Cerebral White Matter Hyperintensities Research Articles

Randomized Trial of Marine n-3 Polyunsaturated Fatty Acids for the Prevention of Cerebral Small Vessel Disease and Inflammation in Aging (PUFA Trial): Rationale, Design and Baseline Results.

Vascular risk factors for age-related cognitive decline are significant, and their management may ultimately prove the most successful strategy for reducing risk and sustaining cognitive health. This randomized, double-blinded, placebo-controlled trial with parallel group allocation to either marine n-3 polyunsaturated fatty acids (n-3 PUFA) or soybean oil placebo assesses the effects on the total volume of accumulation in cerebral white matter hyperintensities (WMH), a potentially modifiable neurovascular component of age-related cognitive decline. Total WMH accumulation over 3 years is the primary endpoint. The safety and efficacy of n-3 PUFA is evaluated in older adults with significant WMH and suboptimum plasma n-3 PUFA as inclusion criteria. One hundred and two non-demented older adults were enrolled with a mean age of 81.1 (±4.4) years, WMH of 19.4 (±16.1) cm3, and a plasma n-3 PUFA of 86.64 (±29.21) µg/mL. 61% were female, 28% were apolipoprotein E epsilon 4 carriers, and the mean mini-mental state exam (MMSE) was 27.9 (±1.7). This trial provides an initial evaluation of n-3 PUFA effects on WMH, a reproducible and valid risk biomarker for cognitive decline, as well as on inflammatory biomarkers thought to play a role in WMH accumulation. We present the baseline results and operational experience of enriching a study population on advanced age, blood n-3 PUFA, and magnetic resonance imaging (MRI) derived WMH with biomarker outcomes (WMH, inflammation markers) in a dementia prevention paradigm.

Serum alkaline phosphatase level is correlated with the incidence of cerebral small vessel disease.

Vascular calcification is one of the mechanisms underlying the pathogenesis of cerebral small vessel disease (CSVD). Whether higher levels of serum alkaline phosphatase (ALP), a predictor of vascular calcification, are independently associated with CSVD remains inconclusive. The present study explored the link between levels of circulating ALP and CSVD in a Chinese population. A total of 568 participants were recruited from the healthcare center at the affiliated Zhongshan Hospital of Dalian University and the Fifth People Hospital of Dalian between January 2010 and December 2016. The subjects were divided into three groups based on the infarct and severity of white matter hyper-intensities (WMH) as categorized by brain magnetic resonance imaging (MRI) analysis and Fazekas rating scales: no/mild cerebral WMH (nm-WMH); moderate-to-severe WMH (MS-WMH); and silent lacunar infarct (SLI). The subjects were also divided into three tertiles based on circulating levels of ALP: ≤64, 65-105 and ≥106 (IU/L). Information regarding the risk factors, such as coronary artery disease, diabetes mellitus, hypertension and serum ALP level, C-reactive protein, homocysteine (HCY), and other laboratory results, were collected. The associations of ALP with WMH and SLI were evaluated using logistic regression analysis. After adjustment for vascular risk factors, subjects with MS-WMH and SLI were more likely to have ALP levels ≥106 IU/L than ≤64 IU/L. The mean circulating level of ALP was substantially increased in patients with MS-WMH or SLI compared with patients with nm-WMH. The multivariate model revealed that this significant difference remained when MS-WMH or SLI was added to the model, after adjustment for confounding factors. The circulating level of ALP was positively correlated with a high risk of silent lacunar infarct and white matter hyperintensity; important indicators of small vessel disease.

Standardized Assessment of Automatic Segmentation of White Matter Hyperintensities and Results of the WMH Segmentation Challenge.

Quantification of cerebral white matter hyperintensities (WMH) of presumed vascular origin is of key importance in many neurological research studies. Currently, measurements are often still obtained from manual segmentations on brain MR images, which is a laborious procedure. The automatic WMH segmentation methods exist, but a standardized comparison of the performance of such methods is lacking. We organized a scientific challenge, in which developers could evaluate their methods on a standardized multi-center/-scanner image dataset, giving an objective comparison: the WMH Segmentation Challenge. Sixty T1 + FLAIR images from three MR scanners were released with the manual WMH segmentations for training. A test set of 110 images from five MR scanners was used for evaluation. The segmentation methods had to be containerized and submitted to the challenge organizers. Five evaluation metrics were used to rank the methods: 1) Dice similarity coefficient; 2) modified Hausdorff distance (95th percentile); 3) absolute log-transformed volume difference; 4) sensitivity for detecting individual lesions; and 5) F1-score for individual lesions. In addition, the methods were ranked on their inter-scanner robustness; 20 participants submitted their methods for evaluation. This paper provides a detailed analysis of the results. In brief, there is a cluster of four methods that rank significantly better than the other methods, with one clear winner. The inter-scanner robustness ranking shows that not all the methods generalize to unseen scanners. The challenge remains open for future submissions and provides a public platform for method evaluation.

Influence de la leucopathie vasculaire sur l’issue clinique des patients traités par thrombectomie mécanique à la phase aiguë de l’AVC ischémiques : résultats dans l’essai THRACE associé à une cohorte multicentrique

Introduction Cerebral white matter hyperintensity (WMH) on FLuid Attenuated Inversion Recovery (FLAIR) is linked to less favourable outcome in patients with acute ischemic stroke (AIS) but data on their relevance in patients with large vessel occlusion (LVO) treated with mechanical thrombectomy (MT) are sparse. In this post-hoc analysis of the MT arm of the THRACE trial and multicenter retrospective cohorts, we aimed to determine the influence of WMH burden on clinical outcome, rate of symptomatic intracranial hemorrhage (ICH) and procedural success in AIS patients treated by MT with current stentriever/aspiration devices. Patients and methods Patients from the MT arm of THRACE trial, and prospective cohorts from two academic comprehensive stroke centers were pooled and retrospectively analyzed. WMH volumes were obtained by semi-automated planimetric segmentation and tested in association with the rate of favourable outcome (mRS 0-2 at at 90 days), successful recanalization after MT (mTICI ≥ 2B), and symptomatic ICH. Results A total of 535 subjects met inclusion criteria between 2015 and 2018 (49 % female, mean age 68,0 years ± 15,0 Overall, 458 (85,6 %) patients presented with detectable WMH (median volume 5,7cc IQR [2,8–12,7]). Patients demonstrated increasingly worse outcomes with increasing WMH volumes), with 57 % of patients in the 1st quartile of WMH volume demonstrating favourable outcome vs. 27 % in the 4th (p Conclusion Our study provides evidence that patients with AIS due to LVO and severe WMH as assessed by pre-treatment MRI, are at higher risk for less favourable outcome following MT, despite similar rates of sICH and procedural success. Since 27 % of patients with severe WMH in our sample experienced favourable outcome at 3 months, severe WMH burden may not preclude MT.

Cognitive functions and jugular venous reflux in severe mitral regurgitation: A pilot study.

Cardiac diseases with elevated central venous pressure have higher frequency of jugular venous reflux (JVR), which is associated with decreased cerebral blood flow and white matter hyperintensities. Whether patients with severe mitral-regurgitation (SMR) have poorer cognitive functions and whether JVR is involved were determined in this pilot study. Patients with SMR and age/sex-matched controls were prospectively recruited. Neuropsychological tests such as global cognitive (Mini-Mental State Examination, MMSE), verbal memory, executive, and visuospatial domains were performed. Cardiac parameters by cardiac catheterisation and echocardiography, and the frequency of JVR by colour-coded duplex ultrasonography were obtained. Forty patients with SMR and 40 controls (71.1±12.2, 38–89 years; 75% men) were included. Compared with the controls, patients with SMR had lower scores in all neuropsychological tests but only MMSE and visuospatial test scores were statistically significant after adjusting for age, sex, and educational level. We further adjusted for cardiovascular risk factors; the significance remained in the visuospatial test but diminished in MMSE. Multivariate linear regression analyses adjusted for age, sex, and educational level showed that JVR combined with high right-atrial-pressure (RAP > 50th-percentile, 12 mmHg) was significantly associated with poorer performances in both MMSE [right JVR: B coefficient(95% confidence interval,p) = -2.83(-5.46–0.20, 0.036); left JVR: -2.77(-5.52–0.02, 0.048)] and visuospatial test [right JVR: -4.52(-8.89–0.16, 0.043); left JVR: -4.56(-8.81–0.30, 0.037)], with significances that remained after further adjusting for cardiovascular risk factors. Our pilot results suggest that retrogradely-transmitted venous pressure might be involved in the mechanisms mediating the relationship between cardiac diseases and brain functions.

Risk Factor Analysis of Severe Cerebral White Matter Hyperintensities in Type 2 Diabetes Patients: A Retrospective Single-Center Observational Study

Background: Bone is recently confirmed to be an endocrine organ, and may influence the neuron, leading to the cognitive decline and emotional disorder. However, the interaction between bone and cerebral white matter hyperintensities (WMH) is still unclarified in type 2 diabetes patients. Methods: WMH was quantified on magnetic resonance imaging (MRI) using the Fazekas and Schmidt's scoring protocol. Patients with scores ranging from 0 to 1 were defined as none or mild WMH (Group 1), and patients with scores ranging from 2 to 3 as severe WMH (Group 2). Logistic regression analysis was done to determine the association between WMH severity and selected clinical factors. Findings: Of the 194 subjects who were included in the study, there were significant differences among the two groups with respect to age and osteocalcin. After adjustment for possible confounders, age (odds ratio (OR): 1.07; 95% confidence interval (CI): 1.04-1.12; P < 0.001) and low density lipoprotein (OR: 1.51; 95% CI: 1.09-2.08; P =0.012) were associated with severe WMH, while osteocalcin could decrease the severity of WMH (OR: 0.96; 95% CI: 0.84-0.98; P =0.014). Interpretation: Our data indicate that aging, lower osteocalcin and higher LDL are associated with severe WMH in type 2 diabetes patients. The mechanism of the relationship between osteocalcin and WMH needs further research. Funding Statement: This work was supported by General Scientific Research Project of Zhejiang Education Department (Y201838964), Project of medicine and health technology program in Zhejiang province (2019314900). Declaration of Interests: All authors declare that they have no conflict of interest. Ethics Approval Statement: Ethics approval was obtained from the Ethics Board of Shanghai Tenth People’s Hospital.

Abstract TMP117: Relationship of Cerebral White Matter Hyperintensity Progression and Leukocyte Activation

Background: Cerebral white matter hyperintensities (WMH) are an important contributor to injury in the aging brain. Progression in WMH volume is associated with cognitive decline and gait impairment. Understanding the factors associated with WMH progression may provide insight to pathogenesis and identify novel treatment targets to improve cognitive health. Methods: In 60 patients assessed for a cognitive complaint, an MRI brain was obtained at baseline and then repeated at a median of 5.9 years (IQR 3.5-8.2 years) from start of study. WMH was measured by semi-automated segmentation protocol and rate of progression per year determined. A blood sample was acquired at baseline in a PAXgene tube and used to measure whole genome RNA expression by RNA sequencing. The relationship between rate of WMH progression over time and leukocyte RNA expression was analyzed. Results: The mean age was 76.1 (SD 8.3) years and 61% of participants were female. The median rate of WMH progression over 5.8 years was 1.3 mm 3 /year (IQR 0.27-3.3mm 3 /year). The median WMH volume was 5.5 mL (IQR 2.2-14.2). Patients in the quartile with the highest rate of WMH progression had increased leukocyte expression of genes involved in pattern recognition receptors (INFK, NLRP3, OAS1, TGFB1), interferon signaling (IFI6, IFIT1, IFITM3), and leukocyte extravasation (CLDN5, ICAM1, ITGB3, NCF1, TIMP2). A gene model could predict patients likely to experience a high rate of WMH progression over time with &gt;80% accuracy. This remained significant when adjusted for factors associated with WMH progression. Conclusions: Progression of WMH over time is associated with increased expression of genes involved in leukocyte extravasation, pattern recognition receptor activation and interferon signaling. Patients at risk for WMH progression may be identified by leukocyte RNA expression. Further studies are needed to evaluate the role of peripheral inflammation in relation to rate of WMH progression and contribution to cognitive decline.

Abstract WP216: Epigenome-Wide Association Study of Cerebral White Matter Hyperintensities

Background: Cerebral white matter hyperintensities (WMH) on MRI are typical markers of small vessel disease and strong radiological correlates of stroke and age-related cognitive decline. Despite a recognized high heritability, the molecular basis of WMH has not been fully characterized. In particular, the contribution of epigenetic modifications, such as DNA methylation, has not been explored. Methods: We conducted a meta-analysis of epigenome-wide association studies of WMH burden in up to 5777 elderly participants of European and African ancestry from 9 population-based cohorts using blood-derived DNA methylation measured on the Infinium HumanMethylation450 BeadChip. Cohort-specific associations between burden of WMH and DNA methylation beta values were estimated using linear mixed-effect models and combined in a sample-size weighted fixed-effect meta-analysis. In addition, we used two different approaches to identify differentially methylated regions (DMRs), which may be more informative than individual loci. Bonferroni correction and False Discovery Rates were used to account for the multiple tests. Results: Single-site analyses identified a CpG site within the CLDN5 gene significantly associated with WMH (P= 2.3x10 -7 ). Claudin-5 is an endothelial-specific component in the brain vasculature and regulates blood brain barrier permeability. Region-based analyses, which leverage the correlations between nearby CpG sites identified several DMRs significantly associated with WMH burden including: PRMT1, BTBD17, and IFITM10 (P=1.4x10 -10 , 2.3x10 -8 , and 3.6x10 -7 , respectively). PRMT1 encodes the Protein Arginine N-methylase 1, which methylates histones in genes involved in glioblastomagenesis. Mice lacking this gene are characterized by severe defects in oligodendrocyte maturation processes. The function of BTBD17 and IFITM10 is not characterized but both are expressed in the brain and exhibit changes in expression in response to viral infection. Conclusions: Consistent with our previously reported genetic association studies, this genome-wide DNA methylation analysis supports a role of genes involved in glial cell function in WMH etiology. It also suggests a novel role of genes involved in viral response.

Abstract TP546: Association of Near-Infrared Spectroscopy Defined Regional Cerebral Oxygen Saturation with Progression of Cerebral White Matter Hyperintensity Lesions in Comatose Patients

Background: Real-time regional cerebral oxygen saturation (rScO 2 ) measurement using near-infrared spectroscopy (NIRS) may aid in the identification of intracerebral ischemia in critically ill patients. Ischemia to the cerebral white matter results in injury detectable by brain MRI as white matter hyperintensities (WMH). We hypothesized that rScO 2 as assessed by NIRS correlates with the degree of WMH progression in patients admitted to a neurocritical care unit (NCCU). Materials and Methods: Retrospective study of eight comatose patients (Glasgow Coma Scale ≤8) in the NCCU who were continuously monitored for three days after their coma onset with NIRS to assess rScO 2, and who had a brain MRI upon admission and before their hospital discharge. Semi-automated volumetry based on intensity thresholding was used to quantify the WMH volume on FLAIR sequences. The degree of WMH progression was calculated by subtracting the WMH volume of the admission MRI from discharge MRI. Spearman rank correlation was used to determine the strength of association between the rScO 2 (averaged over the monitoring period) and the degree of WMH progression. Results: The median averaged rScO 2 was 61 (IQR (48-73) and the lowest 45. Overall, rScO 2 inversely correlated with WMH progression (rho -.738, p= 0.037); i.e., a lower rScO 2 was associated with greater WMH progression (Figure 1). Patients with greater WMH progression had a worse modified Rankin Scale on discharge (rho .769, p= 0.026). Interpretation: Our study provides proof of principle that rScO 2 as assessed by non-invasive NIRS monitoring may aid detection of cerebral white matter injury.

Cerebral White Matter Hyperintensities, Kidney Function Decline, and Recurrent Stroke After Intensive Blood Pressure Lowering: Results From the Secondary Prevention of Small Subcortical Strokes ( SPS 3) Trial.

BackgroundWe aimed to determine whether cerebral white matter hyperintensities (WMHs) can distinguish stroke survivors susceptible to rapid kidney function decline from intensive blood pressure (BP) lowering.Methods and ResultsThe SPS3 (Secondary Prevention of Small Subcortical Strokes) trial randomized participants with recent lacunar stroke to systolic BP targets of 130 to 149 and <130 mm Hg. We included 2454 participants with WMH measured by clinical magnetic resonance imaging at baseline and serum creatinine measured during follow‐up. We tested interactions between BP target and WMH burden on the incidence of rapid kidney function decline (≥30% decrease from baseline estimated glomerular filtration rate at 1‐year follow‐up) and recurrent stroke. Rapid kidney function decline incidence was 11.0% in the lower‐BP‐target arm and 8.1% in the higher‐target arm (odds ratio=1.40; 95% CI=1.07–1.84). Odds ratio for rapid kidney function decline between lower‐ and higher‐target groups ranged from 1.26 in the lowest WMH tertile (95% CI, 0.80–1.98) to 1.71 in the highest tertile (95% CI, 1.05–2.80; P for interaction=0.65). Overall incidence of recurrent stroke was 7.9% in the lower‐target arm and 9.6% in the higher‐target arm (hazard ratio=0.80; 95% CI, 0.63–1.03). Hazard ratio for recurrent stroke in the lower‐target group was 1.13 (95% CI, 0.73–1.75) within the lowest WMH tertile compared with 0.73 (95% CI, 0.49–1.09) within the highest WMH tertile (P for interaction=0.04).ConclusionsParticipants with higher WMH burden appeared to experience greater benefit from intensive BP lowering in prevention of recurrent stroke. By contrast, intensive BP lowering increased the odds of kidney function decline, but WMH burden did not significantly distinguish this risk.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059306.

Effects of sartans and low-dose statins on cerebral white matter hyperintensities and cognitive function in older patients with hypertension: a randomized, double-blind and placebo-controlled clinical trial.

Cerebral white matter hyperintensities (WMHs) and cognitive impairment are common in elderly hypertensive patients, and more needs to be learned about their prevention and treatment. Our aim was to investigate the effect of low-dose statins on WMH and cognitive function in elderly patients undergoing antihypertensive treatment. A total of 732 elderly hypertensive patients taking hydrochlorothiazide as their baseline medication were randomized using a 2 × 2 factorial design with antihypertensive (telmisartan vs. placebo) and lipid-modulating (low-dose rosuvastatin vs. placebo) arms. Brain magnetic resonance imaging (MRI) and cognitive function data were obtained. After a mean follow-up time of 59.8 (range 12-65) months, there were no differences in WMH progression and cognitive function decline over time between the groups in the antihypertensive arm. The risks of new-incident WMH Fazekas scale scores ≥ 2 and the incidence of cognitive impairment did not differ between the telmisartan and placebo groups. Rosuvastatin use was associated with lower risks of new-incident Fazekas scale scores ≥2 (hazard ratio = 0.500; 95% confidence interval: 0.34-0.74) and cognitive impairment (hazard ratio = 0.54; 95% confidence interval: 0.36-0.80). Telmisartan interacted with rosuvastatin on reducing WMH progression and cognitive function decline. Findings suggest that low-dose rosuvastatin could reduce WMH progression and cognitive function decline in antihypertensive patients, as demonstrated by the interaction between telmisartan and low-dose rosuvastatin to this effect.

Differential characteristics between aortic pressure augmentation and carotid flow augmentation: clinical implications for cerebral white matter hyperintensities

BackgroundAortic stiffness and pressure wave reflection have been found to be associated with age-related cerebral microvascular disease, but the underlying mechanism remains obscure. We hypothesized that cerebral (carotid) flow augmentation potentially mediates these associations.MethodsDoppler waveforms were recorded in 286 patients with hypertension to measure the carotid flow augmentation index (FAIx) as the late/early systolic velocity amplitude ratio. Tonometric waveforms were recorded to estimate the aortic pressure augmentation index (PAIx), aortic compliance, and carotid-femoral and carotid-radial pulse wave velocities (PWVs). Additionally, white matter hyperintensities (WMH) on brain MRI were evaluated using the Fazekas scale.ResultsWith increasing age, the carotid late-systolic velocity increased whereas the early-systolic velocity decreased, although the aortic augmented pressure increased in parallel with the incident wave height (P<0.001). Both FAIx and PAIx increased with age, but the age-dependent curves were upwardly concave and convex, respectively. FAIx increased exponentially with increasing PAIx (r = 0.71). Compared to PAIx, FAIx was more closely (P ≤ 0.001) correlated with the aortic PWV, aortic compliance, and aortic/peripheral PWV ratio. FAIx was associated with WMH scores independently of confounders including age, gender, diabetes, hypercholesterolemia and aortic PWV (P = 0.02), and was more predictive of WMH presence than PAIx.ConclusionsCarotid FAIx had closer associations with age, aortic stiffness and cerebral WMH than did aortic PAIx. These results indicate that carotid flow augmentation (enhanced by aortic stiffening and pressure wave reflection from the lower body) causes microcerebrovascular injury potentially through increasing cerebral flow pulsations, but this detrimental effect is even greater than that estimated from PAIx.

Orthostatic Hypotension and Cognitive Function in Parkinson’s Disease

Background Although orthostatic hypotension (OH) and cognitive impairment (CI) are common non- motor symptoms of Parkinson’s disease (PD), the relationship between OH and CI remains to be clarified. This study was aimed to investigate the relationship between OH and CI in PD. Methods We recruited 192 patients who were diagnosed as PD based on the UK Brain Bank diagnostic criteria. The Hoehn & Yahr stages were ranged I to III and patients underwent extensive clinical evaluation, including brain magnetic resonance imaging (MRI) for cerebral white matter hyperintensity (WMH), tilt table test, the Korean version of Montreal Cognitive Assessments and the Korean version of Mini-Mental Status Examination in one month from the first clinic visit. The participants were divided into two groups according to the presence of OH (OH+ vs. OH-) and cognitive function (cognitive normal, CN vs. CI), respectively. Results Significant relationship between OH and cognitive function (p=0.04) was found in our patients. The patients with OH+ had higher risk of CI by 2.6 times than that of OH- patients. Maximum heart rate change during tilt table test was correlated with cognitive function and white matter changes, whereas blood pressure change during tilt table test showed no correlation with those parameters. Conclusions There was significant relationship between OH and CI in PD. Therefore, PD patients with either symptom may need periodic evaluation and proper management for OH and cognitive functions. Key Words: Orthostatic hypotension, Parkinson disease, Autonomic nervous system, Cognition

The associations between bone mineral density and cerebral white matter hyperintensity in elderly stroke patients

The associations between bone mineral density and cerebral white matter hyperintensity in elderly stroke patients

The effect of midlife cardiovascular risk factors on white matter hyperintensity volume and cognition two decades later in normal ageing women

Cerebral White Matter Hyperintensity (WMH) lesions have been identified as markers of cerebrovascular diseases and they are associated with increased risk of cognitive impairment. In this study, we investigated the relationship between midlife cardiovascular risk factors and late life WMH volumes two decades later, and examined their association with cognitive performance. 135 participants from the Women's Healthy Ageing Project had completed midlife cardiovascular risk measurement in 1992 and late life brain MRI scan and cognitive assessment in 2012. In these community-dwelling normal aging women, we found that higher midlife Framingham Cardiovascular Risk Profile (FCRP) score was associated with greater WMH volume two decades later, and was predominantly driven by the impact of HDL cholesterol level, controlling for age, education and APOE ε4 status. Structural equation modelling demonstrated that the relationship between midlife FCRP score and late life executive function was mediated by WMH volume. These findings suggest intervention strategies that target major cardiovascular risk factors at midlife might be effective in reducing the development of WMH lesions and thus late life cognitive decline.

Cerebral white matter Hyperintensities in HIV-positive patients.

White matter hyperintensities (WMHs) have been associated with neurological complications including cognitive impairment. WMHs have been often described in HIV positive subjects and they have been linked to neurocognitive impairment, cerebrospinal fluid (CSF) residual viral replication and biomarkers of monocyte activation. Aim of this study was to grade WMHs in HIV-positive individuals using a simple visual scale and to explore their severity with clinical, neurocognitive and biomarker characteristics. Brain MRIs were retrospectively evaluated by two reviewers who rated WMHs following the "age-related white matter changes (ARWMC)" scale. 107 adult HIV-positive patients receiving lumbar punctures for clinical reasons were included. 70 patients (66.6%) were diagnosed with WMHs. Average WMH scores were higher in treated [7 (1-11)] vs. naïve individuals [3 (0-6)] (p = 0.008). Higher WHMs scores were observed in patients with chronic renal impairment along with chronic hepatitis (naïve) and longer HIV duration (treated participants). No consistent associations between plasma, CSF biomarkers and WMHs scores were found. 45 patients underwent full neurocognitive tests and WMHs scores were non-significantly higher in patients diagnosed with HAND [6.5 (0.5-8.3) vs. 1.5 (0-7), p = 0.165]; screening (IHDS and FAB), visuo-spatial (Corsi's) and auditory-verbal memory (disillabic words repetition) tests scored worse in patients with higher WMHs. In our population of HIV-positive patients with low CD4 nadir and partial CD4 cell recovery the burden of WMHs was associated with the duration of HIV infection and with commonly observed comorbidities (such as renal and hepatic impairment). Given the association with worse neurocognition, further studies on tailored interventions are needed.

Abstract P333: Effect of Autonomous Cortisol Secretion on Cerebrovasuclular Events in Patients With Primary Aldosteronism

Background: Primary aldosteronism (PA) display a higher risk of cerebrovascular events (CVE) compared with essential hypertension (EH).On the one hand, it was also reported that the PA patients associated with autonomous cortisol secretion had high incidence of CVE. Objective: Our objective was to investigate the effect of autonomous cortisol secretion on the prevalence of CVE in the patients with PA and/or Cushing syndrome (CS). Design and Setting: This was a retrospective cross-sectional study from Tohoku University Hospital between 2008 and 2017. Patient: 291 patients were analyzed. In the patients with PA, the recent continuous cases performed adrenal venous sampling (AVS) were extracted. They were divided into four groups. Group A: 32 CS patients, Group B: 34 PA patients with autonomous cortisol secretion, Group C:121 PA patients with aldosterone producing adenoma (APA) and Group D: 104 PA patients with idiopathic hyperaldosteronism (IHA). They were also performed and analyzed MRI brain scans during a hospitalization and examined 1-mg dexamethasone suppression test . The patients in Group A, B and C were underwent adrenalectomy. Results: In Group A and Group B, the female-to-male ratio was significantly high (about 4:1). The prevalence of symptomatic stroke prevalence of symptomatic stroke before the confirmed diagnosis in each group were as follows: Group A:2/32, Group B: 0/34, Group C:13/121 and Group D: 3/104. The unruptured cerebral aneurysms were detected in Group A:1/32, Group B: 0/34,Group C:2/121 and Group D: 3/104. Aside from this results, 3 patients underwent surgical clipping for unruptured cerebral aneurysms. During this follow-up period, 5 patients had new onset of CVE(cerebral infarction: 1, cerebellar hemorrhage: 4) in Group C albeit carried out adrenalectomy. In comparison with MRI findings between Group A and B, we found no significant difference in the prevalence of Cerebral microbleeds (CMBs:5.8-9.3%) and High grade white matter hyperintensities (HWHs:43-50%). Conclusion: In this study, we could not demonstrate that the patients with PA associated with autonomous cortisol secretion had high incidence of CVE. Nevertheless, we demonstrate that the patients with APA had relatively high incidence of CVE.

Correlation between Fibrinogen and White Matter Hyperintensities among Nondiabetic Individuals with Noncardiogenic Ischemic Stroke

The aim of the present study is to confirm the correlation between fibrinogen and the severity of cerebral white matter hyperintensities (WMHs) among nondiabetic patients with noncardiogenic acute ischemic stroke. A cross-sectional study of 170 consecutive patients with noncardiogenic acute ischemic stroke who underwent magnetic resonance imaging and vascular imaging was conducted. WMHs were classified into periventricular hyperintensity (PVH) and deep and subcortical WMH (DSWMH) using Fazekas rating scale. After adjustment for fibrinogen and other vascular risk factors, we determined which factors were independent of WMHs. After adjustment for the vascular risk factors, prior ischemic stroke (odds ratio [OR] 4.153, 95% confidence interval [CI] 1.077-16.020, P = .039), fibrinogen level (OR 2.114, 95% CI 1.034-4.322, P = .040), and glycosylated hemoglobin A1c (OR .633, 95% CI .423-.947, P = .026) were independently and positively associated with PVH (P < .05); prior ischemic stroke (OR 2.841, 95% CI 1.469-5.493, P = .002), lipoprotein(a) (OR 1.002, 95% CI 1.000-1.005, P = .047), and fibrinogen levels (OR 1.788, 95% CI 1.170-2.732, P = .007) were independently and positively associated with DSWMH (P < .05). Our study demonstrated that prior ischemic stroke and higher fibrinogen are associated with WMHs, regardless of PVH and DSWMH, in nondiabetic patients with noncardiogenic acute ischemic stroke. In addition, lipoprotein(a) might be an independent predictor of DSWMH in patients with noncardiogenic acute ischemic stroke.

STRUCTURAL INTEGRITY OF THE MEDIAL TEMPORAL LOBE AND RECOGNITION MEMORY FOLLOWING NATURAL AND SURGICAL MENOPAUSE

Women bear the greatest burden of Alzheimer's disease (AD). Menopause-associated estrogen (E) loss may contribute to the higher rate among women, and surgical menopause prior to the age of 45 may further increase the risk. Neurodegeneration and atrophy in medial temporal lobe (MTL) structures including the perirhinal (PRC) and entorhinal (ERC) cortices occur in the very early stages of AD (e.g. Khan et al., 2013; Wolk et al., 2017). Emerging evidence suggests that visual recognition memory (VRM), which depends on the PRC, is impaired in individuals at risk for AD. While studies in rodents demonstrate that estrogens mediate PRC and VRM performance, limited data exists in humans. The present study asked whether oophorectomy prior to 45 years is associated with smaller relative volumes of the ERC and PRC, and impaired VRM relative to age-matched controls and naturally postmenopausal women. Demographic and cognitive measures were administered to women with either 1) an oophorectomy at 45 years or younger, 2) intact ovaries and not yet in menopause, and 3) naturally postmenopausal women. Total gray/white matter, cerebral spinal fluid and white matter hyperintensity load were quantified from whole-brain T1-weighted imaging scans. Volumes of hippocampal subfields and medial temporal cortical regions were quantified using high-resolution T2-weighted scans using a 3T Siemens scanner. In addition, urine samples were collected for ovarian hormone measures (estrogen and progesterone metabolites). VRM was assessed using the interference-match-to-sample (IMTS) task. Preliminary group analyses were conducted on relative volumes of each quantified structure and show smaller volumes for PRC and ERC among women that had an oophorectomy (p < .01). Performance on the IMTS was also examined, and correlations between performance (accuracy and response times) and relative volumes were conducted. The results of the present study provide preliminary evidence implicating the usefulness of medial temporal lobe measurements and the evaluation of associated cognitive abilities in early detection among middle-aged women at increased risk of AD.

Domain-specific impact of cerebral white matter hyperintensities on Parkinson’s disease cognitive functioning (P3.068)

Domain-specific impact of cerebral white matter hyperintensities on Parkinson’s disease cognitive functioning (P3.068)