Measures Of White Matter Hyperintensities Research Articles

Amyloid-PET and White Matter Hyperintensities Have Independent Effects on Baseline Cognitive Function and Synergistic Effects on Longitudinal Executive Function.

Co-occurrence of beta amyloid (Aβ) and white matter hyperintensities (WMHs) increase the risk of dementia and both are considered biomarkers of preclinical dementia. Moderation and mediation modeling were used to define the interplay between global and regional Aβ and WMHs measures in relation to executive function (EF) and memory composite scores outcomes at baseline and after approximately 2 years across a sample of 714 clinically normal participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI 2). The moderation regression analysis showed additive effects of Aβ and WMHs over baseline memory and EF scores (p = 0.401 and 0.061, respectively) and synergistic effects over follow-up EF (p < 0.05). Through mediation analysis, the data presented demonstrate that WMHs effects, mediated by global and regional amyloid burden, are responsible for baseline cognitive performance deficits in memory and EF. These findings suggest that Aβ and WMHs contribute to baseline cognition independently while WMHs volumes exert effects on baseline cognitive performance directly and through influences on Aβ accumulation.

Actigraphy-estimated physical activity is associated with functional and structural brain connectivity among older adults

Higher physical activity levels are associated with reduced cognitive decline among older adults; however, current understanding of underlying brain mechanisms is limited. This cross-sectional study investigated the relationship between actigraphy-estimated total volume of physical activity (TVPA) and magnetic resonance imaging (MRI) measures of white matter hyperintensities (WMH), and functional and structural brain connectivity, measured by resting-state functional MRI and diffusion tensor imaging. Study participants (N = 156, mean age = 71 years) included 136 with normal cognition and 20 with Mild Cognitive Impairment. Higher TVPA was associated with greater functional connectivity within the default-mode network and greater network modularity (a measure of network specialization), as well as with greater anisotropy and lower radial diffusion in white matter, suggesting better structural connectivity. These associations with functional and structural connectivity were independent of one another and independent of the level of vascular risk, APOE-ε4 status, cognitive reserve, and WMH volume, which were not associated with TVPA. Findings suggest that physical activity is beneficial for brain connectivity among older individuals with varying levels of risk for cognitive decline.

Treatment response in late-life depression: the absence of a relationship with white matter hyperintensity volume, executive functioning, and processing speed

Treatment response in late-life depression: the absence of a relationship with white matter hyperintensity volume, executive functioning, and processing speed

Right hemispheric white matter hyperintensities improve the prediction of spatial neglect severity in acute stroke

White matter hyperintensities (WMH) are frequently observed in brain scans of elderly people. They are associated with an increased risk of stroke, cognitive decline, and dementia. However, it is unknown yet if measures of WMH provide information that improve the understanding of poststroke outcome compared to only state-of-the-art stereotaxic structural lesion data.We implemented high-dimensional machine learning models, based on support vector regression, to predict the severity of spatial neglect in 103 acute right hemispheric stroke patients.We found that (1) the additional information of right hemispheric or bilateral voxel-based topographic WMH extent indeed yielded a significant improvement in predicting acute neglect severity (compared to the voxel-based stroke lesion map alone). (2) Periventricular WMH appeared more relevant for prediction than deep subcortical WMH. (3) Among different measures of WMH, voxel-based maps as measures of topographic extent allowed more accurate predictions compared to the use of traditional ordinally assessed visual rating scales (Fazekas-scale, Cardiovascular Health Study-scale).In summary, topographic WMH appear to be a valuable clinical imaging biomarker for predicting the severity of cognitive deficits and bears great potential for rehabilitation guidance of acute stroke patients.

White Matter Hyperintensities Quantification in Healthy Adults: A Systematic Review and Meta-Analysis.

Although white matter hyperintensities (WMH) volumetric assessment is now customary in research studies, inconsistent WMH measures among homogenous populations may prevent the clinical usability of this biomarker. To determine whether a point estimate and reference standard for WMH volume in the healthy aging population could be determined. Systematic review and meta-analysis. In all, 9716 adult subjects from 38 studies reporting WMH volume were retrieved following a systematic search on EMBASE. 1.0T, 1.5T, or 3.0T/fluid-attenuated inversion recovery (FLAIR) and/or proton density/T2 -weighted fast spin echo sequences or gradient echo T1 -weighted sequences. After a literature search, sample size, demographics, magnetic field strength, MRI sequences, level of automation in WMH assessment, study population, and WMH volume were extracted. The pooled WMH volume with 95% confidence interval (CI) was calculated using the random-effect model. The I2 statistic was calculated as a measure of heterogeneity across studies. Meta-regression analysis of WMH volume on age was performed. Of the 38 studies analyzed, 17 reported WMH volume as the mean and standard deviation (SD) and were included in the meta-analysis. Mean and SD of age was 66.11 ± 10.92 years (percentage of men 50.45% ± 21.48%). Heterogeneity was very high (I2 =99%). The pooled WMH volume was 4.70 cm3 (95% CI: 3.88-5.53 cm3 ). At meta-regression analysis, WMH volume was positively associated with subjects' age (β=0.358 cm3 per year, P < 0.05, R2 =0.27). The lack of standardization in the definition of WMH together with the high technical variability in assessment may explain a large component of the observed heterogeneity. Currently, volumes of WMH in healthy subjects are not comparable between studies and an estimate and reference interval could not be determined. 1 TECHNICAL EFFICACY STAGE: 1.

Cognitive reserve and rate of change in Alzheimer's and cerebrovascular disease biomarkers among cognitively normal individuals

We examined whether cognitive reserve (CR) impacts level of, or rate of change in, biomarkers of Alzheimer's disease (AD) and small-vessel cerebrovascular disease in >250 individuals who were cognitively normal and middle-aged and older at the baseline. The four primary biomarker categories commonly examined in studies of AD were measured longitudinally: cerebrospinal fluid measures of amyloid (A) and tau (T); cerebrospinal fluid and neuroimaging measures of neuronal injury (N); and neuroimaging measures of white matter hyperintensities (WMHs) to assess cerebrovascular pathology (V). CR was indexed by a composite score including years of education, reading, and vocabulary test performance. Higher CR was associated with lower levels of WMHs, particularly among those who subsequently progressed from normal cognition to MCI. CR was not associated with WMH trajectories. In addition, CR was not associated with either levels of, or rate of change in, A/T/N biomarkers. This may suggest that higher CR is associated with lifestyle factors that reduce levels of cerebrovascular disease, allowing individuals with higher CR to better tolerate other types of pathology.

Global Burden of Small Vessel Disease-Related Brain Changes on MRI Predicts Cognitive and Functional Decline.

Background and Purpose- Cerebral small vessel disease is characterized by a wide range of focal and global brain changes. We used a magnetic resonance imaging segmentation tool to quantify multiple types of small vessel disease-related brain changes and examined their individual and combined predictive value on cognitive and functional abilities. Methods- Magnetic resonance imaging scans of 560 older individuals from LADIS (Leukoaraiosis and Disability Study) were analyzed using automated atlas- and convolutional neural network-based segmentation methods yielding volumetric measures of white matter hyperintensities, lacunes, enlarged perivascular spaces, chronic cortical infarcts, and global and regional brain atrophy. The subjects were followed up with annual neuropsychological examinations for 3 years and evaluation of instrumental activities of daily living for 7 years. Results- The strongest predictors of cognitive performance and functional outcome over time were the total volumes of white matter hyperintensities, gray matter, and hippocampi (P<0.001 for global cognitive function, processing speed, executive functions, and memory and P<0.001 for poor functional outcome). Volumes of lacunes, enlarged perivascular spaces, and cortical infarcts were significantly associated with part of the outcome measures, but their contribution was weaker. In a multivariable linear mixed model, volumes of white matter hyperintensities, lacunes, gray matter, and hippocampi remained as independent predictors of cognitive impairment. A combined measure of these markers based on Z scores strongly predicted cognitive and functional outcomes (P<0.001) even above the contribution of the individual brain changes. Conclusions- Global burden of small vessel disease-related brain changes as quantified by an image segmentation tool is a powerful predictor of long-term cognitive decline and functional disability. A combined measure of white matter hyperintensities, lacunar, gray matter, and hippocampal volumes could be used as an imaging marker associated with vascular cognitive impairment.

The relationship between white matter hyperintensities and cognitive reference abilities across the life span

We examined the relationship between white matter hyperintensities (WMH) burden and performance on 4 reference abilities: episodic memory, perceptual speed, fluid reasoning, and vocabulary. Cross-sectional data of 486 healthy adults from 20 to 80 years old enrolled in an ongoing longitudinal study were analyzed. A piecewise regression across age identified an inflection point at 43 years old, where WMH total volume began to increase with age. Subsequent analyses focused on participants above that age (N = 351). WMH total volume had significant inverse correlations with perceptual speed and memory. Regional measures of WMH showed inverse correlations with all reference abilities. We performed principal component analysis of the regional WMH data to create a model of principal components regression. Parietal WMH regional volume burden mediated the relationship between age and perceptual speed in simple and multiple mediation models. The principal components regression pattern associated with perceptual speed also mediated the relationship between age and perceptual speed performance. These results across the extended adult life span help clarify the influence of WMH on cognitive aging.

Medial temporal lobe atrophy is independently associated with behavioural and psychological symptoms in Alzheimer's disease.

Evidence describing the contribution of cerebral white matter disease and medial temporal atrophy (MTA) to behavioural and psychological symptoms of dementia (BPSD) has been conflicting. The aim of this study was to assess the relationship of white matter hyperintensities (WMH) and MTA observed on magnetic resonance imaging with BPSD among patients with Alzheimer's disease. In a cross-sectional study of a prospective cohort of patients attending a memory clinic, 46 patients with probable Alzheimer's disease (mean age: 72.38 ± 7.05 years) were studied. Sociodemographic, cognitive, and BPSD data were collected. BPSD were assessed using the Neuropsychiatric Inventory. Magnetic resonance imaging, WMH, and MTA were rated using the Scheltens scales for the assessment of signal hyperintensities and atrophy of medial temporal lobes. For multivariate analysis, two binary logistic regression analyses were carried out, with presence or absence of each BPSD as the dependent variable and with WMH or MTA as the predictor variable. Results of the logistic regression were analyzed to see if the significance of the WMH or MTA score was maintained in a model that factored in other possible confounding variables identified in univariate analysis. The results of binary logistic regression analysis showed that in models that accounted for confounding variables, increased total MTA was significantly associated with apathy (odds ratio = 1.605, adjusted P = 0.042) and disinhibition (odds ratio = 0.607, adjusted P = 0.042). WMH measures did not significantly predict any BPSD item. These findings indicate that MTA potentially contributes to the aetiology of BPSD, and they provide evidence to support the hypothesis that Alzheimer's disease pathology itself can contribute to BPSD.

Visual Rating Scales of White Matter Hyperintensities and Atrophy: Comparison of Computed Tomography and Magnetic Resonance Imaging

GoalMagnetic resonance imaging (MRI) is the preferred modality for research on structural age-related brain changes. However, computed tomography (CT) is widely available and has practical and cost advantages over MRI for large-scale brain imaging research studies in acutely unwell patients. However, the relationships between MRI and CT measures of white matter hyperintensities (WMH) and atrophy are unclear. We examined the relationships between visual ratings of WMH, atrophy, and old infarcts in patients who had both CT and MRI scans.Materials and MethodsPatients who had both CT and MRI scans in the International Stroke Trial-3 were studied. In both modalities, 2 raters independently completed standardized visual rating scales for WMH, and for central and superficial atrophy using a 5-point scale. In addition, 1 rater recorded old infarcts according to size and location.FindingsSeventy patients with a mean age of 69 years were studied. There were moderate to substantial intrarater CT–MRI agreements for periventricular components of WMH scales (weighted Κappa = .55-.75). Agreements for basal ganglia ratings were lower (weighted Κappa = .18-.44), partly because of the misclassification of prominent perivascular spaces. Atrophy scales showed moderate to substantial CT–MRI agreements (weighted Κappa = .44-.70). MRI was more sensitive in the detection of smaller infarcts and cavitated lesions.ConclusionsStandardized visual rating scales of white matter lesions and atrophy mostly show substantial agreement between CT and MRI. Clinical CT scans have a strong potential for wider exploitation in research studies, particularly in acutely unwell populations.

Race-Ethnicity and Cerebral Small Vessel Disease – Comparison between Chinese and White Populations

Studies in stroke patients suggest that lacunar stroke and intracerebral hemorrhage might be more common in Chinese than Whites. We hypothesized that other manifestations of subclinical cerebral small vessel disease, namely white matter hyperintensities (WMH), lacunes, and microbleeds, are also more common in Chinese than Whites. We compared the community prevalence of these lesions between Han Chinese and White Australians. Magnetic resonance imaging (1·5-Tesla) was performed on participants of the Shanghai Aging Study (n = 321, mean age 69 ± 6 years) and Tasmanian Study of Cognition and Gait (n = 397, mean age 72 ± 7 years). A single-rater recorded measures of WMH, lacunes, and microbleeds. We compared lesion prevalence between age- and gender-matched subgroups from the two cohorts. Among all subjects (n = 718), we performed multivariable logistic regression to examine if race-ethnicity was independently associated with these lesions. Among age- and gender-matched subjects, confluent WMH were significantly more prevalent in Chinese (38·5%) than Whites (28·4%; P = 0·01). There was no difference in the prevalence of lacunes (Chinese 29·1% vs. Whites 29·5%, P = 0·93) and microbleeds (Chinese 10·1% vs. 9·0%, P = 0·67) between Chinese and Whites. In multivariable logistic regression, Chinese ethnicity was associated with confluent WMH (odds ratio 1·7, 95% confidence interval 1·1-2·6, P = 0·01), but no differences were seen for lacunes and microbleeds. The association between Chinese ethnicity with confluent WMH became insignificant when subjects with history of stroke were excluded. In this population-based cross-national comparison, Han Chinese had a higher prevalence of confluent WMH than White Australians, but had a similar prevalence of lacunes and microbleeds.

Reconsidering harbingers of dementia: progression of parietal lobe white matter hyperintensities predicts Alzheimer's disease incidence

Accumulating evidence implicates small vessel cerebrovascular disease, visualized as white matter hyperintensities (WMH) on T2-weighted magnetic resonance imaging, in the pathogenesis and diagnosis of Alzheimer's disease (AD). Cross-sectional volumetric measures of WMH, particularly in the parietal lobes, are associated with increased risk of AD. In the present study, we sought to determine whether the longitudinal regional progression of WMH predicts incident AD above-and-beyond traditional radiological markers of neurodegeneration (i.e., hippocampal atrophy and cortical thickness). Three hundred three nondemented older adults (mean age = 79.24 ± 5.29) received high-resolution magnetic resonance imaging at baseline and then again 4.6 years (standard deviation = 1.01) later. Over the follow-up interval 26 participants progressed to AD. Using structural equation modeling, we calculated latent difference scores of parietal and nonparietal WMH, hippocampus volumes, and cortical thickness values in AD-related regions. Within the structural equation modeling framework, we determined whether baseline or change scores or both predicted AD conversion, while controlling for several time-invariant relevant variables. Smaller baseline hippocampus volume, change in hippocampus volume (i.e., atrophy), higher baseline parietal lobe WMH, and increasing parietal lobe WMH volume but not WMH in other regions or measures of cortical thickness, independently predicted progression to AD. The findings provide strong evidence that regionally accumulating WMH predict AD onset in addition to hallmark neurodegenerative changes typically associated with AD.

THE IMPACT OF FIBER-TRACT-SPECIFIC WHITE MATTER HYPERINTENSITIES ON RESTING STATE FUNCTIONAL CONNECTIVITY IN ALZHEIMER'S DISEASE

White matter hyperintensities (WMH), a marker of small vessel disease, are common in Alzheimer's disease (AD) and global measures of WMH have been associated with increased neurodegeneration (MRI atrophy, FDG-PET hypometabolism). However, the impact of local WMH onto neural network function in AD remains unclear. The current study aimed to test the association between WMH within particular fiber tracts of the default mode network (DMN) and resting state fMRI based functional connectivity (FC) within the DMN. We hypothesized that higher WMH volume in a particular DMN fiber tract is associated with reduced functional connectivity between those brain areas that the fiber tract connects. Patients with AD dementia (N=22), and subjects at high risk of AD, i.e. mild cognitive impairment (MCI, N=40) and healthy controls (HC, N=14) with abnormally high brain levels of beta-amyloid (as measured by AV45-PET (>1.11)) were included from the data bank of the Alzheimer's Disease Neuroimaging Initiative (ADNI). WMH were segmented in a semi-automated way, from MRI FLAIR images. The ratio of WMH within each tract was determined (WMH-ratio), in selected DMN fiber tracts including the inferior fronto-occipital fasciculus (IFOF), cingulum, cingulum-hippocampal and superior longitudinal fasciculus (plus temporal branch). To identify areas of significant FC within the DMN, independent component analysis (ICA) was applied to the resting state fMRI scans. FC ROI was defined as the overlap between the grey matter area surrounding the specific DMN fiber tract terminal and the ICA-DMN map. In a linear regression analysis, tract specific WMH ratio was tested as a predictor of the tract's FC ROI value, controlled for age, global AV45-PET, diagnosis and education in the pooled group. Higher WMH ratio in the IFOF was associated with decreased FC in the medial prefrontal cortex and the angular gyrus ROIs (t(73) = -2.295, p = .02) across all subjects. The WMH ratios in other tracts of the DMN were not associated with FC. The results suggest that WMH disrupt functional connectivity in a fiber-tract specific way, independent from beta-amyloid. Future research needs to address whether WMH in particular neural networks are associated with specific cognitive deficits.

Vascular risk factors, large-artery atheroma, and brain white matter hyperintensities.

Objective:To determine the magnitude of potentially causal relationships among vascular risk factors (VRFs), large-artery atheromatous disease (LAD), and cerebral white matter hyperintensities (WMH) in 2 prospective cohorts.Methods:We assessed VRFs (history and measured variables), LAD (in carotid, coronary, and leg arteries), and WMH (on structural MRI, visual scores and volume) in: (a) community-dwelling older subjects of the Lothian Birth Cohort 1936, and (b) patients with recent nondisabling stroke. We analyzed correlations, developed structural equation models, and performed mediation analysis to test interrelationships among VRFs, LAD, and WMH.Results:In subjects of the Lothian Birth Cohort 1936 (n = 881, mean age 72.5 years [SD ±0.7 years], 49% with hypertension, 33% with moderate/severe WMH), VRFs explained 70% of the LAD variance but only 1.4% to 2% of WMH variance, of which hypertension explained the most. In stroke patients (n = 257, mean age 74 years [SD ±11.6 years], 61% hypertensive, 43% moderate/severe WMH), VRFs explained only 0.1% of WMH variance. There was no direct association between LAD and WMH in either sample. The results were the same for all WMH measures used.Conclusions:The small effect of VRFs and LAD on WMH suggests that WMH have a large “nonvascular,” nonatheromatous etiology. VRF modification, although important, may be limited in preventing WMH and their stroke and dementia consequences. Investigation of, and interventions against, other suspected small-vessel disease mechanisms should be addressed.

Processing speed in normal aging: Effects of white matter hyperintensities and hippocampal volume loss

ABSTRACTChanges in cognitive functioning are said to be part of normal aging. Quantitative MRI has made it possible to measure structural brain changes during aging which may underlie these decrements which include slowed information processing and memory loss. Much has been written on white matter hyperintensities (WMH), which are associated with cognitive deficits on tasks requiring processing speed and executive functioning, and hippocampal volume loss, which is associated with memory decline. Here we examine volumetric MRI measures of WMH and hippocampal volume loss together in relation to neuropsychological tests considered to be measures of executive functioning and processing speed in 81 non-demented elderly individuals, aged 75–90. Correlational analysis showed that when controlling for age, both greater WMH volume and smaller hippocampal volume were correlated with slower performances on most tests with the exception of a battery of continuous performance tests in which only WMH was correlated with slower reaction time (RT). We then performed a series of hierarchical multiple regression analyses to examine the independent contributions of greater WMH volume and reduced hippocampal volume to executive functioning and processing speed. The results showed that for the four measures requiring executive functioning and speed of processing, WMH volume and hippocampal volume combined predicted between 21.4% and 37% of the explained variance. These results suggest that WM integrity and hippocampal volume influence cognitive decline independently on tasks involving processing speed and executive function independent of age.

Regional White Matter Hyperintensity Volume, Not Hippocampal Atrophy, Predicts Incident Alzheimer Disease in the Community

BACKGROUND New-onset Alzheimer disease (AD) is often attributed to degenerative changes in the hippocampus. However, the contribution of regionally distributed small vessel cerebrovascular disease, visualized as white matter hyperintensities (WMHs) on magnetic resonance imaging, remains unclear. OBJECTIVE To determine whether regional WMHs and hippocampal volume predict incident AD in an epidemiological study. DESIGN A longitudinal community-based epidemiological study of older adults from northern Manhattan, New York. SETTING The Washington Heights/Inwood Columbia Aging Project. PARTICIPANTS Between 2005 and 2007, 717 participants without dementia received magnetic resonance imaging scans. A mean (SD) of 40.28 (9.77) months later, 503 returned for follow-up clinical examination and 46 met criteria for incident dementia (45 with AD). Regional WMHs and relative hippocampal volumes were derived. Three Cox proportional hazards models were run to predict incident dementia, controlling for relevant variables. The first included all WMH measurements; the second included relative hippocampal volume; and the third combined the 2 measurements. MAIN OUTCOME MEASURE Incident AD. RESULTS White matter hyperintensity volume in the parietal lobe predicted time to incident dementia (hazard ratio [HR]=1.194; P=.03). Relative hippocampal volume did not predict incident dementia when considered alone (HR=0.419; P=.77) or with the WMH measures included in the model (HR=0.302; P=.70). Including hippocampal volume in the model did not notably alter the predictive utility of parietal lobe WMHs (HR=1.197; P=.049). CONCLUSIONS The findings highlight the regional specificity of the association of WMHs with AD. It is not clear whether parietal WMHs solely represent a marker for cerebrovascular burden or point to distinct injury compared with other regions. Future work should elucidate pathogenic mechanisms linking WMHs and AD pathology.

Coronary Artery Disease Is Associated with Cognitive Decline Independent of Changes on Magnetic Resonance Imaging in Cognitively Normal Elderly Adults

To examine in cognitively normal elderly adults whether vascular factors predict cognitive decline and whether these associations are mediated by magnetic resonance imaging (MRI) measures of subclinical vascular brain injury. Prospective multisite longitudinal study of subcortical ischemic vascular diseases. Memory and aging centers in California. Seventy-four participants who were cognitively normal at entry and underwent at least two neuropsychological evaluations and two MRI examinations over an average follow-up of 6.9 years. Item response theory was used to create composite scores of global, verbal memory, and executive functioning. Volumetric MRI measures included white matter hyperintensities (WMHs), silent brain infarcts (SBIs), hippocampus, and cortical gray matter (CGM). Linear mixed-effects models were used to examine the associations between vascular factors, MRI measures, and cognitive scores. History of coronary artery disease (CAD) was associated with greater declines in global cognition, verbal memory, and executive function. The CAD associations remained after controlling for changes in WMHs, SBIs, and hippocampal and CGM volumes. History of CAD may be a surrogate marker for clinically significant atherosclerosis, which also affects the brain. Structural MRI measures of WMHs and SBIs do not fully capture the potential adverse effects of atherosclerosis on the brain. Future longitudinal studies of cognition should incorporate direct measures of atherosclerosis in cerebral arteries, as well as more sensitive neuroimaging measures.

Childhood intelligence and brain white matter hyperintensities predict fluid intelligence age 78–81 years: a 1921 Aberdeen birth cohort study

to evaluate the role of childhood intelligence and white matter hyperintensities (WMH) in the prediction of the trajectory of fluid intelligence in healthy old people from age 78 to 81. observational follow-up study from 1999 to 2002. a university teaching hospital in Aberdeen, UK. a total of 106 volunteers born in 1921, with childhood intelligence records at 11, recruited 1997-98 to a follow-up study. participants underwent brain MRI in 1999-2000, to obtain measurements of brain WMH using Scheltens' scale and a test of fluid intelligence (Raven's Progressive Matrices) on three occasions between 1999 and 2002. in a latent growth model, we found a significant association between childhood intelligence and the intercept, but not the slope, of fluid cognitive ability in late adulthood. Similarly, baseline WMH score was associated with the intercept of late life cognitive ability, but not the slope. Age at imaging was associated with slope but not intercept. There was no significant association between sex and intercept or slope of late life cognitive ability. results suggest that brain MRI measures of WMH (attributed to cerebrovascular disease) and childhood intelligence significantly contribute to late life fluid cognitive ability but not to the trajectory of age-related change in fluid intelligence. We also show that age is associated with the cognitive trajectory from 78 to 81 years, even within our narrow age range sample. This may be a consequence of the recruitment pattern, with those having greater WMH burden, and who subsequently declined, being recruited later in the study.

Longitudinal Changes in White Matter Disease and Cognition in the First Year of the Alzheimer Disease Neuroimaging Initiative

To evaluate relationships between magnetic resonance imaging (MRI)-based measures of white matter hyperintensities (WMHs), measured at baseline and longitudinally, and 1-year cognitive decline using a large convenience sample in a clinical trial design with a relatively mild profile of cardiovascular risk factors. Convenience sample in a clinical trial design. A total of 804 participants in the Alzheimer Disease Neuroimaging Initiative who received MRI scans, cognitive testing, and clinical evaluations at baseline, 6-month follow-up, and 12-month follow-up visits. For each scan, WMHs were detected automatically on coregistered sets of T1, proton density, and T2 MRI images using a validated method. Mixed-effects regression models evaluated relationships between risk factors for WMHs, WMH volume, and change in outcome measures including Mini-Mental State Examination (MMSE), Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and Clinical Dementia Rating Scale sum of boxes scores. Covariates in these models included race, sex, years of education, age, apolipoprotein E genotype, baseline clinical diagnosis (cognitively normal, mild cognitive impairment, or Alzheimer disease), cardiovascular risk score, and MRI-based hippocampal and brain volumes. Higher baseline WMH volume was associated with greater subsequent 1-year increase in ADAS-Cog and decrease in MMSE scores. Greater WMH volume at follow-up was associated with greater ADAS-Cog and lower MMSE scores at follow-up. Higher baseline age and cardiovascular risk score and more impaired baseline clinical diagnosis were associated with higher baseline WMH volume. White matter hyperintensity volume predicts 1-year cognitive decline in a relatively healthy convenience sample that was similar to clinical trial samples, and therefore should be considered as a covariate of interest at baseline and longitudinally in future AD treatment trials.

The Impact of Subcortical White Matter Disease on Mood in Euthymic Older Adults: A Diffusion Tensor Imaging Study

Clinical depression in the elderly is associated with cerebral small vessel disease. It is less certain whether the endorsement of depressive symptoms in the absence of clinical depression, relatively common in euthymic older adults, is also associated with white matter damage. The majority of studies exploring this issue have produced mixed results, perhaps due, in part, to differences in defining the threshold for depression, notating vascular risk factors, and/or the neuroimaging tools used to quantify white matter damage. We aimed to address these issues with non-demented euthymic older adults. We performed diffusion tensor imaging (DTI) and T2-weighted magnetic resonance imaging (MRI) in a population based cohort of 79 individuals (mean age = 68 years). In addition to neuroimaging, the authors report assessments of overall cognition, executive functioning, and depression. Scores on the Geriatric Depression Scale 15-item (GDS-15) correlated with DTI measures of mean diffusivity (r [77] = 0.23, p = 0.039) and fractional anisotropy (r [77] = -0.22, p = 0.045) but only approached significance for T2-weighted MRI measures of white matter hyperintensities (WMH; r [77] = 0.21, p = 0.053). After adjusting for factors known to influence the development of WMH and depression, including age and vascular risks, DTI-derived indices of white matter integrity remained significantly associated with GDS-15 scores. Furthermore, only DTI-derived measures of white matter integrity contributed to the variance in GDS-15 scores in logistical regression modeling. These findings demonstrate an association between white matter damage and the endorsement of depressive symptoms in euthymic older adults and suggest that DTI may be more sensitive to this damage than T2-WMH in an aging cohort with multiple vascular risk factors.