Executive function and cortical thickness in biomarker aMCI.

INTRODUCTION: Memory deficits are the primary symptom in amnestic Mild Cognitive Impairment (aMCI); however, executive function (EF) deficits are common. The current study examined EF in aMCI based upon amyloid status (A+/A-) and regional atrophy in signature areas of Alzheimer's disease (AD). METHOD: Participants included 110 individuals with aMCI (A+ = 66; A- = 44) and 33 cognitively healthy participants (HP). EF was assessed using four neuropsychological assessment measures. The cortical thickness of the AD signature areas was calculated using structural MRI data. RESULTS: A + had greater EF deficits and cortical atrophy relative to A - in the supramarginal gyrus and superior parietal lobule. A - had greater EF deficits relative to HP, but no difference in signature area cortical thickness. DISCUSSION: The current study found that the degree of EF deficits in aMCI are a function of amyloid status and cortical thinning in the parietal cortex.

Cortical Thickness Correlates of Go/No-go and Motor Sequencing in Mild Cognitive Impairment and Suspected Alzheimer Disease Dementia.

BACKGROUND: While the cognitive hallmark of typical Alzheimer disease (AD) is impaired memory consolidation, increasing evidence suggests that the frontal lobes and associated executive functions are also impacted. OBJECTIVE: We examined two neurobehavioral executive function tasks and associations with cortical thickness in patients diagnosed with mild cognitive impairment (MCI), suspected AD dementia, and a healthy control group. METHODS: First, we compared group performances on a go/no-go (GNG) task and on Luria's Fist-Edge-Palm (FEP) motor sequencing task. We then examined correlations between neurobehavioral task performance and the thickness of frontal cortical regions, AD signature regions, broader unbiased brain regions, and white matter hyperintensities (WMH). RESULTS: Participants with MCI performed worse than healthy controls, but better than participants with suspected AD dementia on both tasks. Both GNG and FEP (to a slightly greater extent) tasks showed diffuse associations with most AD signature regions and multiple additional regions within the temporal, parietal, and occipital cortices. Similarly, both tasks showed significant associations with all other cognitive tasks examined. Of the frontal regions examined, only the middle frontal gyrus and pars opercularis were associated with performance on these tasks. Interactions between the precuneus and transtemporal gyri were most predictive of GNG task performance, while the interaction between superior temporal and lingual gyri was most predictive of FEP task performance. CONCLUSION: This study replicates difficulties with both GNG and FEP tasks in participants with MCI and AD dementia. Both tasks showed widespread associations with the cortical thickness of various brain structures rather than localizing to frontal regions, consistent with the diffuse nature of AD.

More Similar than Different: Memory, Executive Functions, Cortical Thickness, and Glucose Metabolism in Biomarker-Positive Alzheimer's Disease and Behavioral Variant Frontotemporal Dementia.

Background: Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are typically associated with very different clinical and neuroanatomical presentations; however, there is increasing recognition of similarities. Objective: To examine memory and executive functions, as well as cortical thickness, and glucose metabolism in AD and bvFTD signature brain regions. Methods: We compared differences in a group of biomarker-defined participants with Alzheimer's disease and a group of clinically diagnosed participants with bvFTD. These groups were also contrasted with healthy controls (HC). Results: As expected, memory functions were generally more impaired in AD, followed by bvFTD, and both clinical groups performed more poorly than the HC group. Executive function measures were similar in AD compared to bvFTD for motor sequencing and go/no-go, but bvFTD had more difficulty with a set shifting task. Participants with AD showed thinner cortex and lower glucose metabolism in the angular gyrus compared to bvFTD. Participants with bvFTD had thinner cortex in the insula and temporal pole relative to AD and healthy controls, but otherwise the two clinical groups were similar for other frontal and temporal signature regions. Conclusions: Overall, the results of this study highlight more similarities than differences between AD and bvFTD in terms of cognitive functions, cortical thickness, and glucose metabolism. Further research is needed to better understand the mechanisms mediating this overlap and how these relationships evolve longitudinally.

Surface-based correlates of cognition along the Alzheimer's continuum in a memory clinic population.

Composite cognitive measures in large-scale studies with biomarker data for amyloid and tau have been widely used to characterize Alzheimer's disease (AD). However, little is known about how the findings from these studies translate to memory clinic populations without biomarker data, using single measures of cognition. Additionally, most studies have utilized voxel-based morphometry or limited surface-based morphometry such as cortical thickness, to measure the neurodegeneration associated with cognitive deficits. In this study, we aimed to replicate and extend the biomarker, composite study relationships using expanded surface-based morphometry and single measures of cognition in a memory clinic population. We examined 271 clinically diagnosed symptomatic individuals with mild cognitive impairment (N = 93) and Alzheimer's disease dementia (N = 178), as well as healthy controls (N = 29). Surface-based morphometry measures included cortical thickness, sulcal depth, and gyrification index within the "signature areas" of Alzheimer's disease. The cognitive variables pertained to hallmark features of Alzheimer's disease including verbal learning, verbal memory retention, and language, as well as executive function. The results demonstrated that verbal learning, language, and executive function correlated with the cortical thickness of the temporal, frontal, and parietal areas. Verbal memory retention was correlated to the thickness of temporal regions and gyrification of the inferior temporal gyrus. Language was related to the temporal regions and the supramarginal gyrus' sulcal depth and gyrification index. Executive function was correlated with the medial temporal gyrus and supramarginal gyrus sulcal depth, and the gyrification index of temporal regions and supramarginal gyrus, but not with the frontal areas. Predictions of each of these cognitive measures were dependent on a combination of structures and each of the morphometry measurements, and often included medial temporal gyrus thickness and sulcal depth. Overall, the results demonstrated that the relationships between cortical thinning and cognition are widespread and can be observed using single measures of cognition in a clinically diagnosed AD population. The utility of sulcal depth and gyrification index measures may be more focal to certain brain areas and cognitive measures. The relative importance of temporal, frontal, and parietal regions in verbal learning, language, and executive function, but not verbal memory retention, was replicated in this clinic cohort.

Frontal and temporal lobe correlates of verbal learning and memory in aMCI and suspected Alzheimer's disease dementia.

Alzheimer's disease is primarily known for deficits in learning and retaining new information. This has long been associated with pathological changes in the mesial temporal lobes. The role of the frontal lobes in memory in Alzheimer's disease is less well understood. In this study, we examined the role of the frontal lobes in learning, recognition, and retention of new verbal information, as well as the presence of specific errors (i.e., intrusions and false-positive errors). Participants included one hundred sixty-seven patients clinically diagnosed with amnestic mild cognitive impairment or suspected Alzheimer's disease dementia who were administered the California Verbal Learning Test and completed high-resolution MRI. We confirmed the role of the mesial temporal lobes in learning and retention, including the volumes of the hippocampus, entorhinal cortex, and parahippocampal gyrus. In addition, false-positive errors were associated with all volumes of the mesial temporal lobes and widespread areas within the frontal lobes. Errors of intrusion were related to the supplementary motor cortex and hippocampus. Most importantly, the mesial temporal lobes interacted with the frontal lobes for learning, recognition, and memory errors. Lower volumes in both regions explained more performance variance than any single structure. This study supports the interaction of the frontal lobes with the temporal lobes in many aspects of memory in Alzheimer's disease.

Procedural learning and retention relative to explicit learning and retention in mild cognitive impairment and Alzheimer's disease using a modification of the trail making test.

Amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) dementia are characterized by pathological changes to the medial temporal lobes, resulting in explicit learning and retention reductions. Studies demonstrate that implicit/procedural memory processes are relatively intact in these populations, supporting different anatomical substrates for differing memory systems. This study examined differences between explicit and procedural learning and retention in individuals with aMCI and AD dementia relative to matched healthy controls. We also examined anatomical substrates using volumetric MRI. Results revealed expected difficulties with explicit learning and retention in individuals with aMCI and AD with relatively preserved procedural memory. Explicit verbal retention was associated with medial temporal cortex volumes. However, procedural retention was not related to medial temporal or basal ganglia volumes. Overall, this study confirms the dissociation between explicit relative to procedural learning and retention in aMCI and AD dementia and supports differing anatomical substrates.

CHA2DS2-VASc Stroke Risk Index and Executive Functioning in Older Adults.

OBJECTIVE: CHA2DS2-VASc is a stroke risk classification system developed to improve the precision of stroke risk classification. The current study examined the validity of CHA2DS2-VASc in a sample of healthy older adults using executive function measures of processing speed, working memory, and cognitive flexibility that are sensitive to cerebrovascular risk factors. METHODS: Participants included 51 community-dwelling, healthy older adults (ages 53-86) recruited from both the community and cardiology clinics. CHA2DS2-VASc was utilized as a measure of stroke risk. Measures of executive functioning and processing speed included the Paced Auditory Serial Addition Test (PASAT), Delis-Kaplan Executive Function System (DKEFS) Number-Letter Switching, and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Coding. RESULTS: CHA2DS2-VASc scores significantly predicted scores on the PASAT, DKEFS Number-Letter Switching, and RBANS Coding, such that greater stroke risk was associated with poorer performances on tests of executive functioning and processing speed. These relationships were observed over and above the potential influence of educational attainment and symptoms of depression. CONCLUSION: Significant relations between stroke risk classification and performance on several measures of executive functioning provide support for a wider and more generalized use of CHA2DS2-VASc with healthy older adults. These findings further highlight the importance of early identification and treatment of stroke risk factors associated with cognitive decline. Findings suggest that CHA2DS2-VASc is a practical and useful tool for patients and their providers in the early detection of stroke risk and development of individualized treatment plans.

Conflict and performance monitoring throughout the lifespan: An event-related potential (ERP) and temporospatial component analysis.

Cognitive control includes higher-level cognitive processes used to evaluate environmental conflict. Given the importance of cognitive control in regulating behavior, understanding the developmental course of these processes may contribute to a greater understanding of normal and abnormal development. We examined behavioral (response times [RTs], error rates) and event-related potential data (N2, error-related negativity [ERN], correct-response negativity [CRN], error positivity [Pe]) during a flanker task in cross-sectional groups of 45 youth (ages 8-18), 52 younger adults (ages 20-28), and 58 older adults (ages 56-91). Younger adults displayed the most efficient processing, including significantly reduced CRN and N2 amplitude, increased Pe amplitude, and significantly better task performance than youth or older adults (e.g., faster RTs, fewer errors). Youth displayed larger CRN and N2, attenuated Pe, and significantly worse task performance than younger adults. Older adults fell either between youth and younger adults (e.g., CRN amplitudes, N2 amplitudes) or displayed neural and behavioral performance that was similar to youth (e.g., Pe amplitudes, error rates). These findings point to underdeveloped neural and cognitive processes early in life and reduced efficiency in older adulthood, contributing to poor implementation and modulation of cognitive control in response to conflict. Thus, cognitive control processing appears to reach peak performance and efficiency in younger adulthood, marked by improved task performance with less neural activation.

Parents Perceive Improvements in Socio-emotional Functioning in Adolescents with ASD Following Social Skills Treatment.

The current study examined the effectiveness of a social skills treatment (PEERS) for improving socio-emotional competencies in a sample of high-functioning adolescents with ASD. Neuropsychological and self- and parent-report measures assessing social, emotional, and behavioral functioning were administered before and after treatment. Following social skills treatment, adolescents with ASD exhibited decreased aggression, anxiety, and withdrawal, as well as improvements in emotional responsiveness, adaptability, leadership, and participation in activities of daily living, though no change was found in affect recognition abilities. These findings suggest that PEERS social skills treatment improves particular aspects of emotional, behavioral, and social functioning that may be necessary for developing and maintaining quality peer relationships and remediating social isolation in adolescents with ASD.

Orbitofrontal Cortex and the Early Processing of Visual Novelty in Healthy Aging.

Event-related potential (ERP) studies have previously found that scalp topographies of attention-related ERP components show frontal shifts with age, suggesting an increased need for compensatory frontal activity to assist with top-down facilitation of attention. However, the precise neural time course of top-down attentional control in aging is not clear. In this study, 20 young (mean: 22 years) and 14 older (mean: 64 years) adults completed a three-stimulus visual oddball task while high-density ERPs were acquired. Colorful, novel distracters were presented to engage early visual processing. Relative to young controls, older participants exhibited elevations in occipital early posterior positivity (EPP), approximately 100 ms after viewing colorful distracters. Neural source models for older adults implicated unique patterns of orbitofrontal cortex (OFC; BA 11) activity during early visual novelty processing (100 ms), which was positively correlated with subsequent activations in primary visual cortex (BA 17). Older adult EPP amplitudes and OFC activity were associated with performance on tests of complex attention and executive function. These findings are suggestive of age-related, compensatory neural changes that may driven by a combination of weaker cortical efficiency and increased need for top-down control over attention. Accordingly, enhanced early OFC activity during visual attention may serve as an important indicator of frontal lobe integrity in healthy aging.

Cognitive control adjustments in healthy older and younger adults: Conflict adaptation, the error-related negativity (ERN), and evidence of generalized decline with age.

Older adults display alterations in neural reflections of conflict-related processing. We examined response times (RTs), error rates, and event-related potential (ERP; N2 and P3 components) indices of conflict adaptation (i.e., congruency sequence effects) a cognitive control process wherein previous-trial congruency influences current-trial performance, along with post-error slowing, correct-related negativity (CRN), error-related negativity (ERN) and error positivity (Pe) amplitudes in 65 healthy older adults and 94 healthy younger adults. Older adults showed generalized slowing, had decreased post-error slowing, and committed more errors than younger adults. Both older and younger adults showed conflict adaptation effects; magnitude of conflict adaptation did not differ by age. N2 amplitudes were similar between groups; younger, but not older, adults showed conflict adaptation effects for P3 component amplitudes. CRN and Pe, but not ERN, amplitudes differed between groups. Data support generalized declines in cognitive control processes in older adults without specific deficits in conflict adaptation.

P300 Amplitude in Alzheimer's Disease: A Meta-Analysis and Meta-Regression.

Alzheimer's disease accounts for 60% of all dementia. Numerous biomarkers have been developed that can help in making an early diagnosis. The P300 is an event-related potential that may be abnormal in Alzheimer's disease. Given the possible association between P300 amplitude and Alzheimer's disease and the need for biomarkers in early Alzheimer's disease, the main purpose of this meta-analysis and meta-regression was to characterize P300 amplitude in probable Alzheimer's disease compared to healthy controls. Using online search engines, we identified peer-reviewed articles containing amplitude measures for the P300 in response to a visual or auditory oddball stimulus in subjects with Alzheimer's disease and in a healthy control group and pooled effect sizes for differences in P300 amplitude between Alzheimer's disease and control groups to obtain summary effect sizes. We also used meta-regression to determine whether age, sex, educational attainment, or dementia severity affected the association between P300 amplitude and Alzheimer's disease. Twenty articles containing a total of 646 subjects met inclusion and exclusion criteria. The overall effect size from all electrode locations was 1.079 (95% confidence interval=0.745-1.412, P<.001). The pooled effect sizes for the Cz, Fz, and Pz locations were 1.226 (P<.001), 0.724 (P=.0007), and 1.430 (P<.001), respectively. Meta-regression showed an association between amplitude and educational attainment, but no association between amplitude and age, sex, and dementia severity. In conclusion, P300 amplitude is smaller in subjects with Alzheimer's disease than in healthy controls.

The effect of premorbid attention-deficit/hyperactivity disorder on neuropsychological functioning in individuals with acute mild traumatic brain injuries.

INTRODUCTION: Mild traumatic brain injury (mTBI) is a frequent, yet undertreated condition that typically manifests with transient neurological and cognitive symptoms that resolve over the course of several weeks. In contrast, attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that presents initially in childhood but often persists into adulthood. mTBI and ADHD include overlapping symptomatology, making it difficult for clinicians to disentangle the sequelae of each condition when they co-occur in the same individual. We hypothesized that neuropsychological tests would be sensitive to preexisting ADHD in inpatients with acute mTBIs. METHOD: We retrospectively examined the medical charts of 100 inpatients, aged 18-40 years (96% Caucasian; 77% male) with mTBIs in an acute care setting, half of whom had self-reported the presence of premorbid ADHD, and half of whom were matched controls. We analyzed group differences across neuropsychological tests of attention, processing speed, and executive functions, examined the profile ratings of independent, blinded, board-certified neuropsychologists, and correlated cognitive performance with time from traumatic injury to testing. RESULTS: Individuals with premorbid ADHD (a) performed significantly worse than their matched counterparts on several tests of attention, processing speed, and working memory, and (b) were significantly more likely to produce profiles later rated as impaired by independent, board-certified clinical neuropsychologists. In addition, time from traumatic injury to testing was found to be negatively correlated with neurocognitive performance. CONCLUSIONS: These findings (a) argue for the utility of a brief assessment of premorbid ADHD in the acute care of individuals with mTBIs and (b) provide clinicians with a barometer for gauging the relative contributions of premorbid ADHD to neuropsychological impairments in the neurocognitive profiles of individuals with mTBIs. Reported effect sizes will assist clinicians in accurately weighing the impact of premorbid ADHD when interpreting such profiles.