Hypermethylation of ERа-A gene and high serum homocysteine level are correlated with cognitive impairment in white matter hyperintensity patients

The objective of this study was to investigate the cross-sectional associations of atrial fibrillation with neuroimaging measures of cerebrovascular disease and Alzheimer’s disease-related pathology, and their interaction with cognitive impairment. MRI scans of non-demented individuals (n=1044) from the population-based Mayo Clinic Study of Aging were analyzed for infarctions, total grey matter, hippocampal and white matter hyperintensity volumes. A subset of 496 individuals underwent FDG and C-11 Pittsburgh compound B (PiB) PET scans. We assessed the associations of atrial fibrillation with i) categorical MRI measures (cortical and subcortical infarctions) using multivariable logistic regression models, and with ii) continuous MRI measures ( hippocampal, total grey matter, and white matter hyperintensity volumes) and FDG-PET and PiB-PET measures using multivariable linear regression models, and adjusting for confounders. Among participants who underwent MRI (median age, 77.8, 51.6% male), 13.5% had atrial fibrillation. Presence of atrial fibrillation was associated with subcortical infarctions (odds ratio [OR], 1.83; p=0.002), cortical infarctions (OR, 1.91; p=0.03), total grey matter volume (Beta [β], -.025, p<.0001) after controlling for age, education, gender, APOE e4 carrier status, coronary artery disease, diabetes, history of clinical stroke, and hypertension. However, atrial fibrillation was not associated with white matter hyperintensity volume, hippocampal volume, Alzheimer’s pattern of FDG hypometabolism or PiB uptake. There was a significant interaction of cortical infarction (p for interaction=0.004) and subcortical infarction (p for interaction =0.015) with atrial fibrillation with regards to odds of mild cognitive impairment (MCI). Using subjects with no atrial fibrillation and no infarction as the reference, the OR (95% confidence intervals [CI]) for MCI was 2.98 (1.66, 5.35;p = 0.0002) among participants with atrial fibrillation and any infarction, 0.69 (0.36, 1.33;p= 0.27) for atrial fibrillation and no infarction, and 1.50 (0.96, 2.32;p = 0.07) for no atrial fibrillation and any infarction. These data highlight that atrial fibrillation is associated with MCI in the presence of infarctions.

Download Full-text

Regional White Matter Hyperintensity Influences Grey Matter Atrophy in Mild Cognitive Impairment

Journal of Alzheimer s Disease ◽

10.3233/jad-180280 ◽

2018 ◽

Vol 66 (2) ◽

pp. 533-549 ◽

Cited By ~ 5

Author(s):

Ashwati Vipin ◽

Heidi Jing Ling Foo ◽

Joseph Kai Wei Lim ◽

Russell Jude Chander ◽

Ting Ting Yong ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

White Matter ◽

Grey Matter ◽

White Matter Hyperintensity ◽

Grey Matter Atrophy

Download Full-text

Poor nutrition and alcohol consumption are related to high serum homocysteine level at post-stroke

Nutrition Research and Practice ◽

10.4162/nrp.2015.9.5.503 ◽

2015 ◽

Vol 9 (5) ◽

pp. 503 ◽

Cited By ~ 8

Author(s):

Seung-Hye Choi ◽

Smi Choi-Kwon ◽

Min-Sun Kim ◽

Jong-Sung Kim

Keyword(s):

Alcohol Consumption ◽

Homocysteine Level ◽

High Serum ◽

Post Stroke ◽

Serum Homocysteine ◽

Poor Nutrition

Download Full-text

Trial of remote ischaemic preconditioning in vascular cognitive impairment (TRIC-VCI): protocol

BMJ Open ◽

10.1136/bmjopen-2020-040466 ◽

2020 ◽

Vol 10 (10) ◽

pp. e040466

Author(s):

Aravind Ganesh ◽

Philip Barber ◽

Sandra E Black ◽

Dale Corbett ◽

Thalia S Field ◽

...

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Cognitive Impairment ◽

White Matter ◽

Diffusion Tensor ◽

Vascular Cognitive Impairment ◽

White Matter Injury ◽

White Matter Hyperintensity ◽

Limb Ischaemia ◽

Ischaemic Brain

IntroductionCerebral small vessel disease (cSVD) accounts for 20%–25% of strokes and is the most common cause of vascular cognitive impairment (VCI). In an animal VCI model, inducing brief periods of limb ischaemia-reperfusion reduces subsequent ischaemic brain injury with remote and local protective effects, with hindlimb remote ischaemic conditioning (RIC) improving cerebral blood flow, decreasing white-matter injury and improving cognition. Small human trials suggest RIC is safe and may prevent recurrent strokes. It remains unclear what doses of chronic daily RIC are tolerable and safe, whether effects persist after treatment cessation, and what parameters are optimal for treatment response.Methods and analysisThis prospective, open-label, randomised controlled trial (RCT) with blinded end point assessment and run-in period, will recruit 24 participants, randomised to one of two RIC intensity groups: one arm treated once daily or one arm twice daily for 30 consecutive days. RIC will consistent of 4 cycles of blood pressure cuff inflation to 200 mm Hg for 5 min followed by 5 min deflation (total 35 min). Selection criteria include: age 60–85 years, evidence of cSVD on brain CT/MRI, Montreal Cognitive Assessment (MoCA) score 13–24 and preserved basic activities of living. Outcomes will be assessed at 30 days and 90 days (60 days after ceasing treatment). The primary outcome is adherence (completing ≥80% of sessions). Secondary safety/tolerability outcomes include the per cent of sessions completed and pain/discomfort scores from patient diaries. Efficacy outcomes include changes in cerebral blood flow (per arterial spin-label MRI), white-matter hyperintensity volume, diffusion tensor imaging, MoCA and Trail-Making tests.Ethics and disseminationResearch Ethics Board approval has been obtained. The results will provide information on feasibility, dose, adherence, tolerability and outcome measures that will help design a phase IIb RCT of RIC, with the potential to prevent VCI. Results will be disseminated through peer-reviewed publications, organisations and meetings.Trial registration numberNCT04109963.

Download Full-text

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.

Download Full-text

Association between white matter hyperintensity load and grey matter atrophy in mild cognitive impairment is not unidirectional

Aging ◽

10.18632/aging.202977 ◽

2021 ◽

Author(s):

Ashwati Vipin ◽

Benjamin Yi Xin Wong ◽

Dilip Kumar ◽

Audrey Low ◽

Kok Pin Ng ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

White Matter ◽

Grey Matter ◽

White Matter Hyperintensity ◽

Grey Matter Atrophy

Download Full-text

Homocysteine Level Is Associated with White Matter Hyperintensity Locations in Patients with Acute Ischemic Stroke

PLoS ONE ◽

10.1371/journal.pone.0144431 ◽

2015 ◽

Vol 10 (12) ◽

pp. e0144431 ◽

Cited By ~ 8

Author(s):

Yuan Gao ◽

Sen Wei ◽

Bo Song ◽

Jie Qin ◽

Hui Fang ◽

...

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Acute Ischemic Stroke ◽

Homocysteine Level ◽

White Matter Hyperintensity

Download Full-text

Abstract TP439: Temporary Cognitive Impairment in Transient Ischemic Attack and Minor Stroke Patients is Predicted by Chronic White Matter Hyperintensity Volume

Stroke ◽

10.1161/str.44.suppl_1.atp439 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Leka Sivakumar ◽

Thomas Jeerakathil ◽

Negar Asdaghi ◽

Richard Camicioli ◽

Christian Beaulieu ◽

...

Keyword(s):

Cognitive Impairment ◽

White Matter ◽

White Matter Hyperintensity ◽

Minor Stroke ◽

Lesion Volume ◽

Cognitive Changes ◽

Mini Mental Status Examination ◽

History Of ◽

Ischemic Attack ◽

Patients Experience

Background: Cognitive changes have been described in subacute TIA/minor stroke (TIA/MIS), but the temporal profile is unknown. We tested the hypothesis that TIA/MIS patients experience transient cognitive impairment, and that this can be predicted by Diffusion-Weighted Imaging (DWI) lesion volume. Methods: Acute TIA/MIS stroke (NIH stroke scale score ≤3) patients with no history of cognitive impairment were prospectively recruited within 72 h of onset. Patients underwent Montreal Cognitive Assessment (MoCA), Mini-Mental Status Examination (MMSE) and MRI, including DWI and Fluid-Attenuated Inverse Recovery (FLAIR) sequences, at baseline, days 7 and 30. DWI lesion and FLAIR chronic white matter hyperintensity (WMH) volumes were measured planimetrically. Results: Fifty patients (mean age 68 ±15.1 years) were imaged at a median (IQR) of 26.5 (28.5) h after onset. Cognitive impairment (scores ≤26) was detected more frequently with MoCA (31/50, 62%) than MMSE (13/50, 26%, p=0.009). Acute ischemic lesions (DWI) were present in 33 (66%) patients. Mean DWI volume at baseline was 4.5 ± 11.1ml. Patients with DWI lesions (22/33, 67%) had similar impairment rates as those without (9/17, 53%; p=0.34). Linear regression indicated no relationship between acute DWI lesion volume (log transformed) and baseline MoCA scores (β=0.028, 95% CI [-2.09, 2.44]). Impaired patients had larger WMH volumes (13.6 ± 21.9 ml) than unaffected patients (2.6 ± 3.2 ml, p=0.01). Log transformed WMH volumes were inversely predictive of baseline MoCA scores (β=-0.54, 95% CI [-7.84, -2.28]). Median MoCA scores improved over time (27(5) at day 7 and 28(5) at day 30). Patients with baseline impairment and an increase of ≥2 points on MoCA by day 30 were defined as reverters (N=20). DWI lesion frequency was similar in reverters and those with persisting impairment (75% vs 64%, p= 0.50), as was DWI (6.9 ±14.3 ml vs 1.2 ±1.9 ml; p= 0.113) and WMH lesion volume (17.0 ± 26.2 ml vs 8.1 ± 8.1 ml; p= 0.18). Conclusions: Most TIA/MIS patients have evidence of temporary acute cognitive impairment when assessed with MoCA. Deficits are correlated with chronic WMH, suggesting an unmasking of subclinical cognitive impairment. Temporary cognitive deficits should be considered in the management of TIA/MIS patients.

Download Full-text