White Matter Hyperintensities Predict Cognitive Decline: A Community-Based Study

ABSTRACT:Introduction: White matter hyperintensities (WMHs) were commonly seen in brain magnetic resonance imaging (MRI) of the elderly. Many studies found that WMHs were associated with cognitive decline and dementia. However, the association between WMHs in different brain regions and cognitive decline remains debated. Methods: We explored the association of the severity of WMHs and cognitive decline in 115 non-demented elderly (≥50 years old) sampled from the Wuliqiao Community located in urban area of Shanghai. MRI scans were done during 2009–2011 at the beginning of the study. Severity of WMHs in different brain regions was scored by Improved Scheltens Scale and Cholinergic Pathways Hyperintensities Scale (CHIPS). Cognitive function was evaluated by Mini-Mental State Examination (MMSE) every 2 to 4 years during 2009–2018. Results: After adjusting for confounding factors including age, gender, education level, smoking status, alcohol consumption, depression, hypertension, diabetes, hyperlipidemia, brain infarcts, brain atrophy, apoE4 status, and baseline MMSE score, periventricular and subcortical WMH lesions as well as WMHs in cholinergic pathways were significantly associated with annual MMSE decline ( p < 0.05), in which the severity of periventricular WMHs predicted a faster MMSE decline (–0.187 points/year, 95% confidence interval: –0.349, –0.026, p = 0.024). Conclusions: The severity of WMHs at baseline was associated with cognitive decline in the non-demented elderly over time. Interventions on WMH lesions may offer some benefits for cognitive deterioration.

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Abstract MP057: Subclinical Cerebrovascular Disease is Associated with Worsening Gait and Balance in an Elderly Multi-Ethnic Population: The Northern Manhattan Study (NOMAS)

Circulation ◽

10.1161/circ.135.suppl_1.mp057 ◽

2017 ◽

Vol 135 (suppl_1) ◽

Author(s):

Joshua Z Willey ◽

Yeseon Park Moon ◽

Janet DeRosa ◽

Erin Kulick ◽

Sandino Cespedes ◽

...

Keyword(s):

White Matter ◽

Cerebrovascular Disease ◽

White Matter Hyperintensities ◽

Physical Aging ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

The Elderly ◽

Brain Regions ◽

Periventricular White Matter ◽

Age Related

Introduction: Age-related decline in gait and balance is a contributor to morbidity in the elderly. Subclinical cerebrovascular disease, seen on magnetic resonance imaging (MRI) as white matter hyperintensities (WMH) and silent brain infarcts (SBI), is associated with impaired mobility. Less is known about the association of WMH in specific brain regions and mobility impairment. We hypothesized that anterior WMH volume would be associated with lower scores on the Short Physical Performance Battery (SPPB), a well-validated mobility scale associated with falls and mortality in the elderly. Methods: Participants in the Northern Manhattan Study MRI cohort had the SPPB measured a median of 5 years after enrollment. The SPPB has three domains with a maximum total score of 12: gait speed, chair stands, standing balance. Volumetric distributions for WMH volume across 14 brain regions (brainstem, cerebellum, and bilateral frontal, occipital, temporal, and parietal lobes, and bilateral anterior and posterior periventricular white matter) were determined separately for each hemisphere by combining bimodal image intensity distribution and atlas based methods. Multi-variable linear regression was performed to examine the association between SBI and total and regional (frontal, parietal, occipital, temporal, anterior, posterior, and brainstem) head size-corrected WMH volumes, with the total SPPB score; models were adjusted for cardiovascular disease risk factors, osteo-arthritis, and grip strength. Results: Among 668 stroke-free participants with the SPPB available, mean age at the time of assessment was 74 ±9 years, 37% were male and 70% Hispanic; the mean SPPB score was 8.2 ± 2.9, interquartile range 7-10. Mean total WMHV was 0.55±0.75cc, mean anterior WMH volume 0.18±0.24cc, and 12% of participants had SBI. In multi-variable models, total WMHV was associated with a lower SPPB (beta = -0.3 per SD of logWMH, p=0.004), while SBI was not (beta= -0.12, p=0.7). For regional WMH volumes, only greater anterior periventricular WMHV was associated with SPPB (beta= -0.29 per SD, p=0.009). Conclusions: White matter hyperintensities, especially in the anterior cerebral regions, are associated with a lower SPPB. Prevention of subclinical cerebrovascular disease is a potential target to prevent physical aging in the elderly.

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Structural neuroimaging in Altheimer's disease: do white matter hyperintensities matter?

Dialogues in Clinical Neuroscience ◽

10.31887/dcns.2009.11.2/ambrickman ◽

2009 ◽

Vol 11 (2) ◽

pp. 181-190 ◽

Cited By ~ 13

Keyword(s):

Older Adults ◽

White Matter ◽

Cognitive Decline ◽

White Matter Hyperintensities ◽

Significant Proportion ◽

Cognitive Change ◽

Brain Regions ◽

Potential Contribution ◽

Structural Neuroimaging ◽

Multiple Imaging

The targeted brain dysfunction that accompanies aging can have a devastating effect on cognitive and intellectual abilities. A significant proportion of older adults experience precipitous cognitive decline that negatively impacts functional activities. Such individuals meet clinical diagnostic criteria for dementia, which is commonly attributed to Alzheimer's disease (AD). Structural neuroimaging, including magnetic resonance imaging (MRI), has contributed significantly to our understanding of the morphological and pathology-related changes that may underlie normal and disease-associated cognitive change in aging. White matter hyperintensities (WMH), which are distributed patches of increased hyperintense signal on T2-weighted MRI, are among the most common structural neuroimaging findings in older adults. In recent years, WMH have emerged as robust radiological correlates of cognitive decline. Studies suggest that WMH distributed in anterior brain regions are related to decline in executive abilities that is typical of normal aging, whereas WMH distributed in more posterior brain regions are common in AD. Although epidemiological, observational, and pathological studies suggest that WMH may be ischemic in origin and caused by consistent or variable hypoperfusion, there is emerging evidence that they may also reflect vascular deposition of beta-amyloid, particularly when they are distributed in posterior areas and are present in patients with AD. Findings from the literature highlight the potential contribution of small-vessel cerebrovascular disease to the pathogenesis of AD, and suggest a mechanistic interaction, but future longitudinal studies using multiple imaging modalities are required to fully understand the complex role of WMH in AD.

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Brain Magnetic Resonance Imaging (MRI) White Matter Hyperintensities in Cyclic Vomiting Syndrome With or Without Migraine

Journal of Child Neurology ◽

10.1177/08830738211027972 ◽

2021 ◽

pp. 088307382110279

Author(s):

Salman Rashid ◽

Samantha Weaver ◽

Khaled Al-Robaidi ◽

Leon Dure ◽

Sumit Singh

Keyword(s):

Magnetic Resonance Imaging ◽

White Matter ◽

Magnetic Resonance ◽

White Matter Hyperintensities ◽

Brain Magnetic Resonance Imaging ◽

Cyclic Vomiting Syndrome ◽

Resonance Imaging ◽

Mri Findings ◽

Magnetic Resonance Imaging Mri ◽

Cyclic Vomiting

Background: Cyclic vomiting syndrome is classified as a possible subset of migraine. Brain magnetic resonance imaging (MRI) findings of white matter hyperintensities are well documented in migraineurs, but not in patients with cyclic vomiting syndrome. This study focuses on white matter hyperintensities in children with cyclic vomiting syndrome. Methods: We investigated our database of outpatient medical records for the diagnosis codes associated with cyclic vomiting syndrome from January 2008 to October 2018. Results: Brain MRIs were obtained in 31 of 185 patients (∼17%) with a diagnosis code related to cyclic vomiting syndrome. We excluded 13 of 31 patients because of the inaccessibility of images or a confounding diagnosis. Remaining patients were divided into 2 groups: 13 of 18 cyclic vomiting syndrome with migraine (CVS+M), and 5 of 18 cyclic vomiting syndrome without migraine (CVS-M). We found that 3 of the 13 patients in the CVS +M group had migraine-like white matter hyperintensities compared to 0 of the 5 in the CVS-M group. Conclusion: This small study suggests a possible relationship between white matter hyperintensities and CVS+M. A larger study is required to validate these findings.

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The Characteristics of White Matter Hyperintensities in Patients With Migraine

10.21203/rs.3.rs-773741/v1 ◽

2021 ◽

Author(s):

Catherine Chong ◽

Todd J Schwedt ◽

Meesha Trivedi ◽

Brian W Chong

Keyword(s):

White Matter ◽

Basal Ganglia ◽

White Matter Hyperintensities ◽

Rating Scale ◽

Right Hemisphere ◽

Brain Magnetic Resonance Imaging ◽

Brain Regions ◽

Visual Rating ◽

Radiology Reports ◽

Visual Rating Scale

Abstract BackgroundThe presence of white matter hyperintensities (WMH) in migraine is well-documented, but the location of brain WMH in patients with migraine are insufficiently researched. Although recent semi-automatic software packages have been developed for calculating WMH, visual inspection remains the gold standard for measuring WMH. The goal of this study was to assess WMH in patients with migraine using a modified version of the Scheltens visual rating scale, a semiquantitative scale for categorizing WMH in the following brain regions: periventricular, lobar (frontal, temporal, parietal, occipital), basal ganglia, and infratentorial regions.Methods263 patients with migraine (31 male/232 female; mean age: 48.0) who were enrolled in the American Registry for Migraine Research from Mayo Clinic with a diagnosis of episodic (n = 46; 17.5%) or chronic migraine (n = 217; 82.5%) and who had brain magnetic resonance imaging were included in this study. Those with imaging evidence for gross anatomical abnormalities other than WMH were excluded. WMH were identified on axial T2 and FLAIR sequences by a board certified neuroradiologist. WMH were characterized via manual inspection and categorized according to the scale’s criteria.Results95 patients (36.1 %: mean age: 41.8) had no WMH on axial T2 and FLAIR imaging and 168 patients (63.9%, mean age: 51.4) had WMH. Of those with WMH, 94.1% (n = 158) had lobar hyperintensities (frontal: 148/158, 93.7%; parietal: 57/158, 36.1%; temporal: 35/158, 22.1%; occipital: 9/158, 5.7%), 13/168, 7.7% had basal ganglia WMH, 49/168, 29.1% had periventricular WMH, and 17/168, 10.1% had infratentorial WMH. 101/168 patients (60.1%) had bilateral WMH and 67/168 (39.9%) had unilateral WMH (34 right hemisphere /33 left hemisphere). 30.0% of patients with WMH did not have WMH reported in their clinical radiology reports.DiscussionNearly 2/3 of patients with migraine had WMH. They were most common in the lobar regions, specifically in the frontal lobe. The categorization of WMH in migraine using the modified Scheltens visual rating scale could help in future studies to clarify the relationship between WMH and headache features and might be a useful method for developing classifiers that differentiate between migraine-specific WMH and other causes of WMH.

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Brain Structural Changes in Schizophrenia Patients Compared to the Control: A MRI-Based Cavalieri’s Method

Basic and Clinical Neuroscience Journal ◽

10.32598/bcn.2021.3481.1 ◽

2021 ◽

pp. 1-20

Author(s):

Zahra Heidari ◽

◽

Hamidreza Mahmoudzadeh-Sagheb ◽

Mansour Shakiba ◽

Enam Alhagh Charkhat Gorgich ◽

...

Keyword(s):

White Matter ◽

Structural Changes ◽

Brain Mri ◽

Brain Regions ◽

Volume Density ◽

Slice Thickness ◽

Brain Disorder ◽

Mri Scans ◽

Magnetic Resonance Imaging Mri ◽

Treatment Trends

Introduction: Schizophrenia is a severe psychotic brain disorder. One of the probable mechanisms can be volumetric changes in some brain regions. Therefore, the aim of the present study was to estimate quantitative analysis of the brain by magnetic resonance imaging (MRI) in patients with schizophrenia compared to the controls. Methods: This case–control study was conducted on MRI scans of 20 patients with schizophrenia and 20 healthy controls in Zahedan, Southeastern Iran. MRIs with 4 mm slice thickness and 5 mm intervals in coronal and sagittal planes were captured. Then, quantitative parameters including volume and volume density of various brain regions were estimated in both groups using Cavalieri's point counting method. Data analyses performed using Mann-Whitney U test. Results: The findings of this investigation revealed that volumes of gray matter, hippocampus, and gray/white matter in patients with schizophrenia were significantly lower than the controls (p˂0.05). The volumes of lateral ventricles in patients with schizophrenia (36.60±4/32 mm3) were significantly higher than the healthy individuals (30.10±7.98 mm3). However, there were no statistically significant changes in the total volume of brain, cerebral hemispheres, white matter, brain stem, cerebellum, and corpus callosum between the two groups (p˃0.05). Conclusion: Volumetric estimations on brain MRI-based stereological technique can be helpful for elucidation of structural changes, follow-up the treatment trends, and evaluating the therapeutic situation in schizophrenia patients. Volumetric alternations in specific brain areas might be linked to cognitive impairments and severity of symptoms in patients with schizophrenia. Further researches are needed in this regards.

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Topological relationships between perivascular spaces and progression of white matter hyperintensities: a pilot study in a sample of the Lothian Birth Cohort 1936

10.1101/2021.09.18.21263770 ◽

2021 ◽

Author(s):

Abbie N Barnes ◽

Lucia Ballerini ◽

Maria Del Carmen Valdes Hernandez ◽

Francesca M Chappell ◽

Susana Munoz Maniega ◽

...

Keyword(s):

White Matter ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Automatic Segmentation ◽

Brain Magnetic Resonance Imaging ◽

Spatial Proximity ◽

Perivascular Spaces ◽

Longitudinal Mri ◽

Lothian Birth Cohort ◽

Magnetic Resonance Imaging Mri

Enlarged perivascular spaces (PVS) and white matter hyperintensities (WMH) are features of cerebral small vessel disease which can be seen in brain magnetic resonance imaging (MRI). Given the associations and proposed mechanistic link between PVS and WMH, they are hypothesised to also have topological proximity. However, this, and the influence of their spatial proximity on WMH progression are unknown. We analysed longitudinal MRI data from 29/32 participants (mean age at baseline = 71.9 years) in a longitudinal study of cognitive ageing, from three waves of data collection at 3-year intervals, alongside semi-automatic segmentation masks for PVS and WMH, to assess relationships. The majority of deep WMH clusters were found adjacent to or enclosing PVS (Wave 1: 77%; 2: 76%; 3: 69%), especially in frontal, parietal and temporal regions. Of the WMH clusters in the deep white matter that increased between waves, most increased around PVS (Waves 1-2: 73%; 2-3: 72%). Formal statistical comparisons of severity of each if these two SVD markers yielded no associations between deep WMH progression and PVS proximity. These findings may suggest deep WMH clusters preferentially form and grow around PVS, possibly reflecting the consequences of impaired interstitial fluid drainage via PVS. The utility of these relationships as predictors of WMH progression remains unclear.

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The Cerebellum Is Related to Cognitive Dysfunction in White Matter Hyperintensities

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.670463 ◽

2021 ◽

Vol 13 ◽

Author(s):

Shanshan Cao ◽

Jiajia Nie ◽

Jun Zhang ◽

Chen Chen ◽

Xiaojing Wang ◽

...

Keyword(s):

Cognitive Impairment ◽

White Matter ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Gray Matter Volume ◽

Brain Regions ◽

Anterior Cingulate ◽

Magnetic Resonance Imaging Mri ◽

Fazekas Scale ◽

And Function

ObjectiveWhite matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) is frequently presumed to be secondary to cerebral small vessel disease (CSVD) and associated with cognitive decline. The cerebellum plays a key role in cognition and has dense connections with other brain regions. Thus, the aim of this study was to investigate if cerebellar abnormalities could occur in CSVD patients with WMHs and the possible association with cognitive performances.MethodsA total of 104 right-handed patients with WMHs were divided into the mild WMHs group (n = 39), moderate WMHs group (n = 37), and severe WMHs group (n = 28) according to the Fazekas scale, and 36 healthy controls were matched for sex ratio, age, education years, and acquired resting-state functional MRI. Analysis of voxel-based morphometry of gray matter volume (GMV) and seed-to-whole-brain functional connectivity (FC) was performed from the perspective of the cerebellum, and their correlations with neuropsychological variables were explored.ResultsThe analysis revealed a lower GMV in the bilateral cerebellum lobule VI and decreased FC between the left- and right-sided cerebellar lobule VI with the left anterior cingulate gyri in CSVD patients with WMHs. Both changes in structure and function were correlated with cognitive impairment in patients with WMHs.ConclusionOur study revealed damaged GMV and FC in the cerebellum associated with cognitive impairment. This indicates that the cerebellum may play a key role in the modulation of cognitive function in CSVD patients with WMHs.

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The association between systolic blood pressure variability with depression, cognitive decline and white matter hyperintensities: the 3C Dijon MRI study

Psychological Medicine ◽

10.1017/s0033291717002756 ◽

2017 ◽

Vol 48 (9) ◽

pp. 1444-1453 ◽

Cited By ~ 9

Author(s):

P. J. Tully ◽

S. Debette ◽

C. Tzourio

Keyword(s):

Blood Pressure ◽

White Matter ◽

Cognitive Decline ◽

Blood Pressure Variability ◽

White Matter Hyperintensities ◽

Late Onset ◽

Brain Magnetic Resonance Imaging ◽

Longitudinal Association ◽

Finger Tapping Test ◽

Mri Study

AbstractBackgroundAccumulating evidence links blood pressure variability (BPV) with white matter hyperintensities (WMH) and stroke. The longitudinal association between BPV with late onset depression (LOD) and cognitive decline remains unexplored.MethodsProspective cohort study of 2812 participant's age ⩾65 years (median age 72 years, 63.6% female) without dementia or stroke. Serial clinic visits assessed blood pressure, cognitive function, depression disorder, and depressive symptoms. A brain magnetic resonance imaging (MRI) substudy was performed in 1275 persons to examine possible associations with WMH.ResultsThe interaction between symptomatic LOD and systolic BPV was associated with cognitive decline on the Isaac Set Test [slope −4.45; 95% confidence interval (CI) −8.92 to −0.16, p = 0.04], Benton Visual Retention Test (slope −0.89; 95% CI −1.77 to −0.01, p = 0.049), Mini Mental State Examination (slope −1.08; 95% CI −1.86 to −0.30, p = 0.007) and Finger Tapping Test (slope −7.53; 95% CI −13.71 to −1.34, p = 0.017) but not Trail Making Test-A or -B/A. The MRI substudy demonstrated that systolic BPV was associated with cognitive decline via interactions with depression and total WMH volume, but this was not dependent on either deep or periventricular WMH volumes.ConclusionsThe findings show that the interaction between systolic BPV with symptomatic depression and WMH increases cognitive decline in persons ⩾65 years of age. Future work could extend these findings by examining systolic BPV in relation to cognitive decline and WMH in older populations with depression.

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Predictors for cognitive decline in patients with confluent white matter hyperintensities

Alzheimer s & Dementia ◽

10.1016/j.jalz.2011.10.004 ◽

2012 ◽

Vol 8 ◽

pp. S96-S103 ◽

Cited By ~ 13

Author(s):

Vincent Mok ◽

Yunyun Xiong ◽

Kelvin K. Wong ◽

Adrian Wong ◽

Reinhold Schmidt ◽

...

Keyword(s):

White Matter ◽

Cognitive Decline ◽

White Matter Hyperintensities

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The Effects of Longitudinal White Matter Hyperintensity Change on Cognitive Decline and Cortical Thinning over Three Years

Journal of Clinical Medicine ◽

10.3390/jcm9082663 ◽

2020 ◽

Vol 9 (8) ◽

pp. 2663

Author(s):

Seung Joo Kim ◽

Dong Kyun Lee ◽

Young Kyoung Jang ◽

Hyemin Jang ◽

Si Eun Kim ◽

...

Keyword(s):

Cognitive Impairment ◽

White Matter ◽

Cognitive Decline ◽

Dynamic Change ◽

Surrogate Marker ◽

Brain Magnetic Resonance Imaging ◽

Longitudinal Change ◽

White Matter Hyperintensity ◽

Cortical Thinning ◽

Automated Method

White matter hyperintensity (WMH) has been recognised as a surrogate marker of small vessel disease and is associated with cognitive impairment. We investigated the dynamic change in WMH in patients with severe WMH at baseline, and the effects of longitudinal change of WMH volume on cognitive decline and cortical thinning. Eighty-seven patients with subcortical vascular mild cognitive impairment were prospectively recruited from a single referral centre. All of the patients were followed up with annual neuropsychological tests and 3T brain magnetic resonance imaging. The WMH volume was quantified using an automated method and the cortical thickness was measured using surface-based methods. Participants were classified into WMH progression and WMH regression groups based on the delta WMH volume between the baseline and the last follow-up. To investigate the effects of longitudinal change in WMH volume on cognitive decline and cortical thinning, a linear mixed effects model was used. Seventy patients showed WMH progression and 17 showed WMH regression over a three-year period. The WMH progression group showed more rapid cortical thinning in widespread regions compared with the WMH regression group. However, the rate of cognitive decline in language, visuospatial function, memory and executive function, and general cognitive function was not different between the two groups. The results of this study indicated that WMH volume changes are dynamic and WMH progression is associated with more rapid cortical thinning.

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