The diagnosis of lifetime major depressive disorders (MDDs) and of current major depressive episodes (MDEs) are relatively common in HIV-infected individuals, and often are assumed to influence neuropsychological (NP) performance. Although cross-sectional studies of HIV-infected individuals generally have found no systematic link between current MDE or depressive symptoms and NP performance, longitudinal studies are needed to clarify whether incident MDE may impact NP functioning in at least some cases. Two hundred twenty-seven human immunodeficiency virus (HIV)-infected adult men, who did not meet criteria for a current MDE at baseline, participated in a longitudinal NP study for an average of two years. Participants received repeated NP assessments, as well as structured psychiatric interviews to ascertain presence or absence of both lifetime MDD and current MDE. Ninety-eight participants had a lifetime history of MDD, and 23 participants met criteria for incident MDE at one of their follow-up evaluations. Groups with and without lifetime MDD and/or incident MDE had comparable demographics, HIV disease status and treatment histories at baseline, and numbers of intervening assessments between baseline and the final follow-up. Lifetime MDD was associated with greater complaints of cognitive difficulties in everyday life, and such complaints were increased at the times of incident MDE. However, detailed group comparisons revealed no NP performance differences in association with either lifetime or incident major depression. Finally, NP data from consistently nondepressed participants were used to develop “norms for change” and these findings failed to show any increased rates of NP worsening among individuals with incident MDE. Our results suggest that neurocognitive impairment and major depression should be considered as two independent processes. (JINS, 2007, 13, 1–11.)

Unawareness of deficit is a common feature of degenerative dementia. The present study explored awareness and correction of naturalistic action errors in 54 dementia participants and 10 healthy controls while they performed a series of everyday tasks, such as toast preparation and gift-wrapping. Awareness for everyday task performance and cognitive functioning was also assessed with questionnaire discrepancy scores, and a neuropsychological test protocol was administered. Dementia participants were aware of and corrected a significantly smaller proportion of errors compared to controls (z = 4.59, p < 001). Awareness and correction of action errors was not significantly correlated with the number of naturalistic errors committed, questionnaire discrepancy scores, or neuropsychological test data. Within-group analyses showed awareness differed across error types, such that participants were aware of a greater proportion of substitution and sequence errors compared to omissions, perseverations, and action addition (i.e., utilization behavior) errors (z ≤ −3.2,p≤.002 for all analyses). Taken together these data suggest that error awareness and correction during the course of action is not related to error production or awareness measured via questionnaire discrepancy scores. Rather, direct assessment of error detection and correction may provide novel information about behavioral monitoring that can not be extrapolated from measures of dementia severity or traditional neuropsychological assessment.

Limbic system atrophy and memory dysfunction are common in patients with temporal lobe epilepsy (TLE). However, the relationship between extrahippocampal limbic structures and memory functioning within TLE has received little attention. The present study examined associations of MRI volumetric measurements of the mammillary body, fornix, amygdala, and hippocampus to measures of episodic verbal and visual memory. The Logical Memory and Visual Reproduction subtests from the Wechsler Memory Scale were administered to 47 unilateral TLE patients (25 right, 22 left). Normalized right and left MRI volumes were determined for each patient by cursor tracing 1.5 mm slices from 3D-MRI. Significant associations were found between left hippocampal volume and the immediate, delayed, and percent retention scores of the Logical Memory Test; between the left mammillary body volume and the Logical Memory Test delayed and percent retention scores; immediate Visual Reproduction performance was significantly related to the right and left amygdala volumes, and right mammillary body volume; only the right amygdala and right mammillary body volume were associated with the delayed Visual Reproduction trial. However, neither right nor left hippocampal volumes were related to visual memory performance. Multiple limbic system structural volumes were independently associated with verbal and nonverbal memory performance. Results suggest that visual memory, as measured by the Visual Reproduction Test, may be uniquely associated with extrahippocampal volumes in patients with TLE. (JINS, 1999, 5, 540–548.)

Patients with end-stage renal disease (ESRD) who receive dialysis have been shown to have impaired neuropsychological performance. It remains unclear, however, whether cognitive deficits associated with ESRD and/or dialysis are reversible after successful kidney transplantation. Thus, the main purpose of this study was to longitudinally compare the cognitive performance of adequately dialyzed patients with ESRD before and shortly after kidney transplantation. Twenty-two dialyzed patients with ESRD who subsequently received a kidney transplant, 20 dialyzed patients who were medically qualified and awaiting kidney transplant but did not receive it, and 30 matched controls were the participants for this study. Overall, our results demonstrate that a successful kidney transplant is associated with improved neuropsychological performance in patients with ESRD. Specifically, a significant improvement was seen on measures of psychomotor speed, visual planning, retrieval of learnt material, and abstract thinking. Additionally, the degree of cognitive improvement following kidney transplant was significantly associated with some pre-, intra-, and postoperative factors (e.g., age, duration of chronic kidney disease, postoperative graft function). The results of this study also show that the cognitive performance of adequately dialyzed patients without a kidney transplant, although often below that of matched controls, remains relatively stable over time . (JINS, 2009, 15, 684–694.)

The aim of this study was to examine cross-sectionally whether higher cardiorespiratory fitness (CRF) might favorably modify amyloid-β (Aβ)-related decrements in cognition in a cohort of late-middle-aged adults at risk for Alzheimer’s disease (AD). Sixty-nine enrollees in the Wisconsin Registry for Alzheimer’s Prevention participated in this study. They completed a comprehensive neuropsychological exam, underwent 11C Pittsburgh Compound B (PiB)-PET imaging, and performed a graded treadmill exercise test to volitional exhaustion. Peak oxygen consumption (VO2peak) during the exercise test was used as the index of CRF. Forty-five participants also underwent lumbar puncture for collection of cerebrospinal fluid (CSF) samples, from which Aβ42 was immunoassayed. Covariate-adjusted regression analyses were used to test whether the association between Aβ and cognition was modified by CRF. There were significant VO2peak*PiB-PET interactions for Immediate Memory (p=.041) and Verbal Learning & Memory (p=.025). There were also significant VO2peak*CSF Aβ42 interactions for Immediate Memory (p<.001) and Verbal Learning & Memory (p<.001). Specifically, in the context of high Aβ burden, that is, increased PiB-PET binding or reduced CSF Aβ42, individuals with higher CRF exhibited significantly better cognition compared with individuals with lower CRF. In a late-middle-aged, at-risk cohort, higher CRF is associated with a diminution of Aβ-related effects on cognition. These findings suggest that exercise might play an important role in the prevention of AD. (JINS, 2015, 21, 841–850)

Evaluating the ecological validity of neuropsychological tests has become an increasingly important topic. Previous research suggests that neuropsychological tests have a moderate level of ecological validity when predicting everyday functioning. The presence of depressive symptoms, however, may impact the relationship between neuropsychological tests and real world performance. The current study empirically tests this hypothesis in a sample of 216 participants with moderate to severe traumatic brain injury (TBI) who completed neuropsychological testing, self-report of mood symptoms, and report of everyday functioning six months post-injury. Contrary to some previous research and clinical lore, results indicated that depression was weakly related to neuropsychological test performance, although it was more strongly related to everyday functioning. Neuropsychological test performance was also significantly related to everyday functioning. The ecological validity of the neuropsychological tests together was not impacted by depressive symptoms, when predicting significant other ratings of functional status. However, patient self-report seems somewhat less related to neuropsychological performance in those with significant depressive symptoms. Neuropsychological test performance was equally related to self and other report of everyday functioning in patients without significant depressive symptoms. (JINS, 2007, 13, 377–385.)

Memory tests that are in a recall format have almost universally measured accuracy in terms of the number of target items reported by the examinee. However, this traditional scoring method can, in certain cases, result in artificially inflated memory accuracy scores. That is, just as a “yes” response bias and high false-positive rate on recognition testing can artificially inflate a patient's hit rate, so, too, a liberal response bias and high intrusion rate on recall testing can artificially inflate a patient's level of target recall. Recognition tests correct for this problem by using a discriminability measure that provides a single score of hit rate relative to false-positive rate; however, recall tests rarely provide a single score of recall accuracy that corrects for intrusion rate. In the present study, we examined the utility of a new recall discriminability measure that analyzes target recall relative to intrusion rate. Patients with Alzheimer's disease (AD) or Huntington's disease (HD) were administered the CVLT–II, which provides both the traditional measure of target recall and a new measure of recall discriminability. The results indicate that the new recall discriminability measure was superior to the traditional level of target recall measure in distinguishing the recall performance of AD and HD patients. Implications of these results for clinical practice and theories of memory disorder in dementia are discussed. (JINS, 2005, 11, 708–715.)

The most common treatment for sleep disordered breathing (SDB) is adenotonsillectomy (AT). Following AT, SDB resolves in most cases, and gains in cognitive and behavior scores are consistently reported, although persistent neuropsychological deficits or further declines also have been noted. This study presents results of the comprehensive 1-year follow-up neuropsychological examinations for children in the Washtenaw County Adenotonsillectomy Cohort I (95% return rate). After adjusting for normal developmental and practice-effect related changes in control children, significant improvements 1 year following AT were noted in polysomnography and sleepiness, as well as parental reports of behavior, although cognitive outcomes were mixed. Children undergoing AT with and without polysomnography-confirmed obstructive sleep apnea improved across a range of academic achievement measures, a measure of delayed visual recall, short-term attention/working memory, and executive functioning, along with parental ratings of behavior. On the other hand, measures of verbal abstraction ability, arithmetic calculations, visual and verbal learning, verbal delayed recall, sustained attention, and another measure of visual delayed recall demonstrated declines in ability, while other measures did not improve over time. These findings call into question the expectation that AT resolves most or all behavioral and cognitive difficulties in children with clinical, office-based diagnoses of SDB. (JINS, 2012, 18, 212–222)

The purpose of the present study was to investigate construct validity of parent ratings of working memory in children, using a multi-trait/multi-method design including neuroimaging, rating scales, and performance-based measures. Thirty-five typically developing children completed performance-based tests of working memory and nonexecutive function (EF) skills, received volumetric MRI, and were rated by parents on both EF-specific and broad behavior rating scales. After controlling for total cerebral volume and age, parent ratings of working memory were significantly correlated with frontal gray, but not temporal, parietal, or occipital gray, or any lobar white matter volumes. Performance-based measures of working memory were also moderately correlated with frontal lobe gray matter volume; however, non-EF parent ratings and non-EF performance-based measures were not correlated with frontal lobe volumes. Results provide preliminary support for the convergent and discriminant validity of parent ratings of working memory, and emphasize their utility in exploring brain–behavior relationships in children. Rating scales that directly examine EF skills may potentially have ecological validity, not only for “everyday” function, but also as correlates of brain volume. (JINS, 2009, 15, 31–41.)

Parkinson’s disease (PD) has several negative effects on speech production and communication. However, few studies have looked at how speech patterns in PD contribute to linguistic and social impressions formed about PD patients from the perspective of listeners. In this study, discourse recordings elicited from nondemented PD speakers (n = 18) and healthy controls (n = 17) were presented to 30 listeners unaware of the speakers’ disease status. In separate conditions, listeners rated the discourse samples based on their impressions of the speaker or of the linguistic content. Acoustic measures of the speech samples were analyzed for comparison with listeners’ perceptual ratings. Results showed that although listeners rated the content of Parkinsonian discourse as linguistically appropriate (e.g., coherent, well-organized, easy to follow), the PD speakers were perceived as significantly less interested, less involved, less happy, and less friendly than healthy speakers. Negative social impressions demonstrated a relationship to changes in vocal intensity (loudness) and temporal characteristics (dysfluencies) of Parkinsonian speech. Our findings emphasize important psychosocial ramifications of PD that are likely to limit opportunities for communication and social interaction for those affected, because of the negative impressions drawn by listeners based on their speaking voice. (JINS, 2010, 16, 49–57.)

Researchers of cognitive processing in illiteracy have proposed that the acquisition of literacy modifies the functional organization of the brain. They have suggested that, while illiterate individuals have access only to innate semantic processing skills, those who have learned the correspondence between graphemes and phonemes have several mechanisms available to them through which to process oral language. We conducted 2 experiments to verify that suggestion with respect to language processing, and to elucidate further the differences between literate and illiterate individuals in the cognitive strategies used to process oral language, as well as hemispheric specialization for these processes. Our findings suggest that semantic processing strategies are qualitatively the same in literates and illiterates, despite the fact that overall performance is augmented by increased education. In contrast, explicit processing of oral information based on phonological characteristics appears to be qualitatively different between literates and illiterates: effective strategies in the processing of phonological information depend upon having had a formal education, regardless of the level of education. We also confirmed the differential abilities needed for the processing of semantic and phonological information and related them to hemisphere-specific processing. (JINS, 2004, 10, 818–827.)

The current pilot study examined functional magnetic resonance imaging (fMRI) activation in children with mild traumatic brain injury (mTBI) during tasks of working memory and inhibitory control, both of which are vulnerable to impairment following mTBI. Thirteen children with symptomatic mTBI and a group of controls completed a version of the Tasks of Executive Control (TEC) during fMRI scanning. Both groups showed greater prefrontal activation in response to increased working memory load. Activation patterns did not differ between groups on the working memory aspects of the task, but children with mTBI showed greater activation in the posterior cerebellum with the addition of a demand for inhibitory control. Children with mTBI showed greater impairment on symptom report and “real world” measures of executive functioning, but not on traditional “paper and pencil” tasks. Likewise, cognitive testing did not correlate significantly with imaging results, whereas increased report of post-concussive symptoms were correlated with increased cerebellar activation. Overall, results provide some evidence for the utility of symptom report as an indicator of recovery and the hypothesis that children with mTBI may experience disrupted neural circuitry during recovery. Limitations of the study included a small sample size, wide age range, and lack of in-scanner accuracy data. (JINS, 2011, 17, 1143–1152)

Previous research has demonstrated dissociations between categorization and recognition performance in amnesic patients, supporting the idea that separate memory systems govern these tasks. However, previous research has also demonstrated that these dissociations are predicted by a single-system model that allows for reasonable parameter differences across groups. Generally, previous studies have employed categorization tasks that are less demanding than the recognition tasks. In this study, we distinguish between single-system and multiple-system accounts by testing memory-impaired individuals in a more demanding categorization task. These patients, just like previous amnesic participants, show a dissociation between categorization and recognition when tested in previously employed paradigms. However, they display a categorization deficit when tested in the more challenging categorization task. The results are interpreted as support for a single-system framework in which categorization and recognition depend on one representational system. (JINS, 2003, 9, 394–406.)

An objective in current research on children with fetal alcohol spectrum disorders (FASD) is to determine neurobehavioral profiles to identify affected individuals. Deficits observed when children with FASD are compared to typically developing controls may be confounded by lower IQ scores in the subjects with FASD. To determine if prenatal alcohol exposure is associated with neurobehavioral deficits after controlling for IQ differences, multivariate analyses were conducted to compare alcohol-exposed (ALC) subjects to a comparison group closely matched on IQ (IQC). The initial analysis included a broad neuropsychological battery with measures of language, executive function, visual–motor integration, motor ability, and academic achievement. Additional, in depth comparisons focused on visual sustained attention, verbal learning and memory and parent/guardian-reported behavior problems. Group differences (ALC < IQC) were found on verbal learning and parent-rated behavior problems. Group differences were marginally significant (measures within the broad neuropsychological comparison) or not significant (visual attention, retention of verbal material) on the remaining comparisons. Therefore, some deficits (e.g., verbal learning and behavior problems) in children with heavy prenatal alcohol exposure cannot be explained by the lower FSIQ observed in the population. These areas of relative weakness could be useful in distinguishing children with FASD from other children with lowered IQ. (JINS, 2011, 17, 463–473)

The present study aimed to examine the clinical validity and applicability of the Chinese version of Mattis Dementia Rating Scale (CDRS) for elderly Chinese individuals. The scale was found to have good reliability with internal consistency ranging from 0.7 to 0.9. Its significant correlation with the Chinese version of Mini-Mental State Examination (CMMSE) suggested satisfactory construct validity of the scale. The discriminant validity of the CDRS in differentiating Alzheimer's disease (AD) patients and Normal Control (NC) elderly was also supported by the Receiver Operating Characteristics (ROC) analysis. Several cut-off points were presented for different clinical or research applications, and formulas to adjust for the age and educational level of the CDRS total score were provided. The Initiation/Perseveration and Memory subscales were suggested to be an abbreviated version of the CDRS for a quick screening. The present results also showed the association between the impairment of the CDRS performance and the progress of the AD. (JINS, 2003, 9, 45–55.)

Objectives: Research demonstrates heterogeneous neuropsychological profiles among individuals with mild cognitive impairment (MCI). However, few studies have included visuoconstructional ability or used latent mixture modeling to statistically identify MCI subtypes. Therefore, we examined whether unique neuropsychological MCI profiles could be ascertained using latent profile analysis (LPA), and subsequently investigated cerebrospinal fluid (CSF) biomarkers, genotype, and longitudinal clinical outcomes between the empirically derived classes. Methods: A total of 806 participants diagnosed by means of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) MCI criteria received a comprehensive neuropsychological battery assessing visuoconstructional ability, language, attention/executive function, and episodic memory. Test scores were adjusted for demographic characteristics using standardized regression coefficients based on “robust” normal control performance (n=260). Calculated Z-scores were subsequently used in the LPA, and CSF-derived biomarkers, genotype, and longitudinal clinical outcome were evaluated between the LPA-derived MCI classes. Results: Statistical fit indices suggested a 3-class model was the optimal LPA solution. The three-class LPA consisted of a mixed impairment MCI class (n=106), an amnestic MCI class (n=455), and an LPA-derived normal class (n=245). Additionally, the amnestic and mixed classes were more likely to be apolipoprotein e4+ and have worse Alzheimer’s disease CSF biomarkers than LPA-derived normal subjects. Conclusions: Our study supports significant heterogeneity in MCI neuropsychological profiles using LPA and extends prior work (Edmonds et al., 2015) by demonstrating a lower rate of progression in the approximately one-third of ADNI MCI individuals who may represent “false-positive” diagnoses. Our results underscore the importance of using sensitive, actuarial methods for diagnosing MCI, as current diagnostic methods may be over-inclusive. (JINS, 2017, 23, 564–576)

Design Fluency (DF) is typically assumed to assess planning, cognitive flexibility, and fluency in generation of visual patterns, above and beyond contributions from motor speed (Delis, Kaplan, & Kramer, 2001; Ruff, 1998). The present study examined these assumptions, as little construct validation research has been done in the past. Sixty one community-dwelling elderly participants were administered the DF, Trail Making, and Letter Fluency tests from the Delis-Kaplan Executive Function System (D-KEFS), as well as electronically administered measures of motor planning and motor sequence fluency. Hierarchical regressions were used to parse out unique variance contributions to DF performance. The results showed that generation of novel designs (i.e., the first two trials on the D-KEFS DF) relied primarily on motor planning, the ability to generate novel motor actions, and, to a lesser extent, speed of drawing with a writing implement. In contrast, generation of unique designs while switching (i.e., the third trial on the D-KEFS DF) relied primarily on visual scanning and perhaps visual-attentional resources. These findings highlight the wisdom of interpreting the switching trial of the D-KEFS DF separately. Interestingly, cognitive flexibility did not contribute to performance on any of the three D-KEFS DF trials. (JINS, 2010, 16, 26–37.)

The aim of this study was to analyze whether physical activity (PA) is a protective factor for the incidence of dementia after 3 years of follow-up. The Neurological Disorders in Central Spain (NEDICES) is a prospective population-based survey of older adults (age 65 years and older) that comprised 5278 census-based participants at baseline (1994–1995). A broad questionnaire was used to assess participants’ sociodemographic characteristics, health status, and lifestyle. Subsequently, a modified version of Rosow-Breslau questionnaire was applied to classify individuals’ baseline PA into groups (i.e., sedentary, light, moderate, and high). Cox regression models adjusted for several covariates (age, sex, education, previous stroke, alcohol consumption, hypertension, health related variables) were carried out to estimate the association between the PA groups and risk of dementia at the 3-year follow-up (1997–1998). A total of 134 incident dementia cases were identified among 3105 individuals (56.6% female; mean age=73.15±6.26) after 3 years. Hazard ratios (HRs) of the light, moderate, and high PA groups (vs. sedentary group) were 0.40 (95% confidence interval {CI} [0.26, 0.62]; p<.001), 0.32 (95% CI [0.20, 0.54]; p<.001) and 0.23 (95% CI [0.13, 0.40]; p<.001), respectively. Even after controlling for covariates and the exclusion of doubtful dementia cases, HRs remained significant. However, a supplementary analysis showed that the dose-effect hypothesis did not reach statistical significance. PA is a protective factor of incident dementia in this population-based cohort. (JINS, 2015, 21, 861–867)