Higher White Matter Lesion Volume Research Articles

Associations of carotid atherosclerosis with cognitive function and brain health: Findings from a UK tri-ethnic cohort study (Southall and Brent Revisited)

BackgroundCognitive function has an important role in determining the quality of life of older adults. Cardiovascular disease (CVD) is common in older people and may compromise cognitive performance; however, the extent to which this is related to carotid atherosclerosis is unclear. AimWe investigated associations between carotid atherosclerosis and cognitive function and neuroimaging markers of brain health in a UK multi-ethnic community-based sample including older people of European, South Asian, and African-Caribbean ethnicity. MethodsCarotid plaques and intima-media thickness (cIMT) were assessed using ultrasound in 985 people (mean age 73.2y, 56 % male). Associations of carotid atherosclerosis with cognitive function (memory, executive function, language and CSI-D, a global measure of cognitive state) and neuroimaging measures (total brain volume, hippocampal volume, white matter (WM) lesion volume and coalescence score) were analysed using regression analyses, with and without adjustment for potential confounders using two models: 1) adjustment for age, sex, and ethnicity; 2) model 1 plus education, physical activity category, body mass index, hypertension, diabetes, total and high density lipoprotein cholesterol, atrial fibrillation, smoking, previous CVD, alcohol consumption, and presence of chronic kidney disease. ResultsPeople with carotid plaque or higher cIMT had lower CSI-D score, poorer memory poorer executive function and higher WM lesion volume and coalescence. Language was poorer in people with plaque but was not correlated with cIMT. Associations with plaque were preserved after full adjustment (model 2) but relationships for cIMT were attenuated. Associations with other plaque characteristics were generally unconvincing after adjustment. ConclusionsThis multi-ethnic cohort study provides evidence that presence of carotid plaque, is associated with poorer cognitive function and brain health.

35 Impact of Cardiorespiratory Fitness and White Matter Lesions on Processing Speed with Age

Objective:Processing speed declines with age and is a strong predictor of age-related cognitive decline in other domains, and in predicting who will need help with tasks of daily living in later years. Higher cardiorespiratory fitness (CRF) reflects better cardiopulmonary health and is related to maintenance of processing speed and cognition into late life. On the other hand, white matter lesions (WML) are reflective of age-related brain network disconnections from damage to white matter tracts in the brain. Lower CRF and higher WML burden have each been related to poorer cognitive performance. Although higher CRF provides a protective effect on cognition, the combined effects of CRF and WML on processing speed have yet to be determined. Specifically, whether CRF and WML independently affect processing speed or if WML moderates the effect of CRF on processing speed is yet to be established. We predicted WML may moderate CRF benefits on cognitive aging if CRF-related cognitive benefits are weakened by high WML load. Here, we test this question with the gold-standard measure of CRF, maximal exercise oxygen uptake (relative VO2 max, mL/kg/min) during a graded exercise test, and a validated neuropsychological measure of processing speed, the Digit Symbol Substitution Test (DSST).Participants and Methods:CRF, DSST scores, and WML volumes of cognitively normal adults (n=91) aged 55-80 years were included in this analysis. The WML data was corrected for total intracranial volume and was log transformed. A linear regression model included the number of accurately completed items on the DSST as the dependent variable and age, sex, relative VO2 max, WML volumes and the interaction between relative VO2 max and WML volume as the predictor variables.Results:Main effects of age, sex, VO2 max and WML volume on the DSST were observed. Greater age, higher WML volume, and lower relative VO2 max were associated with poorer performance on the DSST. In addition, females (n=55) performed better than males (n=36) on the DSST. No significant interaction was observed between VO2 max and WML volume on DSST scores.Conclusions:Our results show that 1) WML and relative VO2 max independently contribute to processing speed performance in older adults as measured by the DSST, and 2) WML do not moderate the relation between VO2 max and the DSST. Strengths of this study include gold-standard measurement of CRF and WML volumes as predictors of performance on the DSST in older adults. Further research is warranted to understand how vascular aging and brain health indicators interactively or interdependently impact cognition in aging.

Association between 10‐year cardiovascular mortality‐risk and neuroimaging biomarkers in the FINGER trial

AbstractBackgroundCardiovascular risk factors are associated with cognitive decline and dementia. Timely estimation and targeting of cardiovascular risk burden may contribute towards the prevention of cognitive decline. The cardiovascular risk scores of the European Society of Cardiology’s, SCORE (for adults up to 64 years) and SCORE‐OP (for older adults aged 65 years or more), are commonly used tool for estimation of 10‐year CVD mortality and may reflect the impact of cardiovascular risk burden on brain pathology if validated against neuroimaging biomarkers.MethodThis study investigated associations between (i) baseline SCORE/SCORE‐OP and baseline neuroimaging biomarkers (brain magnetic resonance imaging [MRI] and Pittsburgh Compound B‐positron emission tomography [PiB‐PET] measures) (ii) change in SCORE/SCORE‐OP and change in neuroimaging measures during the 2‐year Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER). FINGER targeted at‐risk older adults, aged 60‐77 years, from the general population. Participants were randomized to either multidomain intervention (diet, exercise, cognitive training, and vascular risk management) or control group (general health advice). Neuroimaging (MRI and PiB‐PET) data from baseline and 2‐year visits were used. A total of 112 participants had repeated brain MRI measures (hippocampus, total grey matter, and white matter lesion volumes, and Alzheimer’s disease signature cortical thickness). Repeated PiB‐PET scans were available for 39 participants.ResultPreliminary results suggest that at baseline higher SCORE/SCORE‐OP, indicating increased risk of CVD mortality was significantly associated with lower hippocampus volume (estimate = ‐0.010; p = 0.004), lower total grey matter volume (estimate = ‐0.016; p = 0.007), higher white matter lesion volume (estimate = 0.048; p = 0.015), and lower AD signature cortical thickness (‐0.004; p = 0.048) but not with PiB‐PET. No significant associations were found for change in neuroimaging measures and baseline SCORE/SCORE‐OP or change in SCORE/SCORE‐OP during the 2‐year follow‐up.ConclusionCardiovascular risk scores need to be validated against different brain pathology markers in diverse populations. This will enable more precise identification and estimation of dementia risk profiles, guiding at‐risk persons to precise intervention strategies, good for both, heart, and brain.

CKD, Brain Atrophy, and White Matter Lesion Volume: The Japan Prospective Studies Collaboration for Aging and Dementia

Chronic kidney disease, defined by albuminuria and/or reduced estimated glomerular filtration rate (eGFR), has been reported to be associated with brain atrophy and/or higher white matter lesion volume (WMLV), but there are few large-scale population-based studies assessing this issue. This study aimed to examine the associations between the urinary albumin-creatinine ratio (UACR) and eGFR levels and brain atrophy and WMLV in a large-scale community-dwelling older population of Japanese. Population-based cross-sectional study. A total of 8,630 dementia-free community-dwelling Japanese aged greater than or equal to 65 years underwent brain magnetic resonance imaging scanning and screening examination of health status in 2016-2018. UACR and eGFR levels. The total brain volume (TBV)-to-intracranial volume (ICV) ratio (TBV/ICV), the regional brain volume-to-TBV ratio, and the WMLV-to-ICV ratio (WMLV/ICV). The associations of UACR and eGFR levels with the TBV/ICV, the regional brain volume-to-TBV ratio, and the WMLV/ICV were assessed by using an analysis of covariance. Higher UACR levels were significantly associated with lower TBV/ICV and higher geometric mean values of the WMLV/ICV (P for trend= 0.009 and <0.001, respectively). Lower eGFR levels were significantly associated with lower TBV/ICV, but not clearly associated with WMLV/ICV. In addition, higher UACR levels, but not lower eGFR, were significantly associated with lower temporal cortex volume-to-TBV ratio and lower hippocampal volume-to-TBV ratio. Cross-sectional study, misclassification of UACR or eGFR levels, generalizability to other ethnicities and younger populations, and residual confounding factors. The present study demonstrated that higher UACR was associated with brain atrophy, especially in the temporal cortex and hippocampus, and with increased WMLV. These findings suggest that chronic kidney disease is involved in the progression of morphologic brain changes associated with cognitive impairment.

NODDI, diffusion tensor microstructural abnormalities and atrophy of brain white matter and gray matter contribute to cognitive impairment in multiple sclerosis.

Pathologically specific MRI measures may elucidate in-vivo the heterogeneous processes contributing to cognitive impairment in multiple sclerosis (MS). Using diffusion tensor and neurite orientation dispersion and density imaging (NODDI), we explored the contribution of focal lesions and normal-appearing (NA) tissue microstructural abnormalities to cognitive impairment in MS. One hundred and fifty-two MS patients underwent 3T brain MRI and a neuropsychological evaluation. Forty-eight healthy controls (HC) were also scanned. Fractional anisotropy (FA), mean diffusivity (MD), intracellular volume fraction (ICV_f) and orientation dispersion index (ODI) were assessed in cortical and white matter (WM) lesions, thalamus, NA cortex and NAWM. Predictors of cognitive impairment were identified using random forest. Fifty-two MS patients were cognitively impaired. Compared to cognitively preserved, impaired MS patients had higher WM lesion volume (LV), lower normalized brain volume (NBV), cortical volume (NCV), thalamic volume (NTV), and WM volume (p ≤ 0.021). They also showed lower NAWM FA, higher NAWM, NA cortex and thalamic MD, lower NAWM ICV_f, lower WM lesion ODI, and higher NAWM ODI (false discovery rate-p ≤ 0.026). Cortical lesion number and microstructural abnormalities were not significantly different. The best MRI predictors of cognitive impairment (relative importance) (out-of-bag area under the curve = 0.727) were NAWM FA (100%), NTV (96.0%), NBV (84.7%), thalamic MD (43.4%), NCV (40.6%), NA cortex MD (26.0%), WM LV (23.2%) and WM lesion ODI (17.9%). Our multiparametric MRI study including NODDI measures suggested that neuro-axonal damage and loss of microarchitecture integrity in focal WM lesions, NAWM, and GM contribute to cognitive impairment in MS.

Oxygen extraction efficiency and white matter lesion burden in older adults exhibiting radiological evidence of capillary shunting

White matter lesions (WML) have been linked to cognitive decline in aging as well as in Alzheimer’s disease. While hypoperfusion is frequently considered a cause of WMLs due to the resulting reduction in oxygen availability to brain tissue, such reductions could also be caused by impaired oxygen exchange. Here, we tested the hypothesis that venous hyperintense signal (VHS) in arterial spin labeling (ASL) magnetic resonance imaging (MRI) may represent a marker of impaired oxygen extraction in aging older adults. In participants aged 60–80 years (n = 30), we measured cerebral blood flow and VHS with arterial spin labeling, maximum oxygen extraction fraction (OEFmax) with dynamic susceptibility contrast, and WML volume with T1-weighted MRI. We found a significant interaction between OEFmax and VHS presence on WML volume (p = 0.02), where lower OEFmax was associated with higher WML volume in participants with VHS, and higher OEFmax was associated with higher WML volume in participants without VHS. These results indicate that VHS in perfusion-weighted ASL data may represent a distinct cerebrovascular aging pattern involving oxygen extraction inefficiency as well as hypoperfusion.

Alcohol drinking and brain morphometry in apparently healthy community-dwelling Japanese men.

The clinical implications of alcohol consumption have been extensively examined; however, its effects on brain structures in apparently healthy community-dwellers remain unclear. Therefore, we investigated the relationship between alcohol consumption and brain gray matter volume (GMV) in community-dwelling Japanese men using voxel-based morphometry (VBM). We recruited cognitively intact Japanese men, aged 40-79 years, from a population-based cohort in Shiga, Japan. Brain magnetic resonance imaging was performed, on average, 2 years after demographic and medical information was obtained in 2010-2014. A multivariable linear regression analysis of 639 men was conducted to elucidate the relationship between the amount of alcohol consumed and GMV. VBM statistics were analyzed by threshold-free cluster enhancement with a family-wise error rate of <0.05. The results obtained demonstrated that the amount of alcohol consumed was associated with lower GMV. The VBM analysis showed lower GMV within the parahippocampal, entorhinal, cingulate, insular, temporal, and frontal cortices and cerebellum in very heavy drinkers (≥42 ethanol g/day) than in non-drinkers. Furthermore, alcohol consumption was associated with a higher white matter lesion volume. These results suggest subclinical structural changes similar to alcohol-related neurological diseases.

Alcohol Consumption, Brain Amyloid-β Deposition, and Brain Structural Integrity Among Older Adults Free of Dementia.

Light to moderate alcohol consumption has been variably associated with lower or higher risk of dementia, but effects on Alzheimer's disease pathology are less clear. We determined whether late-life alcohol consumption was associated with Alzheimer's disease pathology among older adults. We assessed the associations of alcohol consumption self-reported in 2000-2002 with brain amyloid-β deposition on PET scans, and white matter lesion and hippocampal volume on MRIs measured 7-9 years later in 189 participants of the Ginkgo Evaluation of Memory Study (age 75-87 years at baseline) who were free of clinical dementia, using multivariable-adjusted and inverse probability-weighted robust linear regression models. Alcohol consumption was not statistically significantly associated with amyloid-β deposition (standardized uptake value ratio difference per drink: -0.013 [95% CI: -0.027, 0.002]). Both non-drinkers and participants consuming ≥1 drink(s)/week had higher white matter lesion volume (% intracranial volume) than did the reference group of those consuming <1 drink/week (differences: 0.25 % [95% CI: 0.01, 0.50]; 0.26 % [95% CI: 0.02, 0.50]). The association of alcohol consumption and hippocampal volume was modified by age (p = 0.02). Among participants younger than 77 years, participants consuming 1-7 drinks/week had larger hippocampal volume compared with participants consuming <1 drink/week. Alcohol consumption was not statistically significantly associated with amyloid-β deposition 7-9 years later. Non-drinking and greater alcohol consumption were associated with higher white matter lesion volume compared with drinking <1 drink/week. Moderate drinking was associated with higher hippocampal volume in younger individuals. Given the selective nature of this population and adverse health effects of excessive alcohol consumption, these findings warrant further investigation, but cannot be translated into clinical recommendations.

Do cerebral microbleeds affect cognition in patients with symptomatic small vessel disease?

BackgroundDementia and cognitive impairment are becoming increasingly a major health problem, pronounced by increased life expectancy. Cerebral small vessel disease (cSVD) is among the major causes of cognitive deterioration, yet cerebral microbleeds (CMBs) which are a common association of cSVD are still not sure to be related to cognition.Aim of the studyThe study aims to determine whether the number and localization of CMBs correlate with cognition in patients with symptomatic small vessel disease (SVD), according to Montreal Cognitive Assessment (MoCA) test.Subjects and methodsThis cross-sectional study included 85 Egyptian patients with symptomatic SVD, from the neuropsychiatry clinic of the Main Suez Hospital in Suez City, in the period between February 2017 and February 2018. Subjects were classified according to CMB presence into CMB-positive and CMB-negative groups. Both groups are assessed using MRI imaging and MoCA test for cognitive function.ResultsIn our study, CMBs recorded a high prevalence rate of SVD patients. Subjects with MBs were mainly males and significantly older, with higher white matter lesion volume and more lacunar infarcts. MoCA test detected significant impairment in visuospatial/executive function, attention, and total scores in CMB-positive group. Both frontal and parietal MBs showed independent association with visuospatial/executive impairment. Deep MBs in the basal ganglia were proved to be independent risk factor for attention affection.ConclusionNumber and localization of MBs proved to be important in determining cognitive consequences. The relations with cognitive performance were mainly driven by frontal, parietal, and deep located MBs in the basal ganglia. Memory affection in frontal MBs was dependent to severe white matter intensities and lacunes.

483Blood pressure and white matter lesions in patients with atrial fibrillation

Abstract Background Hypertension (HTN) is one of the most common cardiovascular risk factors in patients with atrial fibrillation (AF). As a potential risk factor for cerebral white matter lesions (WML), HTN might explain the increased risk of cognitive dysfunction in AF patients. Methods In a multicenter cohort study of patients with documented AF in Switzerland, systolic and diastolic blood pressure (SBP, DBP) was measured up to three times in a supine position and the mean was calculated. HTN was defined as controlled, when SBP was &lt;140 and DBP &lt;90 mmHg with treatment, and uncontrolled when SBP was ≥140 or DBP ≥90 mmHg with treatment. All patients underwent brain magnetic resonance imaging. Volumes of WML were assessed and graded using the Fazekas scale. A Fazekas score of ≥2 was defined as moderate or severe WML. Multivariable adjusted regression models were used to assess the association between BP and WML. Results Overall, 1738 patients were enrolled in this cross-sectional analysis (mean age 73 years, 73% males). Mean BP was 135/79 mmHg, 69% had a history of HTN. Any WMLs were found in 99% of the patients and 54% had at least moderate WMLs. The prevalence of Fazekas ≥2 was 47%, 50% and 61% among AF patients with SBP &lt;120, 120–140 and ≥140mmHg (p&lt;0.001), respectively. Volumes of WMLs significantly increased across the same SBP categories (2943, 3512 and 4988 mm3, p&lt;0.001). Among patients with normotension, controlled and uncontrolled HTN, moderate or severe WMLs were present in 173 (42.5%), 345 (55%) and 307 (61%), respectively. SBP was associated with Fazekas ≥2 and WML volume after multivariable adjustment (Table). Compared to normotension, both controlled and uncontrolled HTN were significantly associated with higher WML volume (Table). Association between blood pressure and white matter lesions Blood pressure Fazekas ≥2 OR (95% CI) Volume WML β-coefficient (95% CI) &lt;120 mmHg Ref Ref 120–140 mmHg 1.17 (0.88; 1.55) 0.14 (−0.01; 0.30) ≥140 mmHg 1.49 (1.11; 2.00) 0.28 (0.12; 0.43) Continuous, per SD 1.20 (1.09; 1.36), p&lt;0.001 0.12 (0.06; 0.18), p&lt;0.001 Normotension Ref Ref Treated hypertension 1.26 (0.94; 1.68), p=0.12 0.22 (0.07; 0.38), p=0.005 Treated, uncontrolled hypertension 1.52 (1.13; 2.05), p=0.005 0.38 (0.21; 0.54), p&lt;0.001 Regression analyses were adjusted for age, sex, BMI, smoking status, stroke, diabetes, coronary heart disease, AF type, and antihypertensive treatment. One standard Deviation (SD) of SBP = 18 mmHg. Volume of WML was log-transformed. Conclusion Moderate or severe cerebral WMLs are highly prevalent in AF patients and strongly associated with SBP. Our data suggests that optimal treatment of HTN might play an essential role in preventing WMLs. Acknowledgement/Funding Swiss National Science Foundation

MRI evaluation of the relationship between carotid artery endothelial shear stress and brain white matter lesions in migraine

Although white matter lesions are frequently detected in migraine patients, underlying mechanisms remain unclear. Low carotid artery endothelial shear stress has been associated with white matter lesions. We aimed to investigate the association between carotid artery endothelial shear stress and white matter lesions in migraine. In 40 elderly migraine patients (n = 29 females, 75 years [SD 3]) and 219 controls (n = 80 females, 74 years [SD 3]) from the PROSPER-MRI study, carotid artery endothelial shear stress was estimated on 1.5 T gradient-echo phase contrast MRI. White matter lesion volumes were calculated from structural MRI scans. Analyses were adjusted for age, sex, cardiovascular risk factors and cardiovascular disease. Migraine patients had lower mean endothelial shear stress compared to controls (0.90 [SD 0.15] vs. 0.98 [SD 0.16] Pa; P = 0.03). The association between mean endothelial shear stress and white matter lesion volume was greater for the migraine group than control group (P for interaction = 0.05). Within the migraine group, white matter lesion volume increased with decreasing endothelial shear stress (β-0.421; P = 0.01). In conclusion, migraine patients had lower endothelial shear stress which was associated with higher white matter lesion volume.

Association of White Matter Hyperintensities With Short-Term Outcomes in Patients With Minor Cerebrovascular Events.

White matter lesions (WML) are associated with cognitive decline, increased stroke risk, and disability in old age. We hypothesized that superimposed acute cerebrovascular occlusion on chronic preexisting injury (leukoaraiosis) leads to worse outcome after minor cerebrovascular event, both using quantitative (volumetric) and qualitative (Fazekas scale) assessment, as well as relative total brain volume. WML volume assessment was performed in 425 patients with high-risk transient ischemic attack (TIA; motor/speech deficits >5 minutes) or minor strokes from the CATCH study (CT and MRI in the Triage of TIA and Minor Cerebrovascular Events to Identify High Risk Patients). Complete baseline characteristics and outcome assessment were available in 412 patients. Primary outcome was disability at 90 days, defined as modified Rankin Scale score of >1. Secondary outcomes were stroke progression, TIA recurrence, and stroke recurrence. Analysis was performed using descriptive statistics and regression models including interaction terms. Median age was 69 years, 39.8% were female. Sixty-two patients (15%) had unfavorable outcome with disability at 90 days (modified Rankin Scale score >1). Higher Fazekas scores were strongly correlated with higher WML volume (r=0.79). Both higher Fazekas score and higher WMH volume were associated with disability at 90 days in univariate regression (odds ratio 1.22; 95% confidence interval, 1.04-1.43 and odds ratio, 1.25 per milliliter increase; 95% confidence interval, 1.02-1.54, respectively) but not with stroke progression, TIA recurrence, or stroke recurrence. In multivariable-adjusted analyses, additive interaction terms were associated with unfavorable outcome (adjusted odds ratio 3.99, 95% confidence interval, 1.87-8.49). Our data suggest that quantitative and qualitative WML assessments are highly correlated and comparable in TIA/minor stroke patients. WML burden is associated with short-term outcome of patients with good prestroke function in the presence of intracranial stenosis/occlusion.

Apolipoproteins and Alzheimer's pathophysiology

IntroductionApolipoproteins of demonstrated importance to brain cholesterol and ß-amyloid metabolism may serve as novel risk markers for Alzheimer's pathology. MethodsWe measured apolipoproteins (apoE, apoJ, apoA-I, and apoC-III and their uniquely defined subspecies) by enzyme-linked immunosorbent assay in plasma collected in 2000 and 2008 from 176 dementia-free participants of the Ginkgo Evaluation of Memory Study and related these to ß-amyloid on positron emission tomography scans, hippocampal volume, and white matter lesion volume in 2009. ResultsHigher apoE was associated with lower ß-amyloid deposition. Despite apoA-I being unrelated to hippocampal volume, subspecies of apoA-I containing or lacking apoJ or apoC-III showed opposite associations with hippocampal volume. Higher apoJ and apoE lacking apoJ were associated with higher hippocampal volume and higher white matter lesion volume, respectively. Associations were similar in participants without cognitive impairment or APOE ε4 noncarrier and when analyzing apolipoproteins in 2000–2002. DiscussionApolipoproteins may be important minimally invasive biomarkers indicative of Alzheimer's pathology.

Carotid Plaque Morphology and Ischemic Vascular Brain Disease on MRI.

Vulnerable carotid plaque components are reported to increase the risk of cerebrovascular events. Yet, the relation between plaque composition and subclinical ischemic brain disease is not known. We studied, in the general population, the association between carotid atherosclerotic plaque characteristics and ischemic brain disease on MR imaging. From the population-based Rotterdam Study, 951 participants underwent both carotid MR imaging and brain MR imaging. The presence of intraplaque hemorrhage, lipid core, and calcification and measures of plaque size was assessed in both carotid arteries. The presence of plaque characteristics in relation to lacunar and cortical infarcts and white matter lesion volume was investigated and adjusted for cardiovascular risk factors. Stratified analyses were conducted to explore effect modification by sex. Additional analyses were conducted per carotid artery in relation to vascular brain disease in the ipsilateral hemisphere. Carotid intraplaque hemorrhage was significantly associated with the presence of cortical infarcts (OR, 1.9; 95% confidence interval, 1.1-3.3). None of the plaque characteristics were related to the presence of lacunar infarcts. Calcification was the only characteristic that was associated with higher white matter lesion volume. There was no significant interaction by sex. The presence of carotid intraplaque hemorrhage on MR imaging is independently associated with MR imaging-defined cortical infarcts, but not with lacunar infarcts. Plaque calcification, but not vulnerable plaque components, is related to white matter lesion volume.

Associations of Early Kidney Disease With Brain Magnetic Resonance Imaging and Cognitive Function in African Americans With Type 2 Diabetes Mellitus

Relationships between early kidney disease, neurocognitive function, and brain anatomy are poorly defined in African Americans with type 2 diabetes mellitus (T2DM). Cross-sectional associations were assessed between cerebral anatomy and cognitive performance with estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) in African Americans with T2DM. African Americans with cognitive testing and cerebral magnetic resonance imaging (MRI) in the African American-Diabetes Heart Study Memory in Diabetes (AA-DHS MIND; n=512; 480 with MRI) and Action to Control Cardiovascular Risk in Diabetes (ACCORD) MIND (n=484; 104 with MRI) studies. eGFR (CKD-EPI creatinine equation), spot UACR. MRI-based cerebral white matter volume (WMV), gray matter volume (GMV), and white matter lesion volume; cognitive performance (Mini-Mental State Examination, Digit Symbol Coding, Stroop Test, and Rey Auditory Verbal Learning Test). Multivariable models adjusted for age, sex, body mass index, scanner, intracranial volume, education, diabetes duration, hemoglobin A1c concentration, low-density lipoprotein cholesterol concentration, smoking, hypertension, and cardiovascular disease were used to test for associations between kidney phenotypes and the brain in each study; a meta-analysis was performed. Mean participant age was 60.1±7.9 (SD) years; diabetes duration, 12.1±7.7 years; hemoglobin A1c concentration, 8.3%±1.7%; eGFR, 88.7±21.6mL/min/1.73m2; and UACR, 119.2±336.4mg/g. In the fully adjusted meta-analysis, higher GMV associated with lower UACR (P<0.05), with a trend toward association with higher eGFR. Higher white matter lesion volume was associated with higher UACR (P<0.05) and lower eGFR (P<0.001). WMV was not associated with either kidney parameter. Higher UACR was associated with lower Digit Symbol Coding performance (P<0.001) and a trend toward association with higher Stroop interference; eGFR was not associated with cognitive tests. Cross-sectional; single UACR measurement. In African Americans with T2DM, mildly high UACR and mildly low eGFR were associated with smaller GMV and increased white matter lesion volume. UACR was associated with poorer processing speed and working memory.

Higher subcortical and white matter cerebral blood flow in perinatally HIV-infected children.

This study aimed to evaluate cerebral blood flow (CBF) in pediatric human immunodeficiency virus (HIV)-infection, and its role in HIV-related cerebral injury and cognitive impairment.This cross-sectional observational study compared 28 perinatally HIV-infected children (8–18 years) to 34 healthy controls matched for age, sex, ethnicity, and socio-economic status. All participants underwent 3-Tesla magnetic resonance imaging, using arterial spin labeling to assess CBF in gray matter (GM), white matter (WM), basal ganglia, and thalamus. We used linear regression analysis to evaluate group differences and associations with HIV disease and treatment characteristics, macrostructural (volume loss, WM lesions) or microstructural injury (increased WM diffusivity, neurometabolite alterations), or poorer cognitive performance.HIV-infected children had higher CBF in WM (+10.2%; P = 0.042), caudate nucleus (+4.8%; P = 0.002), putamen (+3.6%; P = 0.017), nucleus accumbens (+3.9%; P = 0.031), and thalamus (+5.5%; P = 0.032). Thalamus CBF was highest in children with a Centers for Disease Control and Prevention stage B (Coef. = 6.45; P = 0.005) or C (Coef. = 8.52; P = 0.001) diagnosis. Lower GM CBF was associated with higher WM lesion volume in HIV-infected children (Coef. = −0.053; P = 0.001). No further associations with HIV-related cognitive impairment or cerebral injury were found.CBF was higher in WM, basal ganglia, and thalamus in combination antiretroviral therapy (cART)-treated perinatally HIV-infected children, but this was not associated with cerebral injury or cognitive impairment. HIV-infected children with lower GM CBF had a higher volume of WM lesions, which could reflect vascular disease as potential contributing factor to white matter injury. Lifelong exposure to HIV and cART in this population warrants longitudinal assessment of CBF and how it relates to (neuro)inflammation, vascular dysfunction, and cerebral injury in pediatric HIV.

White Matter Lesions, Carotid and Coronary Atherosclerosis in Late-Onset Depression and Healthy Controls

Cerebral white matter lesions (WMLs) are more common in individuals with late-onset or late-life depression. It has been proposed that carotid atherosclerosis may predispose to WMLs by inducing cerebral hypoperfusion. This hemodynamic effect of carotid atherosclerosis could be important for the formation of WMLs in depression. The case-control study included 29 patients with late-onset major depressive disorder and 27 controls matched for sex, age, and tobacco use. WML volume, carotid intima-media thickness, and coronary plaque volume were assessed using magnetic resonance imaging, ultrasound scan, and coronary computed tomography (CT) angiography, respectively. The mean age for the total sample was 59.7 ± 4.7 years. There was no difference in carotid intima-media thickness between patients and controls (p = 0.164), whereas a higher WML volume in the patients was found (p = 0.051). In both patients and controls, WML volume was associated with carotid but not with coronary atherosclerosis. In adjusted multiple linear regression, a 0.1mm increase in averaged carotid intima-media thickness was associated with a 52% (95% CI: 8.4-112, p = 0.032) increase in WML volume. The association between carotid intima-media thickness and WML volume was, however, similar in patients and controls. In older persons aged between 50 and 70 years, WMLs do not seem to be a part of generalized atherosclerotic disease, but seem to be dependent on atherosclerosis in the carotid arteries. Carotid atherosclerosis, however, could not explain the higher WML load observed in the depressed patients, and thus, studies are needed to establish the mechanisms linking depression and WMLs.

Cerebral small vessel disease is related to disturbed 24-h activity rhythms: a population-based study.

Cerebral small vessel disease is common in elderly persons. Patients with dementia or stroke frequently have cerebral small vessel disease and often experience disturbances in the sleep-wake rhythm. It is unknown whether cerebral small vessel disease is related to disturbances in sleep and 24-h activity rhythms. This study was conducted in the Rotterdam Study. A total of 970 community-dwelling persons (mean age 59.2years) underwent brain magnetic resonance imaging and actigraphy. Cerebral small vessel disease was defined as white matter lesions (total volume in millilitres) and the presence of cerebral microbleeds and lacunar infarcts. Twenty-four hour activity rhythms and sleep were measured with actigraphy by estimating the instability and fragmentation of the activity rhythm and total sleep time. Sleep quality was assessed with the Pittsburgh Sleep Quality Index. White matter lesions, instability, fragmentation and sleep quality were standardized for analyses. Higher white matter lesion volume (B=0.09 per SD, 95% confidence interval0.02; 0.15) and cerebral microbleeds (B=0.19 per SD, 95% confidence interval0.02; 0.37) were significantly related to more fragmented 24-h activity rhythms. None of the small vessel disease markers was related to total sleep time or sleep quality. White matter lesion volume and the presence of cerebral microbleeds are related to disturbed activity rhythms. This suggests that subclinical brain damage affects the 24-h activity rhythm.

Cerebral Structural Changes in Diabetic Kidney Disease: African American–Diabetes Heart Study MIND

OBJECTIVEAlbuminuria and reduced kidney function are associated with cognitive impairment. Relationships between nephropathy and cerebral structural changes remain poorly defined, particularly in African Americans (AAs), a population at higher risk for both cognitive impairment and diabetes than European Americans. We examined the relationship between urine albumin:creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), and cerebral MRI volumes in 263 AAs with type 2 diabetes.RESEARCH DESIGN AND METHODSCross-sectional associations between renal parameters and white matter (WM), gray matter (GM), hippocampal, and WM lesion (WML) volumes were assessed using generalized linear models adjusted for age, education, sex, BMI, hemoglobin A1c (HbA1c) level, and hypertension.RESULTSParticipants had a mean (SD) age of 60.2 years (9.7 years), and 62.7% were female. Mean diabetes duration was 14.3 years (8.9 years), HbA1c level was 8.2% (2.2%; 66 mmol/mol), eGFR was 86.0 mL/min/1.73 m2 (23.2 mL/min/1.73 m2), and UACR was 155.8 mg/g (542.1 mg/g; median 8.1 mg/g). Those with chronic kidney disease (CKD) (eGFR <60 mL/min/1.73 m2 or UACR >30 mg/g) had smaller GM and higher WML volumes. Higher UACR was significantly associated with higher WML volume and greater atrophy (larger cerebrospinal fluid volumes), and smaller GM and hippocampal WM volumes. A higher eGFR was associated with larger hippocampal WM volumes. Consistent with higher WML volumes, participants with CKD had significantly poorer processing speed and working memory. These findings were independent of glycemic control.CONCLUSIONSWe found albuminuria to be a better marker of cerebral structural changes than eGFR in AAs with type 2 diabetes. Relationships between albuminuria and brain pathology may contribute to poorer cognitive performance in patients with mild CKD.

Diabetes, markers of brain pathology and cognitive function

We investigated whether, and the extent to which, vascular and degenerative lesions in the brain mediate the association of diabetes with poor cognitive performance. This cross-sectional study included 4,206 participants (age > 65 years; 57.8% women) of the Age, Gene/Environment Susceptibility-Reykjavik Study. Data were collected through interview, clinical examination, psychological testing, and laboratory tests. The composite scores on memory, information-processing speed, and executive function were derived from a cognitive test battery. Markers of cerebral macrovascular (cortical infarcts), microvascular (subcortical infarcts, cerebral microbleeds, and higher white matter lesion volume), and neurodegenerative (lower gray matter, normal white matter, and total brain tissue volumes) processes were assessed on magnetic resonance images. Mediation models were employed to test the mediating effect of brain lesions on the association of diabetes with cognitive performance controlling for potential confounders. There were 462 (11.0%) persons with diabetes. Diabetes was significantly associated with lower scores on processing speed and executive function, but not with memory function. Diabetes was significantly associated with all markers of brain pathology. All of these markers were significantly associated with lower scores on memory, processing speed, and executive function. Formal mediation tests suggested that markers of cerebrovascular and degenerative pathology significantly mediated the associations of diabetes with processing speed and executive function. Diabetes is associated with poor performance on cognitive tests of information-processing speed and executive function. The association is largely mediated by markers of both neurodegeneration and cerebrovascular disease. Older people with diabetes should be monitored for cognitive problems and brain lesions.