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Objective: To examine whether history of traumatic brain injury (TBI) is associated with more rapid progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD)., Method: Data from 2,719 subjects with MCI were obtained from the National Alzheimer's Coordinating Center. TBI was categorized based on presence (TBI+) or absence (TBI-) of reported TBI with loss of consciousness (LOC) without chronic deficit occurring >1 year prior to diagnosis of MCI. Survival analyses were used to determine if a history of TBI predicted progression from MCI to AD up to 8 years. Random regression models were used to examine whether TBI history also predicted rate of decline on the Clinical Dementia Rating scale Sum of Boxes score (CDR-SB) among subjects who progress to AD., Results: Across 8 years, TBI history was not significantly associated with progression from MCI to a diagnosis of AD in unadjusted (HR = 0.80; 95% CI [0.63, 1.01]; p = .06) and adjusted (p = .15) models. Similarly, a history of TBI was a nonsignificant predictor for rate of decline on CDR-SB among subjects who progressed to AD (b = 0.15, p = .38). MCI was, however, diagnosed a mean of 2.6 years earlier (p < .001) in TBI+ subjects compared with the TBI- group., Conclusions: A history of TBI with LOC was not associated with progression from MCI to AD, but was linked to an earlier age of MCI diagnosis. These findings add to a growing literature suggesting that TBI might reduce the threshold for onset of MCI and certain neurodegenerative conditions, but appears unrelated to progression from MCI to AD. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)

Objective: The aim of this study was to examine the effects of an alertness-maintaining task (AMT) in older, fatigued drivers., Background: Fatigue during driving increases crash risk, and previous research suggests that alertness and driving in younger adults may be improved using a secondary AMT during boring, fatigue-eliciting drives. However, the potential impact of an AMT on driving has not been investigated in older drivers whose ability to complete dual tasks has been shown to decline and therefore may be negatively affected with an AMT in driving., Method: Younger ( n = 29) and older drivers ( n = 39) participated in a 50-minute simulated drive designed to induce fatigue, followed by four 10-minute sessions alternating between driving with and without an AMT., Results: Younger drivers were significantly more affected by fatigue on driving performance than were older drivers but benefitted significantly from the AMT. Older drivers did not demonstrate increased driver errors with fatigue, and driving did not deteriorate significantly during participation in the AMT condition, although their speed was significantly more variable with the AMT., Conclusion: Consistent with earlier research, an AMT applied during fatiguing driving is effective in improving alertness and reducing driving errors in younger drivers. Importantly, older drivers were relatively unaffected by fatigue, and use of an AMT did not detrimentally affect their driving performance., Application: These results support the potential use of an AMT as a new automotive technology to improve fatigue and promote driver safety, though the benefits of such technology may differ between different age groups.

Background and Objective: In half to two thirds of patients who are diagnosed with mild cognitive impairment (MCI), the diagnosis neither converts to dementia nor reverts to normal cognition; however, little is known about predictors of MCI stability. Our study aimed to identify those predictors., Methods: We obtained 3-year longitudinal data from the National Alzheimer's Coordinating Center Uniform Data Set for patients with a baseline diagnosis of MCI. To predict MCI stability, we used the patients' baseline data to conduct three logistic regression models: demographics, global function, and neuropsychological performance., Results: Our final sample had 1059 patients. At the end of 3 years, 596 still had MCI and 463 had converted to dementia. The most reliable predictors of stable MCI were higher baseline scores on delayed recall, processing speed, and global function; younger age; and absence of apolipoprotein E4 alleles., Conclusions: Not all patients with MCI progress to dementia. Of the protective factors that we identified from demographic, functional, and cognitive data, the absence of apolipoprotein E4 alleles best predicted MCI stability. Our predictors may help clinicians better evaluate and treat patients, and may help researchers recruit more homogeneous samples for clinical trials.

Background/aims: Few studies have examined predictors of reversion from mild cognitive impairment (MCI) to normal cognition. We sought to identify baseline predictors of reversion, using the National Alzheimer's Coordinating Center Uniform Data Set, by comparing MCI individuals who reverted to normal cognition to those who progressed to dementia., Methods: Participants (n = 1,208) meeting MCI criteria were evaluated at the baseline visit and 3 subsequent annual visits. Clusters of baseline predictors of MCI reversion included demographic/genetic data, global functioning, neuropsychological functioning, medical health/dementia risk score, and neuropsychiatric symptoms. Stepwise logistic regression models identified predictors of MCI reversion per cluster, which were then entered into a final comprehensive model to find overall predictor(s)., Results: At 2 years, 175 (14%) reverted to normal cognition, 612 (51%) remained MCI, and 421 (35%) progressed to dementia, with sustained diagnoses at 3 years. Significant variables associated with MCI reversion were younger age, being unmarried, absence of APOE ε4 allele, lower CDR-SOB score, and higher memory/language test scores., Conclusion: A relatively sizable proportion of MCI individuals reverted to normal cognition, which is associated with multiple factors previously noted. Findings may enhance MCI prognostic accuracy and increase precision of early intervention studies of dementia., (© 2017 S. Karger AG, Basel.)

Introduction: Some studies of Posttraumatic Stress Disorder (PTSD) find executive dysfunction, whereas others do not. We meta-analytically examined the association between executive function and PTSD and used meta-regression to examine the potential moderating effect of PTSD severity on executive function., Methods: We conducted a meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We identified published peer-reviewed articles containing measures of executive function and PTSD symptom severity in subjects with PTSD compared to trauma-unexposed controls or trauma-exposed controls without PTSD, or both. We calculated an effect size for each study containing at least one measure of executive function and PTSD symptom severity., Results: PTSD subjects for whom the Clinician-Administered PTSD Scale (CAPS) score was available had worse executive function compared to both trauma-unexposed controls (g = 0.464, p < .001) and to trauma-exposed controls without PTSD (g = 0.414, p = .001), as did PTSD subjects for whom the Mississippi Scale for Combat-Related PTSD (M-PTSD) score was available (g = 0.390, p < .001). Neither CAPS nor M-PTSD scores significantly moderated the effect size of executive function., Conclusions: PTSD is associated with executive dysfunction, but this association was not moderated by PTSD symptom severity, suggesting that once PTSD occurs, executive dysfunction may occur regardless of PTSD severity.

Mild cognitive impairment (MCI) has often been studied in its association with dementia, yet higher rates of reversion to normal cognition than progression to dementia suggest that MCI does not necessarily lead to dementia. Compared to the numerous studies on MCI progression, relatively few have examined reversion. This paper highlights the current literature on characteristics and predictive factors of MCI reversion, along with an overview of studies on MCI patients who remain diagnostically stable (i.e., MCI stability). Of the available studies, predictors of reversion have been noted in areas of cognitive/global functioning, demographic/genetic/biomarker data, and personality/lifestyle factors. However, there is a need for increased study of MCI reversion, considering that patients in this group can fluctuate between different trajectories of MCI (e.g., normal cognition back to MCI or even progression to dementia) within a given follow-up time period. Further examination of reversion via a longitudinal, multifactorial approach would better inform clinicians regarding the likelihood of reversion amongst MCI patients and subsequently modify treatment methods accordingly. Furthermore, researchers would have greater power in detecting treatment effects in their clinical intervention studies of early dementia by improving selection criteria to exclude MCI participants who are more likely to revert and remain cognitively normal than progress to a dementia., (Copyright © 2016 Elsevier B.V. All rights reserved.)

This study examined whether history of traumatic brain injury (TBI) is associated with increased risk and earlier onset of mild cognitive impairment (MCI). Subjects with MCI (n = 3,187) and normal cognition (n = 3,244) were obtained from the National Alzheimer's Coordinating Center database. TBI was categorized based on lifetime reported TBI with loss of consciousness (LOC) without chronic deficit. Logistic regression was used to examine TBI history as a predictor of MCI, adjusted for demographics, apolipoprotein E-ɛ4 (ApoE4), a composite vascular risk score, and history of psychiatric factors. ANCOVA was used to examine whether age at MCI diagnosis and estimated age of onset differed between those with (TBI+) and without (TBI-) a history of TBI. TBI history was a significant predictor (p <  0.01) and associated with increased odds of MCI diagnosis in unadjusted (OR = 1.25; 95% CI = 1.05-1.49) and adjusted models, accounting for age, education, ApoE4, and a composite vascular score (OR = 1.32; 95% CI = 1.10-1.58). This association, however, was largely attenuated (OR = 1.14; 95% CI = 0.94-1.37; p = 0.18) after adjustment for reported history of depression. MCI was diagnosed a mean of 2.3 years earlier (p <  0.001) in the TBI+ group, and although TBI+ subjects had an estimated mean of decline 1.7 years earlier, clinician-estimated age of onset failed to differ (p = 0.13) when gender and psychiatric factors were controlled. This is the first report of a possible role for TBI as a risk factor in MCI, but its association may be related to other factors such as gender and depression and requires further investigation.

Rationale: Survivors of critical illness have a high rate of cognitive impairments that may persist years after hospital discharge. Data are lacking regarding whether cognitive screening tests administered at hospital discharge can be used to predict which critically ill patients are likely to have long-term cognitive sequelae., Objectives: This prospective study assessed whether two cognitive screening tests, the Mini-Mental State Examination (MMSE) and Mini-Cog, administered at hospital discharge, predict cognitive sequelae in survivors of critical illness 6 months after hospital discharge., Methods: Seventy critically ill patients completed the MMSE and Mini-Cog just before hospital discharge. Of these 70 patients, 53 completed a neuropsychological battery 6 months after hospital discharge., Measurements and Main Results: At hospital discharge, 45 patients (64%) had impaired performance on the MMSE (score < 27, mean = 24.4) and 32 (45%) on the Mini-Cog. Twenty-seven patients (39%) were impaired on both the MMSE and Mini-Cog, whereas only 20 patients (28%) had scores in the normal range on both tests. Cognitive sequelae occurred in 57% of survivors (30 of 53) at 6 months, with predominant dysfunction in the memory (38%) and executive (36%) domains. Logistic regression analyses showed that neither the MMSE nor the Mini-Cog predicted cognitive sequelae at 6 months., Conclusions: A large number of critically ill survivors had cognitive impairments, as assessed by the MMSE and Mini-Cog, at hospital discharge. However, the MMSE and Mini-Cog scores did not predict long-term cognitive sequelae at 6-month follow-up and cannot be used as surrogate endpoints for long-term cognitive impairment.

Clinical use of functional magnetic resonance imaging (fMRI) in obsessive-compulsive disorder (OCD) is limited by a relative absence of fMRI task development, standardization, and normative performance databases. We investigated the fMRI-based verbal fluency test (f-VFT) by quantitatively evaluating brain activation patterns in OCD participants (8 females and 4 males) compared with a normative database (16 females and 16 males). At the group level, OCD participants and references had highly similar activation in left-hemisphere language regions, including the precentral/premotor cortex, thalamus, basal ganglia, and inferior frontal gyrus/frontal operculum. At the interindividual level, however, the OCD group had highly variable activation patterns in the dorsal and ventral regions of the pre-supplementary motor area (pre-SMA) that may correspond with differences in demographic and clinical variables. Further, there were significant correlations in the OCD participants between pre-SMA dorsal and ventral activation and between dorsal pre-SMA activation and perfectionism. Our findings suggest considerable functional anatomical overlap in left-hemisphere language regions between OCD participants and references but significantly higher pre-SMA interindividual variability in OCD compared to the reference group that may be relevant in clinical fMRI application and the theoretical understanding of OCD.

Posttraumatic stress disorder (PTSD) may be associated with structural abnormalities in the amygdala. To better characterize amygdala volume in PTSD, the authors conducted a meta-analysis comparing amygdala volumes in PTSD patients and comparison subjects. Using electronic databases, the authors found nine studies comparing amygdala volumes in adult subjects with PTSD with amygdala volumes in comparison subjects (participants unexposed to trauma and participants exposed to trauma but without PTSD). Results showed no significant differences in amygdala volumes between the groups. Within each group, the right amygdala was significantly larger than the left, indicating an asymmetrically lateralized amygdala volume that is preserved in trauma exposure and in PTSD.

Little work has directly examined the course of hippocampal volume in children and adults with childhood maltreatment-related posttraumatic stress disorder (PTSD). Data from adults suggest that hippocampal volume deficits are associated with PTSD, whereas findings from children with PTSD generally show no hippocampal volume deficits in PTSD. Additionally, the role of the amygdala in emotional response makes it a possible region for investigation in children and adults with childhood maltreatment-related PTSD. The objectives of this study were 2-fold: (1) to meta-analytically determine whether hippocampal and amygdala volumes in children and adults with PTSD from childhood maltreatment differ from those in healthy controls, and (2) to use cross-sectional findings performed with meta-analyses as a proxy for longitudinal studies to estimate the course of hippocampal and amygdala volumes in child and adult subjects with PTSD from childhood maltreatment. Using electronic databases, we identified articles containing hippocampal and amygdala data for children with PTSD and adults with PTSD from childhood maltreatment. Data were extracted and effect sizes were calculated using Comprehensive Meta-Analysis Version 2.0. Reduced bilateral hippocampal volume was found in adults with childhood maltreatment-related PTSD compared with healthy controls, but this deficit was not seen in children with maltreatment-related PTSD, suggesting hippocampal volume deficits from childhood maltreatment may not be apparent until adulthood. Greater left than right hippocampal volume was found in the adult healthy control group but not in the PTSD group. Amygdala volume in children with maltreatment-related PTSD did not differ from that in healthy controls. Hippocampal volume is normal in children with maltreatment-related PTSD but not in adults with PTSD from childhood maltreatment, suggesting an initially volumetrically normal hippocampus with subsequent abnormal volumetric development occurring after trauma exposure. However, longitudinal studies are needed to support these preliminary findings., ((c) 2008 Wiley-Liss, Inc.)