High-grade White Matter Hyperintensities Research Articles

Characteristics of Cognitive Impairment and Their Relationship With Total Cerebral Small Vascular Disease Score in Parkinson's Disease.

BackgroundThis study aimed to investigate the characteristics of cognitive dysfunctions and their relationship with total cerebral small vascular disease (CSVD) in Parkinson’s disease (PD).MethodsA total of 174 idiopathic PD patients who underwent brain magnetic resonance imaging (MRI) were recruited. Demographic information, vascular disease risk factors, motor function (MDS-UPDRS III score), and cognitive level (MoCA, MMSE) were collected for these patients. The total CSVD burden was scored based on lacunes, enlarged perivascular spaces (EPVS), high-grade white matter hyperintensities (WMH), and cerebral microbleeds (CMBs) for each subject.ResultsCognitive scores on MoCA for language, delayed recall, and orientation were significantly reduced in PD patients with CSVD burden ≥ 1 than in those with CSVD burden = 0. Educational level, PDQ 39, and CSVD burden were significantly associated with MoCA scores in individuals with PD. For the whole group, the full model accounted for 33.6% variation in total MoCA scores. In which, CSVD burden explained 2.7% of the results, and the detection of lacunes, WMH, EPVS, and strictly lobar CMBs were significantly correlated with MoCA scores. The stability of the outcomes was confirmed by sensitivity analysis.ConclusionCSVD can independently contribute to cognitive decline in PD and cause damage in specific cognitive domains. Promoting neurovascular health may help preserve cognitive functions in PD.

Initial serum GM-CSF levels are associated with the severity of cerebral small vessel disease in microscopic polyangiitis patients

Serum cytokine levels were comprehensively measured, and the association with cerebrovascular lesions on brain magnetic resonance imaging (MRI) in microscopic polyangiitis (MPA) patients was investigated. The initial serum granulocyte-macrophage colony-stimulating factor (GM-CSF) levels were significantly higher in the high-grade white matter hyperintensities (WMH) group than those in the low-grade WMH group. In multivariate analyses, high serum levels of GM-CSF were independently associated with high-grade WMH. The initial serum GM-CSF levels correlated positively with the Birmingham Vasculitis Activity Score and semi-quantitative scales of WMH. The initial serum GM-CSF levels were associated with the severity of WMH in MPA patients.

Total Cerebral Small Vessel Score Association With Hoehn and Yahr Stage in Parkinson's Disease.

Background: This study aimed to evaluate the total cerebral small vessel disease (CSVD) score in patients with Parkinson’s disease (PD) at different stages and related factors.Methods: A 100 and seven patients with idiopathic PD and 62 normal controls (NCs) who underwent brain magnetic resonance imaging (MRI) were enrolled. PD patients were divided into two groups: early PD [(Hoehn and Yahr (H&Y) 1–1.5, n = 36)] and advanced PD (H&Y 2–4, n = 71) groups. We calculated the total CSVD score for each participant based on lacunes, high-grade white matter hyperintensities (WMH), enlarged perivascular spaces (EPVS), and cerebral microbleeds (CMBs). Differences in total CSVD score between the PD and NCs and between the two subgroups were compared. In addition, a multivariate logistic regression analysis was conducted to investigate the association between CSVD markers and clinical variables in PD.Results: Lacunes were found in 9.3% of patients with PD, periventricular WMH (PVWMH) in 89.7%, deep WMH (DWMH) in 81.3%, EPVS in 85%, and CMBs in 2.8%. Compared with NCs, patients with PD showed higher PVWMH and DWMH scores. Advanced PD patients exhibited greater PVWMH (P = 0.041), DWMH (P = 0.046), and total CSVD score (P = 0.044) than the early PD group. After adjusting for multiple variables, higher H&Y stage was independently correlated with increased total CSVD score (OR = 2.667, 95% CI 1.154–2.266) and PVWMH score (OR = 2.237, 95% CI 1.084–1.696).Conclusions: CSVD may play a critical role in patients with PD. The total CSVD score is a potential neuroimaging marker for monitoring the progression of PD.

Correlation Between Internal Carotid Artery Tortuosity and Imaging of Cerebral Small Vessel Disease.

Background and Purpose: An association between artery tortuosity and neuroimaging of cerebral small vessel disease (SVD) has been reported, especially in the posterior circulation. However, few studies involved the whole magnetic resonance imaging (MRI) spectrum of SVD in association with anterior circulation arterial tortuosity. This study aimed to investigate the relationship between internal carotid artery (ICA) tortuosity and the neuroimaging of SVD.Methods: Data of 1,264 consecutive patients in whom cerebral vessel diseases were suspected and who underwent both MRI and computed tomography angiography were reviewed from a prospective registry. Internal carotid artery tortuosity was evaluated using the tortuosity index (TI), which was defined as the ratio of the vessel centerline length divided by the straight length. Magnetic resonance imaging was used to assess cerebral microbleeds (CMBs), white matter hyperintensities (WMHs), enlarged perivascular spaces (EPVSs), and lacunes.Results: The TIs of the ICA for patients with and without SVD MRI markers were 1.81 ± 0.42 and 1.72 ± 0.33, respectively (P < 0.001). Univariate analysis showed that the ICA TI were positively correlated with each SVD MRI marker (P < 0.001), and the correlation coefficients (rs) were 0.57, 0.42, 0.30, and 0.26 for EPVSs, WMHs, CMBs, and lacunes, respectively. The adjusted ORs of the ICA TI were 1.52 (95% CI 1.44–1.60, P < 0.001) for EPVS grade 1, 2.05 (95% CI 1.93–2.18, P < 0.001) for EPVS grades 2–4, and 1.09 (95% CI 1.03–1.15, P = 0.004) for WMH grade 3.Conclusions: The TI of ICA was higher in patients with neuroimaging of SVD. Internal carotid arteries tortuosity was associated with MRI-defined markers of SVD, including EPVS and high-grade WMH, and positively correlated with EPVS severity. Arterial tortuosity might be a risk factor for SVD. This finding may have potential clinical significance for identifying patients with suspected SVD.

Plasma Klotho concentration is associated with the presence, burden and progression of cerebral small vessel disease in patients with acute ischaemic stroke.

Klotho is a soluble or membrane-bound anti-aging protein, whose protective actions are important for a prudential function of many organs. Because Klotho and cerebral small vessel disease (SVD) are associated with ageing process and endothelial dysfunction, it is possible that Klotho has an association with cerebral SVD. We aimed to investigate the association of plasma Klotho concentration with the presence, burden and progression of cerebral SVD. We prospectively enrolled 262 patients with first-ever acute cerebral infarction, performed brain MRI and collected their blood samples within 24 hours of admission. An enzyme-linked immunosorbent assay was used for evaluating plasma Klotho concentration. We estimated the total SVD score of each patient after determining the presence and burden of high-grade white matter hyperintensities (HWMHs), cerebral microbleeds (CMBs), high-grade perivascular spaces (HPVSs) and asymptomatic lacunar infarctions (ALIs). Univariate and multivariate analyses were conducted to investigate association of Klotho with cerebral SVD and the total SVD score. Of the 262 patients, 152 (58.0%) were men. The mean age of these patients was 64.7 years. The mean ± standard deviation of plasma Klotho concentration was 329.8 ± 194.1 pg/mL. In multivariate analysis, plasma Klotho concentration was negatively associated with the presence of HWMHs [Odds ratio (OR): 0.13, p = 0.047], HPVSs (OR: 0.22, p = 0.024) and ALIs (OR: 0.53, p = 0.021) but not associated with the presence of CMBs (OR: 0.39, p = 0.404). Plasma Klotho concentration was also negatively related to the total SVD score (unstandardized coefficients beta: −0.895, standard error = 0.317, p = 0.005, R2 = 0.239). Furthermore, plasma Klotho concentration was negatively related to the presence (OR: 0.75, 95% CI: 0.59–0.96, p = 0.025) and severity of cerebral SVD progression (OR: 0.72, 95% CI: 0.56–0.92, p = 0.009). In conclusion, plasma Klotho concentration was negatively associated with the presence, burden and progression of cerebral SVD.

Medial Temporal Lobe Atrophy is Related to Learning Strategy Changes in Amnestic Mild Cognitive Impairment.

Deficits in the semantic learning strategy were observed in subjects with amnestic mild cognitive impairment (aMCI) in our previous study. In the present study, we explored the contributions of executive function and brain structure changes to the decline in the semantic learning strategy in aMCI. A neuropsychological battery was used to test memory and executive function in 96 aMCI subjects and 90 age- and gender-matched healthy controls (HCs). The semantic clustering ratio on the verbal learning test was calculated to evaluate learning strategy. Medial temporal lobe atrophy (MTA) and white matter hyperintensities (WMH) were measured on MRI with the MTA and Fazekas visual rating scales, respectively. Compared to HCs, aMCI subjects had poorer performance in terms of memory, executive function, and the semantic clustering ratio (P < .001). In aMCI subjects, no significant correlation between learning strategy and executive function was observed. aMCI subjects with obvious MTA demonstrated a lower semantic clustering ratio than those without MTA (P < .001). There was no significant difference in the learning strategies between subjects with high-grade WMH and subjects with low-grade WMH. aMCI subjects showed obvious impairment in the semantic learning strategy, which was attributable to MTA but independent of executive dysfunction and subcortical WMH. These findings need to be further validated in large cohorts with biomarkers identified using volumetric brain measurements. (JINS, 2019, 25, 706-717).

Association between remote diffusion-weighted imaging lesions and cerebral small vessel disease in primary intracerebral hemorrhage.

The aim of this study was to examine the association amongst remote diffusion-weighted imaging lesions (R-DWILs), imaging markers of cerebral small vessel disease (cSVD) and total cSVD burden in patients with primary intracerebral haemorrhage (ICH). In total, 344 consecutive primary ICH patients were enrolled prospectively. R-DWILs on magnetic resonance imaging as well as four imaging markers of cSVD, including cerebral microbleeds (CMBs), white matter hyperintensities (WMHs), lacunes and enlarged perivascular spaces, were rated with validated scales. The total cSVD score was calculated by adding up these four markers. Univariate and multivariate analyses were performed. Remote DWI lesions were detected in 57 (16.6%) primary ICH patients. On multivariate logistic regression analysis, the presence of CMBs [odds ratio (OR) 5.26, 95% confidence interval (CI) 1.72-16.12], of high-grade WMHs (OR 4.68, 95% CI 2.01-10.90), the presence of lacunes (OR 2.69, 95% CI 1.20-6.06), mixed CMBs (OR 2.93, 95% CI 1.35-6.36), mixed lacunes (OR 3.60, 95% CI 1.25-10.37), periventricular WMHs (OR 2.19, 95% CI 1.40-3.44), deep WMHs (OR 1.92, 95% CI 1.24-2.97) and total WMHs (OR 1.52, 95% CI 1.20-1.94) were associated with the presence of R-DWILs. A significant association was also found between high-grade total cSVD score and R-DWILs (OR 1.97, 95% CI 1.36-2.84). This association remained significant in patients stratified by an age of 60years or more than 60 years. Remote DWI lesions are correlated with the severity of each imaging marker of cSVD and with the total burden of cSVD.

Neuroimaging findings in midlife and risk of late-life dementia over 20 years of follow-up.

To examine the association between neuroimaging features in a predominantly middle-aged cohort and risk of late-life dementia. Cerebral MRI was performed on 1,881 individuals with no history of stroke from the Atherosclerosis Risk in Communities Study cohort in 1993 to 1995. White matter hyperintensities (WMH), ventricular size, and sulcal size were graded on a semiquantitative scale, and presence of silent cerebral infarcts was identified. In 2011 to 2013, dementia was determined from neuropsychological testing, informant interview, hospital ICD-9 codes, and death certificate dementia codes. Cox regression was used to evaluate associations between MRI findings and dementia. Over 20 years of follow-up, dementia developed in 279 participants (14.8%). High-grade WMH and high-grade ventricular size were independently associated with increased dementia risk (hazard ratio [HR] for WMH 1.62, 95% confidence interval [CI] 1.14-2.30; HR for ventricular size 1.46, 95% CI 1.06-2.03). There was an increased risk of dementia for diabetic participants with silent infarcts (HR 2.56, 95% CI 1.23-5.31) but not among nondiabetic participants (HR 0.87, 95% CI 0.56-1.37). Each 1-unit increase in the total number of high-grade cerebral abnormalities at baseline (count values range 0-4) showed increased dementia risk, with a considerably higher risk among diabetic participants (HR for diabetes mellitus 1.97, 95% CI 1.44-2.69; HR for no diabetes mellitus 1.20, 95% CI 1.03-1.39). In adults without evidence of clinical stroke, MRI-detected WMH and ventricular enlargement in midlife may represent markers of brain injury that increase risk for later-life cognitive impairment. The presence of diabetes mellitus may modify the association between silent infarcts and dementia.

Interarm Blood Pressure Difference has Various Associations with the Presence and Burden of Cerebral Small-Vessel Diseases in Noncardioembolic Stroke Patients.

Background and PurposeAn interarm blood pressure difference (IABD) is independently related to the occurrence of cardiovascular disease and mortality. Cerebral small-vessel diseases (SVDs) are important risk factors for stroke, cognitive dysfunction, and mortality. We aimed to determine whether IABD is related to cerebral SVDs.MethodsThis study included 1,205 consecutive noncardioembolic ischemic stroke patients as confirmed by brain MRI and simultaneously measured the bilateral brachial blood pressures. We investigated cerebral SVDs based on high-grade white-matter hyperintensities (HWHs), presence of cerebral microbleeds (CMBs), high-grade perivascular spaces (HPVSs), and asymptomatic lacunar infarctions (ALIs) on brain MRI.ResultsIn multivariate logistic regression, an interarm systolic blood pressure difference (IASBD) ≥10 mm Hg was independently related to the existence of HWHs [odds ratio (OR)=1.94, 95% CI=1.32–2.84, p=0.011] and had a tendency to be associated with the presence of HPVSs (OR=1.45, 95% CI=0.49–2.23, p=0.089) and ALIs (OR=1.42, 95% CI=0.96–2.11, p=0.052), but not with the presence of CMBs (OR=1.09, 95% CI=0.73–1.61, p=0.634). In multivariate linear regression adjusted for age, sex, and variables with p<0.1 in the univariate analysis, IASBD ≥10 mm Hg and interarm diastolic blood pressure difference ≥10 mm Hg were significantly correlated with an increased total burden of SVDs (β=0.080 and p=0.006, and β=0.065 and p=0.023, respectively).ConclusionsThis study found that IABD ≥10 mm Hg was associated with the presence and increased burden of cerebral SVDs in noncardioembolic stroke patients. This suggests that IABD ≥10 mm Hg could be a useful indicator of the presence and burden of cerebral SVDs in stroke patients.

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.

High dietary glycemic load was associated with the presence and burden of cerebral small vessel diseases in acute ischemic stroke patients

Cerebral small vessel diseases (SVDs) are closely associated with stroke. Elevated postprandial blood glucose is also an important risk factor for stroke. Dietary glycemic load (GL) and glycemic index (GI) are frequently used as markers of postprandial blood glucose response used as an estimator of the overall glycemic effect of the diet. We hypothesized that high dietary GL or GI will be associated with presence of cerebral SVDs in patients with acute ischemic stroke. We prospectively included 263 patients who had experienced first-ever symptomatic cerebral infarction within 7 days after symptom onset and who submitted a fully filled-in semi-quantitative food frequency questionnaire. The dietary GL and GI values of food were constructed through an International table based on glucose. The presence and burden of high-grade white matter hyperintensities (HWMHs), cerebral microbleeds (CMBs), high-grade perivascular spaces (HPVSs) and asymptomatic lacunar infarctions (ALIs) were investigated. Mean age of the total patient population was 65.4 ± 11.7 years. After adjusting for age, sex, and variables with P < .1 in univariate analysis, high dietary GL was independently associated with an increased risk of presence of HWMHs (odds ratio (OR) (95% confidence interval (CI)) comparing the top quartile with the bottom quartile: 3.31 (1.37-7.98); P (for trend) = .006), CMBs (OR (95% CI): 3.06 (1.06-8.85); P = .032), PVSs (OR (95% CI): 3.24 (0.75-13.90); P = .039), and ALIs (OR (95% CI): 2.44 (0.97-6.13); P = .037). In conclusion, high dietary GL was associated with the presence and burden of cerebral SVDs in patients with acute cerebral infarction.

Total Cerebral Small-Vessel Disease Score is Associated with Mortality during Follow-Up after Acute Ischemic Stroke.

Background and PurposeThe recently developed total cerebral small-vessel disease (CSVD) score might appropriately reflect the total burden or severity of CSVD. We investigated whether the total CSVD score is associated with long-term outcomes during follow-up in patients with acute ischemic stroke.MethodsIn total, 1,096 consecutive patients with acute ischemic stroke who underwent brain magnetic resonance imaging were enrolled. We calculated the total CSVD score for each patient after determining the burden of cerebral microbleeds (CMBs), high-grade white-matter hyperintensities (HWHs), high-grade perivascular spaces (HPVSs), and asymptomatic lacunar infarctions (ALIs). We recorded the date and cause of death for all of the patients using data from the Korean National Statistical Office. We compared the long-term mortality rate with the total CSVD score using Cox proportional-hazards models.ResultsCMBs were found in 26.8% of the subjects (294/1,096), HWHs in 16.4% (180/1,096), HPVSs in 19.3% (211/1,096), and ALIs in 38.0% (416/1,096). After adjusting for age, sex, and variables that were significant at p<0.1 in the univariate analysis, the total CSVD score was independently associated with long-term death from all causes [hazard ratio (HR)=1.18 per point, 95% confidence interval (CI)=1.07–1.30], ischemic stroke (HR=1.20 per point, 95% CI=1.01–1.42), and hemorrhagic stroke (HR=2.05 per point, 95% CI=1.30–3.22), but not with fatal cardiovascular events (HR=1.17 per point, 95% CI=0.82–1.67).ConclusionsThe total CSVD score is a potential imaging biomarker for predicting mortality during follow-up in patients with acute ischemic stroke.

Association between Aortic Atheroma and Cerebral Small Vessel Disease in Patients with Ischemic Stroke

Background and PurposeCerebral small vessel disease (SVDs) are related with large artery atherosclerosis. However, the association between aortic atheroma (AA) and cerebral small vessel disease has rarely been reported. This study evaluated the relationship between presence and burden of AAs and those of SVDs in patients with acute ischemic stroke.MethodsWe included 737 consecutive patients who underwent transesophageal echocardiography (TEE) and brain magnetic resonance imaging (MRI) for evaluation of acute stroke. AA subtypes were classified as complex aortic plaque (CAP) and simple aortic plaque (SAP). Presence and burden of SVDs including cerebral microbleeds (CMBs), white matter hyperintensities (WMHs), perivascular spaces (PVSs), asymptomatic lacunar infarctions (ALIs), and total SVD score, were investigated.ResultsAA was found by TEE in 360 (48.8%) patients including 11.6% with CAP and 37.2% with SAP. One or more types of SVDs was found in 269 (36.4%) patients. In multivariable analysis, presence of CMBs (odds ratio [OR] 4.68), high-grade WMHs (OR 3.13), high-grade PVSs (OR 3.35), and ALIs (OR 4.24) were frequent in patients with AA than those without AA. Each 1-point increase in total SVD score increased the odds of presence of CAP (OR 1.94, 95% confidence interval (CI) 1.44-1.85) and SAP (OR 1.54, 95% CI 1.35-1.75).ConclusionsIn this study, patients with AA frequently had cerebral SVDs. Larger burden of AA was associated with advanced cerebral SVDs. Our findings give an additional information for positive relationship with systemic atherosclerosis and coexisting cerebral SVDs in acute ischemic stroke patients.

Moderate-to-severe obstructive sleep apnea is associated with cerebral small vessel disease

BackgroundCerebral small vessel disease (SVD) is associated with increased risk of cerebral infarction and hemorrhage. Obstructive sleep apnea (OSA) is known to increase the risk of cerebrovascular disease. This study aimed to investigate the association between cerebral SVD and severity of OSA. MethodsA total of 170 patients were included from the patient registry at the present Sleep Center; these patients underwent both magnetic resonance imaging (MRI) of the brain and polysomnography (PSG) for suspected OSA. The presence and burden of white matter hyperintensities (WMHs), asymptomatic lacunar infarctions (ALIs), cerebral microbleeds (CMBs), and perivascular spaces (PVSs) were determined by MRI, and their relationships with the apnea–hypopnea index (AHI), as determined by PSG, were investigated. ResultsAmong the 170 patients, 25 (14.7%) had high-grade WMHs, 21 (12.4%) had ALIs, 21 (12.4%) had CMBs, and 34 (20.0%) had high-grade PVSs. In the multivariable analysis, after adjusting for factors including age, sex, and other variables for which p < 0.1 in univariable analysis (hypertension, diabetes mellitus, previous stroke, minimal SaO2 and arousal index), moderate-to-severe OSA was associated with high-grade WMHs (odds ratio [OR] 4.72; 95% confidence interval [CI] 1.14–19.47), CMBs (OR 3.47; 95% CI 0.89–15.18), or high-grade PVSs (OR 3.64; 95% CI 1.02–13.01), but not with ALIs. The total SVD score was independently associated with increased AHI (p = 0.017), particularly in patients with moderate-to-severe OSA (β [standard error] = 0.448 (0.204), p = 0.030]. ConclusionModerate-to-severe OSA is positively associated with multiple indicators of cerebral SVD, including WMHs, CMBs, and PVSs.

Topography of cortical thinning associated with white matter hyperintensities in Parkinson's disease.

Although white matter hyperintensities (WMHs) are associated with cognitive impairments in Parkinson's disease (PD), the relationships between WMHs and cortical atrophy in regard to cognitive impairments are unknown. Here, we investigated the topography of cortical thinning related to deep (DWMHs) and periventricular WMHs (PWMHs) and their differential impacts on cognitive performance in PD. We enrolled 87 patients with non-demented PD and evaluated WMH scores using a semi-quantitative visual rating system. The patients were divided into low-, moderate-, and high-grade groups based on WMH severity for total WMHs (TWMHs), DWMHs, and PWMHs, and cortical thickness was measured using a surface-based method according to the WMHs severity. Additionally, the correlations between WMH-associated cortical thinning and neuropsychological performance were analyzed. The detailed neuropsychological test demonstrated that PD patients with high-grade WMHs showed poorer performance on frontal lobe-based cognitive tasks compared with those with low-grade DWMHs. The areas of cortical thinning were more extensive in patients with DWMHs, involving the entire frontal areas and restricted temporoparietal areas, whereas in patients with PWMHs, cortical thinning was localized in the small frontal areas. A multiple regression analysis of the relationships between WMH-associated cortical thickness and cognition revealed that DWMH-associated frontal thickness had an independent effect on frontal lobe-based cognition, while frontal thickness related to PWMHs did not have a significant correlation with cognitive tasks. These data suggest that in patients with PD, DWMHs are closely coupled with decreased cortical thickness in the frontal areas and may lead to declines in executive function.

Vitamin D and subclinical cerebrovascular disease: the Atherosclerosis Risk in Communities brain magnetic resonance imaging study.

Vitamin D deficiency has been associated with hypertension, diabetes mellitus, and incident stroke. Little is known about the association between vitamin D and subclinical cerebrovascular disease. To examine the relationship of 25-hydroxyvitamin D (25[OH]D) levels with cerebrovascular abnormalities as assessed on brain magnetic resonance imaging (MRI) among participants of the Atherosclerosis Risk in Communities (ARIC) Brain MRI study. Participants were white and black adults aged 55 to 72 years with no history of clinical stroke who underwent a cerebral MRI at ARIC visit 3 (n = 1622) and a second cerebral MRI approximately 10 years later (n = 888). The 25(OH)D level was measured by mass spectrometry at visit 3, with levels adjusted for calendar month and categorized using race-specific quartiles. The cross-sectional and prospective associations of 25(OH)D levels with white matter hyperintensities (WMHs) and MRI-defined infarcts were investigated using multivariable regression models. The mean age of the participants was 62 years, 59.6% were women, and 48.6% were black. Lower 25(OH)D levels were not significantly associated with WMH score of severity, prevalent high-grade WMH score (≥3), or prevalent infarcts in cross-sectional, multivariable-adjusted models (all P > .05). Similarly, no significant prospective associations were found for lower 25(OH)D levels with change in WMH volume, incident high WMH score (≥3), or incident infarcts on the follow-up MRI, which occurred approximately 10 years later. A single measure of 25(OH)D was not cross-sectionally associated with WMH grade or prevalent subclinical infarcts and was not prospectively associated with WMH progression or subclinical brain infarcts seen on serial cerebral MRIs obtained approximately 10 years apart. These findings do not support optimizing vitamin D levels for brain health.

Markers of cholesterol metabolism in the brain show stronger associations with cerebrovascular disease than Alzheimer's disease.

Cholesterol metabolism is believed to play a role in the development of Alzheimer's disease (AD). Oxysterol metabolites of cholesterol, 24S-hydroxycholesterol (24-OHC, a brain-derived oxysterol) and 27-hydroxycholesterol (27-OHC, a peripherally derived oxysterol) cross the blood brain barrier and have been associated with AD. We investigated whether oxysterols were associated with markers of cerebrovascular disease prior to the onset of cognitive impairment. Oxysterols were quantified in 105 participants (average age: 80 ± 4 years) from the Pittsburgh Cardiovascular Health Study Cognition Study who remained cognitively normal at blood draw in 2002, had MRI in 1992 and 1998, and annual cognitive assessment for incident AD and mild cognitive impairment made by consensus conference between 1998 and 2010. Higher plasma levels of 24-OHC were associated with age, gender, the presence of high grade white matter hyperintensities, and brain infarcts on prior MRI. Participants with higher plasma 24-OHC and a greater ratio of 24-OHC/27-OHC were also more likely to develop incident cognitive impairment over 8 years of follow-up. Higher levels of 24-OHC suggest increased cholesterol metabolism occurring in the brains of participants with cerebrovascular disease prior to the onset of cognitive impairment. Measurement of oxysterols may provide information about cholesterol metabolism and brain disease over the cognitive impairment process.