Victoria J. Williams

Association between white matter microstructure, executive functions, and processing speed in older adults: The impact of vascular health

Cerebral white matter damage is not only a commonly reported consequence of healthy aging, but is also associated with cognitive decline and dementia. The aetiology of this damage is unclear; however, individuals with hypertension have a greater burden of white matter signal abnormalities (WMSA) on MR imaging than those without hypertension. It is therefore possible that elevated blood pressure (BP) impacts white matter tissue structure which in turn has a negative impact on cognition. However, little information exists about whether vascular health indexed by BP mediates the relationship between cognition and white matter tissue structure. We used diffusion tensor imaging to examine the impact of vascular health on regional associations between white matter integrity and cognition in healthy older adults spanning the normotensive to moderate–severe hypertensive BP range (43–87 years; N = 128). We examined how white matter structure was associated with performance on tests of two cognitive domains, executive functioning (EF) and processing speed (PS), and how patterns of regional associations were modified by BP and WMSA. Multiple linear regression and structural equation models demonstrated associations between tissue structure, EF and PS in frontal, temporal, parietal, and occipital white matter regions. Radial diffusivity was more prominently associated with performance than axial diffusivity. BP only minimally influenced the relationship between white matter integrity, EF and PS. However, WMSA volume had a major impact on neurocognitive associations. This suggests that, although BP and WMSA are causally related, these differential metrics of vascular health may act via independent pathways to influence brain structure, EF and PS. Hum Brain Mapp, 2013.

Inter-individual variation in blood pressure is associated with regional white matter integrity in generally healthy older adults

Prior studies have documented a range of brain changes that occur as a result of healthy aging as well as neural alterations due to profound dysregulation in vascular health such as extreme hypertension, cerebrovascular disease and stroke. In contrast, little information exists about the more transitionary state between the normal and abnormal physiology that contributes to vascular disease and cognitive decline. Specifically, little information exists with regard to the influence of systemic vascular physiology on brain tissue structure in older individuals with low risk for cerebrovascular disease and with no evidence of cognitive impairment. We examined the association between resting blood pressure and diffusion tensor imaging (DTI) indices of white matter microstructure in 128 healthy older adults (43-87 years) spanning the normotensive to moderate-severe hypertensive range. Mean arterial blood pressure (MABP) was related to diffusion measures in several regions of the brain with greatest associations in the anterior corpus callosum and lateral frontal, precentral, superior frontal, lateral parietal and precuneus white matter. Associations between white matter integrity and blood pressure remained when controlling for age, when controlling for white matter lesions, and when limiting the analyses to only normotensive, pharmacologically controlled and pre-hypertensive individuals. Of the diffusion measures examined, associations were strongest between MABP and radial diffusivity which may indicate that blood pressure has an influence on myelin structure. Associations between MABP and white matter integrity followed spatial patterns resembling those often attributed to the effects of chronological age, suggesting that systemic cerebrovascular health may play a role in neural tissue degeneration classically ascribed to aging. These results demonstrate the importance of the consideration of vascular physiology in studies of cognitive and neural aging, and that this significance extends to even the normotensive and medically controlled population. These data additionally suggest that optimal management of blood pressure may require consideration of the more subtle influence of vascular health on neural health in addition to the primary goal of prevention of a major cerebrovascular event.

Reduced cortical thickness in abstinent alcoholics and association with alcoholic behavior.

BACKGROUND Chronic misuse of alcohol results in widespread damage to the brain. Prior morphometric studies have examined cortical atrophy in individuals with alcoholism; however, no previous studies have examined alcohol-associated atrophy using cortical thickness measurements to obtain regional mapping of tissue loss across the full cortical surface. METHODS We compared cortical thickness measures from 31 abstinent individuals with a history of prior alcohol abuse to 34 healthy nonalcoholic control participants (total sample size = 65). Cortical surface models were created from high-resolution T1-weighted images, and cortical thickness was then estimated as the distance between the gray matter/white matter boundary and the outer cortical surface. RESULTS Abstinent alcoholics showed reduced whole-brain thickness as compared to nonalcoholic participants. Decreases in thickness were found bilaterally in (i) superior frontal, (ii) precentral, (iii) postcentral, (iv) middle frontal, (v) middle/superior temporal, (vi) middle temporal, and (vii) lateral occipital cortical regions. Decreased cortical thickness in the alcoholic group was associated with severity of alcohol abuse. CONCLUSIONS These findings demonstrate widespread reduction in cortical thickness as a consequence of chronic alcoholism, with most severe reductions in frontal and temporal brain regions.

Interindividual variation in serum cholesterol is associated with regional white matter tissue integrity in older adults.

Prior research has demonstrated links among vascular health and the occurrence of stroke, mild cognitive decline, and dementia in older adults. However, little is known about whether normal variation in vascular indicators may be related to changes in neural tissue integrity. Even less is known about how the brain is affected by cholesterol levels in the normal to moderate risk range, leading up to overt disease pathology. This study examined associations between serum lipid levels and DTI indicators of white matter (WM) structural integrity in a sample of 125 generally healthy older adults aged 43–87 years. Whole‐brain voxelwise analysis, controlling for age and gender, revealed low density lipoprotein levels (LDL) as the most robust correlate of regional WM structural integrity of the measured lipids. Higher LDL was associated with decreased WM integrity in right frontal and temporal regions, the superior longitudinal fasciculus and internal/external capsules. Increasing LDL was associated with increased radial and axial diffusivity; however, more widespread statistical effects were found for radial diffusivity. These findings suggest that normal interindividual variation in lipid levels is associated with compromised regional WM integrity, even in individuals below clinical thresholds for hyperlipidemia. Given the prevalence of cholesterol‐associated sequelae in older adults, and mounting evidence suggesting a vascular role in the etiology of dementia, the current data suggest that understanding the relationship between cholesterol and brain tissue microstructure may have important clinical implications for early detection of vascular‐related cognitive disorders and optimal regulation of serum lipids to maintain neural health in older adults. Hum Brain Mapp, 2013.

Variation in Blood Pressure is Associated with White Matter Microstructure but not Cognition in African Americans

Although hypertension is a major risk factor for cerebrovascular disease (CVD) and is highly prevalent in African Americans, little is known about how blood pressure (BP) affects brain-behavior relationships in this population. In predominantly Caucasian populations, high BP is associated with alterations in frontal-subcortical white matter and in executive functioning aspects of cognition. We investigated associations among BP, brain structure, and neuropsychological functioning in 52 middle-older-age African Americans without diagnosed history of CVD. All participants underwent diffusion tensor imaging for examination of white matter integrity, indexed by fractional anisotropy (FA). Three regions of interest were derived in the anterior (genu) and posterior (splenium) corpus callosum and across the whole brain. A brief neuropsychological battery was administered from which composite scores of executive function and memory were derived. Blood pressure was characterized by mean arterial blood pressure (MABP). When controlling for age, higher MABP was associated with lower FA in the genu, and there was a trend for this same relationship with regard to whole-brain FA. When the sample was broken into groups on the basis of treatment for BP regulation (medicated vs. nonmedicated), MABP was related to genu and whole-brain FA only in the nonmedicated group. Neither MABP nor FA was significantly related to either neuropsychological composite score regardless of medication use. These data provide important evidence that variation in BP may contribute to significant alterations in specific neural regions of white matter in nonmedicated individuals without symptoms of overt CVD.

Associations between T1 white matter lesion volume and regional white matter microstructure in aging

White matter lesions, typically manifesting as regions of signal intensity abnormality (WMSA) on MRI, increase in frequency with age. However, the role of this damage in cognitive decline and disease is still not clear, as lesion volume has only loosely been associated with clinical status. Diffusion tensor imaging (DTI) has been used to examine the quantitative microstructural integrity of white matter, and has applications in the examination of subtle changes to tissue that appear visually normal on conventional imaging. The primary goal of this study was to determine whether major macrostructural white matter damage, (total WMSA volume), is associated with microstructural integrity of normal appearing white matter, and if these macrostructural changes fully account for microstructural changes. Imaging was performed in 126 nondemented individuals, ages 43–85 years, with no history of cerebrovascular disease. Controlling for age, greater WMSA volume was associated with decreased fractional anisotropy (FA) in widespread brain regions. Patterns were similar for FA and radial diffusivity but in contrast, WMSA was associated with axial diffusivity in fewer areas. Age was associated with FA in several regions, and many of these effects remained even when controlling for WMSA volume, suggesting the etiology of WMSAs does not fully account for all age‐associated white matter deterioration. These results provide evidence that WMSA volume is associated with the integrity of normal‐appearing white matter. In addition, our results suggest that overt lesions may not account for the association of increasing age with decreased white matter tissue integrity. Hum Brain Mapp 35:1085–1100, 2014.

Cardiorespiratory fitness is differentially associated with cortical thickness in young and older adults

Abstract Aging is associated with reductions in gray matter volume and cortical thickness. One factor that may play a role in mitigating age‐associated brain decline is cardiorespiratory fitness (CRF). Although previous work has identified a positive association between CRF and gray matter volume, the relationship between CRF and cortical thickness, which serves as a more sensitive indicator of gray matter integrity, has yet to be assessed in healthy young and older adults. To address this gap in the literature, 32 young and 29 older adults completed treadmill‐based progressive maximal exercise testing to assess CRF (peak VO2), and structural magnetic resonance imaging (MRI) to determine vertex‐wise surface‐based cortical thickness metrics. Results indicated a significant CRF by age group interaction such that Peak VO2 was associated with thicker cortex in older adults but with thinner cortex in young adults. Notably, the majority of regions demonstrating a positive association between peak VO2 and cortical thickness in older adults overlapped with brain regions showing significant age‐related cortical thinning. Further, when older adults were categorized as high or low fit based on normative data, we observed a stepwise pattern whereby cortex was thickest in young adults, intermediate in high fit older adults and thinnest in low fit older adults. Overall, these results support the notion that CRF‐related neuroplasticity may reduce although not eliminate age‐related cortical atrophy. HighlightsFew studies have examined peak VO2 and cortical integrity in young and older adults.Greater peak VO2 was associated with thicker cortex in healthy older adults.Greater peak VO2 was associated with thinner cortex in healthy younger adults.Multiple regions that show cortical decline in aging are also sensitive to fitness.Relation between fitness and cortical thickness appears to be age dependent.

Examination of Frontal and Parietal Tectocortical Attention Pathways in Spina Bifida Meningomyelocele Using Probabilistic Diffusion Tractography

Abnormalities of the midbrain tectum are common but variable malformations in spina bifida meningomyelocele (SBM) and have been linked to neuropsychological deficits in attention orienting. The degree to which variations in tectum structure influence white matter (WM) connectivity to cortical regions is unknown. To assess the relationship of tectal structure and connectivity to frontal and parietal cortical regions, probabilistic diffusion tractography was performed on 106 individuals (80 SBM, 26 typically developing [TD]) to isolate anterior versus posterior tectocortical WM pathways. Results showed that those with SBM exhibited significantly reduced tectal volume, along with decreased fractional anisotropy (FA) in posterior but not anterior tectocortical WM pathways when compared with TD individuals. The group with SBM also showed greater within-subject discrepancies between frontal and parietal WM integrity compared with the TD group. Of those with SBM, qualitative classification of tectal beaking based on radiological review was associated with increased axial diffusivity across both anterior and posterior tectocortical pathways, relative to individuals with SBM and a normal appearing tectum. These results support previous volumetric findings of greater impairment to posterior versus anterior brain regions in SBM, and quantifiably relate tectal volume, tectocortical WM integrity, and tectal malformations in this population.

Postshunt lateral ventricular volume, white matter integrity, and intellectual outcomes in spina bifida and hydrocephalus

OBJECT No previous reports exist that have evaluated the relationships of white matter (WM) integrity with the number of shunt revisions, ventricular volume after shunting, and cognition in medically stable children who have spina bifida and hydrocephalus (SBH). The authors hypothesized that enlarged ventricles and a greater number of shunt revisions decrease WM integrity in children. METHODS In total, 80 children (mean age 13.7 years) who had SBH underwent MRI and IQ testing. Probabilistic diffusion tractography was performed to determine mean diffusion tensor imaging (DTI) metrics along the frontal and parietal tectocortical pathways. The DTI metrics were evaluated for significant correlation with a composite IQ measure and with the total number of shunt revisions and the total lateral ventricular volume obtained through semiautomated parcellation of T1-weighted MRI scans. RESULTS An enlargement in total lateral ventricle volume and an increase in the number of shunt revisions were both associated with higher fractional anisotropy (FA) and with lower radial diffusivity (RD) along both frontal and parietal tectocortical pathways. Children who had not undergone a shunt revision had on average a greater lateral ventricle volume and higher FA and lower RD along frontal and parietal pathways than those who had undergone multiple shunt revisions. The mean DTI metrics along parietal pathways predicted IQ scores, but intellectual ability was not significantly correlated with ventricular volume or with the number of lifetime shunt revisions. CONCLUSIONS Significant changes in DTI metrics were observed as a function of ventricular volume. An increased lateral ventricle volume was associated with elevated FA and decreased RD. Given that the participants were medically stable at the time of the MRI examination, the results suggested that those who have enlarged ventricles show a DTI pattern consistent with axonal compression due to increased intracranial pressure (ICP) in attenuated hydrocephalus. Although limited by a cross-sectional design, the studys findings suggest that DTI metrics may serve as sensitive indicators for chronic, mild hydrocephalus in the absence of overt clinical symptoms due to increased ICP. Having enlarged ventricles and undergoing multiple shunt revisions did not affect intellectual ability in children with SBH.

Cortical Thickness and Local Gyrification in Children with Developmental Dyslexia

Developmental dyslexia is frequently associated with atypical brain structure and function within regions of the left hemisphere reading network. To date, few studies have employed surface-based techniques to evaluate cortical thickness and local gyrification in dyslexia. Of the existing cortical thickness studies in children, many are limited by small sample size, variability in dyslexia identification, and the recruitment of prereaders who may or may not develop reading impairment. Further, no known study has assessed local gyrification index (LGI) in dyslexia, which may serve as a sensitive indicator of atypical neurodevelopment. In this study, children with dyslexia (n = 31) and typically decoding peers (n = 45) underwent structural magnetic resonance imaging to assess whole-brain vertex-wise cortical thickness and LGI. Children with dyslexia demonstrated reduced cortical thickness compared with controls within previously identified reading areas including bilateral occipitotemporal and occipitoparietal regions. Compared with controls, children with dyslexia also showed increased gyrification in left occipitotemporal and right superior frontal cortices. The convergence of thinner and more gyrified cortex within the left occipitotemporal region among children with dyslexia may reflect its early temporal role in processing word forms, and highlights the importance of the ventral stream for successful word reading.