The Relationship Between Health-Related Quality of Life and Lower-Extremity Visuomotor Reaction Time in Young Adult Women Following Ankle Sprain.

CONTEXT: Many individuals who sustain a lateral ankle sprain (LAS) fail to return to prior activity due to residual symptoms; and report elevated levels of injury-related fear, decreased function, and decreased health-related quality of life (HRQOL). Additionally, individuals with history of LAS exhibit deficits in neurocognitive functional measures like visuomotor reaction time (VMRT), which contributes to worse patient-reported outcome scores. The aim of this study was to examine the relationship between HRQOL and lower-extremity (LE) VMRT in individuals with LAS history. DESIGN: Cross-sectional. METHODS: Young adult female volunteers with history of LAS (n = 22; age = 24 [3.5] y; height = 163.1 [9.8] cm; mass = 65.1 [11.5] kg; and time since last LAS = 67.8 [50.5] mo) completed HRQOL outcomes including the following: (1) Tampa Scale of Kinesiophobia-11, (2) Fear-Avoidance Beliefs Questionnaire, (3) Penn State Worry Questionnaire, (4) modified Disablement in the Physically Active Scale, and (5) Foot and Ankle Disability Index (FADI). Additionally, participants completed a LE-VMRT task by responding to a visual stimulus using their foot to deactivate light sensors. Participants completed trials bilaterally. Separate Spearman rho correlations were performed to assess the relationship between patient-reported outcomes assessing constructs of HRQOL and LE-VRMT bilaterally. Significance was set at P < .05. RESULTS: There was a strong, significant negative correlation between FADI-Activities of Daily Living (ρ = -.68; P = .002) and FADI-Sport (ρ = -.76; P = .001) scores and injured limb LE-VMRT; moderate, significant negative correlations between the uninjured limb LE-VMRT and FADI-Activities of Daily Living (ρ = -.60; P = .01) and FADI-Sport (ρ = -.60; P = .01) scores; and moderate, significant positive correlations between the injured limb LE-VMRT and modified Disablement in the Physically Active Scale-Physical Summary Component (ρ = .52; P = .01) and modified Disablement in the Physically Active Scale-Total (ρ = .54; P = .02) scores. All other correlations were not statistically significant. CONCLUSIONS: Young adult women with history of LAS demonstrated an association between self-reported constructs of HRQOL and LE-VMRT. As LE-VMRT is a modifiable injury risk factor, future studies should examine the effectiveness of interventions designed to improve LE-VMRT and the impact on self-reported HRQOL.

Resting state functional connectivity responses post-mild traumatic brain injury: a systematic review.

Mild traumatic brain injuries (mTBI) are associated with functional network connectivity alterations throughout recovery. Yet, little is known about the adaptive or maladaptive nature of post-mTBI connectivity and which networks are predisposed to altered function and adaptation. The objective of this review was to determine functional connectivity changes post-mTBI and to determine the adaptive or maladaptive nature of connectivity through direct comparisons of connectivity and behavioral data. Literature was systematically searched and appraised for methodological quality. A total of 16 articles were included for review. There was conflicting evidence of post-mTBI connectivity responses as decreased connectivity was noted in 4 articles, 6 articles reported increased connectivity, 5 reported a mixture of increased and decreased connectivity, while 1 found no differences in connectivity. Supporting evidence for adaptive post-mTBI increases in connectivity were found, particularly in the frontoparietal, cerebellar, and default mode networks. Although initial results are promising, continued longitudinal research that systematically controls for confounding variables and that standardizes methodologies is warranted to adequately understand the neurophysiological recovery trajectory of mTBI.

Bend Don't Break: Stretching Improves Scores on a Battery of Fall Assessment Tools in Older Adults.

CONTEXT: Falls and loss of autonomy are often attributed in large part to musculoskeletal impairments in later adulthood. Age-related declines in flexibility contribute to late adulthood musculoskeletal impairment. The novel sitting-rising test has been proposed to be a quick, effective screening of musculoskeletal fitness, fall risk, and all-cause mortality in older adults. The timed up and go and 5 times sit-to-stand tests are two of the 3 most evidence-supported performance measures to assess fall risk. OBJECTIVE: This study aimed to determine if 5 weeks of flexibility training could increase sitting-rising test, timed up and go, and 5 times sit-to-stand scores in community-dwelling older adults. PARTICIPANTS: Forty-seven adults aged 60 years and older (mean age = 66.7 y, SD = 4.1) participated in this study. Participants completed a static stretching protocol consisting of 3 weekly 1-hour stretching sessions. RESULTS: The protocol improved flexibility as seen in sit-and-reach scores and improved scores on all outcome variables. Specifically, there was a significant increase in sitting-rising test scores from preintervention (M = 7.45, SD = 1.45) to postintervention (M = 8.04, SD = 1.36), t(42) = -5.21, P < .001. Timed up and go scores demonstrated a significant decrease from preintervention (M = 8.85, SD = 1.32) to postintervention (M = 8.20, SD = 1.35), t(46) = 5.10, P < .001. Five times sit-to-stand scores demonstrated a significant decrease from preintervention (M = 12.57, SD = 2.68) to postintervention (M = 10.46, SD = 2.06), t(46) = 6.62, P < .001. Finally, significant increases in sit-and-reach scores were associated with improved functional performance (r = -.308, P = .03). CONCLUSION: Findings suggest that flexibility training can be an effective mode of low-level exercise to improve functional outcomes. Static stretching may help to improve musculoskeletal health, promote autonomy, and decrease mortality in community-dwelling older adults.

Dynamic range of frontoparietal functional modulation is associated with working memory capacity limitations in older adults.

Older adults tend to over-activate regions throughout frontoparietal cortices and exhibit a reduced range of functional modulation during WM task performance compared to younger adults. While recent evidence suggests that reduced functional modulation is associated with poorer task performance, it remains unclear whether reduced range of modulation is indicative of general WM capacity-limitations. In the current study, we examined whether the range of functional modulation observed over multiple levels of WM task difficulty (N-Back) predicts in-scanner task performance and out-of-scanner psychometric estimates of WM capacity. Within our sample (60-77years of age), age was negatively associated with frontoparietal modulation range. Individuals with greater modulation range exhibited more accurate N-Back performance. In addition, despite a lack of significant relationships between N-Back and complex span task performance, range of frontoparietal modulation during the N-Back significantly predicted domain-general estimates of WM capacity. Consistent with previous cross-sectional findings, older individuals with less modulation range exhibited greater activation at the lowest level of task difficulty but less activation at the highest levels of task difficulty. Our results are largely consistent with existing theories of neurocognitive aging (e.g. CRUNCH) but focus attention on dynamic range of functional modulation asa novel marker of WM capacity-limitations in older adults.

Cardiorespiratory fitness modifies the relationship between myocardial function and cerebral blood flow in older adults.

A growing body of evidence indicates that cardiorespiratory fitness attenuates some age-related cerebral declines. However, little is known about the role that myocardial function plays in this relationship. Brain regions with high resting metabolic rates, such as the default mode network (DMN), may be especially vulnerable to age-related declines in myocardial functions affecting cerebral blood flow (CBF). This study explored the relationship between a measure of myocardial mechanics, global longitudinal strain (GLS), and CBF to the DMN. In addition, we explored how cardiorespiratory affects this relationship. Participants were 30 older adults between the ages of 59 and 69 (mean age=63.73years, SD=2.8). Results indicated that superior cardiorespiratory fitness and myocardial mechanics were positively associated with DMN CBF. Moreover, results of a mediation analysis revealed that the relationship between GLS and DMN CBF was accounted for by individual differences in fitness. Findings suggest that benefits of healthy heart function to brain function are modified by fitness.

Reduced frontal cortex efficiency is associated with lower white matter integrity in aging.

Increased frontal cortex activation during cognitive task performance is common in aging but remains poorly understood. Here we explored patterns of age-related frontal brain activations under multiple task performance conditions and their relationship to white matter (WM) microstructure. Groups of younger (N = 28) and older (N = 33) participants completed a task-switching paradigm while functional magnetic resonance imaging (fMRI) was performed, and rested while diffusion tensor imaging was performed. Results from fMRI analyses indicated age-related increases in frontal brain activations under conditions of poorer performance in the older group (the nonswitch and switch conditions) and for a contrast in which behavioral performance was equated (older group nonswitch condition vs. younger group switch condition). Within the older adult group, higher frontal activation was associated with poorer behavioral performance under all task conditions. In 2 regions in right frontal cortex, blood oxygen level-dependent (BOLD) magnitudes were negatively correlated with WM integrity in tracts connecting these structures with other task-relevant frontoparietal and striatal regions. Our results link age-related declines in the efficiency of frontal cortex functioning with lower WM integrity in aging.

Lifelong bilingualism maintains neural efficiency for cognitive control in aging.

Recent behavioral data have shown that lifelong bilingualism can maintain youthful cognitive control abilities in aging. Here, we provide the first direct evidence of a neural basis for the bilingual cognitive control boost in aging. Two experiments were conducted, using a perceptual task-switching paradigm, including a total of 110 participants. In Experiment 1, older adult bilinguals showed better perceptual switching performance than their monolingual peers. In Experiment 2, younger and older adult monolinguals and bilinguals completed the same perceptual task-switching experiment while functional magnetic resonance imaging (fMRI) was performed. Typical age-related performance reductions and fMRI activation increases were observed. However, like younger adults, bilingual older adults outperformed their monolingual peers while displaying decreased activation in left lateral frontal cortex and cingulate cortex. Critically, this attenuation of age-related over-recruitment associated with bilingualism was directly correlated with better task-switching performance. In addition, the lower blood oxygenation level-dependent response in frontal regions accounted for 82% of the variance in the bilingual task-switching reaction time advantage. These results suggest that lifelong bilingualism offsets age-related declines in the neural efficiency for cognitive control processes.

Contralateral thalamocortical connectivity is related to postural control in the uninvolved limb of older adults with history of ankle sprain.

BACKGROUND: Sensorimotor brain connectivity is often overlooked when determining relationships between postural control and motor performance following musculoskeletal injury. Thalamocortical brain connectivity is of particular interest as it represents the temporal synchrony of functionally and anatomically linked brain regions. Importantly, adults over the age of 60 are especially vulnerable to musculoskeletal injury due to age-related declines in postural control and brain connectivity. RESEARCH QUESTION: Is there a relationship between thalamocortical connectivity and static postural control in older adults with a history of LAS? METHODS: Data were analyzed from twenty older adults (mean age = 67.0 ± 4.3 yrs; 13 females) with a history of LAS. The sensorimotor network (SMN) was identified from resting-state MRI data, and a priori thalamic and postcentral gyri regions of interest were selected in order to determine left and right hemisphere thalamocortical connectivity. Balance was assessed for the involved and non-involved limbs via center of pressure velocity (COPV) in the medial-lateral (ML) and anterior-posterior (AP) directions. RESULTS: Contralateral thalamocortical connectivity was significantly associated with COPV_ML COPV_ML (r = -0.474, P = 0.05) and COPV_AP (r = -0.622, P = 0.008) in the non-involved limb. No significant association was observed between involved limb balance and contralateral thalamocortical connectivity (COPV_ML: r = -0.08, P = 0.77; COPV_AP: r = 0.12, P = 0.63). SIGNIFICANCE: A significant relationship between thalamocortical connectivity and static postural control was observed in the non-involved, but not the involved limb in older adults with a history of LAS. Findings suggest that thalamocortical connectivity may lead to or be the product of LAS.

White matter integrity and vulnerability to Alzheimer's disease: preliminary findings and future directions.

Neuroimaging biomarkers that precede cognitive decline have the potential to aid early diagnosis of Alzheimer's disease (AD). A body of diffusion tensor imaging (DTI) work has demonstrated declines in white matter (WM) microstructure in AD and its typical prodromal state, amnestic mild cognitive impairment. The present review summarizes recent evidence suggesting that WM integrity declines are present in individuals at high AD-risk, prior to cognitive decline. The available data suggest that AD-risk is associated with WM integrity declines in a subset of tracts showing decline in symptomatic AD. Specifically, AD-risk has been associated with WM integrity declines in tracts that connect gray matter structures associated with memory function. These tracts include parahippocampal WM, the cingulum, the inferior fronto-occipital fasciculus, and the splenium of the corpus callosum. Preliminary evidence suggests that some AD-risk declines are characterized by increases of radial diffusivity, raising the possibility that a myelin-related pathology may contribute to AD onset. These findings justify future research aimed at a more complete understanding of the neurobiological bases of DTI-based declines in AD. With continued refinement of imaging methods, DTI holds promise as a method to aid identification of presymptomatic AD. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.

Common and distinct mechanisms of cognitive flexibility in prefrontal cortex.

The human ability to flexibly alternate between tasks represents a central component of cognitive control. Neuroimaging studies have linked task switching with a diverse set of prefrontal cortex (PFC) regions, but the contributions of these regions to various forms of cognitive flexibility remain largely unknown. Here, subjects underwent functional brain imaging while they completed a paradigm that selectively induced stimulus, response, or cognitive set switches in the context of a single task decision performed on a common set of stimuli. Behavioral results indicated comparable reaction time costs associated with each switch type. Domain-general task-switching activation was observed in the inferior frontal junction and posterior parietal cortex, suggesting core roles for these regions in switching such as updating and representing task sets. In contrast, multiple domain-preferential PFC activations were observed across lateral and medial PFC, with progressively more rostral regions recruited as switches became increasingly abstract. Specifically, highly abstract cognitive set switches recruited anterior-PFC regions, moderately abstract response switches recruited mid-PFC regions, and highly constrained stimulus switches recruited posterior-PFC regions. These results demonstrate a functional organization across lateral and medial PFC according to the level of abstraction associated with acts of cognitive flexibility.

Cardiorespiratory fitness is positively correlated with cerebral white matter integrity in healthy seniors.

High cardiorespiratory fitness (CRF) is an important protective factor reducing the risk of cardiac-related disability and mortality. Recent research suggests that high CRF also has protective effects on the brain's macrostructure and functional response. However, little is known about the potential relationship between CRF and the brain's white matter (WM) microstructure. This study explored the relationship between a comprehensive measure of CRF (VO(2) peak, total time on treadmill, and 1-minute heart rate recovery) and multiple diffusion tensor imaging measures of WM integrity. Participants were 26 healthy community dwelling seniors between the ages of 60 and 69 (mean=64.79 years, SD=2.8). Results indicated a positive correlation between comprehensive CRF and fractional anisotropy (FA) in a large portion of the corpus callosum. Both VO(2) peak and total time on treadmill contributed significantly to explaining the variance in mean FA in this region. The CRF-FA relationship observed in the corpus callosum was primarily characterized by a negative correlation between CRF and radial diffusivity in the absence of CRF correlations with either axial diffusivity or mean diffusivity. Tractography results demonstrated that portions of the corpus callosum associated with CRF primarily involved those interconnecting frontal regions associated with high-level motor planning. These results suggest that high CRF may attenuate age-related myelin declines in portions of the corpus callosum that interconnect homologous premotor cortex regions involved in motor planning.

Domain general and domain preferential brain regions associated with different types of task switching: a meta-analysis.

One of our highest evolved functions as human beings is our capacity to switch between multiple tasks effectively. A body of research has identified a distributed frontoparietal network of brain regions which contribute to task switching. However, relatively less is known about whether some brain regions may contribute to switching in a domain-general manner while others may be more preferential for different kinds of switching. To explore this issue, we conducted three meta-analyses focusing on different types of task switching frequently used in the literature (perceptual, response, and context switching), and created a conjunction map of these distinct switch types. A total of 36 switching studies with 562 activation coordinates were analyzed using the activation likelihood estimation method. Common areas associated with switching across switch type included the inferior frontal junction and posterior parietal cortex. In contrast, domain-preferential activation was observed for perceptual switching in the dorsal portion of the premotor cortex and for context switching in frontopolar cortex. Our results suggest that some regions within the frontoparietal network contribute to domain-general switching processes while others contribute to more domain-preferential processes, according to the type of task switch performed.

Feasibility of Contrasting Brain Connectivity Patterns in Cognitive and Motor Cerebral Networks to Clinical Outcomes in Patients Surviving Acute Respiratory Failure: A Pilot Study.

BACKGROUND: There is a paucity of research regarding the feasibility and association of cerebral cortex function to patient outcomes after acute respiratory failure (ARF). PURPOSE: To determine the feasibility of functional connectivity measures and examine the association of functional connectivity to a multifaceted battery of outcomes in survivors of ARF. METHODS: Eight ARF patients (age:58±3.7, ICU days:10.4±8.6) completed functional magnetic resonance imaging (fMRI), cognitive, physical-function, anxiety, depression, and driving simulator tests at one month post-hospital discharge. Pearson's correlations assessed the relationship between functional connectivity within the default mode network (FPN), sensorimotor network (SMN), and frontoparietal network (FPN) to outcomes. RESULTS: Low physical-function (r=0.75, p=0.03) and divided-attention (r=-0.86, p=0.03) during the driving simulator task correlated with low FPN connectivity. Low SMN connectivity demonstrated relationships to slower gait speed (r=0.82, p=0.01) and low short physical performance battery (SPPB) scores (r=0.81, p=0.01). CONCLUSIONS: fMRI is feasible to assess ARF patients' post-ICU limitations, as low post-ARF brain connectivity may be linked to low physical function, providing potential development of therapeutic interventions.

Cardiorespiratory fitness diminishes the effects of age on white matter hyperintensity volume.

White matter hyperintensities (WMHs) are among the most commonly observed marker of cerebrovascular disease. Age is a key risk factor for WMH development. Cardiorespiratory fitness (CRF) is associated with increased vessel compliance, but it remains unknown if high CRF affects WMH volume. This study explored the effects of CRF on WMH volume in community-dwelling older adults. We further tested the possibility of an interaction between CRF and age on WMH volume. Participants were 76 adults between the ages of 59 and 77 (mean age = 65.36 years, SD = 3.92) who underwent a maximal graded exercise test and structural brain imaging. Results indicated that age was a predictor of WMH volume (beta = .32, p = .015). However, an age-by-CRF interaction was observed such that higher CRF was associated with lower WMH volume in older participants (beta = -.25, p = .040). Our findings suggest that higher levels of aerobic fitness may protect cerebrovascular health in older adults.

Health-Related Quality of Life Among Middle-Aged Adults With Chronic Ankle Instability, Copers, and Uninjured Controls.

CONTEXT: People with chronic ankle instability (CAI) display a lower regional and global health-related quality of life (HRQoL). Examinations of HRQoL outcomes associated with CAI have addressed younger adults, restricting our understanding of the long-term consequences of CAI. OBJECTIVE: To compare ankle regional and global HRQoL in middle-aged participants with and those without CAI. DESIGN: Cross-sectional study. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 59 middle-aged volunteers, consisting of 18 with CAI (age = 50.2 ± 9.3 years), 17 who were ankle-sprain copers (age = 54.5 ± 8.7 years), and 24 uninjured controls (age = 56.7 ± 10.0 years). MAIN OUTCOME MEASURE(S): Participants completed the Foot and Ankle Disability Index (FADI) and the Patient-Reported Outcomes Measurement Information System Adult Profile. Regional HRQoL was assessed using the FADI Activities of Daily Living and Sport subscales. Global HRQoL was measured using the 43-item Patient-Reported Outcomes Measurement Information System Adult Profile, which contains 7 short forms-Physical Function, Pain Interference, Fatigue, Depression, Sleep Disturbance, Anxiety, and Ability to Participate in Social Roles and Activities. Separate Kruskal-Wallis tests were used to determine between-groups differences. RESULTS: Middle-aged participants with CAI had lower scores on both subscales of the FADI than the coper and control groups (all P values <.001). Participants with CAI scored lower on the Physical Function (U = 116.0, z = -2.78, P = .005) and Ability to Participate in Social Roles and Activities (U = 96.0, z = -3.09, P = .002) subscales but higher on the Pain Interference (U = 144.0, z = -2.36, P = .02), Fatigue (U = 110.0, z = -2.72, P = .006), and Depression (U = 110.5, z = -2.91, P = .004) subscales than the control group. Participants with CAI also scored lower on the Physical Function (U = 74.5, z = -2.79, P = .005) and Ability to Participate in Social Roles and Activities (U = 55.0, z = -3.29, P = .001) subscales but higher on the Fatigue (U = 90.0, z = -2.09, P = .04) and Depression (U = 96.5, z = -1.97, P = .048) subscales than the coper group. CONCLUSIONS: Middle-aged participants with CAI displayed worse ankle regional and global HRQoL than their age-matched healthy counterparts and copers. These results demonstrated that CAI can affect HRQoL outcomes in middle-aged adults.

Decreased ankle and hip isometric peak torque in young and middle-aged adults with chronic ankle instability.

OBJECTIVES: To compare ankle, knee and hip isometric peak torque between young and middle-aged adults with CAI, copers and un-injured controls. DESIGN: Cross-sectional. SETTING: Research Laboratory. PARTICIPANTS: One hundred fifty-six young and middle-aged adults with or without CAI volunteered. MAIN OUTCOME MEASURES: A handheld dynamometer measured isometric dorsiflexion, plantarflexion, knee extension, hip extension and hip abduction peak force during a 5 s trial. Average peak torque was calculated and normalized to body mass. RESULTS: A significant Age by Injury interaction for dorsiflexion suggest middle-aged un-injured controls (p < 0.001) and copers (p < 0.001) had lower isometric peak torque compared to their young adult counterparts, but there were no differences between young and middle-aged adults with CAI (p > 0.05). Significant Injury main effects suggest the CAI group had decreased plantarflexion (p = 0.004) and hip extension (p = 0.010) strength compared to un-injured controls, but not copers (p > 0.05). Significant Age main effects for all primary outcome measures were observed, indicating peak torque decreased with age (p < 0.05). CONCLUSIONS: Regardless of age, isometric ankle and hip peak torque was lower in participants with CAI compared to un-injured controls, but not copers. These findings provide further evidence towards the impact of CAI in both young and middle-aged adults.

Decreased dynamic balance and dorsiflexion range of motion in young and middle-aged adults with chronic ankle instability.

OBJECTIVES: The purpose of this study was to compare dynamic balance and weight-bearing dorsiflexion range of motion between young and middle-aged adults with and without chronic ankle instability. DESIGN: Cross-sectional. METHODS: One hundred and two young adults were classified as either having chronic ankle instability (n = 38), coper (n = 27) or a healthy-control (n = 37). A total of 55 middle-aged adults were identified as having chronic ankle instability (n = 16), coper (n = 15) or a healthy-control (n = 24). Participants completed the weight-bearing lunge test and the anterior, posteromedial and posterolateral reach directions of the star excursion balance test. RESULTS: Middle-aged adults had shorter reach distances for each direction of the star excursion balance test compared to the young adults (p < 0.001). Regardless of age, participants with chronic ankle instability performed worse on the star excursion balance test compared to the coper (p < 0.05) and healthy-control group (p < 0.05). Similarly, participants with chronic ankle instability had less dorsiflexion compared to healthy-controls (p < 0.05), but not the coper group (p > 0.05). CONCLUSIONS: Deficits in dynamic postural control do not continue to decline with advancing age in individuals with chronic ankle instability, however, these impairments appear to continue to persist compared to uninjured controls.

Non-fasting High-Density Lipoprotein Is Associated With White Matter Microstructure in Healthy Older Adults.

A growing body of evidence indicates that biomarkers of cardiovascular risk may be related to cerebral health. However, little is known about the role that non-fasting lipoproteins play in assessing age-related declines in a cerebral biomarker sensitive to vascular compromise, white matter (WM) microstructure. High-density lipoprotein cholesterol (HDL-C) is atheroprotective and low-density lipoprotein cholesterol (LDL-C) is a major atherogenic lipoprotein. This study explored the relationships between non-fasting levels of cholesterol and WM microstructure in healthy older adults. A voxelwise and region of interest approach was used to determine the relationship between cholesterol and fractional anisotropy (FA). Participants included 87 older adults between the ages of 59 and 77 (mean age = 65.5 years, SD = 3.9). Results indicated that higher HDL-C was associated with higher FA in diffuse regions of the brain when controlling for age, sex, and body mass index (BMI). HDL-C was also positively associated with FA in the corpus callosum and fornix. No relationship was observed between LDL-C and FA. Findings suggest that a modifiable lifestyle variable associated with cardiovascular health may help to preserve cerebral WM.

Distinct White Matter Changes Associated with Cerebrospinal Fluid Amyloid-ß1-42 and Hypertension.

BACKGROUND: Alzheimer's disease (AD) pathology and hypertension (HTN) are risk factors for development of white matter (WM) alterations and might be independently associated with these alterations in older adults. OBJECTIVE: To evaluate the independent and synergistic effects of HTN and AD pathology on WM alterations. METHODS: Clinical measures of cerebrovascular disease risk were collected from 62 participants in University of Kentucky Alzheimer's Disease Center studies who also had cerebrospinal fluid (CSF) sampling and MRI brain scans. CSF Aß1-42 levels were measured as a marker of AD, and fluid-attenuated inversion recovery imaging and diffusion tensor imaging were obtained to assess WM macro- and microstructural properties. Linear regression analyses were used to assess the relationships among WM alterations, cerebrovascular disease risk, and AD pathology. Voxelwise analyses were performed to examine spatial patterns of WM alteration associated with each pathology. RESULTS: HTN and CSF Aß1-42 levels were each associated with white matter hyperintensities (WMH). Also, CSF Aß1-42 levels were associated with alterations in normal appearing white matter fractional anisotropy (NAWM-FA), whereas HTN was marginally associated with alterations in NAWM-FA. Linear regression analyses demonstrated significant main effects of HTN and CSF Aß1-42 on WMH volume, but no significant HTN×CSF Aß1-42 interaction. Furthermore, voxelwise analyses showed unique patterns of WM alteration associated with hypertension and CSF Aß1-42. CONCLUSION: Associations of HTN and lower CSF Aß1-42 with WM alteration were statistically and spatially distinct, suggesting independent rather than synergistic effects. Considering such spatial distributions may improve diagnostic accuracy to address each underlying pathology.

Endothelial Function Is Associated with White Matter Microstructure and Executive Function in Older Adults.

Age-related declines in endothelial function can lead to cognitive decline. However, little is known about the relationships between endothelial function and specific neurocognitive functions. This study explored the relationship between measures of endothelial function (reactive hyperemia index; RHI), white matter (WM) health (fractional anisotropy, FA, and WM hyperintensity volume, WMH), and executive function (Trail Making Test (TMT); Trail B - Trail A). Participants were 36 older adults between the ages of 59 and 69 (mean age = 63.89 years, SD = 2.94). WMH volume showed no relationship with RHI or executive function. However, there was a positive relationship between RHI and FA in the genu and body of the corpus callosum. In addition, higher RHI and FA were each associated with better executive task performance. Tractography was used to localize the WM tracts associated with RHI to specific portions of cortex. Results indicated that the RHI-FA relationship observed in the corpus callosum primarily involved tracts interconnecting frontal regions, including the superior frontal gyrus (SFG) and frontopolar cortex, linked with executive function. These findings suggest that superior endothelial function may help to attenuate age-related declines in WM microstructure in portions of the corpus callosum that interconnect prefrontal brain regions involved in executive function.