.)

We examined, among those persons working preinjury, the risk of unemployment 1 year after traumatic brain injury (TBI) relative to expected risk of unemployment for the sample under a validated risk-adjusted econometric model of employment in the U.S. population. Results indicate that 42% of TBI cases were unemployed versus 9% expected, relative risk (RR) = 4.5, 95% confidence interval (CI) (4.12, 4.95). The relative risk for unemployment was higher among males, those with higher education, persons with more severe injuries, and more impaired early neuropsychological or functional status. Difference in unemployment rates gave similar results for gender, severity of injury, and early neuropsychological and functional status. However, for education, the excess was smaller among those more highly educated, but the unemployment rate in the more highly educated in the general population was sufficiently small to yield a larger relative risk. In conclusion, after accounting for underlying risk of unemployment in the general population, unemployment is substantially higher after TBI for people who were employed when they were injured. The differential employment status varies depending on demographics, severity of brain injury, early functional outcome, and neurobehavioral indicators. For characteristics such as education, associated with rates of unemployment in the general population, different methods used to compare the rates may yield different results. (JINS, 2005, 11, 747–752.)

The objective of this study is to determine which pre-existing athlete characteristics, if any, are associated with greater deficits in functioning following sports-related concussion, after controlling for factors previously shown to moderate this effect (e.g., time since injury). Ninety-one independent samples of concussion were included in a fixed+systematic effects meta-analysis (n = 3,801 concussed athletes; 5,631 controls). Moderating variables were assessed using analogue-to-ANOVA and meta-regression analyses. Post-injury assessments first conducted 1–10 days following sports-related concussion revealed significant neuropsychological dysfunction, postural instability and post-concussion symptom reporting (d = −0.54, −1.10, and −1.14, respectively). During this interval, females (d = −0.87), adolescent athletes competing in high school competitions (d = −0.60), and those with 10 years of education (d = −1.32) demonstrated larger post-concussion neuropsychological deficits than males (d = −0.42), adults (d = −0.25), athletes competing at other levels of competition (d = −0.43 to −0.41), or those with 16 years of education (d = −0.15), respectively. However, these sub-groups’ differential impairment/recovery beyond 10 days could not be reliably quantified from available literature. Pre-existing athlete characteristics, particularly age, sex and education, were demonstrated to be significant modifiers of neuropsychological outcomes within 10 days of a sports-related concussion. Implications for return-to-play decision-making and future research directions are discussed. (JINS, 2013, 19, 1–17).

Dementia cases are increasing worldwide; thus, investigators seek to identify interventions that might prevent or ameliorate cognitive decline in later life. Extensive research confirms the benefits of physical exercise for brain health, yet only a fraction of older adults exercise regularly. Interactive mental and physical exercise, as in aerobic exergaming, not only motivates, but has also been found to yield cognitive benefit above and beyond traditional exercise. This pilot study sought to investigate whether greater cognitive challenge while exergaming would yield differential outcomes in executive function and generalize to everyday functioning. Sixty-four community based older adults (mean age=82) were randomly assigned to pedal a stationary bike, while interactively engaging on-screen with: (1) a low cognitive demand task (bike tour), or (2) a high cognitive demand task (video game). Executive function (indices from Trails, Stroop and Digit Span) was assessed before and after a single-bout and 3-month exercise intervention. Significant group × time interactions were found after a single-bout (Color Trails) and after 3 months of exergaming (Stroop; among 20 adherents). Those in the high cognitive demand group performed better than those in the low cognitive dose condition. Everyday function improved across both exercise conditions. Pilot data indicate that for older adults, cognitive benefit while exergaming increased concomitantly with higher doses of interactive mental challenge. (JINS, 2015, 21, 768–779)

Production of complex discourse—lengthy, open-ended utterances and narratives—requires intact basic language operations, but it also requires a series of learned procedures for construction of complex, goal-directed communications. The progression of clinical disorders from transcortical motor aphasia to dynamic aphasia to discourse impairments represents a progression of procedural deficits from basic morpho-syntax to complex grammatical structures to narrative and a progression of lesions from posterior frontal to polar and/or lateral frontal to medial frontal. Two cases of impaired utilization of language exemplify the range of impairments from clearly aphasic agrammatic, nonfluency to less and less “aphasic” and more and more executive impairments from transcortical motor aphasia to dynamic aphasia to narrative discourse disorder. The clinical phenomenology of these disorders gradually comes to be more accurately defined in the terminology of executive deficits than that of aphasia. The executive deficits are, in turn, based on impairments in various components of attention. Specific impairments in energizing attention and setting response criteria associated, respectively, with lesions in superior medial and left ventrolateral frontal regions may cause defective recruitment of the procedures of complex language assembly. (JINS, 2006, 12, 236–247.)

Reduced left-hemispheric language lateralization has been proposed to be a trait marker for schizophrenia, but the empirical evidence is ambiguous. Recent studies suggest that auditory hallucinations are critical for whether a patient shows reduced language lateralization. Therefore, the aim of the study was to statistically integrate studies investigating language lateralization in schizophrenia patients using dichotic listening. To this end, two meta-analyses were conducted, one comparing schizophrenia patients with healthy controls (n = 1407), the other comparing schizophrenia patients experiencing auditory hallucinations with non-hallucinating controls (n = 407). Schizophrenia patients showed weaker language lateralization than healthy controls but the effect size was small (g = −0.26). When patients with auditory hallucinations were compared to non-hallucinating controls, the effect size was substantially larger (g = −0.45). These effect sizes suggest that reduced language lateralization is a weak trait marker for schizophrenia as such and a strong trait marker for the experience of auditory hallucinations within the schizophrenia population. (JINS, 2013, 19, 1–9.)

The Forced Choice Recognition (FCR) and the Critical Item Analysis (CIA) indices of the California Verbal Learning Test-II (CVLT-II) have been identified by the CVLT-II test developers as potentially useful, brief screening indicators of effort in neuropsychological assessment. This retrospective study analyzes performance on these measures in three groups: (1) clinically referred individuals; (2) forensically referred individuals not suspected of inadequate effort; and (3) forensically referred individuals whose performance on freestanding tests of effort suggested inadequate effort. Performances on FCR were analyzed for their relation to actual memory impairment and with regard to concrete and abstract distractor endorsement. FCR and CIA performances were analyzed for agreement with formal tests of inadequate effort and their test characteristics. Incremental validity was assessed by hierarchical logistic regression with previously identified indices for detection of inadequate effort on the CVLT. Results indicate that (1) FCR and CIA performances are not related to decreased memory performance; (2) FCR and CIA indices exhibit higher specificity and lower sensitivity, with higher positive predictive value than negative predictive value; and (3) FCR and CIA indices exhibit modest incremental validity with previously identified indices. Implications for use of FCR and CIA indices in inadequate effort detection are discussed (JINS, 2006, 12, 688–696.)

Objectives: Dysbiosis of the gut microbiome is implicated in numerous human health conditions. Animal studies have linked microbiome disruption to changes in cognitive functioning, although no study has examined this possibility in neurologically healthy older adults. Methods: Participants were 43 community-dwelling older adults (50–85 years) that completed a brief cognitive test battery and provided stool samples for gut microbiome sequencing. Participants performing≥1 SD below normative performance on two or more tests were compared to persons with one or fewer impaired scores. Results: Mann Whitney U tests revealed different distributions of Bacteroidetes (p=.01), Firmicutes (p=.02), Proteobacteria (p=.04), and Verrucomicrobia (p=.003) between Intact and Impaired groups. These phyla were significantly correlated with cognitive test performances, particularly Verrucomicrobia and attention/executive function measures. Conclusions: The current findings suggest that composition of the gut microbiome is associated with cognitive test performance in neurologically healthy older adults. Future studies are needed to confirm these findings and explore possible mechanisms. (JINS, 2017, 23, 700–705)

Cognitive training improves mental abilities in older adults, but the trainability of persons with memory impairment is unclear. We conducted a subgroup analysis of subjects in the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) trial to examine this issue. ACTIVE enrolled 2802 non-demented, community-dwelling adults aged 65 years and older and randomly assigned them to one of four groups: Memory training, reasoning training, speed-of-processing training, or no-contact control. For this study, participants were defined as memory-impaired if baseline Rey Auditory Verbal Learning Test (AVLT) sum recall score was 1.5 SD or more below predicted AVLT sum recall score from a regression-derived formula using age, education, ethnicity, and vocabulary from all subjects at baseline. Assessments were taken at baseline (BL), post-test, first annual (A1), and second annual (A2) follow-up. One hundred and ninety-three subjects were defined as memory-impaired and 2580 were memory-normal. Training gain as a function memory status (impaired vs. normal) was compared in a mixed effects model. Results indicated that memory-impaired participants failed to benefit from Memory training but did show normal training gains after reasoning and speed training. Memory function appears to mediate response to structured cognitive interventions in older adults. (JINS, 2007, 13, 953–960.)

The Paced Auditory Serial Addition Test (PASAT) is a commonly used procedure that combines elements of both a working memory task and a test of information processing speed. Patients with multiple sclerosis (MS) have consistently been found to be impaired on this test and it has been recommended as a core outcome measure in clinical trials. The standard score for this task is the number of correct responses at each stimulus presentation rate but a concern has been raised that subjects may ignore some test items in order to chunk the information into manageable portions and avoid performing several cognitive tasks simultaneously. To account for this strategy, one can examine the proportion of correct responses that are consecutive (termed dyads), since such responses require that the task be performed according to the instructions. We compared a group of 35 mildly to moderately disabled MS patients and matched healthy controls on the PASAT. The MS patients made significantly fewer correct responses at the 2 slowest presentation rates (2.4, 2.0 s/digit) while their scores at faster rates (1.6, 1.2 s/digit) did not discriminate them from controls as well. Nevertheless, the MS patients' percentage of dyads was significantly lower than that of the control sample across all stimulus presentation rates. While our study supports the use of the PASAT as a test that distinguishes MS patients from healthy individuals, our results also illustrate problems that lie in the interpretation of this difference in performance. It appears that a chunking strategy may be common in the PASAT, particularly as task demands increase, and that this may mask actual performance differences. If so, the total correct response score alone is limited as a measure of working memory and information processing speed. More detailed analyses of PASAT performance, coupled with other measures of information processing, may help clarify the underlying cognitive deficits of MS patients. (JINS, 2001, 7, 363–372.)

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. (JINS, 2011, 17, 615–624)

Hazard perception in driving is the one of the few driving-specific skills associated with crash involvement. However, this relationship has only been examined in studies where the majority of individuals were younger than 65. We present the first data revealing an association between hazard perception and self-reported crash involvement in drivers aged 65 and over. In a sample of 271 drivers, we found that individuals whose mean response time to traffic hazards was slower than 6.68 s [the receiver operating characteristic (ROC) curve derived pass mark for the test] were 2.32 times [95% confidence interval (CI), 1.46, 3.22) more likely to have been involved in a self-reported crash within the previous 5 years than those with faster response times. This likelihood ratio became 2.37 (95% CI, 1.49, 3.28) when driving exposure was controlled for. As a comparison, individuals who failed a test of useful field of view were 2.70 (95% CI, 1.44, 4.44) times more likely to crash than those who passed. The hazard perception test and the useful field of view measure accounted for separate variance in crash involvement. These findings indicate that hazard perception testing and training could be potentially useful for road safety interventions for this age group. (JINS, 2010, 16, 939–944.)

Arterial spin labeling (ASL) uses magnetic resonance imaging methods to measure cerebral blood flow (CBF) non-invasively. ASL CBF validly localizes brain function and may be especially useful for studies where the time frame of behavioral change is more than a few minutes, such as in longitudinal and treatment studies. ASL measures of cerebral perfusion are highly accurate in detecting lesion laterality in temporal lobe epilepsy, stenotic-occlusive disease, and brain tumors. Among lesioned patients, ASL CBF has excellent concurrent validity when correlated with CBF measured by Positron Emission Tomography or with dynamic susceptibility-weighted magnetic resonance. ASL CBF can predict tumor grading in vivo and can predict six-month response to the surgical treatment of brain tumors. ASL's capability to selectively and non-invasively tag flow in major vessels may refine the monitoring of treatment of cerebrovascular disease and brain tumors. Conclusions about the utility of ASL are limited by the small sample sizes of the studies currently in the literature and by the uncertainty caused by the effect of brain disease on transit times of the magnetic tag. As the method evolves, ASL techniques will likely become more widely used in clinical research and practice. (JINS, 2007, 13, 526–538.)

Recent evidence suggests that there may be dissociable systems for recognizing emotional expressions from different media including audio and visual channels, and still versus moving displays. In this study, 34 adults with severe traumatic brain injuries (TBI) and 28 adults without brain injuries were assessed for their capacity to recognize emotional expressions from dynamic audiovisual displays, conversational tone alone, moving facial displays, and still photographs. The TBI group were significantly impaired in their interpretation of both audio and audiovisual displays. In addition, eight of the 34 were significantly impaired in their capacity to recognize still facial expressions. In contrast, only one individual was impaired in the recognition of moving visual displays. Information processing speed was not found to play a significant role in producing problems with dynamic emotional expression. Instead the results suggest that visual moving displays may enlist different brain systems to those engaged with still displays, for example, the parietal cortices. Problems with the processing of affective prosody, while present, were not clearly related to other emotion processing problems. While this may attest to the independence of the auditory affective system, it may also reflect problems with the dual demands of listening to conversational meaning and affective tone. (JINS, 2005, 11, 392–399.)