The idea of reserve against brain damage stems from the repeated observation that there does not appear to be a direct relationship between the degree of brain pathology or brain damage and the clinical manifestation of that damage. This paper attempts to develop a coherent theoretical account of reserve. One convenient subdivision of reserve models revolves around whether they envision reserve as a passive process, such as in brain reserve or threshold, or see the brain as actively attempting to cope with or compensate for pathology, as in cognitive reserve. Cognitive reserve may be based on more efficient utilization of brain networks or of enhanced ability to recruit alternate brain networks as needed. A distinction is suggested between reserve, the ability to optimize or maximize normal performance, and compensation, an attempt to maximize performance in the face of brain damage by using brain structures or networks not engaged when the brain is not damaged. Epidemiologic and imaging data that help to develop and support the concept of reserve are presented. (JINS, 2002, 8, 448–460.)

The aim of this study was to clarify which cognitive mechanisms underlie Trail Making Test (TMT) direct and derived scores. A comprehensive review of the literature on the topic was carried out to clarify which cognitive factors had been related to TMT performance. Following the review, we explored the relative contribution from working memory, inhibition/interference control, task-switching ability, and visuomotor speed to TMT performance. Forty-one healthy old subjects participated in the study and performed a battery of neuropsychological tests including the TMT, the Digit Symbol subtest [Wechsler Adult Intelligence Scale (Third Version) (WAIS-III)], a Finger Tapping Test, the Digits Forward and Backward subtests (WAIS-III), Stroop Test, and a task-switching paradigm inspired in the Wisconsin Card Sorting Test. Correlation and regression analyses were used in order to clarify the joint and unique contributions from different cognitive factors to the prediction of TMT scores. The results suggest that TMT-A requires mainly visuoperceptual abilities, TMT-B reflects primarily working memory and secondarily task-switching ability, while B-A minimizes visuoperceptual and working memory demands, providing a relatively pure indicator of executive control abilities. (JINS, 2009, 15, 438–450.)

Research concerned with relations between adult age and cognitive functioning is briefly reviewed. The coverage is necessarily selective, and is organized in terms of five major questions. These are what abilities are related to age, how many distinct influences are contributing to the relations between age and cognitive functioning, do the differences between people increase with advancing age, what is responsible for the discrepancies between cross-sectional and longitudinal age comparisons of cognitive functioning, and what methods can be used to identify causes of age-related influences on cognition. Although definitive answers are not yet possible, quite a bit of information relevant to the questions is now available. Moreover, the existing information has implications for the design, analysis, and interpretation of cognitive and neuropsychological research concerned with aging. (JINS, 2010, 16, 754–760.)

IQ scores are volatile indices of global functional outcome, the final common path of an individual’s genes, biology, cognition, education, and experiences. In studying neurocognitive outcomes in children with neurodevelopmental disorders, it is commonly assumed that IQ can and should be partialed out of statistical relations or used as a covariate for specific measures of cognitive outcome. We propose that it is misguided and generally unjustified to attempt to control for IQ differences by matching procedures or, more commonly, by using IQ scores as covariates. We offer logical, statistical, and methodological arguments, with examples from three neurodevelopmental disorders (spina bifida meningomyelocele, learning disabilities, and attention deficit hyperactivity disorder) that: (1) a historical reification of general intelligence, g, as a causal construct that measures aptitude and potential rather than achievement and performance has fostered the idea that IQ has special status and that in studying neurocognitive function in neurodevelopmental disorders; (2) IQ does not meet the requirements for a covariate; and (3) using IQ as a matching variable or covariate has produced overcorrected, anomalous, and counterintuitive findings about neurocognitive function. (JINS, 2009, 15, 331–343.)

Cognitive impairment occurs in roughly 50% of patients with multiple sclerosis (MS). It is well known that processing speed and episodic memory deficits are the most common neuropsychological (NP) sequelae in this illness. Consensus has emerged about the specific tests that prove most helpful for routine monitoring of MS associated cognitive impairment. The purpose of this study was to examine the validity of the Minimal Assessment of Cognitive Function in MS (MACFIMS), a recommended battery based on the findings of an international conference held in 2001. We tested 291 MS patients and 56 healthy controls. Frequencies of impairment paralleled those reported in previous work for both individual cognitive domains and general impairment. All tests were impaired in the MS group, and distinguished relapsing-remitting (RR) from secondary progressive (SP) course. Principle components analysis showed a distinct episodic memory component. Most of the MACFIMS tests discriminated disabled from employed patients. However, in regression models accounting for all NP tests, those emphasizing verbal memory and executive function were most predictive of vocational status. We conclude that the MACFIMS is a valid approach to routine NP assessment of MS patients. Future work is planned to determine its psychometric properties in a longitudinal study. (JINS, 2006, 12, 549–558.)

HIV-1 infection can be associated with neuropsychological (NP) deficits ranging from subtle to severe. The purpose of this study was to evaluate the functional, or “real-world” impact of HIV-associated NP impairment in a group of 267 HIV-infected participants. All participants received comprehensive NP, neuromedical, and standardized functional evaluations that included laboratory measures of shopping, cooking, financial management, medication management and vocational abilities. Compared to NP-normal participants, those with NP impairment performed significantly worse on all laboratory measures of everyday functioning. Multivariate analyses revealed that the NP ability domains of Abstraction/Executive Function, Learning, Attention/Working Memory and Verbal abilities most strongly and consistently predicted failures on the functional battery. Both NP impairment and impairment on the functional battery were significantly associated with subjective experiences of cognitive difficulties, as well as unemployment and increased dependence in activities of daily living; multivariate prediction models that also considered depressed mood and biological measures of disease progression revealed that impairment on the functional battery and depression were the only unique predictors of all three indicators of “real-world” functioning. The current results add to growing evidence concerning the clinical significance of HIV-associated NP impairment. Objective, laboratory based functional measures, such as those used here, may compliment NP testing in future studies directed at understanding the impact on life quality of central nervous system disorders and their treatments. Finally, there is a need for additional research investigating the apparently independent effect of depression on level of everyday functioning in HIV infected persons.NOTE: Dr. Erin D. Bigler served as action editor during the course of this review. (JINS, 2004, 10, 317–331.)

Ninety-two mixed etiology neurological patients and 216 control participants were assessed on a range of neuropsychological tests, including 10 neuropsychological measures of executive function derived from 6 different tests. People who knew the patients well (relatives or carers) completed a questionnaire about the patient's dysexecutive problems in everyday life, and this paper reports the extent to which the tests predicted the patients' everyday life problems. All of the tests were significantly predictive of at least some of the behavioral and cognitive deficits reported by patients' carers. However, factor analysis of the patients' dysexecutive symptoms suggested a fractionation of the dysexecutive syndrome, with neuropsychological tests loading differentially on 3 underlying cognitive factors (Inhibition, Intentionality, and Executive Memory), supporting the conclusions that different tests measure different cognitive processes, and that there may be limits to the fractionation of the executive system. (JINS, 1998, 4, 547–558.)

Proceeding from the assumptions that specific frontal regions control discrete functions and that very basic cognitive processes can be systematically manipulated to reveal those functions, recent reports have demonstrated consistent anatomical/functional relationships: dorsomedial for energization, left dorsolateral for task setting, and right dorsolateral for monitoring. There is no central executive. There are, instead, numerous domain general processes discretely distributed across several frontal regions that act in concert to accomplish control. Beyond these functions, there are two additional “frontal” anatomical/functional relationships: ventral–medial/orbital for emotional and behavioral regulation, and frontopolar for integrative—even meta-cognitive—functions. (JINS, 2011, 17, 759–765)

There continues to be debate about the long-term neuropsychological impact of mild traumatic brain injury (MTBI). A meta-analysis of the relevant literature was conducted to determine the impact of MTBI across nine cognitive domains. The analysis was based on 39 studies involving 1463 cases of MTBI and 1191 control cases. The overall effect of MTBI on neuropsychological functioning was moderate (d = .54). However, findings were moderated by cognitive domain, time since injury, patient characteristics, and sampling methods. Acute effects (less than 3 months postinjury) of MTBI were greatest for delayed memory and fluency (d = 1.03 and .89, respectively). In unselected or prospective samples, the overall analysis revealed no residual neuropsychological impairment by 3 months postinjury (d = .04). In contrast, clinic-based samples and samples including participants in litigation were associated with greater cognitive sequelae of MTBI (d = .74 and .78, respectively at 3 months or greater). Indeed, litigation was associated with stable or worsening of cognitive functioning over time. The implications and limitations of these findings are discussed. (JINS, 2005, 11, 215–227.)

The Verbal Learning Test (VLT; Rey, 1958) evaluates the declarative memory. Despite its extensive use, it has been difficult to establish normative data because test administration has not been uniform. The purpose of the present study was to gather normative data for the VLT for a large number (N = 1855) of healthy participants aged 24–81 years, using a procedure in which the words to be learned were presented either verbally or visually. The results showed that VLT performance decreased in an age-dependent manner from an early age. The learning capacity of younger versus older adults differed quantitatively rather than qualitatively. Females and higher educated participants outperformed males and lower educated participants over the entire age range tested. Presentation mode affected VLT performance differently: auditory presentation resulted in a better recall on Trial 1 (a short-term or working memory measure), whereas visual presentation yielded a better performance on Trial 3, Trial 4, and Delta (a learning measure). (JINS, 2005, 11, 290–302.)

This article considers the scientific process whereby new and better clinical tests of executive function might be developed, and what form they might take. We argue that many of the traditional tests of executive function most commonly in use (e.g., the Wisconsin Card Sorting Test; Stroop) are adaptations of procedures that emerged almost coincidentally from conceptual and experimental frameworks far removed from those currently in favour, and that the prolongation of their use has been encouraged by a sustained period of concentration on “construct-driven” experimentation in neuropsychology. This resulted from the special theoretical demands made by the field of executive function, but was not a necessary consequence, and may not even have been a useful one. Whilst useful, these tests may not therefore be optimal for their purpose. We consider as an alternative approach a function-led development programme which in principle could yield tasks better suited to the concerns of the clinician because of the transparency afforded by increased “representativeness” and “generalisability.” We further argue that the requirement of such a programme to represent the interaction between the individual and situational context might also provide useful constraints for purely experimental investigations. We provide an example of such a programme with reference to the Multiple Errands and Six Element tests. (JINS, 2006, 12, 194–209.)

The Stop Signal Task (SST) is a measure that has been used widely to assess response inhibition. We conducted a meta-analysis of studies that examined SST performance in patients with various psychiatric disorders to determine the magnitude and generality of deficient inhibition. A five-item instrument was used to assess the methodological quality of studies. We found medium deficits in stop signal reaction time (SSRT), reflecting the speed of the inhibitory process, for attention-deficit hyperactivity disorder (ADHD) (g = 0.62), obsessive compulsive disorder (OCD) (g = 0.77) and schizophrenia (SCZ) (g = 0.69). SSRT was less impaired or normal for anxiety disorder (ANX), autism, major depressive disorder (MDD), oppositional defiant disorder/conduct disorder (ODD/CD), pathological gambling, reading disability (RD), substance dependence, and Tourette syndrome. We observed a large SSRT deficit for comorbid ADHD + RD (g = 0.82). SSRT was less than moderately impaired for ADHD + ANX and ADHD + ODD/CD. Study quality did not significantly affect SSRT across ADHD studies. This confirms an inhibition deficit in ADHD, and suggests that comorbid ADHD has different effects on inhibition in patients with ANX, ODD/CD, and RD. Further studies are needed to firmly establish an inhibition deficit in OCD and SCZ. (JINS, 2010, 16, 1064–1076.)

The present study examined neuropsychological (NP) functioning and associated medical, neurological, brain magnetic resonance imaging (MRI), and psychiatric findings in 389 nondemented males infected with Human Immunodeficiency Virus-Type 1 (HIV-1), and in 111 uninfected controls. Using a comprehensive NP test battery, we found increased rates of impairment at each successive stage of HIV infection. HIV-related NP impairment was generally mild, especially in the medically asymptomatic stage of infection, and most often affected attention, speed of information processing, and learning efficiency; this pattern is consistent with earliest involvement of subcortical or frontostriatal brain systems. NP impairment could not be explained on the bases of mood disturbance, recreational drug or alcohol use, or constitutional symptoms; by contrast, impairment in HIV-infected subjects was related to central brain atrophy on MRI, as well as to evidence of cellular immune activation and neurological abnormalities linked to the central nervous system. (JINS, 1995, 1, 231–251.)

This study aimed to investigate outcome in adults with mild traumatic brain injury (TBI) at 1 week and 3 months postinjury and to identify factors associated with persisting problems. A total of 84 adults with mild TBI were compared with 53 adults with other minor injuries as controls in terms of postconcussional symptomatology, behavior, and cognitive performance at 1 week and 3 months postinjury. At 1 week postinjury, adults with mild TBI were reporting symptoms, particularly headaches, dizziness, fatigue, visual disturbance, and memory difficulties. They exhibited slowing of information processing on neuropsychological measures, namely the WAIS–R Digit Symbol subtest and the Speed of Comprehension Test. By 3 months postinjury, the symptoms reported at 1 week had largely resolved, and no impairments were evident on neuropsychological measures. However, there was a subgroup of 24% of participants who were still suffering many symptoms, who were highly distressed, and whose lives were still significantly disrupted. These individuals did not have longer posttraumatic amnesia (PTA) duration. They were more likely to have a history of previous head injury, neurological or psychiatric problems, to be students, females, and to have been injured in a motor vehicle accident. The majority were showing significant levels of psychopathology. A range of factors, other than those directly reflecting the severity of injury, appear to be associated with outcome following mild TBI. (JINS, 2000, 6, 568–579.)

Two studies assessed the effects of a training procedure (Goal Management Training, GMT), derived from Duncan's theory of goal neglect, on disorganized behavior following TBI. In Study 1, patients with traumatic brain injury (TBI) were randomly assigned to brief trials of GMT or motor skills training. GMT, but not motor skills training, was associated with significant gains on everyday paper-and-pencil tasks designed to mimic tasks that are problematic for patients with goal neglect. In Study 2, GMT was applied in a postencephalitic patient seeking to improve her meal-preparation abilities. Both naturalistic observation and self-report measures revealed improved meal preparation performance following GMT. These studies provide both experimental and clinical support for the efficacy of GMT toward the treatment of executive functioning deficits that compromise independence in patients with brain damage. (JINS, 2000, 6, 299–312.)

Several tests from the CANTAB neuropsychological test battery previously shown to be sensitive to frontal lobe dysfunction were administered to a large group of normal volunteers (N = 341) ranging in age from 21 to 79 years. The main tests included a computerized form of the Tower of London test of planning, a self-ordered spatial working memory task, and a test of attentional set formation and shifting. A computerized form of the Corsi spatial span task was also given. Age-related graded declines in performance were seen, sometimes in a discontinuous manner, especially for the attentional set shifting task (at the extradimensional shift stage). Patterns of deficits reminiscent of frontal lobe or basal ganglia damage were observed in the oldest age group (74–79). However, overall the data were only partially consistent with the hypothesis that frontal lobe functions are the most sensitive to effects of aging. Factor analyses showed that performance in the executive tests was not simply related to a measure of fluid intelligence, and their performance had a factor loading structure distinct from that for the CANTAB tests of visual memory and learning previously administered to the same sample. Finally, only limited support was found for the hypothesis that cognitive aging depends on slowed information processing. (JINS, 1998, 4, 474–490.)

The current study sought to determine if discrepancies in quality of education could explain differences in cognitive test scores between African American and White elders matched on years of education. A comprehensive neuropsychological battery was administered to a sample of African American and non-Hispanic White participants in an epidemiological study of normal aging and dementia in the Northern Manhattan community. All participants were diagnosed as nondemented by a neurologist, and had no history of Parkinson's disease, stroke, mental illness, or head injury. The Reading Recognition subtest from the Wide Range Achievement Test–Version 3 was used as an estimate of quality of education. A MANOVA revealed that African American elders obtained significantly lower scores than Whites on measures of word list learning and memory, figure memory, abstract reasoning, fluency, and visuospatial skill even though the groups were matched on years of education. However, after adjusting the scores for WRAT–3 reading score, the overall effect of race was greatly reduced and racial differences on all tests (except category fluency and a drawing measure) became nonsignificant. These findings suggest that years of education is an inadequate measure of the educational experience among multicultural elders, and that adjusting for quality of education may improve the specificity of certain neuropsychological measures. (JINS, 2002, 8, 341–348.)

Although dementia has been described in ancient texts over many centuries (e.g., “Be kind to your father, even if his mind fail him.” – Old Testament: Sirach 3:12), our knowledge of its underlying causes is little more than a century old. Alzheimer published his now famous case study only 110 years ago, and our modern understanding of the disease that bears his name, and its neuropsychological consequences, really only began to accelerate in the 1980s. Since then we have witnessed an explosion of basic and translational research into the causes, characterizations, and possible treatments for Alzheimer’s disease (AD) and other dementias. We review this lineage of work beginning with Alzheimer’s own writings and drawings, then jump to the modern era beginning in the 1970s and early 1980s and provide a sampling of neuropsychological and other contextual work from each ensuing decade. During the 1980s our field began its foundational studies of profiling the neuropsychological deficits associated with AD and its differentiation from other dementias (e.g., cortical vs. subcortical dementias). The 1990s continued these efforts and began to identify the specific cognitive mechanisms affected by various neuropathologic substrates. The 2000s ushered in a focus on the study of prodromal stages of neurodegenerative disease before the full-blown dementia syndrome (i.e., mild cognitive impairment). The current decade has seen the rise of imaging and other biomarkers to characterize preclinical disease before the development of significant cognitive decline. Finally, we suggest future directions and predictions for dementia-related research and potential therapeutic interventions. (JINS, 2017, 23, 818–831)

We examined the association of social activity with cognitive decline in 1138 persons without dementia at baseline with a mean age of 79.6 (SD = 7.5) who were followed for up to 12 years (mean = 5.2; SD = 2.8). Using mixed models adjusted for age, sex, education, race, social network size, depression, chronic conditions, disability, neuroticism, extraversion, cognitive activity, and physical activity, more social activity was associated with less cognitive decline during average follow-up of 5.2 years (SD = 2.7). A one point increase in social activity score (range = 1–4.2; mean = 2.6; SD = 0.6) was associated with a 47% decrease in the rate of decline in global cognitive function (p < .001). The rate of global cognitive decline was reduced by an average of 70% in persons who were frequently socially active (score = 3.33, 90th percentile) compared to persons who were infrequently socially active (score = 1.83, 10th percentile). This association was similar across five domains of cognitive function. Sensitivity analyses revealed that individuals with the lowest levels of cognition or with mild cognitive impairment at baseline did not drive this relationship. These results confirm that more socially active older adults experience less cognitive decline in old age. (JINS, 2011, 17, 998–1005)

Category and letter fluency tasks have been used to demonstrate psychological and neurological dissociations between semantic and phonological aspects of word retrieval. Some previous neuroimaging and lesion studies have suggested that category fluency (semantic-based word retrieval) is mediated primarily by temporal cortex, while letter fluency (letter-based word retrieval) is mediated primarily by frontal cortex. Other studies have suggested that both letter and category fluency are mediated by frontal cortex. We tested these hypotheses using voxel-based lesion symptom mapping (VLSM) in a group of 48 left-hemisphere stroke patients. VLSM maps revealed that category and letter fluency deficits correlate with lesions in temporal and frontal cortices, respectively. Other regions, including parietal cortex, were significantly implicated in both tasks. Our findings are therefore consistent with the hypothesis that temporal cortex subserves word retrieval constrained by semantics, whereas frontal regions are more critical for strategic word retrieval constrained by phonology. (JINS, 2006, 12, 896–900.)