Prospective Memory in Posttraumatic Stress Disorder.

OBJECTIVES: Neuropsychological studies of posttraumatic stress disorder (PTSD) have revealed deficits in attention/working memory, processing speed, executive functioning, and retrospective memory. However, little is known about prospective memory (PM) in PTSD, a clinically relevant aspect of episodic memory that supports the encoding and retrieval of intentions for future actions. METHODS: Here we examined PM performance in 40 veterans with PTSD compared to 38 trauma comparison (TC) veterans who were exposed to combat but did not develop PTSD. All participants were administered the Memory for Intentions Test (MIST; Raskin, Buckheit, & Sherrod, 2010), a standardized and validated measure of PM, alongside a comprehensive neurocognitive battery, structured diagnostic interviews for psychiatric conditions, and behavioral questionnaires. RESULTS: Veterans with PTSD performed moderately lower than TC on time-based PM, with errors primarily characterized as PM failure errors (i.e., omissions). However, groups did not differ in event-based PM, ongoing task performance, or post-test recognition of PM intentions for each trial. Lower time-based PM performance was specifically related to hyperarousal symptoms of PTSD. Time-based-performance was also associated with neuropsychological measures of retrospective memory and executive functions in the PTSD group. Nevertheless, PTSD was significantly associated with poorer PM above and beyond age and performance in retrospective memory and executive functions. DISCUSSION: Results provide initial evidence of PM dysfunction in PTSD, especially in strategic monitoring during time-based PM tasks. Findings have potential implications for everyday functioning and health behaviors in persons with PTSD, and deserve replication and future study. (JINS, 2016, 22, 724-734).

Neuropsychological Functioning in Veterans with Posttraumatic Stress Disorder: Associations with Performance Validity, Comorbidities, and Functional Outcomes.

OBJECTIVES: Numerous studies have shown that individuals with posttraumatic stress disorder (PTSD) display reduced performances on neuropsychological tests, although most prior research has not adequately accounted for comorbidities or performance validity concerns that are common in this population and could partially account for the observed neurocognitive findings. Moreover, few studies have examined the functional implications of neuropsychological results in PTSD. METHODS: We examined neuropsychological functioning in 44 veterans with PTSD and 40 veteran trauma comparison (TC) participants with combat exposure and no PTSD. RESULTS: After excluding four veterans with PTSD for performance validity concerns, multivariate analyses of variance by neurocognitive domain revealed significantly worse performance by the PTSD group in the domains of speed of information processing (p=.035) and executive functions (p=.017), but no group differences in attention/working memory, verbal/language functioning, visuoconstruction, or episodic memory. Group differences by PTSD status were still present after covarying for depression, a history of head injuries, and substance use disorders. Executive functioning performance was associated with poorer self-reported occupational functioning and physical health-related quality of life, while speed of information processing performance was associated with poorer physical health-related quality of life. DISCUSSION: These results are generally consistent with a fronto-limbic conceptualization of PTSD-associated neuropsychological dysfunction and show that cognitive functioning may be associated with critical functional outcomes. Taken together, results suggest that consideration of neurocognitive functioning may enhance the clinical management of individuals with PTSD.

Altered prefronto-striato-parietal network response to mental rotation in HIV.

The present study used functional magnetic resonance imaging to examine the neural substrates of mental rotation in 11 individuals with HIV infection and 13 demographically similar HIV seronegative volunteers. Individuals with HIV showed increased brain response to mental rotation in prefrontal and posterior parietal cortices, striatum, and thalamus, with significant HIV by angle interactions emerging in the prefrontal cortex and caudate. Results indicate that HIV infection is associated with altered brain response to mental rotation in fronto-striato-parietal pathways, which may reflect compensatory strategies, recruitment of additional brain regions, and/or increased neuroenergetic demands during mental rotation needed to offset underlying HIV-associated neural injury.

Callosal white matter microstructural recovery in abstinent alcoholics: a longitudinal diffusion tensor imaging study.

BACKGROUND: Previous neuroimaging studies of recently detoxified alcohol-dependent patients (RDA) have found significant loss of white matter integrity associated with the shrinkage of the frontal lobes and thinning of the corpus callosum, especially the genu. The current study hypothesized that, in addition to exhibiting the most microstructural white matter disruption in RDA, the genu will also evidence the most recovery after abstinence. This microstructural recovery will be associated with improvements in executive functioning measures. METHODS: Fifteen RDA were examined approximately 2 weeks after abstinence and again after 1 year of abstinence and compared to 15 age- and education-matched nonalcoholic controls using diffusion tensor imaging (DTI). The effects of group, time, and their interactions on fractional anisotropy, radial diffusivity, and axial diffusivity were evaluated with repeated measures MANOVA; in addition, 2 × 2 ANOVA was used to test changes in measures of executive functioning in the 2 groups. RESULTS: At 2 weeks of abstinence, DTI of RDA showed significantly lower fractional anisotropy and greater radial diffusivity compared to controls in the genu and body of the corpus callosum. Reexamination after 1 year showed significant time by group interaction with fractional anisotropy increasing and radial diffusivity decreasing in RDA but not controls in these 2 regions. A smaller relapsed group did not show improvements between the 2 time points. Abstinent RDA also showed improvement on Digit Span Backward, a measure of working memory, but did not benefit from practice effects on the Halstead Category Test compared to controls. CONCLUSIONS: The results suggest susceptibility of the genu and body of the corpus callosum to the effects of alcohol, and the potential for recovery of both these regions after abstinence, perhaps via mechanisms involving myelin reconstitution.

The influence of recency of use on fMRI response during spatial working memory in adolescent marijuana users.

Some neurocognitive recovery occurs within a month of abstinence from heavy marijuana use, yet functional magnetic resonance imaging (fMRI) has revealed altered activation among recent and abstinent adult users. We compared fMRI response during a spatial working memory (SWM) task between adolescent marijuana users with brief and sustained durations of abstinence. Participants were 13 recent users (two to seven days abstinent), 13 abstinent users (27 to 60 days abstinent), and 18 nonusing controls, all ages 15 to 18. Groups were similar on demographics, had no psychiatric or medical disorders, and user groups were similar on substance histories. Teens performed a two-back SWM task during fMRI. Recent users showed greater fMRI response in medial and left superior prefrontal cortices, as well as bilateral insula. Abstinent users had increased response in the right precentral gyrus (clusters > or = 1328 microl, p < .05). Results suggest that adolescents who recently used marijuana show increased brain activity in regions associated with working memory updating and inhibition. This study preliminarily suggests that (1) recent marijuana use may disrupt neural connections associated with SWM and result in compensatory brain response, and (2) sustained abstinence from marijuana may be associated with improvements in SWM response among adolescents.

White matter tract injury and cognitive impairment in human immunodeficiency virus-infected individuals.

Approximately half of those infected with the human immunodeficiency virus (HIV) exhibit cognitive impairment, which has been related to cerebral white matter damage. Despite the effectiveness of antiretroviral treatment, cognitive impairment remains common even in individuals with undetectable viral loads. One explanation for this may be subtherapeutic concentrations of some antiretrovirals in the central nervous system (CNS). We utilized diffusion tensor imaging and a comprehensive neuropsychological evaluation to investigate the relationship of white matter integrity to cognitive impairment and antiretroviral treatment variables. Participants included 39 HIV-infected individuals (49% with acquired immunodeficiency syndrome [AIDS]; mean CD4 = 529) and 25 seronegative subjects. Diffusion tensor imaging indices were mapped onto a common whole-brain white matter tract skeleton, allowing between-subject voxelwise comparisons. The total HIV-infected group exhibited abnormal white matter in the internal capsule, inferior longitudinal fasciculus, and optic radiation; whereas those with AIDS exhibited more widespread damage, including in the internal capsule and the corpus callosum. Cognitive impairment in the HIV-infected group was related to white matter injury in the internal capsule, corpus callosum, and superior longitudinal fasciculus. White matter injury was not found to be associated with HIV viral load or estimated CNS penetration of antiretrovirals. Diffusion tensor imaging was useful in identifying changes in white matter tracts associated with more advanced HIV infection. Relationships between diffusion alterations in specific white matter tracts and cognitive impairment support the potential utility of diffusion tensor imaging in examining the anatomical underpinnings of HIV-related cognitive impairment. The study also confirms that CNS injury is evident in persons infected with HIV despite effective antiretroviral treatment.

Altered white matter integrity in adolescent binge drinkers.

BACKGROUND: White matter integrity has been found to be compromised in adult alcoholics, but it is unclear when in the course of alcohol exposure white matter abnormalities become apparent. This study assessed microstructural white matter integrity among adolescent binge drinkers with no history of an alcohol use disorder. METHODS: We used diffusion tensor imaging to examine fractional anisotropy (FA), a measure of directional coherence of white matter tracts, among teens with (n = 14) and without (n = 14) histories of binge drinking but no history of alcohol use disorder, matched on age, gender, and education. RESULTS: Binge drinkers had lower FA than controls in 18 white matter areas (clusters > or =27 contiguous voxels, each with p < 0.01) throughout the brain, including the corpus callosum, superior longitudinal fasciculus, corona radiata, internal and external capsules, and commissural, limbic, brainstem, and cortical projection fibers, while exhibiting no areas of higher FA. Among binge drinkers, lower FA in 6 of these regions was linked to significantly greater lifetime hangover symptoms and/or higher estimated peak blood alcohol concentrations. CONCLUSIONS: Binge drinking adolescents demonstrated widespread reductions of FA in major white matter pathways. Although preliminary, these results could indicate that infrequent exposure to large doses of alcohol during youth may compromise white matter fiber coherence.

Characterization of white matter microstructure in fetal alcohol spectrum disorders.

BACKGROUND: Exposure to alcohol during gestation is associated with CNS alterations, cognitive deficits, and behavior problems. This study investigated microstructural aspects of putative white matter abnormalities following prenatal alcohol exposure. METHODS: Diffusion tensor imaging was used to assess white matter microstructure in 27 youth (age range: 8 to 18 years) with (n = 15) and without (n = 12) histories of heavy prenatal alcohol exposure. Voxelwise analyses, corrected for multiple comparisons, compared fractional anisotropy (FA) and mean diffusivity (MD) between groups, throughout the cerebrum. RESULTS: Prenatal alcohol exposure was associated with low FA in multiple cerebral areas, including the body of the corpus callosum and white matter innervating bilateral medial frontal and occipital lobes. Fewer between-group differences in MD were observed. CONCLUSIONS: These data provide an account of cerebral white matter microstructural integrity in fetal alcohol spectrum disorders and support extant literature showing that white matter is a target of alcohol teratogenesis. The white matter anomalies characterized in this study may relate to the neurobehavioral sequelae associated with gestational alcohol exposure, especially in areas of executive dysfunction and visual processing deficits.

Altered white matter microstructure in adolescent substance users.

Chronic marijuana use during adolescence is frequently comorbid with heavy alcohol consumption and associated with CNS alterations, yet the influence of early cannabis and alcohol use on microstructural white matter integrity is unclear. Building on evidence that cannabinoid receptors are present in myelin precursors and affect glial cell processing, and that excessive ethanol exposure is associated with persistently impaired myelination, we used diffusion tensor imaging (DTI) to characterize white matter integrity in heavy substance using and non-using adolescents. We evaluated 36 marijuana and alcohol-using (MJ+ALC) adolescents (ages 16-19) and 36 demographically similar non-using controls with DTI. The diffusion parameters fractional anisotropy (FA) and mean diffusivity (MD) were subjected to whole-brain voxelwise group comparisons using tract-based spatial statistics (Smith, S.M., Jenkinson, M., Johansen-Berg, H., Rueckert, D., Nichols, T.E., Mackay, C.E., Watkins, K.E., Ciccarelli, O., Cader, M.Z., Matthews, P.M., Behrens, T.E., 2006. Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage 31, 1487-1505). MJ+ALC teens had significantly lower FA than controls in 10 regions, including left superior longitudinal fasciculus (SLF), left postcentral gyrus, bilateral crus cerebri, and inferior frontal and temporal white matter tracts. These diminutions occurred in the context of increased FA in right occipital, internal capsule, and SLF regions. Changes in MD were less distributed, but increased MD was evident in the right occipital lobe, whereas the left inferior longitudinal fasciculus showed lower MD in MJ+ALC users. Findings suggest that fronto-parietal circuitry may be particularly impacted in adolescent users of the most prevalent intoxicants: marijuana and alcohol. Disruptions to white matter in this young group could indicate aberrant axonal and myelin maturation with resultant compromise of fiber integrity. Findings of increased anisotropic diffusion in alternate brain regions suggest possible neuroadaptive processes and can be examined in future studies of connectivity to determine how aberrancies in specific tracts might influence efficient cognitive processing.

Abstinent adolescent marijuana users show altered fMRI response during spatial working memory.

Marijuana is the most widely used illicit substance among teenagers, yet little is known about the possible neural influence of heavy marijuana use during adolescence. We previously demonstrated an altered functional magnetic resonance imaging (fMRI) activity related to spatial working memory (SWM) among adolescents who were heavy users of after an average of 8 days of abstinence, but the persisting neural effects remain unclear. To characterize the potentially persisting neurocognitive effects of heavy marijuana use in adolescence, we examined fMRI response during SWM among abstinent marijuana-using teens. Participants were 15 MJ teens and 17 demographically similar non-using controls, ages 16-18. Teens underwent biweekly urine toxicology screens to ensure abstinence for 28 days before fMRI acquisition. Groups performed similarly on the SWM task, but MJ teens demonstrated lower activity in right dorsolateral prefrontal and occipital cortices, yet significantly more activation in right posterior parietal cortex. MJ teens showed abnormalities in brain response during a SWM task compared with controls, even after 1 month of abstinence. The activation pattern among MJ teens may reflect different patterns of utilization of spatial rehearsal and attention strategies, and could indicate altered neurodevelopment or persisting abnormalities associated with heavy marijuana use in adolescence.

N-acetyl aspartate in autism spectrum disorders: regional effects and relationship to fMRI activation.

Rapid progress in our understanding of macrostructural abnormalities in autism spectrum disorders (ASD) has occurred in recent years. However, the relationship between the integrity of neural tissue and neural function has not been previously investigated. Single-voxel proton magnetic resonance spectroscopy and functional magnetic resonance imaging of an executive functioning task was obtained in 13 high functioning adolescents and adults with ASD and 13 age-matched controls. The ASD group showed significant reductions in N-acetyl aspartate (NAA) in all brain regions combined and a specific reduction in left frontal cortex compared to controls. Regression analyses revealed a significant group interaction effect between frontal and cerebellar NAA. In addition, a significant positive semi-partial correlation between left frontal lobe NAA and frontal lobe functional activation was found in the ASD group. These findings suggest that widespread neuronal dysfunction is present in high functioning individuals with ASD. Hypothesized developmental links between frontal and cerebellar vermis neural abnormalities were supported, in that impaired neuronal functioning in the vermis was associated with impaired neuronal functioning in the frontal lobes in the ASD group. Furthermore, this study provided the first direct evidence of the relationship between abnormal functional activation in prefrontal cortex and neuronal dysfunction in ASD.

Association between dyads and correct responses on the Paced Auditory Serial Addition Task (PASAT).

The sensitivity of the Paced Auditory Serial Addition Task (PASAT) to working memory deficits may be enhanced by examining "dyads" (i.e., correct responses immediately preceded by a correct response) as a complement to the traditional total correct summary score. In a sample of 397 mostly African American (79%) healthy adults, total dyad and total correct scores were highly correlated (r = .96, p < .001); however, the magnitude of this association diminished in faster stimulus presentation trials, particularly among participants with impaired working memory abilities.

fMRI response to spatial working memory in adolescents with comorbid marijuana and alcohol use disorders.

Alcohol and marijuana use are prevalent in adolescence, yet the neural impact of concomitant use remains unclear. We previously demonstrated functional magnetic resonance imaging (fMRI) response to spatial working memory (SWM) among teens with alcohol use disorders (AUD) compared to controls, and predicted that adolescents with marijuana and alcohol use disorders would show additional abnormalities. Participants were three groups of 15-17-year-olds: 19 non-abusing controls, 15 AUD teens with limited exposure to drugs, and 15 teens with comorbid marijuana and alcohol use disorders (MAUD) and minimal other drug experience. After >2 days' abstinence, participants performed a SWM task during fMRI acquisition. fMRI brain response patterns differed between groups, despite similar performance on the task. MAUD youths showed less activation in inferior frontal and temporal regions than controls, and more response in other prefrontal regions. Compared to AUD teens, MAUD youths also showed less inferior frontal and temporal activation, but more medial frontal response. Overall, MAUD youths showed different brain response abnormalities than teens with AUD alone, despite relatively short histories of substance involvement. This pattern could suggest compensation for marijuana-related attention and working memory deficits. However, relatively recent use and premorbid features may influence results, and should be examined in future studies.

A quantitative meta-analysis of neurocognitive functioning in posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is associated with regional alterations in brain structure and function that are hypothesized to contribute to symptoms and cognitive deficits associated with the disorder. We present here the first systematic meta-analysis of neurocognitive outcomes associated with PTSD to examine a broad range of cognitive domains and describe the profile of cognitive deficits, as well as modifying clinical factors and study characteristics. This report is based on data from 60 studies totaling 4,108 participants, including 1,779 with PTSD, 1,446 trauma-exposed comparison participants, and 895 healthy comparison participants without trauma exposure. Effect-size estimates were calculated using a mixed-effects meta-analysis for 9 cognitive domains: attention/working memory, executive functions, verbal learning, verbal memory, visual learning, visual memory, language, speed of information processing, and visuospatial abilities. Analyses revealed significant neurocognitive effects associated with PTSD, although these ranged widely in magnitude, with the largest effect sizes in verbal learning (d = -.62), speed of information processing (d = -.59), attention/working memory (d = -.50), and verbal memory (d =-.46). Effect-size estimates were significantly larger in treatment-seeking than community samples and in studies that did not exclude participants with attention-deficit/hyperactivity disorder, and effect sizes were affected by between-group IQ discrepancies and the gender composition of the PTSD groups. Our findings indicate that consideration of neuropsychological functioning in attention, verbal memory, and speed of information processing may have important implications for the effective clinical management of persons with PTSD. Results are further discussed in the context of cognitive models of PTSD and the limitations of this literature.

Effects of alcoholism and gender on brain metabolism.

OBJECTIVE: Proton magnetic resonance spectroscopy was used to evaluate gender influences on alcohol-associated changes in brain metabolism. METHOD: Concentrations of N-acetylaspartate, choline-containing compounds, myo-inositol, and creatine plus phosphocreatine in frontal lobe gray matter and white matter were estimated in eight women and 17 men who were recently detoxified from long-term alcoholism. Twelve women and 13 men with no history of alcoholism were used as a comparison group. RESULTS: In male and female alcoholics, frontal lobe white matter concentrations of N-acetylaspartate were significantly lower (-8.8%) than those seen in nonalcoholic comparison subjects. In the frontal lobe gray matter region, a significant alcoholism status-by-gender interaction and follow-up analyses revealed that female alcoholics had significantly lower N-acetylaspartate concentrations (-10.73%) relative to female comparison subjects, while male alcoholics and male comparison subjects had similar levels of this metabolite (<1% difference). CONCLUSIONS: Lower concentrations of white matter N-acetylaspartate, which may indicate neuronal loss or dysfunction, is equally severe in men and women with comparable alcohol abuse histories. However, female alcoholics exhibited significantly less N-acetylaspartate in frontal gray matter relative to female nonalcoholic comparison subjects, which could mean that female alcoholics are more susceptible to gray matter injury than their male counterparts. However, this finding could also be explained by higher-than-expected levels of N-acetylaspartate in the healthy female comparison group.

Neurocognitive performance of methamphetamine users discordant for history of marijuana exposure.

Abuse of the stimulant drug methamphetamine is associated with neural injury and neuropsychological (NP) deficits, while the residual effects of marijuana use remain uncertain. We sought to determine if methamphetamine dependent persons who also met criteria for marijuana abuse or dependence evidenced different NP performance than those with dependence for methamphetamine alone. We examined three groups that did not differ significantly on important demographic factors: (1) subjects with a history of methamphetamine dependence and history of marijuana abuse/dependence (METH+/MJ+, n=27); (2) methamphetamine dependent subjects without history of marijuana abuse/dependence (METH+/MJ-, n=26); (3) a control group with minimal or no drug use (n=41). A comprehensive NP battery was administered and performance was quantified for five cognitive ability areas. The METH+/MJ- group generally demonstrated the greatest NP impairment, with statistically significant differences observed between the METH+/MJ- and control group in learning, retention/retrieval, and a summary score of global NP performance. The METH+/MJ+ group did not differ significantly from the control or METH+/MJ- group on any NP ability. However, there was a significant linear trend in the global NP score suggesting that the METH+/MJ+ performed intermediate to the control and METH+/MJ- groups. Based on these findings, we cannot conclude that there is a protective effect of marijuana use in methamphetamine users; however, marijuana use clearly did not appear to exacerbate methamphetamine neurotoxicity. Further investigations are needed to determine if the emerging literature, suggesting that certain cannabinoids might have neuroprotective actions, is generalizable to community-dwelling substance abusers.

Neural correlates of verbal learning in adolescent alcohol and marijuana users.

AIMS: Alcohol and marijuana are the most widely used intoxicants among adolescents, yet their potential unique and interactive influences on the developing brain are not well established. Brain regions subserving learning and memory undergo continued maturation during adolescence, and may be particularly susceptible to substance-related neurotoxic damage. In this study, we characterize brain response during verbal learning among adolescent users of alcohol and marijuana. DESIGN: Participants performed a verbal paired associates encoding task during functional magnetic resonance imaging (fMRI) scanning. SETTING: Adolescent subjects were recruited from local public schools and imaged at a university-based fMRI center. PARTICIPANTS: Participants were 74 16-18-year-olds, divided into four groups: (i) 22 controls with limited alcohol and marijuana experience, (ii) 16 binge drinkers, (iii) eight marijuana users and (iv) 28 binge drinking marijuana users. MEASUREMENTS: Diagnostic interview ensured that all teens were free from neurological or psychiatric disorders; urine toxicology and breathalyzer verified abstinence for 22-28 days before scanning; a verbal paired associates task was administered during fMRI. FINDINGS: Groups demonstrated no differences in performance on the verbal encoding task, yet exhibited different brain response patterns. A main effect of drinking pointed to decreased inferior frontal but increased dorsal frontal and parietal fMRI response among binge drinkers (corrected P < 0.05). There was no main effect of marijuana use. Binge drinking × marijuana interactions were found in bilateral frontal regions (corrected P < 0.05), where users of either alcohol or marijuana showed greater response than non-users, but users of both substances resembled non-users. CONCLUSIONS: Adolescent substance users demonstrated altered fMRI response relative to non-using controls, yet binge drinking appeared to be associated with more differences in activation than marijuana use. Alcohol and marijuana may have interactive effects that alter these differences, particularly in prefrontal brain regions.

A neuropsychological investigation of multitasking in HIV infection: implications for everyday functioning.

OBJECTIVE: A subset of individuals with HIV-associated neurocognitive impairment experience related deficits in "real world" functioning (i.e., independently performing instrumental activities of daily living [IADL]). While performance-based tests of everyday functioning are reasonably sensitive to HIV-associated IADL declines, questions remain regarding the extent to which these tests' highly structured nature fully captures the inherent complexities of daily life. The aim of this study was to assess the predictive and ecological validity of a novel multitasking measure in HIV infection. METHOD: Participants included 60 individuals with HIV infection (HIV+) and 25 demographically comparable seronegative adults (HIV-). Participants were administered a comprehensive neuropsychological battery, questionnaires assessing mood and everyday functioning, and a novel standardized test of multitasking, which involved balancing the demands of four interconnected performance-based functional tasks (i.e., financial management, cooking, medication management, and telephone communication). RESULTS: HIV+ individuals demonstrated significantly worse overall performance, fewer simultaneous task attempts, and increased errors on the multitasking test as compared to the HIV- group. Within the HIV+ sample, multitasking impairments were modestly associated with deficits on standard neuropsychological measures of executive functions, episodic memory, attention/working memory, and information processing speed, providing preliminary evidence for convergent validity. More importantly, multivariate prediction models revealed that multitasking deficits were uniquely predictive of IADL dependence beyond the effects of depression and global neurocognitive impairment, with excellent sensitivity (86%), but modest specificity (57%). CONCLUSIONS: Taken together, these data indicate that multitasking ability may play an important role in successful everyday functioning in HIV+ individuals.

Stroke risk modifies regional white matter differences in mild cognitive impairment.

Forty non-demented older adults who were divided into two groups on the basis of their cognitive status (MCI: n=20; normal control: n=20) underwent diffusion tensor imaging, and estimates of fractional anisotropy (FA) and mean diffusivity (MD) were obtained for the genu and splenium of the corpus callosum. Results demonstrated the following: (1) group comparisons revealed that splenium FA was significantly lower in MCI participants than in NC participants, despite no differences in gross morphometry or hippocampal volumes; (2) in the overall sample, higher stroke risk was associated with lower white matter integrity, particularly in the genu; (3) increased stroke risk was more strongly associated with poorer splenium FA in those with MCI than in normal elderly; (4) splenium FA significantly predicted performance on verbal memory (adjusting for the effects of age, education, and whole brain volume). Findings demonstrate a relationship between increased vascular burden and white matter changes, and they support the possibility that posterior white matter pathology may contribute to the development of MCI-related cognitive changes.