Larger White Matter Lesion Volume Research Articles

White Matter Lesion Asymmetry: A Potential Indicator of Amyloid Positivity in Patients with Mild Cognitive Impairment

AbstractBackgroundAssessing amyloid‐positivity in patients with mild cognitive impairment (MCI) is crucial as amyloid‐positive individuals have a higher risk of dementia conversion than amyloid‐negative patients. This study aimed to investigate whether the asymmetry of white matter lesions (WML) on T2‐fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI), measured by artificial intelligence (AI) hyperintensity segmentation, could be a potential indicator for amyloid positron emission tomography (PET) positivity in patients with MCI.MethodThis retrospective cohort study included MCI patients who visited the memory clinic of Yeouido St. Mary’s Hospital. All participants underwent a set of clinical and neuropsychological assessments, brain MRI, and amyloid PET using [18F]‐Flutemetamol. Our in‐house AI software was utilized on paired T1 and T2‐FLAIR MRIs to process to segment and separate WML into left and right hemispheres. From the processed segmentation, we measured the subjects' individual WML differences through a volumetric assessment.ResultsTotal 122 subjects were enrolled in this study. By the amyloid‐PET positivity, 53 and 69 patients were in the amyloid‐negative and amyloid‐positive groups, respectively. The two groups were comparable with no significant differences of age (p = 0.189), sex (p = 0.057), education years (p = 0.411) and MMSE scores (p = 0.861). However, the amyloid‐positive group had a significantly higher frequency of having an e4 allele of APOE genotype (p = 0.033) and Clinical Dementia Rating scale (p = 0.024). The average volume between hemispheres significantly differed in the amyloid‐negative group (p = 0.020) but not in the amyloid‐positive group (p = 0.220). Both groups had a larger WML volume in the left hemisphere, which did not differ significantly between groups.ConclusionOur findings suggest that evaluating the asymmetry of WML rather than the total hyperintensity lesion load is necessary in MCI patients, particularly in those without amyloid pathology. In conclusion, WML asymmetry may serve as a potential indicator of amyloid positivity in MCI patients.

Posttraumatic Stress Symptoms After Stroke: The Effects of Anatomy and Coping Style.

Posttraumatic stress disorder (PTSD) can be triggered by life-threatening medical emergencies, such as stroke. Data suggest that up to 25% of stroke survivors will develop PTSD symptomatology, but little is known about predisposing factors. We sought to examine whether neuroimaging measures and coping styles are related to PTSD symptoms after stroke. Participants were survivors of first-ever, mild-moderate ischemic stroke, or transient ischemic attack from the TABASCO study (Tel Aviv Brain Acute Stroke Cohort). All participants underwent a 3T magnetic resonance imaging at baseline and were examined 6, 12, and 24 months thereafter, using neurological, neuropsychological, and functional evaluations. At baseline, coping styles were evaluated by a self-reported questionnaire. PTSD symptoms were assessed using the PTSD checklist. Data were available for 436 patients. Forty-eight participants (11%) developed probable PTSD (PTSD checklist ≥44) during the first year after the stroke/transient ischemic attack. Stroke was more likely to cause PTSD than transient ischemic attack. Stroke severity, larger white matter lesion volume, and worse hippocampal connectivity were associated with PTSD severity, while infarct volume or location was not. In a multivariate analysis, high-anxious and defensive coping styles were associated with a 6.66-fold higher risk of developing poststroke PTSD ([95% CI, 2.08-21.34]; P<0.01) compared with low-anxious and repressive coping styles, after adjusting for age, education, stroke severity, brain atrophy, and depression. In our cohort, PTSD was a common sequela among stroke survivors. We suggest that risk factors for PTSD development include stroke severity, white matter damage, and premorbid coping styles. Early identification of at-risk patients is key to effective treatment.

Plasma and cerebrospinal fluid neurofilament light protein concentrations are differentially associated with biomarker evidence of neurodegeneration in a community‐based population of 70‐year‐olds

AbstractBackgroundNeurofilament light protein (NfL) is the best‐established fluid biomarker for general neurodegeneration, predicting poor outcome in cognitive function across neurodegenerative dementias. Currently, there are few studies examining the correlation of plasma and cerebrospinal fluid (CSF) NfL with other fluid and imaging biomarkers for neurodegeneration.MethodThe sample (n= 287) was derived from the Gothenburg H70 Birth cohort 1944 study, conducted in 2014‐2016. CSF NfL, total‐Tau (t‐Tau), phospho‐Tau (p‐Tau), neurogranin, CSF/serum albumin ratio and plasma NfL were measured and brain magnetic resonance imaging (MRI) was conducted. Participants were examined with comprehensive neuropsychiatric and somatic examinations, and dementia was diagnosed according to DSM III criteria. In linear models adjusted for age and sex, NfL was examined in relation to other demographics, cognitive tests, CSF biomarkers and MRI measurements. Sub analysis were also performed on participants with or without β‐Amyloid pathology, defined as a CSF β‐Amyloid 42 ≤ 530 pg/mL.ResultNfL in plasma and CSF presented a moderate correlation (Spearman’s R=0.41, p&lt;0.001). P‐NfL was associated with worse delayed memory recall (p=0.019), smaller hippocampus volume (p=0.001), larger white matter lesion volume (p=0.004), as well as CSF levels of β‐amyloid 42 (p=0.043), β‐amyloid 42/40 (p=0.049), β‐amyloid 42/t‐Tau (p=0.007), CSF NfL (p&lt;0.001) and BMI (p&lt;0.001). CSF NfL was associated with t‐Tau (p=0.001), p‐Tau (p&lt;0.001), neurogranin (p=0.014), albumin ratio (Qalb) (p=0.001), P‐NfL (p&lt;0.001), and BMI (p=0.033). In participants with prevalent β‐amyloid 42 pathology, P‐NfL was associated with β‐amyloid 42 (p=0.009), β‐amyloid 42/40 (p=0.043), β‐amyloid 42/t‐Tau (p=0.010) and CSF NfL (p&lt;0.001). In participants without β‐amyloid 42 pathology, P‐NfL associated with BMI (p&lt;0.001), smaller hippocampus volume (p=0.007) and CSF NfL (p&lt;0.001).ConclusionAlthough CSF NfL and P‐NfL concentrations are correlated, the biomarker measured in the two sample types presents distinct associations with biomarker evidence of AD pathology and neurodegeneration. P‐NfL was associated with several markers that are characteristic of AD, whereas CSF NfL demonstrated more associations with synaptic and neurodegeneration.

Trimethylamine-N-oxide (TMAO) is associated with cardiovascular mortality and vascular brain lesions in patients with atrial fibrillation

Abstract Introduction Trimethylamine-N-oxide (TMAO) is a well characterized pro-atherogenic metabolite derived from the microbial processing of phosphatidylcholine and carnitine (usually present in red meat) and subsequent hepatic oxydation, which promotes endothelial dysfunction, platelet activation and thrombosis initiation. Its role concerning cerebral and cardiovascular adverse events has been assessed in various patient subpopulations but not for long term in patients with atrial fibrillation. Methods Baseline TMAO plasma levels were measured by high-performance liquid chromatography/mass spectrometry in plasmas of 2,379 subjects from our multicentric study. Among them, 1,722 participants at time of recruitment underwent brain MRI. Participants were stratified into TMAO tertiles and Cox PH models, linear mixed effect models or logistic mixed effect models were employed adjusting for several risk factors (age, sex, BMI, active and past smoke habit, cystatin c levels, heart failure, diabetes mellitus, hypertension, coronary artery disease and history of TIA/stroke). Subjects were prospectively followed with a median observation time of 4 years. Results Subjects in the highest tertile of TMAO were older (75.4 vs. 70.6 years in low tertile p&amp;lt;0.001) and had significantly more often comorbidities, (26.9% of subjects were diabetic vs. 9.1% in low tertile p&amp;lt;0.001), with higher BMI (28.1 vs 27.0, p&amp;lt;0.001) and worse renal function as assessed by serum cystatin C (1.46 vs 1.07, mg/dl; p&amp;lt;0.001). Heart failure was present in 37.9% participants in the upper compared to 15.8% in the lower tertile. (p&amp;lt;0.001). As shown in Figure 1, Kaplan Meier estimates showed increased cardiovascular mortality with increasing TMAO tertiles (p&amp;lt;0.0001). After adjustment for the abovementioned factors the upper tertile (T3) had an increased hazard ratio (HR) compared to the lowest one (HR 2.36 95% CI 1.56–3.58 p&amp;lt;0.01). Similar trends for global and ischemic stroke occurrences were not found although TMAO levels positively weakly correlated with NIHSS severity (Spearman's coefficient 0.31 p=0.02). Concerning brain MRI findings, TMAO tertiles identified individuals with different prevalence of small non-cortical infarcts (30.5%, 18.1% and 17.4% in high, middle and low tertiles respectively; p&amp;lt;0.001) and when present, larger white matter lesions volumes (5061 mm3, 4158 mm3 and 2970 mm3; p&amp;lt;0.001). After adjustment, the association with small non-cortical infarcts with TMAO levels remained significant in the highest tertile (T3) (OR 1.48 95% CI 1.07–2.05; p=0.02) and a trend towards larger white matter lesions volumes was observed (estimate 1307 95% CI −90–2705; p=0.07). Conclusions TMAO represents a robust prognostic independent biomarker identifying multimorbid, high risk patients for cardiovascular mortality and brain damage. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Swiss National Science Foundation (SNSF) and Theodor und Ida Herzog-Egli Foundation Figure 1. CV mortality according to TMAOFigure 2. Brain lesions assessment

Chronic Use of Aspirin and Total White Matter Lesion Volume: Results from the Women's Health Initiative Memory Study of Magnetic Resonance Imaging Study

To investigate the relationship between aspirin and subclinical cerebrovascular heath, we evaluated the effect of chronic aspirin use on white matter lesions (WML) volume among women. Chronic aspirin use was assessed in 1365 women who participated in the Women's Health Initiative Memory Study of Magnetic Resonance Imaging. Differences in WML volumes between aspirin users and nonusers were assessed with linear mixed models. A number of secondary analyses were performed, including lobe-specific analyses, subgroup analyses based on participants' overall risk of cerebrovascular disease, and a dose-response relationship analysis. The mean age of the women at magnetic resonance imaging examination was 77.6 years. Sixty-one percent of participants were chronic aspirin users. After adjusting for demographic variables and comorbidities, chronic aspirin use was nonsignificantly associated with 4.8% (95% CI: -6.8%, 17.9%) larger WML volumes. These null findings were confirmed in secondary and sensitivity analyses, including an active comparator evaluation where aspirin users were compared to users of nonaspirin nonsteroidal anti-inflammatory drugs or acetaminophen. There was a nonsignificant difference in WML volumes between aspirin users and nonusers. Further, our results suggest that chronic aspirin use may not have a clinically significant effect on WML volumes in women.

Brain MRI-markers Associate Differentially with Cognitive Versus Functional Decline Leading to Dementia.

Brain MRI-markers are risk factors of dementia and decline in cognition and daily functioning. It is unknown to what extent the associations of brain MRI-markers with cognition and daily functioning are part of the pathway leading to dementia. We aimed to investigate associations of brain MRI-markers with change in cognition and daily functioning during 15 years of follow-up, including their relation to dementia. Four hundred and sixty three stroke-free and non-demented participants from the population-based Rotterdam Study that underwent brain-MRI, yielding brain volumetrics, between 1995 and 1996. We assessed cognition using the Mini-Mental State Examination (MMSE) and daily functioning using instrumental and basic activities of daily living (IADL and BADL) up to seven times between 1990 and 2011. Analyses were performed both including and excluding incident demented participants. Smaller brain volume associated with larger decline in MMSE, IADL, and BADL. Larger white matter lesion volume associated with larger decline in MMSE. Frontal lobe volume associated strongest with decline in IADL and BADL, and temporal lobe volume with decline in MMSE. After excluding incident demented participants (n = 63), associations with IADL and BADL remained, while associations with MMSE disappeared. Smaller brain volumes and larger white matter volume associate with larger decline in cognition and daily functioning, during 15 years of follow-up. Importantly, the relation of brain volume with cognition, but not daily functioning, was driven by those individuals that ultimately developed dementia.

N-Terminal Pro-B-Type Natriuretic Peptide and Subclinical Brain Damage in the General Population.

Purpose To investigate the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP), which is a marker of heart disease, and markers of subclinical brain damage on magnetic resonance (MR) images in community-dwelling middle-aged and elderly subjects without dementia and without a clinical diagnosis of heart disease. Materials and Methods This prospective population-based cohort study was approved by a medical ethics committee overseen by the national government, and all participants gave written informed consent. Serum levels of NT-proBNP were measured in 2397 participants without dementia or stroke (mean age, 56.6 years; age range, 45.7-87.3 years) and without clinical diagnosis of heart disease who were drawn from the population-based Rotterdam Study. All participants were examined with a 1.5-T MR imager. Multivariable linear and logistic regression analyses were used to investigate the association between NT-proBNP level and MR imaging markers of subclinical brain damage, including volumetric, focal, and microstructural markers. Results A higher NT-proBNP level was associated with smaller total brain volume (mean difference in z score per standard deviation increase in NT-proBNP level, -0.021; 95% confidence interval [CI]: -0.034, -0.007; P = .003) and was predominantly driven by gray matter volume (mean difference in z score per standard deviation increase in NT-proBNP level, -0.037; 95% CI: -0.057, -0.017; P < .001). Higher NT-proBNP level was associated with larger white matter lesion volume (mean difference in z score per standard deviation increase in NT-proBNP level, 0.090; 95% CI: 0.051, 0.129; P < .001), with lower fractional anisotropy (mean difference in z score per standard deviation increase in NT-proBNP level, -0.048; 95% CI: -0.088, -0.008; P = .019) and higher mean diffusivity (mean difference in z score per standard deviation increase in NT-proBNP level, 0.054; 95% CI: 0.018, 0.091; P = .004) of normal-appearing white matter. Conclusion In community-dwelling persons, higher serum NT-proBNP levels are associated with volumetric and microstructural MR imaging markers of subclinical brain damage. © RSNA, 2016 Online supplemental material is available for this article.

Kidney function and cerebral small vessel disease in the general population.

Anatomic and hemodynamic similarities between renal and cerebral vessels suggest a tight link between kidney disease and brain disease. Although several distinct markers are used to identify subclinical kidney and brain disease, a comprehensive assessment of how these markers link damage at both end organs is lacking. To investigate whether measures of kidney function were associated with cerebral small vessel disease on MRI. In 2526 participants of the population-based Rotterdam Study, we measured urinary albumin-to-creatinine ratio, and estimated glomerular filtration rate based on serum creatinine and cystatin C. All participants underwent brain magnetic resonance imaging. We assessed presence of cerebral small vessel disease by calculating white matter lesion volumes and rating the presence of lacunes and cerebral microbleeds. We used multivariable linear and logistic regression to investigate the association between kidney function and cerebral small vessel disease. Worse kidney function was consistently associated with a larger white matter lesion volume (mean difference per standard deviation increase in albumin-to-creatinine ratio: 0.09, 95% confidence interval 0.05; 0.12; per standard deviation decrease in creatinine-based estimated glomerular filtration rate: -0.04, 95% confidence interval -0.08;-0.01, and per standard deviation decrease in cystatin C-based estimated glomerular filtration rate: -0.09, 95% confidence interval -0.13;-0.05). Persons with higher albumin-to-creatinine ratio or lower cystatin C-based estimated glomerular filtration rate levels had a higher prevalence of lacunes (odds ratio per standard deviation increase in albumin-to-creatinine ratio: 1.24, 95% confidence interval 1.07; 1.43). Only participants in the highest quartile of albumin-to-creatinine ratio had a higher frequency of microbleeds compared to the lowest quartile. Worse kidney function is associated with cerebral small vessel disease. Of all measures of kidney function, in particular albumin-to-creatinine ratio is related to cerebral small vessel disease.

Arterial stiffness and progression of structural brain changes: The SMART-MR study.

To examine the cross-sectional and prospective associations between arterial stiffness and structural brain changes within the Second Manifestations of Arterial Disease-Magnetic Resonance (SMART-MR) study, a prospective cohort study among patients with manifest arterial disease. Distension measurements of the common carotid arteries and a brain MRI were performed in 526 patients (mean age 59 ± 10 years). After a mean follow-up of 4.1 years (range 3.6-5.8), brain MRI was repeated in 308 patients. Brain segmentation was used to quantify total brain volume, cortical gray matter volume, ventricular volume, and white matter lesion (WML) volume (relative to intracranial volume). Infarcts were rated visually. Cross-sectional multivariable regression analyses showed that 1 SD decrease in carotid distension, indicating increased arterial stiffness, was associated with smaller relative total brain and cortical gray matter volumes (B = -0.24%, 95% confidence interval [CI] -0.44 to -0.04%, and B = -0.47%, 95% CI -0.75 to -0.19%), with larger WML volume (B = 0.09%, 95% CI -0.01 to 0.19%), and with higher risk of having nonlacunar (cortical or large subcortical) brain infarcts (relative risk = 1.44, 95% CI 1.14 to 1.81). However, our prospective findings showed that carotid distension was not significantly associated with progression of brain atrophy, WML volume, or brain infarcts. In this population of patients with manifest arterial disease, stiffening of the carotid arteries was cross-sectionally associated with more brain atrophy, WML volume, and nonlacunar infarcts, but did not lead to changes in brain volumes or infarcts after 4 years.

Structural and Microstructural Brain Changes Predict Impairment in Daily Functioning

BackgroundBrain changes on magnetic resonance imaging (MRI) reflect accumulating pathology and have clinically disabling consequences, such as dementia. However, little is known on the relation of these MRI markers with daily functioning in nondemented individuals. We investigated whether structural and microstructural brain changes are associated with impairment in activities of daily living in a community-dwelling population. MethodsBetween 2005 and 2009, 2025 stroke-free nondemented participants (aged 59.9 years) from the population-based Rotterdam Study underwent brain MRI, yielding global MRI markers, focal MRI markers, and microstructural MRI markers. We used the Stanford Health Assessment Questionnaire to assess basic activities of daily living, and the Instrumental Activities of Daily Living Scale to assess instrumental activities of daily living. Follow-up on activities of daily living was obtained between 2008 and 2013 (mean follow-up 5.7 years). We used linear regression to analyze continuous scores of daily living and logistic regression for incident impairment. ResultsEighty-two participants became impaired in basic and 33 in instrumental activities of daily living. Smaller brain and hippocampal volume and higher diffusivity were associated with larger change in activities of daily living. Smaller brain volume (odds ratio [OR] 4.05 per SD; 95% confidence interval [CI], 1.81–9.02), larger white matter lesion volume (OR 1.33/SD; 95% CI 1.02–1.72) and higher mean (OR 1.55/SD; 95% CI, 1.11–2.15), axial (OR 1.49/SD; 95% CI, 1.08–2.07), and radial diffusivity (OR 1.51/SD; 95% CI, 1.09-2.10) were associated with higher risk of impairment in basic activities of daily living. ConclusionsIn community-dwelling individuals, brain changes are associated with deterioration and incident impairment in daily functioning.

Extracellular vesicle protein levels are related to brain atrophy and cerebral white matter lesions in patients with manifest vascular disease: the SMART-MR study

ObjectivesExtracellular vesicles (EVs) and their protein levels have been identified as a potential risk marker for the development of vascular disease. In the present study, we assessed whether levels of...

Associations Between Alzheimer Disease Biomarkers, Neurodegeneration, and Cognition in Cognitively Normal Older People

Criteria for preclinical Alzheimer disease (AD) propose β-amyloid (Aβ) plaques to initiate neurodegeneration within AD-affected regions. However, some cognitively normal older individuals harbor neural injury similar to patients with AD, without concurrent Aβ burden. Such findings challenge the proposed sequence and suggest that Aβ-independent precursors underlie AD-typical neurodegenerative patterns. OBJECTIVE To examine relationships between Aβ and non-Aβ factors as well as neurodegeneration within AD regions in cognitively normal older adults. The study quantified neurodegenerative abnormalities using imaging biomarkers and examined cross-sectional relationships with Aβ deposition; white matter lesions (WMLs), a marker of cerebrovascular disease; and cognitive functions. Cross-sectional study in a community-based convenience sample of 72 cognitively normal older individuals (mean [SD] age, 74.9 [5.7] years; 48 women; mean [SD] 17.0 [1.9] years of education) of the Berkeley Aging Cohort. Each individual underwent a standardized neuropsychological test session, magnetic resonance imaging, and positron emission tomography scanning. For each individual, 3 AD-sensitive neurodegeneration biomarkers were measured: hippocampal volume, glucose metabolism, and gray matter thickness, the latter 2 sampled from cortical AD-affected regions. To quantify neurodegenerative abnormalities, each biomarker was age adjusted, dichotomized into a normal or abnormal status (using cutoff thresholds derived from an independent AD sample), and summarized into 0, 1, or more than 1 abnormal neurodegenerative biomarker. Degree and topographic patterns of neurodegenerative abnormalities were assessed and their relationships with cognitive functions, WML volume, and Aβ deposition (quantified using carbon 11-labeled Pittsburgh compound B positron emission tomography). Of our cognitively normal elderly individuals, 40% (n = 29) displayed at least 1 abnormal neurodegenerative biomarker, 26% (n = 19) of whom had no evidence of elevated Pittsburgh compound B retention. In those people who were classified as having abnormal cortical thickness, degree and topographic specificity of neurodegenerative abnormalities were similar to patients with AD. Accumulation of neurodegenerative abnormalities was related to poor memory and executive functions as well as larger WML volumes but not elevated Pittsburgh compound B retention. Our study confirms that a substantial proportion of cognitively normal older adults harbor neurodegeneration, without Aβ burden. Associations of neurodegenerative abnormalities with cerebrovascular disease and cognitive performance indicate that neurodegenerative pathology can emerge through non-Aβ pathways within regions most affected by AD.

Depressive Symptoms, Symptom Dimensions, and White Matter Lesion Volume in Older Adults: A Longitudinal Study

White matter lesions (WMLs) are associated with depressive symptoms in older adults. However, it is not clear whether different symptom dimensions of depression have distinct associations with WMLs. The authors assessed the longitudinal relationships of the Center for Epidemiologic Studies Depression Scale (CES-D) total score and subscale scores with WML volume in the Baltimore Longitudinal Study of Aging. Using a prospective observational design, the authors examined WML volume and depressive symptoms at 1- to 2-year intervals for up to 9 years in 116 dementia-free participants (mean age: 68.78 ± 7.68). At each visit, depressive symptoms were measured with the CES-D and WML volumes were quantified from structural magnetic resonance imaging scans. Higher CES-D full-scale scores were associated with greater WML volume and with a faster rate of volume increases over time in women, especially at older ages. Higher depressed mood and somatic symptoms subscale scores were associated with greater increases in WML volume over time at older ages. In men, depressed mood and somatic symptoms were associated with larger WML volume at baseline. Findings confirm an association between WMLs and depressive symptoms and suggest that depressed mood and somatic symptoms may be stronger predictors of depression-related brain changes than lack of well-being. Age and sex may moderate the relationships between depressive symptoms and WMLs. Understanding particular symptom dimensions of depressive symptoms has implications for treatment and may lead to targeted interventions and more precise knowledge of mechanisms underlying depression.

Diabetes mellitus and progression of vascular brain lesions and brain atrophy in patients with symptomatic atherosclerotic disease. The SMART-MR study

AimDiabetes mellitus (DM) is associated with brain atrophy and vascular brain lesions. Cardiovascular disease is a key determinant in this association. We assessed whether DM increased the rate of progression of brain atrophy, vascular brain lesions, and cognitive decline in patients with symptomatic atherosclerotic disease. MethodsIn 663 patients (58±10years) from the SMART-MR study (n=89 with DM), 1.5T MRI and neuropsychological examination were performed at baseline and after 3.9±0.4years follow-up. ResultsRepeated measures ANCOVA (adjusted for age, sex, and vascular risk factors) showed that patients with DM had smaller total brain volume (mean differences as percentage of intracranial volume (ICV) [95% CI]: −1.36% [−1.81; −0.91]), smaller gray matter volume (−1.23% [−1.85; −0.61]), larger ventricular volume (0.32% [0.14; 0.49]), and larger white matter lesion volume (0.31% [0.09; 0.53]) than patients without DM. Patients with DM had accelerated increase in ventricular volume over time compared with patients without DM (mean differences ventricular volume as percentage of ICV: 0.32% [0.25; 0.39] vs. 0.17% [0.15; 0.19]; p-interaction DM×time<0.01). Poisson regression showed that patients with DM had an increased risk for incident brain infarcts (relative risk [95% CI]: 1.62 [1.04; 2.53]). Patients with and without DM had similar performance on cognition. ConclusionsDM on top of existing symptomatic atherosclerotic disease is associated with increased brain atrophy and vascular brain lesion load that proceed at a slightly higher rate than in patients without DM.

The volumetric relationship of white matter lesion and contrast-enhanced lesion in delayed radiation brain injury: an MRI-based study

Purpose. This study investigated the volumetric relationship of white matter lesion (WML) and contrast-enhanced lesion (CEL) in delayed radiation brain injury (RBI) during the course of evolution. Materials and methods. MRI results in 45 patients with RBI after receiving radiation for nasopharyngeal carcinoma were analyzed. In total there were 75 lobes with RBI and 114 MRI examinations in this study. WML and CEL lesion volumes were measured. The lesion volume change of less than 5% or 0.25 cm3 was regarded as being static. Results. The average WML volume was 16.33 cm3 (ranging 0.11 cm3 to 102.83 cm3), and the average CEL volume was 3.15 cm3 (ranging 0.03 cm3 to 27.85 cm3). WML was larger than CEL in 164 measurements, and CEL was larger than WML in 10 measurements. In 64.3% follow-ups WML and CEL evolved in the same pattern; and in most follow-ups (93.8%) WML and CEL did not evolve in the opposite directions. A larger WML volume tended to have a larger CEL volume though this relationship was not linear. Conclusion. Evolution of WML and CEL tended to follow the same pattern. WML tended to be larger than CEL, and larger WML tended to be associated with larger CEL.

Abstract WP186: Association Between Blood Pressure, Internal Carotid Artery Flow Parameters And Age-related White Matter Disease

Background: White matter lesions (WML) are associated with hypertension. Blood pressure (BP) is transmitted to the brain via the carotid arteries, and autoregulation helps protect the brain. We investigated if BP via carotid waveform parameters were associated with WML. Methods: We obtained BP measurements from a cohort of community dwelling subjects at mean ages 70±1 and 73±1 years; brain MRI and carotid artery ultrasound at mean age 73±1 years. We calculated mean values of BP (systolic, diastolic, mean, variability and pulsatility), measured WML by volume, and Fazekas scale. We calculated internal carotid artery (ICA) mean blood flow velocity, pulsatility index (PI), and resistivity index (RI). We tested associations between BP and ICA flow parameters and WML using multiple linear regression, corrected for intracranial volume (ICV), age, gender, BMI, previous MI, diabetes, hypertension, smoking, hypercholesterolaemia, PVD and stroke. Results: Amongst 694 subjects, diastolic and mean BP decreased and hence BP pulsatility increased significantly between ages 70 and 73 years. Lower diastolic BP and higher BP pulsatility were associated with higher ICA PI (standardized β, age 70= -0.24, age 73= -0.19, both p&lt;0.001; age 70 β=0.18, p&lt;0.001, age 73 β=0.10, p=0.008 respectively). WML volume was weakly associated with BP at age 70 (diastolic β=0.08, systolic β=0.08, mean β=0.09, all p&lt;0.05) but not with BP variability or pulsatility. Similar but weaker associations were seen at age 73. After adjusting for BP, larger WML volume was associated with higher ICA PI (β=0.10, p=0.012), but not any other measures. All associations were the same for WML Fazekas scores. Conclusions: The relatively weak association between BP and WML may be mediated via ICA pulsatility which is largely driven by falling diastolic BP. This questions the nature of the apparent link between BP and WML.

Arterial Stiffness and Cerebral Small Vessel Disease

Aging and vascular risk factors contribute to arterial stiffening. Increased arterial stiffness exposes the small vessels in the brain to abnormal flow pulsations and, as such, may contribute to the pathogenesis of cerebral small vessel disease. In a population-based study, we investigated the association between arterial stiffness, as measured by aortic pulse wave velocity (aPWV), and small vessel disease. Overall, 1460 participants (mean age, 58.2 years) underwent aPWV measurement and brain MRI scanning. We calculated aPWV by measuring time differences and distances between pulse waves in the carotid and femoral arteries. Using automated MRI analysis, we obtained white matter lesion volumes. Infarcts and microbleeds were rated visually. We used linear and logistic regression models to associate aPWV with small vessel disease, adjusting for age, sex, mean arterial pressure, and heart rate and additionally for cardiovascular risk factors. Subsequently, we explored associations in strata of hypertension. In the study group, higher aPWV was associated with larger white matter lesion volume (difference in volume per SD increase in aPWV 0.07; 95% CI, 0.02-0.12) but not with lacunar infarcts or microbleeds. In persons with uncontrolled hypertension, higher aPWV was significantly associated with larger white matter lesion volume (difference in volume per SD increase in aPWV 0.09; 95% CI, 0.00-0.18), deep or infratentorial microbleeds (OR, 2.13; 95% CI, 1.16-3.91), and to a lesser extent also with lacunar infarcts (OR, 1.63; 95% CI, 0.98-2.70). No such associations were present in persons with controlled hypertension or without hypertension. In our study, increased arterial stiffness is associated with a larger volume of white matter lesions.

Antidepressant use is related to larger white matter lesion volume in patients with symptomatic atherosclerotic disease: the SMART-MR study

Although a relation between depression and white matter lesions (WML) is frequently observed, the direction of causation remains unknown. We investigated whether depressed mood was associated with baseline severity and change in WML volume during 4 years of follow-up, and the relative contribution of mood symptoms and antidepressant use to this relation. Within the SMART-MR study 594 patients (58 ± 10 years) with symptomatic atherosclerotic disease had assessments of mood symptoms and antidepressant use and 1.5 T MRI at baseline and after 3.9 ± 0.4 years of follow-up. Mood symptoms were assessed using the Mental Health Index (MHI-5). Depressed mood was defined as antidepressant use and/or MHI-5 score ≤ 52. Volumetric WML measures (deep and periventricular) were obtained with automated segmentation. Linear regression analyses were adjusted for age, sex, baseline WML volume, follow-up time, vascular risk factors and infarcts. Depressed mood was not associated with larger WML volume at baseline. However, when separate contributions were distinguished, antidepressant use was associated with greater deep (B = 0.50 mL, 95 % CI 0.04-0.96) and periventricular WML volume (B = 0.47 mL, 95 % CI 0.05-0.89) at baseline, while mood symptoms were not. Antidepressants were associated with a modest but non-significant increase in progression of periventricular WML volume over 4 years of follow-up (B = 0.21 mL, 95 % CI -0.05 to 0.47). WML at baseline were not associated with new-onset depressed mood at follow-up. Antidepressants, but not mood symptoms, were associated with greater WML volume and a modest, although non-significant increase in periventricular WML volume in patients with symptomatic atherosclerotic disease. Future studies are needed to determine whether this may be a direct effect, or whether other underlying diseases for which antidepressants are prescribed influence this relation.

Cerebral Network Disruption as a Possible Mechanism for Impaired Recovery after Acute Pontine Stroke

Background: Recovery from stroke is presumed to be a function of a widespread cerebral network. Chronic white matter lesions (WML) have been proposed to be a predictor of poor outcome after acute stroke. We tested the hypothesis that the extent of WML has an effect on functional recovery in acute pontine stroke by disrupting the integrity of the supratentorial cerebral network. Methods: Seventeen patients with acute unilateral pontine stroke who had received a standardized stroke workup and additional diffusion tensor imaging (DTI) were studied. After grading the extent of WML according to the Fazekas scale and semiautomated lesion volume calculation, we compared patients with acute pontine infarction and advanced WML to those with absent or minimal WML regarding baseline characteristics, stroke subtype and clinical outcome. In addition, we used tract-based spatial statistics for voxel-wise analysis of the DTI-derived parameter fractional anisotropy in the white matter tracts. Results: The volume of WML ranged between 0.1 and 42.1 cm³ (mean = 15.9) and was graded as follows: 0 in 5.9%, 1 in 35.3%, 2 in 41.2% and 3 in 17.6%. Both patients with Fazekas grades 2–3 (p = 0.014) as well as those with larger WML volumes (p = 0.037) had severer functional deficits at the 3-month follow-up. White matter tracts displaying a significant decrease in fractional anisotropy values were the corpus callosum, the anterior thalamic radiation and the inferior fronto-occipital fasciculus. Conclusions: Chronic WML contribute to a less favorable clinical outcome after pontine stroke depending on (1) the extent of pre-existing WML and (2) the degree of disruption of cerebral connectivity as indicated by reduced tissue integrity in the white matter not affected by WML as detected by DTI and tract-based spatial statistics.

Homocysteine and cerebral small vessel disease in patients with symptomatic atherosclerotic disease. The SMART-MR study

ObjectiveHigh homocysteine level is a risk factor for atherosclerosis and has been associated with lacunar infarcts (LIs), white matter lesions (WML) and cognitive dysfunction. It is unclear whether homocysteine is associated with cerebral small vessel disease (cSVD) on top of pre-existent atherosclerosis. We evaluated the association between homocysteine and cSVD in a large cohort of patients with symptomatic atherosclerotic disease. MethodsWithin the SMART-MR study, a prospective cohort study of patients with symptomatic atherosclerotic disease, we estimated cross-sectional associations of total plasma homocysteine (THCY) and hyperhomocysteinemia (HHCY) with WML volume and presence of LI, using automated brain segmentation in MRIs of 1232 patients and cognitive function in 763 patients. WML were expressed as a logarithmic transformed percentage of total brain volume. ResultsLinear regression analyses adjusted for age, sex, vascular risk factors and extent of atherosclerosis showed that THCY and HHCY were significantly associated with larger WML volumes (B=0.01%: 95% CI 0.002–0.02%, and B=0.21%: 95% CI 0.04–0.39%). Increasing THCY was significantly associated with an increased risk of LIs (OR 1.04, 95% CI 1.01–1.07, per 1μmol). Moreover, HHCY was associated with worse cognitive function (B=−0.12: 95% CI −0.22 to −0.01). ConclusionIn patients with symptomatic atherosclerotic disease, higher homocysteine levels are associated with higher WML volume, presence of LI and slightly worse cognitive function.