Cognitive impairment in cerebral small vessel disease induced by hypertension

Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular disease.Howeve r,the causal relationship between hypertension and cerebral small vessel disease remains unclear.Hypertension has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular disease.Chronic hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and stroke.Hypertension is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of hypertension.This review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive ability.We also discuss drugs to treat cerebral small vessel disease and cognitive impairment.

Vitamin D deficiency and increased inflammatory factor intercellular cell adhesion molecule-1 indicate severe leukoaraiosis in northern China

Background and objective:Commonly plaguing in the frigid zone of the world,vitamin D deficiency,as indicated by low levels of 25-hydroxyvitamin D,exacerbated inflammatory responses and impaired endothelial function.Leukoaraiosis(LA)is a prevalent cause of cognitive dysfunction in the elderly and is potentially associated with inflammatory responses.This study aimed to investigate the impact of vitamin D on the severity of LA.Methods:Patients with LA were categorized based on 3.0 T brain MRI findings into mild(N=43),moderate(N=40),or severe groups(N=29)using the Fazekas scale(scoring 1-6).A control group consisting of 41 healthy individuals was included.Serum fibrinogen C,homocysteine,plasma 25-hydroxyvitamin D,and intercellular cell adhesion molecule-1(ICAM-1)levels were measured using ELISA.Results:All LA severity groups exhibited lower plasma 25-hydroxyvitamin D levels compared to the control group,with a more pronounced decrease observed as LA severity increased.Low plasma 25-hydroxyvitamin D was identified as an independent risk factor for LA(P<0.05)according to Multiple logistic regression analysis.Additionally,a negative association was observed between 25-hydroxyvitamin D and vascular inflammatory factor ICAM-1.Conclusions:Disease severity positively correlated with levels of the inflammatory marker ICAM-1,worsening as plasma 25-hydroxyvitamin D concentration decreased.Low 25-hydroxyvitamin D emerged as an independent risk factor for LA,potentially exacerbating the inflammatory response.These findings suggest 25-hydroxyvitamin D supplementation as a potential therapeutic approach for LA.

Sodium ozagrel and atorvastatin for type 2 diabetes patients with lacunar cerebral infarction

BACKGROUND The main pathological factor of cerebral infarction is atherosclerosis,which is the pathological process of chronic inflammatory diseases such as vascular smooth muscle hyperplasia,inflammatory cell infiltration,extracellular matrix increase,and thrombosis.At present,the focus of clinical treatment is anti-platelet aggregation and improving blood status,and current research is limited to improving symptoms only.AIM To observe the effect of sodium ozagrel and atorvastatin on type 2 diabetes patients with lacunar cerebral infarction.METHODS Eighty-two patients with type 2 diabetes and lacunar cerebral infarction admitted to our hospital from January 2018 to February 2020 were equally categorized into two groups according to their treatment method.The control group was administered atorvastatin,and the observation group was administered sodium ozagrel combined with atorvastatin.The National Institutes of Health stroke scale(NIHSS)score,activities of daily living(ADL)score,blood glucose,lipid levels,inflammatory factors,high-mobility group box 1(HMGB1)levels,paraoxonase-1(PON-1)levels,erythrocyte sedimentation rate(ESR),and macrophage migration inhibitory factor(MIF)levels were recorded before and after treatment.The total effective rate and adverse reaction rate of the two groups were analyzed.RESULTS The total effective rate of the observation group(94.00%)was significantly higher than that of the control group(80.00%)(χ2=3.998;P=0.046).The blood glucose indexes,total cholesterol levels,triglyceride levels,low-density lipoprotein cholesterol levels,high-sensitivity C-reactive protein levels,interleukin-1βlevels,tumor necrosis factor-αlevels,HMGB1 Levels,ESR,MIF levels,platelet aggregation rates,and plasma viscosity of the two groups decreased after treatment;however,high-density lipoprotein cholesterol and PON-1 Levels increased after treatment.After treatment,the blood glucose indexes;blood lipid indexes;inflammatory factors;HMGB1,PON-1,and MIF levels;ESR;platelet aggregation rate;and plasma viscosity of the observation group were better than those of the control group(P<0.05).After treatment,all patients in the observation group had higher ADL scores and lower NIHSS scores than those in the control group(P<0.05).CONCLUSION Sodium ozagrel with atorvastatin can reduce inflammatory reactions;regulate ESR and HMGB1,PON-1,and MIF levels;control blood glucose and lipid indexes;and alleviate nerve injury without increasing adverse effects of atorvastatin alone.

Lacunar infarction with leukoaraiosis may aggravate cognitive dysfunction

This study semi-quantitatively analyzed the effects of leukoaraiosis.Patients with moderate or severe lacunar infarction were found to exhibit low scores on the Montreal Cognitive Assessment Scale （F=12.02,P=0.000）,and prolonged P300 Cz2.0 latency （F=16.04,P=0.000）.Correlation analysis revealed that the occurrence of leukoaraiosis was negatively correlated with Montreal Cognitive Assessment scores （r=-0.416,P=0.000）,and positively correlated with P300 Cz2.0 latency （r=0.538,P=0.000）.These findings indicate that leukoaraiosis aggravates cognitive impairment in patients with lacunar infarction,such that more severe leukoaraiosis is associated with more severe cognitive decline.

Correlation of ischemic ophthalmopathy with lacunar infarction

AIM:To investigate the correlation of ischemic ophthalmopathy(IO)with lacunar infarction(LI),an ischemic lesions in the cerebrovascular system.METHODS:Totally 204 cases of IO without any nervous system symptom and previously diagnosed LI served as the observational group.All 204 cases without IO,nervous system symptoms and previous LI served as the control group.Age and sex between the two groups matched well.LI was diagnosed by magnetic resonance imaging(MRI)and the results of the two groups were statistically analyzed and compared.RESULTS:IO included 174 eyes of 156 patients with non-arteritis anterior ischemic optic neuropathy(NAION),42 eyes of 36 patients with central retinal artery occlusion(CRAO)or branch retinal artery occlusion(BRAO)and 12 eyes of 12 patients with ocular ischemia syndrome(OIS).The detection rate of LI(72.54%)in IO group was obviously higher than that(15.68%)in the control group(P<0.001).IO was positively correlated with LI(r=0.573,P<0.05).In addition,most infarction sites located in the basal ganglia(67.57%),which were not the vital areas of cerebrum and not easy to be found due to their small size.The majority of those first visited IO patients(72.54%)without nervous system symptom and previously diagnosed LI had already suffered from LI.CONCLUSION:According to our studies,there is a positive correlation between IO and LI.IO can be used as an important predictor for the present of LI,especially obvious signs of the patient.

Microbleeds in fronto-subcortical circuits are predictive of dementia conversion in patients with vascular cognitive impairment but no dementia

Cerebral small vessel disease（CSVD） is a common etiology of vascular cognitive impairment with no dementia（V-CIND）. Studies have revealed that cerebral microbleeds（CMBs）, a feature of CSVD, contribute to cognitive impairment. However, the association between CMBs and dementia conversion in individuals with V-CIND is still unclear. Here, we analyzed the predictive role of CMBs in the conversion from V-CIND to dementia in CSVD patients. We recruited and prospectively assessed 85 patients with CSVD and V-CIND. V-CIND was evaluated using a series of comprehensive neuropsychological scales, including the Chinese version of the Montreal Cognitive Assessment and the Clinical Dementia Rating. MRI assessments were used to quantify lacunar infarcts, white matter hyperintensities, CMBs, and medial temporal lobe atrophy. Eighty-two of the 85 patients completed the assessment for dementia conversion at a 1-year follow-up assessment. Multivariate logistic regression analyses were conducted to examine independent clinical and MRI variables associated with dementia conversion. Twenty-four patients（29.3%） had converted to dementia at the 1-year follow-up, and these individuals had significantly more CMBs in the fronto-subcortical circuits. Multivariate logistic regression analyses revealed that the patients with CMBs in the fronto-subcortical circuits（odds ratio = 4.4; 95% confidence interval： 1.602-12.081, P = 0.004） and 5 or more CMBs overall（odds ratio = 17.6, 95% confidence interval： 3.23-95.84, P = 0.001） had a significantly increased risk of dementia at the 1-year follow-up. These findings indicate that CMBs in the fronto-subcortical circuits may be predictive of dementia conversion in CSVD patients with V-CIND, and thus extend the clinical significance of CMBs.

Association of ALOX5AP and PDE4D with the risk of lacunar infarct in people from Jiangsu Province,China

The genes for 5-1ipoxygenase activating protein （ALOX5AP） and phosphodiesterase 4D （PDE4D） have been demonstrated as susceptibility genes for lacunar in the Icelandic and Pakistani populations, but little is known about the role of these genes in Chinese populations. The present study utilized polymerase chain reaction and ligase detection reaction to detect single nucleotide polymorphisms （SNPs） in 280 consecutive stroke patients and 258 unrelated population-based controls from Nanjing, Jiangsu Province, China. The allele frequency, genotypes, and haplotypes of the two SNPs （rs456009 and rs966221） in PDE4D were similar between the two groups. However, A allele frequency of rs4073259 （A/G） and rs4769055 （A/C） in the ALOX5AP gene exhibited differences in two groups, and especially the haplotype of the SNP was significantly different between the two groups. Results suggested that the ALOX5AP gene might be involved in lacunar infarct, while PDE4D gene was not a risk factor for lacunar infarct in individuals from Jiangsu Province, China.

Correlative factors of cognitive impairment in patients with lacunar infarcts

Objective To study the relationships between cognitive impairment in patients with lacunar infarcts and quantitative CT measures and to determine the independent correlative factors of cognitive impairment.Methods Neuropsychological examination was conducted for 128 patients with acute lacunar infarct.Number,location,and volume of infarcts,cerebral atrophy index and severity of white matter lesions(WMLs) were measured and recorded.Results The number of lacunar infarcts in cognitive impairment (CI) group was significantly larger than that in cognitive normal(CN) group.Mean width of sulcus and sylvian fissure,index of frontal horn and ventricular-brain ratio(VBR) were significantly different in both groups.There were more patients with 3 grades or 4 grades WMLs in CI group(62%) than those in CN group(22%).The total volume of lacunar infarcts showed no statistically significant difference.Logistic regression analysis indicated that the number of lacunar infarcts in frontal subcortex and thalamus,the volume of infarcts in anterior periventricular white matter,width of cerebral sulcus and sylvian fissure were correlated with cognitive impairment respectively.Additionally,age and education were correlative factors of cognitive impairment in patients with lacunar infarct.Conclusion Correlative factors of cognitive impairment in patients with lacunar infarct are not merely one feature,but a combination of infarct features(number,location,and volume),cortical atrophy and host factors(age and education).

The relation between prognosis and nocturnal blood pressure variation in hypertensive patients with lacunar infarct

Objective We conducted a study using MRI and ambulatory blood pressure monitoring(ABPM) to determine whether an in-apporpriately low nocturnal blood pressure, or an excess fall in nocturnal blood pressure, might be responsible for lacunar infarct. Method ABPM and Casul blood pressure(CBP) were examined in 35 hypertentives with lacunar infarct(LI)and 33 hypertentives without lacunar infarct as control group. Results There is no significant difference of CBP between two groups. But the mean nighttime systolic blood pressure (nSBP) and diastolic blood pressure (nDBP) in patients with lacunar infarct were significantly smaller than in patients without lacunar infarct. The ratio of nSBP/dSBP and nDBP/dDBP in SI were smaller than in control group respectively. Conclusions The results indicate that an inap-propriately low nocturnal blood pressure, or an excessive fall in nocturnal blood pressure, is associated with lacunar infarct. It is necessary not only to control high blood pressure but also to pay attention to circadian changes of blood pressure during the course of anti-hypertensive treatment.

A 55 Year Old Man with Progressive Neurologic Deficits

At least 50% of the decline in functional abilities associated with the elderly is caused by neurological conditions, particularly vascular dementia, such as occurs in Binswanger disease. Binswanger disease is a rare condition, characterized by acute strokes with symptoms and signs compatible with lacunar infarction. The disease onset is commonly between 55 and 75 years. The majority of patients with Binswanger disease have chronic hypertension and other putative factors including diabetes mellitus, polycythemia, thrombocytosis, hyperlipidemia, hyperglobulinemia and pseudoxanthoma elasticum, increased fibrinogen levels and the antiphospholipid antibody syndrome. We report the case of a 55 year old man, who suffered from involuntary movements of his right ann, slight hemiparesis on the right side, and also had dementia. He had a history of high blood pressure and laboratory tests showed that he had diabetes mellitus. The brain magnetic resonance imaging showed irregular white matter abnormalities with multiple lacunar infarcts in the basal ganglia and pons. The clinical picture is characterized by acute strokes, followed by involuntary movements and also dementia. Therefore we decided to diagnose it as Binswanger disease. After discharge from hospital, the patient has not returned for follow-up.

A Study on the Correlation Between Cerebral Small Vascular Disease and Constitution Types of Traditional Chinese Medicine

Objective:To study the correlation between cerebral small vascular disease and constitution types of Traditional Chinese Medicine(TCM).Methods:The severity of lacunar infarction and leukoaraiosis were graded in 230 patients with cerebral small vascular disease,and they were divided into TCM constitution types.The survey of TCM constitution types was carried out by using standardized TCM constitution scale,and order multivariate Logistic regression was used to analyze the correlation between TCM constitution types with severity of lacunar infarction and leukoaraiosis.Results:Yang-deficiency(阳虚)constitution,blood-stasis constitution and phlegm-dampness constitution were the most common TCM constitution types in patients with lacunar infarction,accounting for 33.7%,12.5%,11.5%respectively.Yang-deficiency constitution,blood-stasis constitution and Yin-deficiency(阴虚)constitution were the most common TCM constitution types in patients with leukoaraiosis,accounting for 28.8%,18.5%,13.7%respectively.There were significant differences in lacunar infarction of Yang-deficiency constitution and blood stasis constitution(P<0.05),and there were significant differences in leukoaraiosis of phlegmdampness constitution and blood-stasis constitution(P<0.05).Single factor analysis showed that the main risk factors of lacunar infarction were age,smoking,alcohol consumption,Yang-deficiency constitution and blood-stasis constitution,and the main risk factors of leukoaraiosis were age,smoking,hypertensive disease,phlegm-dampness constitution and blood-stasis constitution.The ordered multivariate Logistic regression analysis found that the severity of lacunar infarction was closely related to age,and the severity of leukoplosis was closely related to age,smoking and hypertension disease.Conclusion:TCM constitution types of lacunar infarction in patients with small cerebral vascular disease is mainly Yang-deficiency constitution and blood-stasis constitution,and the risk factors include age,smoking,alcohol consumption,Yang-deficiency constitution and blood-stasis constitution.Age is closely related with lacunar infarction.TCM constitution types with leukoaraiosis are mainly phlegm-dampness constitution and blood-stasis constitution,and the risk factors are age,smoking,hypertension disease,phlegm-dampness constitution and blood-stasis constitution.Age,smoking and hypertension disease are closely related with leukoaraiosis.

Multimodal magnetic resonance imaging for assessing lacunar infarction after proximal middle cerebral artery occlusion in a canine model

Background A new lacunar infarction model was recently established in beagle dogs through proximal middle cerebral artery （MCA） occlusion by thrombus. This study aimed to characterize the model by multimodal magnetic resonance imaging （MRI） and to investigate its potential role for the future stroke research. Methods The left proximal MCA was embolized with an autologous thrombus in six beagles. Diffusion-weighted imaging （DWI） and T2-weighted imaging （T2Wl） were performed every half hour during the first six hours after occlusion, followed by three time points at 12 hours, 24 hours, and one week. Perfusion-weighted imaging （PWI） and magnetic resonance angiography （MRA） were carried out at six hours, 24 hours and one week. The PWI-DWI mismatch ratio was defined as （PWI-DWl）/DWl ischemic volume. Results Lacunar infarcts induced by MCA occlusion were located in the left caudate nucleus and internal capsule. All the lesions could be detected within two hours by DWI. Lesion volume on DWl increased in a time dependent manner, from （87.19±67.16） mm3 at one hour up to （368.98±217.05） mm3 at 24 hours （P=0.009）, while that on PWl gradually decreased from （7315.00±2054.38） mm3at six hours to （4900.33±1319.71） mm3 at 24 hours and （3334.33±1195.11） mm3 at one week （P=0.002）. The mismatch ratio was 41.93±22.75 at six hours after ischemia, showing ＂extensive mismatch＂, and decreased to 18.10±13.74 at 24 hours （P=0.002）. No MCA recanalization was observed within 24 hours after MCA occlusion. Conclusions Lacunar infarction induced by proximal MCA occlusion could be detected early by DWl and was characterized by extensive PWI-DWl mismatch. Multimodal MRI is useful to demonstrate the natural evolution of PWI-DWl mismatch. This ischemic model could be further used for investigating early thrombolysis in lacunar stroke showing extensive mismatch.

The clinical manifestations and pathophysiology of cerebral small vessel disease

Small vessel disease （SVD） is responsible for brain chronic circular disorder,and accounts for 20%–30%cases of ischemic stroke as well as cerebral hemorrhage,and to a great extent,encephalopathy.Binswanger’s disease and multiple small strokes,which are common in older people,are also closely associated with SVD.These disorders often cause decline in cognition,vascular dementia,impairment in gait and balance,mood depression,and urinary incontinence,and often brings great social and economic burdens.SVD-related encephalopathy increases the incidences of fall,disability and death in elderly people.With the aging of the society,more attention should be paid to the importance of early diagnosis and prophylactic treatment of SVD.Here the clinical manifestations and pathophysiology of SVD are reviewed.