Magnetic Resonance Imaging (MRI) Analysis of Tissue Sodium Concentration in Chronic Kidney Disease.

Human body sodium is regulated by the kidneys and extrarenal mechanisms. Stored skin and muscle tissue sodium accumulation is associated with kidney function decline, hypertension, and a pro-inflammatory and cardiovascular disease profile. In this chapter, we describe the use of sodium-hydrogen magnetic resonance imaging (23Na/1H MRI) to dynamically quantify tissue sodium concentration in the lower limb of humans. Real-time quantification of tissue sodium is calibrated against known sodium chloride aqueous concentrations. This method may be useful for investigating in vivo (patho-)physiological conditions associated with tissue sodium deposition and metabolism (including in relation to water regulation) to enlighten our understanding of sodium physiology.

Stroke population-specific neuroanatomical CT-MRI brain atlas.

PURPOSE: Development of a freely available stroke population-specific anatomical CT/MRI atlas with a reliable normalisation pipeline for clinical CT. METHODS: By reviewing CT scans in suspected stroke patients and filtering the AIBL MRI database, respectively, we collected 50 normal-for-age CT and MRI scans to build a standard-resolution CT template and a high-resolution MRI template. The latter was manually segmented into anatomical brain regions. We then developed and validated a MRI to CT registration pipeline to align the MRI atlas onto the CT template. Finally, we developed a CT-to-CT-normalisation pipeline and tested its reliability by calculating Dice coefficient (Dice) and Average Hausdorff Distance (AHD) for predefined areas in 100 CT scans from ischaemic stroke patients. RESULTS: The resulting CT/MRI templates were age and sex matched to a general stroke population (median age 71.9 years (62.1-80.2), 60% male). Specifically, this accounts for relevant structural changes related to aging, which may affect registration. Applying the validated MRI to CT alignment (Dice > 0.78, Average Hausdorff Distance < 0.59 mm) resulted in our final CT-MRI atlas. The atlas has 52 manually segmented regions and covers the whole brain. The alignment of four cortical and subcortical brain regions with our CT-normalisation pipeline was reliable for small/medium/large infarct lesions (Dice coefficient > 0.5). CONCLUSION: The newly created CT-MRI brain atlas has the potential to standardise stroke lesion segmentation. Together with the automated normalisation pipeline, it allows analysis of existing and new datasets to improve prediction tools for stroke patients (free download at https://forms.office.com/r/v4t3sWfbKs ).

Effects of a physical activity intervention on brain atrophy in older adults at risk of dementia: a randomized controlled trial.

Lack of physical activity is a risk factor for dementia, however, the utility of interventional physical activity programs as a protective measure against brain atrophy and cognitive decline is uncertain. Here we present the effect of a randomized controlled trial of a 24-month physical activity intervention on global and regional brain atrophy as characterized by longitudinal voxel-based morphometry with T1-weighted MRI images. The study sample consisted of 98 participants at risk of dementia, with mild cognitive impairment or subjective memory complaints, and having at least one vascular risk factor for dementia, randomized into an exercise group and a control group. Between 0 and 24 months, there was no significant difference detected between groups in the rate of change in global, or regional brain volumes.

Assessment of the DTI-ALPS Parameter Along the Perivascular Space in Older Adults at Risk of Dementia.

BACKGROUND AND PURPOSE: Recently, there has been growing interest in the glymphatic system (the functional waste clearance pathway for the central nervous system and its role in flushing solutes (such as amyloid ß and tau), metabolic, and other cellular waste products in the brain. Herein, we investigate a recent potential biomarker for glymphatic activity (the diffusion tensor imaging along the perivascular space [DTI-ALPS] parameter) using diffusion MRI imaging in an elderly cohort comprising 10 cognitively normal, 10 mild cognitive impairment (MCI), and 16 Alzheimer's disease (AD). METHODS: All 36 participants imaged on a Siemens 3.0T Tim Trio. Single-SE diffusion weighted Echo-planar imaging scans were acquired as well as T1 magnetization prepared rapid gradient echo, T2 axial, and susceptibility weighted imaging. Three millimeter regions of interest were drawn in the projection and association fibers adjacent to the medullary veins at the level of the lateral ventricle. The DTI-ALPS parameter was calculated in these regions and correlated with cognitive status, Mini-Mental State Examination (MMSE), and ADASCog11 measures. RESULTS: Significant correlations were found between DTI-ALPS and MMSE and ADASCog11 in the right hemisphere adjusting for age, sex, and APoE ε4 status. Significant differences were also found in the right DTI-ALPS indices between cognitively normal and AD groups (P < .026) and MCI groups (P < .025) in a univariate general linear model corrected for age, sex, and APoE ε4. Significant differences in apparent diffusion coefficient between cognitively normal and AD groups were found in the right projection fibers (P = .028). CONCLUSION: Further work is needed to determine the utility of DTI-ALPS index in larger elderly cohorts and whether it measures glymphatic activity.

Baseline White Matter Is Associated With Physical Fitness Change in Preclinical Alzheimer's Disease.

White matter (WM) microstructure is a sensitive marker to distinguish individuals at risk of Alzheimer's disease. The association of objective physical fitness (PF) measures and WM microstructure has not been explored and mixed results reported with physical activity (PA). Longitudinal studies of WM with PA and PF measures have had limited investigation. This study explored the relationship between objective PF measures over 24-months with "normal-appearing" WM microstructure. Data acquired on magnetic resonance imaging was used to measure "normal-appearing" WM microstructure at baseline and 24-months. Clinical variables such as cognitive and blood-based measures were collected longitudinally. Also, as part of the randomized controlled trial of a PA, extensive measures of PA and fitness were obtained over the 24 months. Bilateral corticospinal tracts (CST) and the corpus callosum showed a significant association between PF performance over 24-months and baseline WM microstructural measures. There was no significant longitudinal effect of the intervention or PF performance over 24-months. Baseline WM microstructural measures were significantly associated with PF performance over 24-months in this cohort of participants with vascular risk factors and at risk of Alzheimer's disease with distinctive patterns for each PF test.

Gradient of Tissue Injury after Stroke: Rethinking the Infarct versus Noninfarcted Dichotomy.

AIM: To evaluate the degree of variability in microstructural injury within and adjacent to regions identified as infarcted tissue using diffusion tensor imaging (DTI). METHODS: In this prospective longitudinal study, 18 patients presenting within 12 h of anterior circulation acute ischemic stroke who underwent CT perfusion (CTP) at baseline followed by fluid-attenuated inversion recovery (FLAIR) and DTI 1-month were analyzed. Four regions of interest (ROI) corresponding to the severity of hypoperfusion on CTP within and beyond the radiological infarct lesion defined on FLAIR were segmented. Fractional anisotropy (FA) and mean diffusivity (MD) were quantified for each ROI and compared to a mirror homologue in the contralateral hemisphere. Ipsilateral to contralateral FA and MD ratios were compared across ROIs. RESULTS: Lower FA and higher MD values were observed within both the infarct lesion and the peri-infarct tissue compared with their homologous contralateral brain regions (all comparisons p ≤ 0.01). No difference was observed in FA and MD between remote nonhypoperfused tissue and its contralateral homologous region (FA p = 0.42, MD p ≥ 0.99). The magnitude of asymmetry (ipsilateral/contralateral ratios) of FA and MD was greater with increasing severity of hypoperfusion in a dose-response pattern. Asymmetry greatest in the area of infarction with severe hypoperfusion, followed by infarction with moderate hypoperfusion, the peri-infarct hypoperfused tissue, and lastly the remote nonhypoperfused normal tissue (median on clustered quantile regression p ≤ 0.01). CONCLUSION: A gradient of microstructural injury corresponding to the severity of ischemic insult is present within and beyond conventionally defined infarct boundaries. The traditional dichotomized notion of infarcted versus noninfarcted tissue widely adopted in clinical research and in practice warrants reexamination.

Effect of a 24-month physical activity program on brain changes in older adults at risk of Alzheimer's disease: the AIBL active trial.

White matter hyperintensities (WMHs) are a risk factor for cognitive decline. Physical activity (PA) is associated with lower WMH. Whether long-term exposure to PA programs has beneficial effects on WMH progression in older adults with memory complaints and comorbid conditions has had limited exploration. This study explored whether a 24-month moderate-intensity PA intervention can delay the progression of WMH and hippocampus loss in older adults at risk for cognitive decline. Data acquired on magnetic resonance imaging were used to measure the progression of WMH and hippocampus loss. The results of this study showed no effect of intervention on either the primary outcome measure "WMH" or the secondary outcome measure "hippocampal volume." In addition, neither beta amyloid status nor the adherence to the intervention had any effect on the outcome. In this cohort of subjective memory complaints and mild cognitive impairment participants with vascular risk factors, there was no effect of long-term moderate-intensity PA on WMH or hippocampal loss.

Clinical Integration of Automated Processing for Brain Quantitative Susceptibility Mapping: Multi-Site Reproducibility and Single-Site Robustness.

BACKGROUND AND PURPOSE: Quantitative susceptibility mapping (QSM) of the brain has become highly reproducible and has applications in an expanding array of diseases. To translate QSM from bench to bedside, it is important to automate its reconstruction immediately after data acquisition. In this work, a server system that automatically reconstructs QSM and exchange images with the scanner using the DICOM standard is demonstrated using a multi-site, multi-vendor reproducibility study and a large, single-site, multi-scanner image quality review study in a clinical environment. METHODS: A single healthy subject was scanned with a 3D multi-echo gradient echo sequence at nine sites around the world using scanners from three manufacturers. A high-resolution (HiRes, .5 × .5 × 1 mm3 reconstructed) and standard-resolution (StdRes, .5 × .5 × 3 mm3 ) protocol was performed. ROI analysis of various white matter and gray matter regions was performed to investigate reproducibility across sites. At one institution, a retrospective multi-scanner image quality review was carried out of all clinical QSM images acquired consecutively in 1 month. RESULTS: Reconstruction times using a GPU were 29 ± 22 seconds (StdRes) and 55 ± 39 seconds (HiRes). ROI standard deviation across sites was below 24 ppb (StdRes) and 17 ppb (HiRes). Correlations between ROI averages across sites were on average .92 (StdRes) and .96 (HiRes). Image quality review of 873 consecutive patients revealed diagnostic or excellent image quality in 96% of patients. CONCLUSION: Online QSM reconstruction for a variety of sites and scanner platforms with low cross-site ROI standard deviation is demonstrated. Image quality review revealed diagnostic or excellent image quality in 96% of 873 patients.

Association between structural changes in brain with muscle function in sarcopenic older women: the women's healthy ageing project (WHAP).

OBJECTIVES: The involvement of changes in brain structure in the pathophysiology of muscle loss (sarcopenia) with aging remains unclear. In this study, we investigated the associations between brain structure and muscle strength in a group of older women. We hypothesized that structural changes in brain could correlate with functional changes observed in sarcopenic older women. METHODS: In 150 women (median age of 70 years) of the Women's Healthy Ageing Project (WHAP) Study, brain grey (total and cortex) volumes were calculated using magnetic resonance imaging (MRI) analyses. Grip strength and timed up and go (TUG) were measured. The brain volumes were compared between sarcopenic vs. non-sarcopenic subjects and women with previous falls vs. those without. RESULTS: Based on handgrip strength and TUG results respectively, 27% and 15% of women were classified as sarcopenic; and only 5% were sarcopenic based on both criteria. At least one fall was experienced by 15% of participants. There was no difference in brain volumetric data between those with vs. without sarcopenia (p>0.24) or between women with falls (as a symptom of weakness or imbalance) vs. those without history of falls (p>0.25). CONCLUSIONS: Brain structure was not associated with functional changes or falls in this population of older women.

Brain network changes and memory decline in aging.

One theory of age-related cognitive decline proposes that changes within the default mode network (DMN) of the brain impact the ability to successfully perform cognitive operations. To investigate this theory, we examined functional covariance within brain networks using regional cerebral blood flow data, measured by 15O-water PET, from 99 participants (mean baseline age 68.6 ± 7.5) in the Baltimore Longitudinal Study of Aging collected over a 7.4 year period. The sample was divided in tertiles based on longitudinal performance on a verbal recognition memory task administered during scanning, and functional covariance was compared between the upper (improvers) and lower (decliners) tertile groups. The DMN and verbal memory networks (VMN) were then examined during the verbal memory scan condition. For each network, group differences in node-to-network coherence and individual node-to-node covariance relationships were assessed at baseline and in change over time. Compared with improvers, decliners showed differences in node-to-network coherence and in node-to-node relationships in the DMN but not the VMN during verbal memory. These DMN differences reflected greater covariance with better task performance at baseline and both increasing and declining covariance with declining task performance over time for decliners. When examined during the resting state alone, the direction of change in DMN covariance was similar to that seen during task performance, but node-to-node relationships differed from those observed during the task condition. These results suggest that disengagement of DMN components during task performance is not essential for successful cognitive performance as previously proposed. Instead, a proper balance in network processes may be needed to support optimal task performance.

Peripheral sphingolipids are associated with variation in white matter microstructure in older adults.

Sphingolipids serve important structural and functional roles in cellular membranes and myelin sheaths. Plasma sphingolipids have been shown to predict cognitive decline and Alzheimer's disease. However, the association between plasma sphingolipid levels and brain white matter (WM) microstructure has not been examined. We investigated whether plasma sphingolipids (ceramides and sphingomyelins) were associated with magnetic resonance imaging-based diffusion measures, fractional anisotropy (FA), and mean diffusivity, 10.5 years later in 17 WM regions of 150 cognitively normal adults (mean age 67.2). Elevated ceramide species (C20:0, C22:0, C22:1, and C24:1) were associated with lower FA in multiple WM regions, including total cerebral WM, anterior corona radiata, and the cingulum of the cingulate gyrus. Higher sphingomyelins (C18:1 and C20:1) were associated with lower FA in regions such as the anterior corona radiata and body of the corpus callosum. Furthermore, lower sphingomyelin to ceramide ratios (C22:0, C24:0, and C24:1) were associated with lower FA or higher mean diffusivity in regions including the superior and posterior corona radiata. However, although these associations were significant at the a priori p < 0.05, only associations with some regional diffusion measures for ceramide C22:0 and sphingomyelin C18:1 survived correction for multiple comparisons. These findings suggest plasma sphingolipids are associated with variation in WM microstructure in cognitively normal aging.

Sleep Duration and Subsequent Cortical Thinning in Cognitively Normal Older Adults.

STUDY OBJECTIVES: To determine the association between self-reported sleep duration and cortical thinning among older adults. METHODS: We studied 122 cognitively normal participants in the Baltimore Longitudinal Study of Aging with a mean age = 66.6 y (range, 51-84) at baseline sleep assessment and 69.5 y (range, 56-86) at initial magnetic resonance imaging (MRI) scan. Participants reported average sleep duration and completed a mean of 7.6 1.5-T MRI scans (range, 3-11), with mean follow-up from initial scan of 8.0 y (range, 2.0-11.8). RESULTS: In analyses adjusted for age, sex, education, race, and interval between sleep assessment and initial MRI scan, participants reporting > 7 h sleep at baseline had thinner cortex in the inferior occipital gyrus and sulcus of the left hemisphere at initial MRI scan than those reporting 7 h (cluster P < 0.05). In adjusted longitudinal analyses, compared to those reporting 7 h of sleep, participants reporting < 7 h exhibited higher rates of subsequent thinning in the superior temporal sulcus and gyrus, inferior and middle frontal gyrus, and superior frontal sulcus of the left hemisphere, and in the superior frontal gyrus of the right hemisphere; those reporting > 7 h of sleep had higher rates of thinning in the superior frontal and middle frontal gyrus of the left hemisphere (cluster P < 0.05 for all). In sensitivity analyses, adjustment for apolipoprotein E (APOE) e4 genotype reduced or eliminated some effects but revealed others. When reports of < 7 h of sleep were compared to reports of 7 or 8 h combined, there were no significant associations with cortical thinning. CONCLUSIONS: Among cognitively normal older adults, sleep durations of < 7 h and > 7 h may increase the rate of subsequent frontotemporal gray matter atrophy. Additional studies, including those that use objective sleep measures and investigate mechanisms linking sleep duration to gray matter loss, are needed.

Lower gray matter integrity is associated with greater lap time variation in high-functioning older adults.

BACKGROUND: Lower integrity of cerebral gray matter is associated with higher gait variability. It is not known whether gray matter integrity is associated with higher lap time variation (LTV), a clinically accessible measure of gait variability, high levels of which have been associated with mortality. This study examines the cross-sectional association between gray matter mean diffusivity (MD) and LTV in community-dwelling older adults. METHODS: Study participants consisted of 449 high-functioning adults aged 50 and older (56.8% female) in the Baltimore Longitudinal Study of Aging, free of overt neurological disease. The magnitude of MD in the gray matter, a measure of impaired tissue integrity, was assessed by diffusion tensor imaging in 16 regions of interest (ROIs) involved with executive function, sensorimotor function, and memory. LTV was assessed as variability in lap time based on individual trajectories over ten 40-m laps. Age, sex, height, and weight were covariates. The model additionally adjusted for mean lap time and health conditions that may affect LTV. RESULTS: Higher levels of average MD across 16 ROIs were significantly associated with higher LTV after adjustment for covariates. Specifically, higher MD in the precuneus and the anterior and middle cingulate cortices was strongly associated with higher LTV, as compared to other ROIs. The association persisted after adjustment for mean lap time, hypertension, and diabetes. CONCLUSIONS: Lower gray matter integrity in selected areas may underlie greater LTV in high-functioning community-dwelling older adults. Longitudinal studies are warranted to examine whether changes in gray matter integrity precede more variable gait.

Diffusion Tensor Imaging Provides Evidence of Possible Axonal Overconnectivity in Frontal Lobes in Autism Spectrum Disorder Toddlers.

BACKGROUND: Theories of brain abnormality in autism spectrum disorder (ASD) have focused on underconnectivity as an explanation for social, language, and behavioral deficits but are based mainly on studies of older autistic children and adults. METHODS: In 94 ASD and typical toddlers ages 1 to 4 years, we examined the microstructure (indexed by fractional anisotropy) and volume of axon pathways using in vivo diffusion tensor imaging of fronto-frontal, fronto-temporal, fronto-striatal, and fronto-amygdala axon pathways, as well as posterior contrast tracts. Differences between ASD and typical toddlers in the nature of the relationship of age to these measures were tested. RESULTS: Frontal tracts in ASD toddlers displayed abnormal age-related changes with greater fractional anisotropy and volume than normal at younger ages but an overall slower than typical apparent rate of continued development across the span of years. Posterior cortical contrast tracts had few significant abnormalities. CONCLUSIONS: Frontal fiber tracts displayed deviant early development and age-related changes that could underlie impaired brain functioning and impact social and communication behaviors in ASD.

The effect of age and microstructural white matter integrity on lap time variation and fast-paced walking speed.

Macrostructural white matter damage (WMD) is associated with less uniform and slower walking in older adults. The effect of age and subclinical microstructural WM degeneration (a potentially earlier phase of WM ischemic damage) on walking patterns and speed is less clear. This study examines the effect of age on the associations of regional microstructural WM integrity with walking variability and speed, independent of macrostructural WMD. This study involved 493 participants (n = 51 young; n = 209 young-old; n = 233 old-old) from the Baltimore Longitudinal Study of Aging. All completed a 400-meter walk test and underwent a concurrent brain MRI with diffusion tensor imaging. Microstructural WM integrity was measured as fractional anisotropy (FA). Walking variability was measured as trend-adjusted variation in time over ten 40-meter laps (lap time variation, LTV). Fast-paced walking speed was assessed as mean lap time (MLT). Multiple linear regression models of FA predicting LTV and MLT were adjusted for age, sex, height, weight, and WM hyperintensities. Independent of WM hyperintensities, lower FA in the body of the corpus callosum was associated with higher LTV and longer MLT only in the young-old. Lower FA in superior longitudinal, inferior fronto-occipital, and uncinate fasciculi, the anterior limb of the internal capsule, and the anterior corona radiate was associated with longer MLT only in the young-old. While macrostructural WMD is known to predict more variable and slower walking in older adults, microstructural WM disruption is independently associated with more variable and slower fast-paced walking only in the young-old. Disrupted regional WM integrity may be a subclinical contributor to abnormal walking at an earlier phase of aging.

Region of interest correction factors improve reliability of diffusion imaging measures within and across scanners and field strengths.

Diffusion tensor imaging (DTI) measures are commonly used as imaging markers to investigate individual differences in relation to behavioral and health-related characteristics. However, the ability to detect reliable associations in cross-sectional or longitudinal studies is limited by the reliability of the diffusion measures. Several studies have examined the reliability of diffusion measures within (i.e. intra-site) and across (i.e. inter-site) scanners with mixed results. Our study compares the test-retest reliability of diffusion measures within and across scanners and field strengths in cognitively normal older adults with a follow-up interval less than 2.25 years. Intra-class correlation (ICC) and coefficient of variation (CoV) of fractional anisotropy (FA) and mean diffusivity (MD) were evaluated in sixteen white matter and twenty-six gray matter bilateral regions. The ICC for intra-site reliability (0.32 to 0.96 for FA and 0.18 to 0.95 for MD in white matter regions; 0.27 to 0.89 for MD and 0.03 to 0.79 for FA in gray matter regions) and inter-site reliability (0.28 to 0.95 for FA in white matter regions, 0.02 to 0.86 for MD in gray matter regions) with longer follow-up intervals were similar to earlier studies using shorter follow-up intervals. The reliability of across field strengths comparisons was lower than intra- and inter-site reliabilities. Within and across scanner comparisons showed that diffusion measures were more stable in larger white matter regions (>1500 mm(3)). For gray matter regions, the MD measure showed stability in specific regions and was not dependent on region size. Linear correction factor estimated from cross-sectional or longitudinal data improved the reliability across field strengths. Our findings indicate that investigations relating diffusion measures to external variables must consider variable reliability across the distinct regions of interest and that correction factors can be used to improve consistency of measurement across field strengths. An important result of this work is that inter-scanner and field strength effects can be partially mitigated with linear correction factors specific to regions of interest. These data-driven linear correction techniques can be applied in cross-sectional or longitudinal studies.

Evaluation of Atlas-Based White Matter Segmentation with Eve.

Multi-atlas labeling has come in wide spread use for whole brain labeling on magnetic resonance imaging. Recent challenges have shown that leading techniques are near (or at) human expert reproducibility for cortical gray matter labels. However, these approaches tend to treat white matter as essentially homogeneous (as white matter exhibits isointense signal on structural MRI). The state-of-the-art for white matter atlas is the single-subject Johns Hopkins Eve atlas. Numerous approaches have attempted to use tractography and/or orientation information to identify homologous white matter structures across subjects. Despite success with large tracts, these approaches have been plagued by difficulties in with subtle differences in course, low signal to noise, and complex structural relationships for smaller tracts. Here, we investigate use of atlas-based labeling to propagate the Eve atlas to unlabeled datasets. We evaluate single atlas labeling and multi-atlas labeling using synthetic atlases derived from the single manually labeled atlas. On 5 representative tracts for 10 subjects, we demonstrate that (1) single atlas labeling generally provides segmentations within 2mm mean surface distance, (2) morphologically constraining DTI labels within structural MRI white matter reduces variability, and (3) multi-atlas labeling did not improve accuracy. These efforts present a preliminary indication that single atlas labels with correction is reasonable, but caution should be applied. To purse multi-atlas labeling and more fully characterize overall performance, more labeled datasets would be necessary.

Longitudinal systolic blood pressure characteristics and integrity of white matter tracts in a cohort of very old black and white adults.

BACKGROUND: We sought to determine which systolic blood pressure (SBP) characteristics are associated with reduced brain integrity and whether these associations are stronger for white or gray matter. We hypothesized that exposure to higher and variable SBP will be associated with lower structural integrity of both gray and white matter. METHODS: Neuroimaging, SBP, and cognition were obtained in 311 community-dwelling adults in 2006-2008 (average age = 83 years; 58% women; 40% black). Antihypertensive medications, SBP, and health-related factors were collected from 1997 to 1998 to time of neuroimaging. SBP values obtained from 1997 to 1998 to time of neuroimaging were used to compute mean; pulse pressure; coefficient of variation; and peak, load, and group-based trajectories. RESULTS: Higher mean SBP was associated with lower white matter integrity in uncinate and superior lateral fasciculi bilaterally, independent of age, stroke history, antihypertensive medication use (odds ratio of having white matter hyperintensities greater than or equal to the median for 10mm Hg of SBP = 10.4, 95% confidence interval = 10.2-10.6, P = 0.0001; standardized beta for fractional anisotropy = -13.54, SE = 4.58, P = 0.003). These neuroimaging markers attenuated the association between higher SBP and lower digit symbol substitution test. Results were similar for trajectories of SBP and stronger for those with previously higher and variable SBP even if SBP was normal at neuroimaging. Results were similar for those without stroke. Associations with gray matter measures were not significant. CONCLUSIONS: If confirmed, these data suggest a history of higher and variable SBP for very old adults may be useful to alert clinicians to potential lower integrity in selected tracts, whereas cross-sectional SBP measurements may obscure the risk of underlying white matter hyperintensities. Whether lowering and/or stabilizing SBP levels in very old adults without a remarkable cardiovascular history would have neuroprotective effects and reduce dementia risk needs further study.

Multimodal MRI markers support a model of small vessel ischemia for depressive symptoms in very old adults.

In older adults, depressive symptoms are associated with lower quality of life, high morbidity and mortality. This study aims to identify brain magnetic resonance imaging (MRI) features associated with late-life depressive symptoms in the population. Older community-dwelling adults (n=314) from the Health ABC study underwent brain MRI. Logistic regression was used to characterize the relationships between depressive symptoms (Center for Epidemiologic Studies of Depression scale, CES-D) and the following whole-brain variables: white matter hyperintensity (WMH) burden, fractional anisotropy (FA), and gray matter volume (GMV). Analyses examining possible regional differences between the CES-D groups controlled for Modified Mini-Mental State Examination score and diabetes status. The relative importance of localization of the markers was examined by comparing the distribution of significant peaks across the brain. Each whole-brain variable showed loss of integrity associated with high CES-D. For GMV, the odds ratio (OR)=0.84 (95% confidence interval (CI) 0.74, 0.96); for FA, OR=0.714 (95% CI 0.57, 0.88); for WMH, OR=1.89 (95%CI 1.33, 2.69). Voxel-wise analyses and patterns of peak significance showed non-specific patterns for white matter measures. Loss of GMV was most significant in the bilateral insula and anterior cingulate cortex. This study supports a cerebrovascular pattern for depressive symptoms in older adults. The localization of gray matter changes to the insula, a watershed area and a hub of affective circuits, suggests an etiological pathway from ischemia to increased depressive burden.