Greater Fractional Anisotropy Research Articles

Free water-corrected fractional anisotropy of the fornix and parahippocampal cingulum predicts longitudinal memory change in cognitively healthy older adults

Prior studies have reported inconsistent results regarding the relationships between the integrity of the fornix and parahippocampal cingulum and both memory performance and longitudinal change in performance. In the present study, we examined associations in a sample of cognitively healthy older adults between free water-corrected fractional anisotropy (FA) metrics derived from the fornix and cingulum, baseline memory performance, and 3-year memory change. Neither fornix nor cingulum FA correlated with memory performance at baseline. By contrast, FA of each tract was predictive of memory change, such that greater FA was associated with less longitudinal decline. These associations remained significant after controlling for FA of other white matter tracts and for performance in other cognitive domains. Furthermore, fornix and cingulum FA explained unique variance in memory change. These results suggest that free water-corrected measures of fornix and parahippocampal cingulum integrity are reliable predictors of future memory change in cognitively healthy older adults. The findings for the fornix in particular highlight the utility of correcting for free water when estimating diffusion tensor imaging metrics of white matter integrity.

A preliminary study of white matter correlates of a laboratory measure of attention and motor stability in attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) is a complex behavioral disorder, often difficult and time consuming to diagnose. Laboratory assessment of ADHD-related constructs of attention and motor activity may be helpful in elucidating neurobiology; however, neuroimaging studies evaluating laboratory measures of ADHD are lacking. In this preliminary study, we assessed the association between fractional anisotropy (FA), a measure of white matter microstructure, and laboratory measures of attention and motor behavior using the QbTest, a widely used measure thought to improve clinician diagnostic confidence. This is the first look at neural correlates of this widely used measure. The sample included adolescents and young adults (ages 12–20, 35% female) with ADHD (n = 31) and without (n = 52). As expected, ADHD status was associated with motor activity, and cognitive inattention and impulsivity in the laboratory. With regard to MRI findings, laboratory observed motor activity and inattention were associated with greater FA in white matter regions of the primary motor cortex. All three laboratory observations were associated with lower FA in regions subserving fronto-striatal-thalamic and frontoparietal (i.e. superior longitudinal fasciculus) circuitry. Further, FA in white matter regions of the prefrontal cortex appeared to mediate the relationship between ADHD status and motor activity on the QbTest. These findings, while preliminary, suggest that performance on certain laboratory tasks is informative with regard to neurobiological correlates of subdomains of the complex ADHD phenotype. In particular, we provide novel evidence for a relationship between an objective measure of motor hyperactivity and white matter microstructure in motor and attentional networks.

Segmental abnormalities of superior longitudinal fasciculus microstructure in patients with schizophrenia, bipolar disorder, and attention-deficit/hyperactivity disorder: An automated fiber quantification tractography study.

Superior longitudinal fasciculus (SLF) is a white matter (WM) tract that connects the frontal, parietal and temporal lobes. SLF integrity has been widely assessed in neuroimaging studies of psychiatric disorders, such as schizophrenia (SZ), bipolar disorder (BD), and attention-deficit/hyperactivity disorder (ADHD). However, prior studies have revealed inconsistent findings and comparisons across disorders have not been fully examined. Here, we obtained data for 113 patients (38 patients with SZ, 40 with BD, 35 with ADHD) and 94 healthy controls from the UCLA Consortium for Neuropsychiatric Phenomic LA5c dataset. We assessed the integrity of 20 major WM tracts with a novel segmentation method by automating fiber tract quantification (AFQ). The AFQ divides each tract into 100 equal parts along the direction of travel, with fractional anisotropy (FA) of each part taken as a characteristic. Differences in FA among the four groups were examined. Compared to healthy controls, patients with SZ showed significantly lower FA in the second half (51-100 parts) of the SLF. No differences were found between BD and healthy controls, nor between ADHD and healthy controls. Results also demonstrated that patients with SZ showed FA reduction in the second half of the SLF relative to patients with BP. Moreover, greater FA in patients in SLF was positively correlated with the manic-hostility score of the Brief Psychiatry Rating scale. These findings indicated that differences in focal changes in SLF might be a key neurobiological abnormality contributing to characterization of these psychiatric disorders.

Associations of body composition with regional brain volumes and white matter microstructure in very preterm infants

ObjectiveTo determine associations between body composition and concurrent measures of brain development including (1) Tissue-specific brain volumes and (2) White matter microstructure, among very preterm infants at term equivalent age.DesignProspective...

Sex and sensitive period differences in potential effects of maltreatment on axial versus radial diffusivity in the corpus callosum.

Corpus callosum (CC) abnormalities have been observed in several psychiatric disorders. Maltreatment has also been associated with marked differences in CC anatomy and microstructure, though rarely controlled for in psychiatric neuroimaging studies. The aim of this study was to identify type and timing of maltreatment associated with alterations in CC microstructure and to ascertain if they differ by sex. T1 and diffusion-weighted MRIs were obtained from 345 (135 M/210 F) healthy 18-25-year-olds. The Maltreatment and Abuse Chronology of Exposure scale provided retrospective data on exposure to ten types of maltreatment across each year of childhood. AI predictive analytics were used to identify the most significant type and time risk factors. The most striking maltreatment-associated alterations in males were in axial diffusivity and were most specifically associated with exposure to emotional abuse or neglect during segment-specific sensitive periods. In contrast, maltreatment was associated with marked alteration in radial diffusivity and fractional anisotropy in females and was most specifically associated with early physical neglect during one common sensitive period involving all segments except the splenium. Overall sex differences, controlling for maltreatment, brain size, and sociodemographic factors were limited to the genu with greater fractional anisotropy in males and radial diffusivity in females. These findings suggest that maltreatment may target myelinization in females and axonal development in males and that these sex differences need to be taken into account in studies seeking to delineate the contribution of CC abnormalities and interhemispheric communication to psychiatric disorders.

The relationship between white matter microstructure, cardiovascular fitness, gross motor skills, and neurocognitive functioning in children.

Recent evidence indicates that both cardiovascular fitness and gross motor skill performance are related to enhanced neurocognitive functioning in children by influencing brain structure and functioning. This study investigates the role of white matter microstructure in the relationship of both cardiovascular fitness and gross motor skills with neurocognitive functioning in healthy children. In total 92 children (mean age 9.1 years, range 8.0–10.7) were included in this study. Cardiovascular fitness and gross motor skill performance were assessed using performance‐based tests. Neurocognitive functioning was assessed using computerized tests (working memory, inhibition, interference control, information processing, and attention). Diffusion tensor imaging was used in combination with tract‐based spatial statistics to assess white matter microstructure as defined by fractional anisotropy (FA), axial and radial diffusivity (AD, RD). The results revealed positive associations of both cardiovascular fitness and gross motor skills with neurocognitive functioning. Information processing and motor response inhibition were associated with FA in a cluster located in the corpus callosum. Within this cluster, higher cardiovascular fitness and better gross motor skills were both associated with greater FA, greater AD, and lower RD. No mediating role was found for FA in the relationship of both cardiovascular fitness and gross motor skills with neurocognitive functioning. The results indicate that cardiovascular fitness and gross motor skills are related to neurocognitive functioning as well as white matter microstructure in children. However, this study provides no evidence for a mediating role of white matter microstructure in these relationships.

Contributions of Cerebellar White Matter Microstructure to Social Difficulty in Nonverbal Learning Disability.

Emerging evidence suggests that the cerebellum may contribute to variety of cognitive capacities, including social cognition. Nonverbal learning disability (NVLD) is characterized by visual-spatial and social impairment. Recent functional neuroimaging studies have shown that children with NVLD have altered cerebellar resting-state functional connectivity, which is associated with various symptom domains. However, little is known about cerebellar white matter microstructure in NVLD and whether it contributes to social deficits. Twenty-seven children (12 with NVLD, 15 typically developing (TD)) contributed useable diffusion tensor imaging data. Tract-based spatial statistics (TBSS) were used to quantify fractional anisotropy (FA) in the cerebellar peduncles. Parents completed the Child Behavior Checklist, providing a measure of social difficulty. Children with NVLD had greater fractional anisotropy in the left and right inferior cerebellar peduncle. Furthermore, right inferior cerebellar peduncle FA was associated with social impairment as measured by the Child Behavior Checklist Social Problems subscale. Finally, the association between NVLD diagnosis and greater social impairment was mediated by right inferior cerebellar peduncle FA. These findings provide additional evidence that the cerebellum contributes both to social cognition and to the pathophysiology of NVLD.

Diffusion properties of the fornix assessed by deterministic tractography shows age, sex, volume, cognitive, hemispheric, and twin relationships in young adults from the Human Connectome Project.

The fornix is the primary efferent pathway of the hippocampus and plays a central role in memory circuitry. Diffusion tensor imaging has shown changes in the fornix with typical development and aging. Here, the fornix was investigated in 903 healthy young adult participants aged 22-36years old from the high-spatial resolution 1.25mm isotropic Human Connectome Project (HCP) diffusion dataset. Manual deterministic tractography was used to assess relationships between fornix diffusion parameters and age, sex, laterality, hippocampus volume, memory scores, and genetic effects in a subgroup of mono- and dizygotic twins. Fornix diffusion metrics were weakly correlated with age over the given age span. While significant hemispheric and sex differences were observed (greater fractional anisotropy (FA) and volume in the right hemisphere; greater FA and volume in females), there was great overlap between the groups. Hippocampus volume measurements showed greater volume in the right hemisphere, were found to be larger in males, and were weakly correlated with fornix FA and volume. Interestingly, all fornix diffusion measurements correlated strongly with fornix volume, suggesting the presence of partial volume effects despite the high-spatial resolution of the data. Both fornix diffusion parameters and hippocampal volumes were able to explain some variance (0.6-5.5%) in the memory tests evaluated. The fornix diffusion parameters were influenced by both genetic and shared environmental factors, displaying greater variability in dizygotic than in monozygotic twins. These findings provide a comprehensive depiction of the fornix in healthy, young individuals, upon which future typical development/aging and pathological studies could anchor.

Rest-activity rhythms and white matter microstructure across the lifespan.

The purpose of this study was to examine how rest-activity (RA) rhythm stability may be associated with white matter microstructure across the lifespan in healthy adults free of significant cardiovascular risk. We analyzed multi-shell diffusion tensor images from 103 healthy young and older adults using tract-based spatial statistics (TBSS) to examine relationships between white matter microstructure and RA rhythm stability. RA measures were computed using both cosinor and non-parametric methods derived from 7 days of actigraphy data. Fractional anisotropy (FA) and mean diffusivity (MD) were examined in this analysis. Because prior studies have suggested that the corpus callosum (CC) is sensitive to sleep physiology and RA rhythms, we also conducted a focused region of interest analysis on the CC. Greater rest-activity rhythm stability was associated with greater FA across both young and older adults, primarily in the CC and anterior corona radiata. This effect was not moderated by age group. While RA measures were associated with sleep metrics, RA rhythm measures uniquely accounted for the variance in white matter integrity. This study strengthens existing evidence for a relationship between brain white matter structure and RA rhythm stability in the absence of health risk factors. While there are differences in RA stability between age groups, the relationship with brain white matter was present across both young and older adults. RA rhythms may be a useful biomarker of brain health across both periods of adult development.

Succeeding in deactivating: associations of hair zinc levels with functional and structural neural mechanisms

Zinc is a biologically essential element and involved in a wide range of cellular processes. Here, we investigated the associations of zinc levels in hair with brain activity during the n-back working memory task using functional magnetic resonance imaging, fractional anisotropy (FA) of diffusion tensor imaging, and cognitive differences in a study cohort of 924 healthy young adults. Our findings showed that greater hair zinc levels were associated with lower brain activity during working memory in extensive areas in the default mode network (i.e., greater task-induced deactivation) as well as greater FA in white matter areas near the hippocampus and posterior limbs of the internal capsule. These findings advance previous non-neuroimaging findings of zinc’s associations with excitability, excitability-associated disorders, and myelination.

Evidence of Neural Microstructure Abnormalities in Type I Chiari Malformation: Associations Among Fiber Tract Integrity, Pain, and Cognitive Dysfunction.

Previous case-control investigations of type I Chiari malformation (CMI) have reported cognitive deficits and microstructural white matter abnormalities, as measured by diffusion tensor imaging (DTI). CMI is also typically associated with pain, including occipital headache, but the relationship between pain symptoms and microstructure is not known. Eighteen CMI patients and 18 adult age- and education-matched control participants underwent DTI, were tested using digit symbol coding and digit span tasks, and completed a self-report measure of chronic pain. Tissue microstructure indices were used to examine microstructural abnormalities in CMI as compared with healthy controls. Group differences in DTI parameters were then reassessed after controlling for self-reported pain. Finally, DTI parameters were correlated with performance on the digit symbol coding and digit span tasks within each group. CMI patients exhibited greater fractional anisotropy (FA), lower radial diffusivity, and lower mean diffusivity in multiple brain regions compared with controls in diffuse white matter regions. Group differences no longer existed after controlling for self-reported pain. A significant correlation between FA and the Repeatable Battery for the Assessment of Neuropsychological Status coding performance was observed for controls but not for the CMI group. Diffuse microstructural abnormalities appear to be a feature of CMI, manifesting predominantly as greater FA and less diffusivity on DTI sequences. These white matter changes are associated with the subjective pain experience of CMI patients and may reflect reactivity to neuroinflammatory responses. However, this hypothesis will require further deliberate testing in future studies.

Missing the forest because of the trees: slower alternations during binocular rivalry are associated with lower levels of visual detail during ongoing thought.

Conscious awareness of the world fluctuates, either through variation in how vividly we perceive the environment, or when our attentional focus shifts away from information in the external environment towards information that we generate via imagination. Our study combined individual differences in experience sampling, psychophysical reports of perception and neuroimaging descriptions of structural connectivity to better understand these changes in conscious awareness. In particular, we examined (i) whether aspects of ongoing thought—indexed via multi-dimensional experience sampling during a sustained attention task—are associated with the white matter fibre organization of the cortex as reflected by their relative degree of anisotropic diffusion and (ii) whether these neurocognitive descriptions of ongoing experience are related to a more constrained measure of visual consciousness through analysis of bistable perception during binocular rivalry. Individuals with greater fractional anisotropy in right hemisphere white matter regions involving the inferior fronto-occipital fasciculus, the superior longitudinal fasciculus and the cortico-spinal tract, described their ongoing thoughts as lacking external details. Subsequent analysis indicated that the combination of low fractional anisotropy in these right hemisphere regions, with reports of thoughts with high levels of external details, was associated with the shortest periods of dominance during binocular rivalry. Since variation in binocular rivalry reflects differences between bottom-up and top-down influences on vision, our study suggests that reports of ongoing thoughts with vivid external details may occur when conscious precedence is given to bottom-up representation of perceptual information.

Association of iron levels in hair with brain structures and functions in young adults

BackgroundIron plays a critical role in normal brain functions and development, but it has also been known to have adverse neurological effects. MethodsHere, we investigated the associations of iron levels in hair with regional gray matter volume (rGMV), regional cerebral blood flow (rCBF), fractional anisotropy (FA), mean diffusivity (MD), and cognitive differences in a study cohort of 590 healthy young adults. ResultsOur findings showed that high iron levels were associated with lower rGMV in areas including the hippocampus, lower rCBF in the anterior and posterior parts of the brain, greater FA in areas including the part of the splenium of the corpus callosum, lower MD in the overlapping area including the splenium of the corpus callosum, as well as greater MD in the left hippocampus and areas including the frontal lobe. ConclusionThese results are compatible with the notion that iron plays diverse roles in neural mechanisms in healthy young adults.

Age-related differences in neural activation and functional connectivity during the processing of vocal prosody in adolescence.

The ability to recognize others' emotions based on vocal emotional prosody follows a protracted developmental trajectory during adolescence. However, little is known about the neural mechanisms supporting this maturation. The current study investigated age-related differences in neural activation during a vocal emotion recognition (ER) task. Listeners aged 8 to 19 years old completed the vocal ER task while undergoing functional magnetic resonance imaging. The task of categorizing vocal emotional prosody elicited activation primarily in temporal and frontal areas. Age was associated with a) greater activation in regions in the superior, middle, and inferior frontal gyri, b) greater functional connectivity between the left precentral and inferior frontal gyri and regions in the bilateral insula and temporo-parietal junction, and c) greater fractional anisotropy in the superior longitudinal fasciculus, which connects frontal areas to posterior temporo-parietal regions. Many of these age-related differences in brain activation and connectivity were associated with better performance on the ER task. Increased activation in, and connectivity between, areas typically involved in language processing and social cognition may facilitate the development of vocal ER skills in adolescence.

The Effects of Family Socioeconomic Status on Psychological and Neural Mechanisms as Well as Their Sex Differences.

Family socioeconomic status (SES) is an important factor that affects an individual’s neural and cognitive development. The two novel aims of this study were to reveal (a) the effects of family SES on mean diffusivity (MD) using diffusion tensor imaging given the characteristic property of MD to reflect neural plasticity and development and (b) the sex differences in SES effects. In a study cohort of 1,216 normal young adults, we failed to find significant main effects of family SES on MD; however, previously observed main effects of family SES on regional gray matter volume and fractional anisotropy (FA) were partly replicated. We found a significant effect of the interaction between sex and family income on MD in the thalamus as well as significant effects of the interaction between sex and parents’ educational qualification (year’s of education) on MD and FA in the body of the corpus callosum as well as white matter areas between the anterior cingulate cortex and lateral prefrontal cortex. These results suggest the sex-specific associations of family SES with neural and/or cognitive mechanisms particularly in neural tissues in brain areas that play key roles in basic information processing and higher-order cognitive processes in a way females with greater family SES level show imaging outcome measures that have been associated with more neural tissues (such as greater FA and lower MD) and males showed opposite.

Early breast milk exposure modifies brain connectivity in preterm infants

Preterm infants are at increased risk of alterations in brain structure and connectivity, and subsequent neurocognitive impairment. Breast milk may be more advantageous than formula feed for promoting brain development in infants born at term, but uncertainties remain about its effect on preterm brain development and the optimal nutritional regimen for preterm infants. We test the hypothesis that breast milk exposure is associated with improved markers of brain development and connectivity in preterm infants at term equivalent age.We collected information about neonatal breast milk exposure and brain MRI at term equivalent age from 47 preterm infants (mean postmenstrual age [PMA] 29.43 weeks, range 23.28–33.0). Network-Based Statistics (NBS), Tract-based Spatial Statistics (TBSS) and volumetric analysis were used to investigate the effect of breast milk exposure on white matter water diffusion parameters, tissue volumes, and the structural connectome.Twenty-seven infants received exclusive breast milk feeds for ≥75% of days of in-patient care and this was associated with higher connectivity in the fractional anisotropy (FA)-weighted connectome compared with the group who had < 75% of days receiving exclusive breast milk feeds (NBS, p = 0.04). Within the TBSS white matter skeleton, the group that received ≥75% exclusive breast milk days exhibited higher FA within the corpus callosum, cingulum cingulate gyri, centrum semiovale, corticospinal tracts, arcuate fasciculi and posterior limbs of the internal capsule compared with the low exposure group after adjustment for PMA at birth, PMA at image acquisition, bronchopulmonary dysplasia, and chorioamnionitis (p < 0.05). The effect on structural connectivity and tract water diffusion parameters was greater with ≥90% exposure, suggesting a dose effect. There were no significant groupwise differences in brain volumes.Breast milk feeding in the weeks after preterm birth is associated with improved structural connectivity of developing networks and greater FA in major white matter fasciculi.

White Matter Abnormalities in Never-Treated Patients With Long-Term Schizophrenia.

This study tested for differences of white matter integrity between treated and never-treated long-term schizophrenia patients, matched on illness duration, and for differential changes in relation to age in these two groups relative to healthy comparison subjects. This cross-sectional diffusion tensor imaging study included 31 never-treated and 46 matched antipsychotic-treated patients with long-term schizophrenia and 58 healthy comparison subjects. Fractional anisotropy measures of white matter tracts were extracted and compared. Linear regression analysis was used to explore the association between age and fractional anisotropy among the three groups. Fractional anisotropy significantly differed among the three groups in 14 of 20 white matter tracts defined in the Johns Hopkins University white matter template. Never-treated patients displayed greater reduction of fractional anisotropy than antipsychotic-treated patients in the left anterior thalamic radiation, the left cingulum-hippocampus pathway, the splenium and genu of the corpus callosum, and the left superior longitudinal fasciculus, and greater fractional anisotropy in the right uncinate fasciculus. Both patient groups showed multiple reductions relative to healthy comparison subjects. Never-treated patients showed an accelerated and clinically relevant age-related reduction of fractional anisotropy in the genu of the corpus callosum. These psychoradiological findings provide insight into the regional distribution of white matter deficits in the years after illness onset in long-term schizophrenia. Findings of greater impairments in never-treated patients, and a greater age-related reduction in the genu of the corpus callosum in these patients, suggest that long-term antipsychotic treatment does not adversely affect white matter tracts over the longer-term course of illness and may confer benefits.

Socioeconomic disparities in academic achievement: A multi-modal investigation of neural mechanisms in children and adolescents

Growing evidence suggests that childhood socioeconomic status (SES) influences neural development, which may contribute to the well-documented SES-related disparities in academic achievement. However, the particular aspects of SES that impact neural structure and function are not well understood. Here, we investigate associations of childhood SES and a potential mechanism—degree of cognitive stimulation in the home environment—with cortical structure, white matter microstructure, and neural function during a working memory (WM) task across development. Analyses included 53 youths (age 6–19 years). Higher SES as reflected in the income-to-needs ratio was associated with higher parent-reported achievement, WM performance, and cognitive stimulation in the home environment. Although SES was not significantly associated with cortical thickness, children raised in more cognitively stimulating environments had thicker cortex in the frontoparietal network and cognitive stimulation mediated the assocation between SES and cortical thickness in the frontoparietal network. Higher family SES was associated with white matter microstructure and neural activation in the frontoparietal network during a WM task, including greater fractional anisotropy (FA) in the right and left superior longitudinal fasciculi (SLF), and greater BOLD activation in multiple regions of the prefrontal cortex during WM encoding and maintenance. Greater FA and activation in these regions was associated higher parent-reported achievement. Together, cognitive stimulation, WM performance, FA in the SLF, and prefrontal activation during WM encoding and maintenance significantly mediated the association between SES and parent-reported achievement. These findings highlight potential neural, cognitive, and environmental mechanisms linking SES with academic achievement and suggest that enhancing cognitive stimulation in the home environment might be one effective strategy for reducing SES-related disparities in academic outcomes.

The lateralized arcuate fasciculus in developmental pitch disorders among mandarin amusics: left for speech and right for music.

The arcuate fasciculus (AF) is a neural fiber tract that is critical to speech and music development. Although the predominant role of the left AF in speech development is relatively clear, how the AF engages in music development is not understood. Congenital amusia is a special neurodevelopmental condition, which not only affects musical pitch but also speech tone processing. Using diffusion tensor tractography, we aimed at understanding the role of AF in music and speech processing by examining the neural connectivity characteristics of the bilateral AF among thirty Mandarin amusics. Compared to age- and intelligence quotient (IQ)-matched controls, amusics demonstrated increased connectivity as reflected by the increased fractional anisotropy in the right posterior AF but decreased connectivity as reflected by the decreased volume in the right anterior AF. Moreover, greater fractional anisotropy in the left direct AF was correlated with worse performance in speech tone perception among amusics. This study is the first to examine the neural connectivity of AF in the neurodevelopmental condition of amusia as a result of disrupted music pitch and speech tone processing. We found abnormal white matter structural connectivity in the right AF for the amusic individuals. Moreover, we demonstrated that the white matter microstructural properties of the left direct AF is modulated by lexical tone deficits among the amusic individuals. These data support the notion of distinctive pitch processing systems between music and speech.

Peripheral inflammatory markers indicate microstructural damage within periventricular white matter hyperintensities in Alzheimer's disease: A preliminary report

IntroductionWhite matter hyperintensities (WMH) presumed to reflect cerebral small vessel disease and increased peripheral inflammatory markers are found commonly in Alzheimer's disease (AD), but their interrelationships remain unclear. MethodsInflammatory markers were assayed in 54 elderly participants (n = 16 with AD). Periventricular WMH were delineated from T1, T2/proton density, and fluid-attenuated magnetic resonance imaging using semiautomated fuzzy lesion extraction and coregistered with maps of fractional anisotropy (FA), a measure of microstructural integrity assessed using diffusion tensor imaging. ResultsMean FA within periventricular WMH was associated with an inflammatory factor consisting of interleukin (IL)-1β, tumor necrosis factor, IL-10, IL-21, and IL-23 in patients with AD (ρ = −0.703, P = .002) but not in healthy elderly (ρ = 0.217, P = .190). Inflammation was associated with greater FA in deep WMH in healthy elderly (ρ = 0.425, P = .008) but not in patients with AD (ρ = 0.174, P = .520). DiscussionPeripheral inflammatory markers may be differentially related to microstructural characteristics within the white matter affected by cerebral small vessel disease in elders with and without AD.