Subclinical Brain Damage Research Articles

Изменения когнитивного статуса у женщин в период постменопаузы при артериальной гипертонии

The aim of the study was to assess relationship between organ damage and changes of cognitive function in postmenopausal women with arterial hypertension during 3 years of follow-up. A total of 55 women (aged 69 ± 9,5 years) with stable course of hypertension were included. During period of observation and treatment cognitive function deteriorated in 40 and improved in 60% of women. Cox regression analysis showed that worsening of cognitive function was associated with low level of education (OR 3.85, p = 0.021), lack of work (OR 5.71, p = 0.035), left ventricular (LV) end-diastolic diameter (OR 6.89, p = 0.019), LV end-systolic diameter (OR 3.21, p = 0.047), left atrium (OR 15.20, p = 0.020), microalbuminuria (OR 11.14, p = 0.041) and duration of chair-rising test (OR 7.0, p = 0.025). Our findings indicate that progressive organ damage, low level of education and lack of work are associated with deterioration of cognitive function and functional mobility in women with hypertension. Our results reinforce the need for early detection of cognitive impairment as a marker of subclinical brain damage to prevent dementia.

Abstract 11658: Riser Pattern is Associated With Mild Cognitive Impairment in Heart Failure Patients

Introduction: The riser pattern, an abnormal blood pressure (BP) pattern in which sleep BP exceeds awake BP, is a predictor of adverse cardiovascular outcomes. Although the riser pattern is associated with various factors, its significance in heart failure (HF) patients has not been established. HF patients often suffer from cognitive impairment (CI), but the relationship between the riser pattern and CI is not clearly understood. Hypothesis: We tested the hypothesis that the riser pattern is associated with mild CI, a form of brain damage that could develop to dementia. Methods: We performed the Mini-Mental State Examination (MMSE), ambulatory BP monitoring, echocardiography, and blood tests in 444 HF patients just before they left the hospital. Mild CI, a measure of cognitive function, was defined as a score <26. Results: The mean age of the patients was 68±13 years; 61.5% were male; and 22.5% exhibited a riser pattern. The MMSE score was significantly lower in the Riser group than in the Non-riser group (23±5 vs 25±5, p<0.01). In multivariable logistic regression analysis, a riser pattern was significantly associated with mild CI (odds ratio 2.07, 95% confidence intervals 1.19-3.61, p<0.01) after adjusting for significant covariates. Conclusions: A riser pattern was associated with mild CI in HF patients. An abnormal circadian BP rhythm in HF patients is clinically significant as a potential indicator of subclinical brain damage.

Type 2 diabetes mellitus and Alzheimer's disease.

Epidemiological and biological evidences support a link between type 2 diabetes mellitus (DM2) and Alzheimer's disease (AD). Persons with diabetes have a higher incidence of cognitive decline and an increased risk of developing all types of dementia. Cognitive deficits in persons with diabetes mainly affect the areas of psychomotor efficiency, attention, learning and memory, mental flexibility and speed, and executive function. The strong epidemiological association has suggested the existence of a physiopathological link. The determinants of the accelerated cognitive decline in DM2, however, are less clear. Increased cortical and subcortical atrophy have been evidenced after controlling for diabetic vascular disease and inadequate cerebral circulation. Most recent studies have focused on the role of insulin and insulin resistance as possible links between diabetes and AD. Disturbances in brain insulin signaling mechanisms may contribute to the molecular, biochemical, and histopathological lesions in AD. Hyperglycemia itself is a risk factor for cognitive dysfunction and dementia. Hypoglycemia may also have deleterious effects on cognitive function. Recurrent symptomatic and asymptomatic hypoglycemic episodes have been suggested to cause sub-clinical brain damage, and permanent cognitive impairment. Future trials are required to clarify the mechanistic link, to address the question whether cognitive decline may be prevented by an adequate metabolic control, and to elucidate the role of drugs that may cause hypoglycemic episodes.

Resistive Cerebral Blood Flow as a Potential Marker of Subclinical Brain Damage in Essential Hypertension

Introduction: Subclinical brain damage in essential hypertension is more prevalent than cardiovascular or renal impairment; nevertheless, screening for nervous system involvement is difficult due to the low accessibility and high costs of these techniques. Objective: To assess the frequency of silent target organ damage in a cohort of asymptomatic hypertensive patients and to evaluate the potential usefulness of carotid ultrasonographic (US) variables as predictors of subclinical brain damage. Patients and Methods: Thirty four neurologically asymptomatic subjects (mean age 59 years) with essential hypertension were included. Target organ damage was evaluated: degree of hypertensive retinopathy, heart, kidney and brain. Structural and hemodynamical carotid Doppler US parameters were also investigated. Results: The brain was the most frequently affected target organ (70.6%), followed by the heart (67.9%) and kidney (58.6%). Carotid US parameters showed no association of intima media thickness with brain MRI results; nevertheless, decreased diastolic flow velocity and increased resistive index pointed to a resistive carotid flow pattern in patients with classical brain MRI lesions and predicted subclinical lesions with a sensitivity of 70% and 74% and a specificity of 72% and 80% respectively. Conclusions: This study supports previous findings that place the brain as the most frequently affected target organ in essential hypertensive patients and sheds more light on the potential usefulness of carotid structure and hemodynamics as imaging biomarkers of subclinical brain lesions.

Transcranial Measurement of Cerebral Microembolic Signals During Pulmonary Vein Isolation

Background— Pulmonary vein isolation has increasingly been used to cure atrial fibrillation, but concerns have recently been raised that subclinical brain damage may occur because of microembolization during these procedures. We compared the occurrence of bubble formation seen on intracardiac echocardiography and the microembolic signals (MESs) detected by transcranial Doppler on the use of different ablation techniques and anticoagulation strategies. Methods and Results— This prospective study included 35 procedures in 34 consecutive patients (age, 52; SD, 12.8 years; female:male 9:25). Pulmonary vein isolation was performed with a cryoballoon and the conventional anticoagulation protocol (activated clotting time >250 s) in 10 procedures (group 1), with a multipolar duty-cycled radiofrequency pulmonary group 2), and with regime a pulmonary vein ablation catheter with an aggressive anticoagulation (activated clotting time >320 s) in 13 procedures (group 3). The mean total numbers of MESs detected during the procedures were 833.7 (SD, 727.4) in group 1, 3142.6 (SD, 1736.4) in group 2, and 2204.6 (SD, 1078.1) in group 3 ( P =0.0005). MESs were detected mostly during energy delivery in the pulmonary vein ablation catheter groups, whereas a relatively even distribution of emboli formation was seen during cryoballoon ablations. A significant correlation was found in all groups between the degree of bubble formation on intracardiac echocardiography and the number of MESs ( P =0.0000). Conclusions— Duty-cycled radiofrequency ablation is associated with significantly more MESs, even when more aggressive anticoagulation is applied. With both techniques most of these microemboli are gaseous in nature.

075 Significant Reduction in Microemboli During Pulmonary Vein Isolation With Multipolar Duty-Cycled Radiofrequency Pulmonary Vein Ablation Catheter Using the Modified Version of the GENius™ Generator

BACKGROUND: Pulmonary vein isolation (PVI) techniques have been increasingly used to cure atrial fibrillation (AF). Recently, concerns have been raised that subclinical brain damage may occur due to microembolisation during these procedures, mostly when multipolar duty-cycled radiofrequency (RF) catheters (PVAC) are used. Technical modification of the GENiusTM 14.0 generator has been recently implemented to avoide high fluctuations in temperature at the electrode-tissue interface and to prevent overheating in order to reduce thrombus formation. We compared the occurence of microembolic signals (MES) detected by transcranial Doppler (TCD) which occured when the older GENiusTM 14.0 versus the modified GENiusTM 14.4 generator was used. METHODS/RESULTS: Data of 7 patients who had PVI for paroxysmal or persistent atrial fibrillation using the PVAC and the GENiusTM 14.0 generator were compared to those 10 who underwent the procedure using the GENiusTM 14.4 generator.There were no significant differences between the two groups regarding demographics, type of AF, CHADS2-score, left atrial size, and intraoperative anticoagulation protocol. Transcranial Doppler was used to detect MESs in middle cerebral arteries (MCA) in different stages of the procedures as follows: transseptal puncture (TP), pulmonary vein angiography (PVA), energy delivery (ED), and the rest of the porcedure (ROP). Mean total number of MESs during the procedures were 4766/ MCA SD:855 with the use of the GENiusTM 14.0 generator versus 1100/MCA SD:343with the GENiusTM 14.4 (p 0.001). Difference in the total number of MES was due to the difference in MES count detected during energy delivery period, while no difference was observed during the other stages of the procedures (figure 1). CONCLUSION: Significant reduction in the number of MES was achieved with the modified version of the GENiusTM generator during PVI. Canadian Cardiovascular Society (CCS) CCS033 Poster PRECLINICAL AND CLINICAL STUDIES IN HYPERTENSION Sunday, October 28, 2012

The diagnostic value of multimodal evoked potentials in the determination of subclinical neurological involvement of Wilson’s disease

Wilson's disease (WD) is a progressive degeneration of hepatolenticular tissue caused by excessive tissue-damaging copper accumulation and in which liver involvement most frequently presents in childhood. Neurological signs also accompany liver disease with time. However, subclinical neurological involvement may occur earlier and diagnostic methods that reveal this subclinical involvement are not well established. The aim of the current study is to assess the subclinical neurological involvement by using multimodality evoked potential (EP) measurements and to explore the relationship between neurological disease and the severity of liver damage. The patient group included 28 children (mean age 11.8 ± 2.9 years, range 5.5-17) diagnosed with WD and a control group included 24 age-matched healthy children. Multimodality EP tests (Nihon Kohden Neuropack 8 4200K) of both groups were performed at the Department of Neurology Electrophysiology Laboratory of Ege University. At least one abnormal EP value was observed in 53.5% of the children in the patient group. At least on one side, there were abnormal values for visual evoked potential (VEP) P100, brainstem auditory evoked potential (BAEP) and somatosensory evoked potential (SEP), where the ratios were 25, 28.5, and 11%, respectively. Absolute latency values of patients with right-side VEP P100 and left-side BAEP I, and the interpeak latency values of right-side BAEP I-III were significantly high. The difference in right-side BAEP I-III interpeak latency between cirrhotic and noncirrhotic groups was found to be statistically significant (P<0.05). The EP examinations can be an indicator of subclinical brain damage in non-neurological WD; however, cirrhosis because of WD does not cause an increase in the EP values. Detection of changes in the EP values periodically, especially at the time of diagnosis and during the treatment follow-up, may be valuable for revealing subclinical impairment.

ORAL PRESENTATION

ORAL PRESENTATION

Age-independent association of pulse pressure with cerebral white matter lesions in asymptomatic elderly individuals

Brachial pulse pressure (PP) is a marker of arterial stiffness in the elderly and a useful tool for measuring vascular aging. The presence of cerebral white matter lesions (WMLs) is a radiological marker of sub-clinical ischemic brain damage. WMLs may be age-related degenerative change, but few studies have addressed the relationship between vascular aging and WMLs. In this study, we assessed whether brachial PP is associated with the presence of WMLs in the elderly. Six hundred and ninety-two asymptomatic elderly individuals (>55 years) who visited for routine health check-up were included. Brachial blood pressure (BP) was measured and brain MRI used to determine the presence of advanced WMLs. Ninety-six (13.9%) were found to have advanced WMLs. In the highest PP quartile (≥54 mmHg), 55 (32.9%) had advanced WMLs, and this was significantly higher than in other quartiles. After controlling for age, hypertension, systolic BP, diastolic BP, aspirin use, C-reactive protein, and other vascular risk factors, the highest quartile of PP was significantly associated with advanced WMLs compared with the lowest quartile [adjusted odds ratio (OR) 2.55; 95% confidence interval (CI) 1.03-6.30]. The authors report for the first time that increased brachial PP is an age-independently associated with WMLs in asymptomatic elderly individuals. This result suggests that PP as a presumed marker of vascular aging may predict the presence of sub-clinical cerebrovascular diseases.

The Aging Mind: Vascular Health in Normal Cognitive Aging

In spite of the breakneck speed at which understanding of the biological basis of the aging process has evolved, the important determinants of aging and longevity have yet to be uncovered. The preservation of cognitive functioning is an essential component of successful aging, and the ability to distinguish those who maintain cognitive health into advanced age from those who experience cognitive decline may influence public health efforts to prevent or delay the onset of cognitive impairment in old age. There is growing evidence implicating vascular risk factors and related subclinical cerebrovascular damage in cognitive impairment and dementia, but Alzheimer's disease is highly prevalent in older populations, and the role of inflammation in vascular and neurodegenerative processes is poorly understood. There is a growing need to examine the effects of these factors on normal cognitive aging. This brief survey of the literature reviews evidence of the roles of subclinical vascular brain damage and exposure to cerebrovascular risk factors in normal cognitive aging.

S.23.04 Vascular depression – causes and outcomes

Arterial hypertension (HT) and other vascular pre-existing conditions (PEC) generate asymptomatic brain damage which increases the occurrence of stroke and cognitive decline. The aim of this work was to explore if serum antibodies against the NR2 subunit of the NMDA receptor (NR2Ab) could predict subclinical brain damage (SBD) in hypertensive patients with PEC. Forty seven neurologically asymptomatic hypertensive subjects were classified according to the number of PEC (retinopathy, overweight/obesity, diabetes mellitus and dyslipidemia). NR2A/B Ab were measured in serum employing an ELISA method. 3.0-T Brain MRI imaging was performed, and visual ratings of white matter hyperintensities (WMH) and counts of dilated Virchow-Robin spaces (DVRS) and lacunes were obtained. Brain atrophy was evaluated with cortical thickness measurements and linear measures. Higher levels of NR2Ab were associated with more severe periventricular WMH (PWMH), more DVRS and more severe SBD; while greater frontal interhemispheric fissure width (IHFW), as a linear measure of frontal atrophy, was inversely related with NR2Ab. Overall and regional cortical thickness were not significantly associated with NR2 Ab. A multivariate analyses showed that IHFW and PWMH were the only variables independently associated with serum NR2Ab concentration. ROC analysis revealed that NR2Ab (cutoff: 1.7 ng/ml) predicted PWMH with a sensitivity and specificity of 65% and 87% respectively.Serum NR2Ab levels may reflect SBD in HT subjects with PEC, especially in younger populations at risk, where age-related cortical atrophy has not yet been fully established.

Evoked potentials in neonates and infants with aseptic meningitis

We investigated 4 infants with aseptic meningitis, 4–38 days of age, by repeated electroencephalography (EEG), flash-visual evoked potentials (F-VEPs), and brainstem auditory evoked potentials. The patients all had mild, acute phases and favorable outcomes at 1–2 years of age. EEGs and F-VEPs obtained within 1 month after onset all were defined as abnormal. In 3 patients, EEG findings were normal 1–2 months after onset, while F-VEP findings were normal at 9–10 months. Brainstem auditory evoked potential findings were normal, except for 1 with otitis media. Evoked potentials suggested that subclinical brain damage, especially due to cortical lesions, persisted during the first year of life in these patients clinically diagnosed with “meningitis.”