Cerebral Microbleeds and White Matter Hyperintensities are Associated with Cognitive Decline in an Asian Memory Clinic Study

Background: Cerebral small vessel disease (SVD); lacunes, cerebral microbleeds (CMBs), and white matter hyperintensities (WMH) have a vital role in cognitive impairment and dementia. SVD in lobar location is related to cerebral amyloid angiopathy, whereas SVD in a deep location with hyper- tensive arteriopathy. It remains unclear how different locations of SVD affect long-term cognitive de- cline. The present study aimed to analyse the association between different locations and severity of SVD with global and domain-specific cognitive decline over the follow-up interval of 3 years. Methods: We studied 428 participants who had performed MRI scans at baseline and at least 3 neuro- psychological assessments. Locations of lacunes and CMBs were categorized into strictly lobar, strictly deep and mixed-location, WMH volume into anterior and posterior. The National Institute of Neurological Disorders and Stroke-Canadian Stroke Network Harmonization Neuropsychological Battery was used to assess cognitive function. To analyse the association between baseline location and severity of SVD with cognitive decline, linear regression models with generalized estimated equations were constructed to calculate the mean difference, 95% confidence interval and two-way interaction factor between time and SVD. Results: Increased numbers of baseline CMBs were associated with a decline in global cognition as well as a decline in executive function and memory domains. Location-specific analysis showed simi- lar results with strictly lobar CMBs. There was no association with strictly deep and mixed-location CMBs with cognitive decline. Baseline WMH volume was associated with a decline in global cogni- tion, executive function and memory. Similar results were obtained with anterior and posterior WMH volumes. Lacunes and their locations were not associated with cognitive decline. Conclusion: Strictly lobar CMBs, as well as WMH volume in anterior and posterior regions, were associated with cognitive decline. Future research focuses are warranted to evaluate interventions that may prevent cognitive decline related to SVD.

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Influence of White Matter Hyperintensities on Baseline and Longitudinal Amyloid-β in Cognitively Normal Individuals

Journal of Alzheimer s Disease ◽

10.3233/jad-210333 ◽

2021 ◽

pp. 1-11

Author(s):

Fennie Choy Chin Wong ◽

Seyed Ehsan Saffari ◽

Chathuri Yatawara ◽

Kok Pin Ng ◽

Nagaendran Kandiah ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Executive Function ◽

White Matter ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Amyloid Β ◽

Intracranial Volume ◽

Linear Regression Models ◽

Cognitively Normal

Background: The associations between small vessel disease (SVD) and cerebrospinal amyloid-β1-42 (Aβ1-42) pathology have not been well-elucidated. Objective: Baseline (BL) white matter hyperintensities (WMH) were examined for associations with month-24 (M24) and longitudinal Aβ1-42 change in cognitively normal (CN) subjects. The interaction of WMH and Aβ1-42 on memory and executive function were also examined. Methods: This study included 72 subjects from the Alzheimer’s Disease Neuroimaging Initiative. Multivariable linear regression models evaluated associations between baseline WMH/intracranial volume ratio, M24 and change in Aβ1-42 over two years. Linear mixed effects models evaluated interactions between BL WMH/ICV and Aβ1-42 on memory and executive function. Results: Mean age of the subjects (Nmales = 36) = 73.80 years, SD = 6.73; mean education years = 17.1, SD = 2.4. BL WMH was significantly associated with M24 Aβ1-42 (p = 0.008) and two-year change in Aβ1-42 (p = 0.006). Interaction between higher WMH and lower Aβ1-42 at baseline was significantly associated with worse memory at baseline and M24 (p = 0.003). Conclusion: BL WMH was associated with M24 and longitudinal Aβ1-42 change in CN. The interaction between higher WMH and lower Aβ1-42 was associated with poorer memory. Since SVD is associated with longitudinal Aβ1-42 pathology, and the interaction of both factors is linked to poorer cognitive outcomes, the mitigation of SVD may be correlated with reduced amyloid pathology and milder cognitive deterioration in Alzheimer’s disease.

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Cognitive consequences of regression of cerebral small vessel disease

European Stroke Journal ◽

10.1177/2396987318820790 ◽

2018 ◽

Vol 4 (1) ◽

pp. 85-89 ◽

Cited By ~ 6

Author(s):

Esther MC van Leijsen ◽

Mayra I Bergkamp ◽

Ingeborg WM van Uden ◽

Sjacky Cooijmans ◽

Mohsen Ghafoorian ◽

...

Keyword(s):

Executive Function ◽

White Matter ◽

Cognitive Decline ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Vessel Disease ◽

Disease Markers ◽

Total Brain

Introduction Recent studies have shown that neuroimaging markers of cerebral small vessel disease can also regress over time. We investigated the cognitive consequences of regression of small vessel disease markers. Patients and methods Two hundred and seventy-six participants of the RUNDMC study underwent neuroimaging and cognitive assessments at three time-points over 8.7 years. We semi-automatically assessed white matter hyperintensities volumes and manually rated lacunes and microbleeds. We analysed differences in cognitive decline and accompanying brain atrophy between participants with regression, progression and stable small vessel disease by analysis of variance. Results Fifty-six participants (20.3%) showed regression of small vessel disease markers: 31 (11.2%) white matter hyperintensities regression, 10 (3.6%) vanishing lacunes and 27 (9.8%) vanishing microbleeds. Participants with regression showed a decline in overall cognition, memory, psychomotor speed and executive function similar to stable small vessel disease. Participants with small vessel disease progression showed more cognitive decline compared with stable small vessel disease (p < 0.001 for cognitive index and memory; p < 0.01 for executive function), although significance disappeared after adjusting for age and sex. Loss of total brain, gray matter and white matter volume did not differ between participants with small vessel disease regression and stable small vessel disease, while participants with small vessel disease progression showed more volume loss of total brain and gray matter compared to those with stable small vessel disease (p < 0.05), although significance disappeared after adjustments. Discussion Regression of small vessel disease markers was associated with similar cognitive decline compared to stable small vessel disease and did not accompany brain atrophy, suggesting that small vessel disease regression follows a relatively benign clinical course. Future studies are required to validate these findings and to assess the role of vascular risk factor control on small vessel disease regression and possible recovery of clinical symptoms. Conclusion Our findings of comparable cognitive decline between participants with regression and stable small vessel disease might suggest that small vessel disease regression has a relative benign cognitive outcome.

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Cerebral microbleeds topography and cerebrospinal fluid biomarkers in cognitive impairment

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x16649401 ◽

2016 ◽

Vol 37 (3) ◽

pp. 1006-1013 ◽

Cited By ~ 18

Author(s):

Sara Shams ◽

Tobias Granberg ◽

Juha Martola ◽

Andreas Charidimou ◽

Xiaozhen Li ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

White Matter ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Cerebral Microbleeds ◽

Amyloid Angiopathy ◽

Resonance Imaging ◽

Vessel Disease ◽

Cerebrospinal Fluid Biomarkers ◽

Cerebral Amyloid

Cerebral microbleeds, a marker of small vessel disease, are thought to be of importance in cognitive impairment. We aimed to study topographical distribution of cerebral microbleeds, and their involvement in disease pathophysiology, reflected by cerebrospinal fluid biomarkers; 1039 patients undergoing memory investigation underwent lumbar puncture and a brain magnetic resonance imaging scan. Cerebrospinal fluid samples were analyzed for amyloid β(Aβ)42, total tau(T-tau), tau phosphorylated at threonine 18(P-tau) and cerebrospinal fluid/serum albumin ratios. Magnetic resonance imaging sequences were evaluated for small vessel disease markers, including cerebral microbleeds, white matter hyperintensities and lacunes. Low Aβ42 levels were associated with lobar cerebral microbleeds in the whole cohort and Alzheimer’s disease ( P < 0.001). High cerebrospinal fluid/serum albumin ratios were seen with increased number of cerebral microbleeds in the brainstem ( P < 0.001). There were tendencies for increased Aβ42 levels and decreased Tau levels with deep and infratentorial cerebral microbleeds ( P < 0.05). Lobar cerebral microbleeds were associated with white matter hyperintensities and lacunes ( P < 0.001). Probable cerebral amyloid angiopathy-related cerebral microbleeds were associated with low Aβ42 levels and lacunes, whereas probable cerebral amyloid angiopathy-unrelated cerebral microbleeds were associated with white matter hyperintensities ( P < 0.001). Our findings show that cerebral microbleed distribution is associated with different patterns of cerebrospinal fluid biomarkers, supporting different pathogenesis of deep/infratentorial and lobar cerebral microbleeds.

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Sexual Assault and White Matter Hyperintensities Among Midlife Women

10.21203/rs.3.rs-248769/v1 ◽

2021 ◽

Author(s):

Rebecca Thurston ◽

Karen Jakubowski ◽

Minjie Wu ◽

Howard Aizenstein ◽

Yuefang Chang ◽

...

Keyword(s):

White Matter ◽

Sexual Assault ◽

Traumatic Stress ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Midlife Women ◽

Traumatic Experiences ◽

Linear Regression Models ◽

Post Traumatic Stress ◽

Post Traumatic

Abstract Background Traumatic experiences have been linked to poor mental and physical health. However, there has been little examination of their relationship to neuroimaging markers of cerebrovascular risk. White matter hyperintensities (WMHs) are markers of brain small vessel disease. WMHs can be detected decades before the onset of dementia and other disorders and can serve as early markers for these brain disorders. We tested whether traumatic experiences were associated with brain WMH volume among midlife women. Methods In the MsBrain study, 145 women (mean age = 59 years) without cardiovascular disease, stroke, or dementia were recruited. Women completed questionnaires [trauma checklist, depression, post-traumatic stress measures]; physical measures [body mass index (BMI), blood pressure (BP)]; phlebotomy; actigraphy sleep measurement, and 3 Tesla magnetic resonance brain imaging for WMHs. Cross-sectional associations between traumatic experiences and WMH volume were assessed in linear regression models. Covariates were age, race/ethnicity, education, BMI, BP, lipids, preeclampsia, sleep, and additionally depressive and post-traumatic stress disorder symptoms. Results 68% of women endorsed at least one of the traumas assessed. The most common trauma was sexual assault (23% of women). Women with trauma exposure had greater WMH volume than women without trauma [B(SE) = .24 (.09), p = .01, multivariable]. The single trauma most associated with WMH was sexual assault [B(SE) = .25 (.11), p = .02, multivariable]. Results persisted adjusting for depressive or post-traumatic stress symptoms. Conclusions A trauma history, particularly sexual assault, was associated with greater WMH volume controlling for covariates, including depressive and post-traumatic symptoms. Sexual assault may place women at risk for poor brain health.

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Abstract TP181: Serum Eiocosapentaenoic Acids Is Protective Against White Matter Lesions

Stroke ◽

10.1161/str.44.suppl_1.atp181 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Daiki Takano ◽

Takashi Yamazaki ◽

Tetsuya Maeda ◽

Yuichi Satoh ◽

Yasuko Ikeda ◽

...

Keyword(s):

White Matter ◽

Cognitive Decline ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

White Matter Lesions ◽

White Matter Hyperintensity ◽

Partial Regression Coefficient ◽

The Relationship ◽

Total Pufa ◽

Periventricular Hyperintensity

[Introduction] White matter hyperintensities (WMH) are considered manifestation of arteriosclerotic small vessel disease and WMH burden increases risk of ischemic stroke and cognitive decline. There are only a few evidences concerning the relationship between polyunsaturated fatty acids (PUFA) and WMH. The present study was designed to elucidate the association between WMH and PUFA profile including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and arachidonic acid (AA) in patients with Alzheimer’s disease (AD). [Methods] The present study was based on 119 patients who were diagnosed as having a probable AD according to the NINCDS-ADRDA criteria. Their mean age was 78.3 years old. All subjects underwent neuropsychological evaluation including mini mental state exam (MMSE) and 1.5-Tesla MRI. Fasting blood samples were also collected for the PUFA measurements. We measured the ratio of serum EPA, DHA and AA concentration to the total PUFA concentration. The WMH were evaluated on T2-weight images and classified into periventricular hyperintensity (PVH) and deep white matter hyperintensity (DWMH). The severity of WMH was graded 5 categories. We investigated the relationship between WMH and PUFA profiles. [Results] The EPA ratio correlated negatively with both PVH (rs=-0.2036, p=0.0264) and DWMH grade (rs=-0.3155, p=0.0005). It remained still significant after adjustment for age, sex, statins use, antithrombotics use, mean blood pressure and presence of hypertension (standardized partial regression coefficient(β)=-0.2516, p=0.0122 for PVH, β=-0.3598, p=0.0001 for DWMH). Neither DHA nor AA ratio correlated with DWMH or PVH grade. The EPA ratio but not DHA or AA ratio correlated positively with total MMSE score (rs=0.2310, p=0.0115). [Conclusions] Our data revealed that the serum EPA was protective against WMH as well as cognitive decline in AD patients. Pathophysiology underlying WMH is complex and the possible mechanisms involved in the pathogenesis of WMH encompass incomplete brain ischemia, increased permeability of blood-brain barrier, and inflammation responses. The relationship between serum EPA and WMH can be partly explained by those anti-ischemic and anti-arteriosclerotic effects of EPA.

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Collateral Recruitment Is Impaired by Cerebral Small Vessel Disease

Stroke ◽

10.1161/strokeaha.119.027661 ◽

2020 ◽

Vol 51 (5) ◽

pp. 1404-1410 ◽

Cited By ~ 3

Author(s):

Michelle P. Lin ◽

Thomas G. Brott ◽

David S. Liebeskind ◽

James F. Meschia ◽

Kevin Sam ◽

...

Keyword(s):

White Matter ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Cerebral Microbleeds ◽

Large Vessel ◽

Small Vessel ◽

Perivascular Spaces ◽

Vessel Disease ◽

Poor Recruitment

Background and Purpose— Cerebral small vessel disease (SVD) is associated with increased stroke risk and poor stroke outcomes. We aimed to evaluate whether chronic SVD burden is associated with poor recruitment of collaterals in large-vessel occlusive stroke. Methods— Consecutive patients with middle cerebral artery or internal carotid artery occlusion presenting within 6 hours after stroke symptom onset who underwent thrombectomy from 2012 to 2017 were included. The prespecified primary outcome was poor collateral flow, which was assessed on baseline computed tomographic angiography (poor, ≤50% filling; good, >50% filling). Markers of chronic SVD on brain magnetic resonance imaging were rated for the extent of white matter hyperintensities, enlarged perivascular spaces, chronic lacunar infarctions and cerebral microbleeds using the Standards for Reporting Vascular Changes on Neuroimaging criteria. Severity of SVD was quantified by adding the presence of each SVD feature, with a total possible score of 0 to 4; each SVD type was also evaluated separately. Multivariable logistic regression analyses were performed to evaluate the relationships between SVD and poor collaterals, with adjustment for potential confounders. Results— Of the 100 eligible patients, the mean age was 65±16 years, median National Institutes of Health Stroke Scale score was 15, and 68% had any SVD. Poor collaterals were observed in 46%, and those with SVD were more likely to have poor collaterals than patients without SVD (aOR, 1.9 [95% CI, 1.1–3.2]). Of the SVD types, poor collaterals were significantly associated with white matter hyperintensities (aOR, 2.9 per Fazekas increment [95% CI, 1.6–5.3]) but not with enlarged perivascular spaces (adjusted odds ratio [aOR], 1.3 [95% CI, 0.4–4.0]), lacunae (aOR, 2.1 [95% CI, 0.6–7.1]), or cerebral microbleeds (aOR, 2.1 [95% CI, 0.6–7.8]). Having a greater number of different SVD markers was associated with a higher odds of poor collaterals (crude trend P <0.001; adjusted P =0.056). There was a dose-dependent relationship between white matter hyperintensity burden and poor collaterals: adjusted odds of poor collaterals were 1.5, 3.0, and 9.7 across Fazekas scores of 1 to 3 ( P trend=0.015). No patient with an SVD score of 4 had good collaterals. Conclusions— Chronic cerebral SVD is associated with poor recruitment of collaterals in large vessel occlusive stroke. A prospective study to elucidate the potential mechanism of how SVD may impair the recruitment of collaterals is ongoing.

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Cerebral Microbleeds and White Matter Hyperintensities in Cognitively Healthy Elderly: A Cross-Sectional Cohort Study Evaluating the Effect of Arterial Stiffness

Cerebrovascular Diseases Extra ◽

10.1159/000377710 ◽

2015 ◽

Vol 5 (2) ◽

pp. 41-51 ◽

Cited By ~ 21

Author(s):

Anna-Märta Gustavsson ◽

Erik Stomrud ◽

Kasim Abul-Kasim ◽

Lennart Minthon ◽

Peter M. Nilsson ◽

...

Keyword(s):

Cognitive Function ◽

White Matter ◽

Arterial Stiffness ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Cerebral Microbleeds ◽

Small Vessel ◽

Cognitive Tests ◽

Vessel Disease ◽

Healthy Elderly

Background: Arterial stiffness reflects the ageing processes in the vascular system, and studies have shown an association between reduced cognitive function and cerebral small vessel disease. Small vessel disease can be visualized as white matter hyperintensities (WMH) and lacunar infarcts but also as cerebral microbleeds on brain magnetic resonance imaging (MRI). We aimed to investigate if arterial stiffness influences the presence of microbleeds, WMH and cognitive function in a population of cognitively healthy elderly. Methods: The study population is part of the Swedish BioFinder study and consisted of 208 individuals without any symptoms of cognitive impairment, who scored >27 points on the Mini-Mental State Examination. The participants (mean age, 72 years; 59% women) underwent MRI of the brain with visual rating of microbleeds and WMH. Arterial stiffness was measured with carotid-femoral pulse wave velocity (cfPWV). Eight cognitive tests covering different cognitive domains were performed. Results: Microbleeds were detected in 12% and WMH in 31% of the participants. Mean (±standard deviation, SD) cfPWV was 10.0 (±2.0) m/s. There was no association between the presence of microbleeds and arterial stiffness. There was a positive association between arterial stiffness and WMH independent of age or sex (odds ratio, 1.58; 95% confidence interval, 1.04-2.40, p < 0.05), but the effect was attenuated when further adjustments for several cardiovascular risk factors were performed (p > 0.05). Cognitive performance was not associated with microbleeds, but individuals with WMH performed slightly worse than those without WMH on the Symbol Digit Modalities Test (mean ± SD, 35 ± 7.8 vs. 39 ± 8.1, p < 0.05). Linear regression revealed no direct associations between arterial stiffness and the results of the cognitive tests. Conclusions: Arterial stiffness was not associated with the presence of cerebral microbleeds or cognitive function in cognitively healthy elderly. However, arterial stiffness was related to the presence of WMH, but the association was attenuated when multiple adjustments were made. There was a weak negative association between WMH and performance in one specific test of attention. Longitudinal follow-up studies are needed to further assess the associations.

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Rivaroxaban for Prevention of Covert Brain Infarcts and Cognitive Decline

Stroke ◽

10.1161/strokeaha.120.029762 ◽

2020 ◽

Vol 51 (10) ◽

pp. 2901-2909

Author(s):

Mukul Sharma ◽

Robert G. Hart ◽

Eric E. Smith ◽

Jacqueline Bosch ◽

John W. Eikelboom ◽

...

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Magnetic Resonance ◽

Cognitive Decline ◽

Odds Ratio ◽

White Matter Hyperintensities ◽

Cerebral Microbleeds ◽

Cognitive Tests ◽

Brain Infarcts ◽

End Point

Background and Purpose: Covert brain infarcts are associated with cognitive decline. It is not known whether therapies that prevent symptomatic stroke prevent covert infarcts. COMPASS compared rivaroxaban with and without aspirin with aspirin for the prevention of stroke, myocardial infarction, and vascular death in participants with stable vascular disease and was terminated early because of benefits of rivaroxaban 2.5 mg twice daily plus aspirin over aspirin. We obtained serial magnetic resonance imagings and cognitive tests in a consenting subgroup of COMPASS patients to examine treatment effects on infarcts, cerebral microbleeds, and white matter hyperintensities. Methods: Baseline and follow-up magnetic resonance imagings were completed in 1445 participants with a mean (SD) interval of 2.0 (0.7) years. Whole-brain T1, T2 fluid-attenuated inversion recovery, T2* sequences were centrally interpreted by blinded, trained readers. Participants had serial measurements of cognition and function. The primary end point was the proportion of participants with incident covert infarcts. Secondary end points were the composite of clinical stroke and covert brain infarcts, cerebral microbleeds, and white matter hyperintensities. Results: At baseline, 493 (34.1%) participants had infarcts. Incident covert infarcts occurred in 55 (3.8%) participants. In the overall trial rivaroxaban plus aspirin reduced ischemic stroke by 49% (0.7% versus 1.4%; hazard ratio [95% CI], 0.51 [0.38–0.68]). In the magnetic resonance imaging substudy the effects of rivaroxaban+aspirin versus aspirin were: covert infarcts: 2.7% versus 3.5% (odds ratio [95% CI], 0.77 [0.37–1.60]); Covert infarcts or ischemic stroke: 2.9% versus 5.3% (odds ratio [95% CI], 0.53 [0.27–1.03]). Incident microbleeds occurred in 6.6% of participants and 65.7% of participants had an increase in white matter hyperintensities volume with no effect of treatment for either end point. There was no effect on cognitive tests. Conclusions: Covert infarcts were not significantly reduced by treatment with rivaroxaban and aspirin but estimates for the combination of ischemic stroke and covert infarcts were consistent with the effect on ischemic stroke in the overall trial. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01776424.

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White matter hyperintensities: relationship to amyloid and tau burden

Brain ◽

10.1093/brain/awz162 ◽

2019 ◽

Vol 142 (8) ◽

pp. 2483-2491 ◽

Cited By ~ 23

Author(s):

Jonathan Graff-Radford ◽

Eider M Arenaza-Urquijo ◽

David S Knopman ◽

Christopher G Schwarz ◽

Robert D Brown ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

White Matter ◽

White Matter Hyperintensities ◽

Cerebral Microbleeds ◽

Amyloid Angiopathy ◽

Amyloid Pet ◽

Gradient Recall Echo ◽

Tau Pet ◽

Topographic Pattern

Abstract Although white matter hyperintensities have traditionally been viewed as a marker of vascular disease, recent pathology studies have found an association between white matter hyperintensities and Alzheimer’s disease pathologies. The objectives of this study were to investigate the topographic patterns of white matter hyperintensities associated with Alzheimer’s disease biomarkers measured using PET. From the population-based Mayo Clinic Study of Aging, 434 participants without dementia (55% male) with FLAIR and gradient recall echo MRI, tau-PET (AV-1451) and amyloid-PET scans were identified. A subset had cerebral microbleeds detected on T2* gradient recall echo scans. White matter hyperintensities were semi-automatically segmented using FLAIR MRI in participant space and normalized to a custom template. We used statistical parametric mapping 12-based, voxel-wise, multiple-regression analyses to detect white matter hyperintense regions associated with Alzheimer’s biomarkers (global amyloid from amyloid-PET and meta-regions of interest tau uptake from tau-PET) after adjusting for age, sex and hypertension. For amyloid associations, we additionally adjusted for tau and vice versa. Topographic patterns of amyloid-associated white matter hyperintensities included periventricular white matter hyperintensities (frontal and parietal lobes). White matter hyperintense volumes in the detected topographic pattern correlated strongly with lobar cerebral microbleeds (P < 0.001, age and sex adjusted Cohen’s d = 0.703). In contrast, there were no white matter hyperintense regions significantly associated with increased tau burden using voxel-based analysis or region-specific analysis. Among non-demented elderly, amyloid load correlated with a topographic pattern of white matter hyperintensities. Further, the amyloid-associated, white matter hyperintense regions strongly correlated with lobar cerebral microbleeds suggesting that cerebral amyloid angiopathy contributes to the relationship between amyloid and white matter hyperintensities. The study did not support an association between increased tau burden and white matter hyperintense burden.

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Association of Blood Pressure, Its Treatment, and Treatment Efficacy With Volume of White Matter Hyperintensities in the Population-Based 1000BRAINS Study

Hypertension ◽

10.1161/hypertensionaha.121.18135 ◽

2021 ◽

Author(s):

Janine Gronewold ◽

Martha Jokisch ◽

Sara Schramm ◽

Christiane Jockwitz ◽

Tatiana Miller ◽

...

Keyword(s):

Blood Pressure ◽

White Matter ◽

Treatment Efficacy ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Population Based ◽

Small Vessel ◽

Linear Regression Models ◽

Cerebral Magnetic Resonance Imaging ◽

Vessel Disease

White matter hyperintensities (WMHs) of presumed vascular origin are a frequent finding in cerebral magnetic resonance imaging of older people. They are attributed to small vessel disease and involved in the pathogenesis of cognitive decline. Since vascular risk factors, especially arterial hypertension, predispose to small vessel disease, we analyzed the association of systolic blood pressure (SBP), diastolic blood pressure (DBP), and antihypertensive medications with WMH volume in 560 participants of the 1000BRAINS study, drawn from the population-based Heinz Nixdorf Recall study (65.2±7.5 years; 51.4% men). Further, we analyzed treatment efficacy using a classification of 6 BP treatment groups defined by antihypertensive medication and level of BP: (1) untreated BP <120/<80 mm Hg, (2) untreated SBP 120 to 139 or DBP 80 to 89 mm Hg, (3) untreated BP ≥140 or ≥90 mm Hg, (4) treated BP <120/<80 mm Hg, (5) treated SBP 120 to 139 or DBP 80 to 89 mm Hg, and (6) treated BP ≥140 or ≥90 mm Hg. Median WMH volume (Q1–Q3) was 4.6 (3.0–7.8) cm 3 ; mean±SD of SBP and DBP was 128.6±17.4 and 76.1±9.8 mm Hg. In multivariable linear regression models, continuous SBP (β=0.63 cm 3 per 10 mm Hg [95% CI, 0.32–0.94]), DBP (0.64 cm 3 per 5 mmHg [95% CI, 0.37–0.91]), and antihypertensive treatment (1.23 cm 3 [95% CI, 0.14–2.23]) were significantly associated with WMH volume. Regarding treatment efficacy, only participants with hypertension despite treatment (treated BP ≥140 or ≥90 mm Hg) had significantly increased WMH volume (4.24 cm 3 [2.36–6.13]) compared with normotension without treatment (untreated BP <120/<80 mm Hg). Our results suggest that WMHs represent a marker of advanced hypertension pathology. Hence, early treatment should prevent WMHs.

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