Laura Buratti

Blood pressure variability and stroke outcome in patients with internal carotid artery occlusion

PURPOSE The aim of this study was to evaluate the relationship between arterial blood pressure (BP) variability during the acute phase and the 3-month outcome in ischemic stroke patients with internal carotid artery (ICA) occlusion. METHODS At least 10 BP measurements during the first 48 h after stroke onset were obtained in 89 patients with ICA occlusion. BP profile was described using various parameters: average of recordings, maximum (max), minimum (min), difference between max and min (max-min), standard deviation (SD) and coefficient of variation (CV) for both systolic and diastolic BP. Outcome at 3 months was defined using the modified Rankin Scale (mRS) score corrected for baseline stroke severity. RESULTS Fifty-five patients had a good and 34 a poor outcome. Max values, max-min, SD and CV of both systolic and diastolic BP resulted significantly higher in patients with poor outcome compared to those with good outcome (p<0.05, multivariate adjusted model). CONCLUSIONS In a cohort of acute ischemic stroke patients with ipsilateral ICA occlusion BP variability, assessed in the acute phase, was associated with poor clinical outcome. These preliminary exploratory findings are worthy of further study to be conducted to confirm or confute the role of BP variability in predicting stroke outcome. In order to obtain more comprehensive information, it would also be appropriate to consider the possibility of acquiring data related to the pathophysiology of stroke and to cerebral hemodynamic changes.

Vascular Impairment in Alzheimer's Disease: The Role of Obstructive Sleep Apnea

Epidemiological studies have suggested a pathophysiological link between obstructive sleep apnea syndrome (OSAS) and Alzheimers disease (AD). The mechanism by which sleep disturbance can affect cognitive impairment is not clear. The aim of this study was to investigate whether AD patients with OSAS have an impairment in cerebrovascular disease markers. We included 69 patients without OSAS and 93 patients with OSAS. They underwent an ultrasonographic assessment of common carotid arteries intima-media thickness (IMT) and carotid plaque index. Cerebrovascular reactivity to hypercapnia in the middle cerebral arteries was calculated with the Breath-Holding Index (BHI). Pathological values of IMT and BHI were significantly associated with the presence of OSAS (IMT > 1.0 mm: OR 2.98, 95%CI: 1.37-6.46; p < 0.05; BHI < 0.69: OR 5.25, 95%CI: 2.35-11.74; p < 0.05, multivariate adjusted analysis). Furthermore, the extent of cerebrovascular impairment was correlated with the severity of OSAS. The finding of alterations of cerebral vessel functional and anatomic status in AD patients with OSAS suggests the potential for effective treatment for sleep-related disturbances in a subgroup of AD patients.

Cognitive Deterioration in Bilateral Asymptomatic Severe Carotid Stenosis

Background and Purpose— This study aimed to monitor cognitive performance during a 3-year period in subjects with bilateral asymptomatic severe internal carotid artery stenosis and to explore the role of cerebral hemodynamics and atherosclerotic disease in the development of cognitive dysfunction. Methods— One hundred fifty-nine subjects with bilateral asymptomatic severe internal carotid artery stenosis were included and prospectively evaluated for a 3-year period. At entry, demographics, vascular risk profile, and pharmacological treatments were defined. Cognitive status was evaluated using the Mini-Mental State Examination at baseline and at follow-up. Cerebral hemodynamics was assessed by transcranial Doppler–based breath-holding index test. As a measure of the extent of systemic atherosclerotic disease, common carotid artery intima-media thickness was measured. A cutoff for pathological values was set at 0.69 for breath-holding index and 1.0 mm for intima-media thickness. Results— The risk of decreasing in Mini-Mental State Examination score increased progressively from patients with bilaterally normal to those with unilaterally abnormal breath-holding index, reaching the highest probability in patients with bilaterally abnormal breath-holding index (P<0.0001). Pathological values of intima-media thickness did not influence the risk of Mini-Mental State Examination score change. Conclusions— Our findings suggest that patients with asymptomatic bilateral severe internal carotid artery stenosis may be at risk of developing cognitive impairment. The evaluation of the hemodynamic status, besides providing insights about the possible mechanism behind the cognitive dysfunction present in carotid atherosclerotic disease, may be of help for the individuation of subjects deserving earlier and more aggressive treatments.

Markers for the Risk of Progression from Mild Cognitive Impairment to Alzheimer's Disease

BACKGROUND Defining reliable markers of conversion to dementia could be the first step in order to identify appropriate treatment strategies for mild cognitive impairment (MCI) patients. OBJECTIVE To develop a tool able to predict the risk of progression from MCI to Alzheimers disease (AD). METHODS 406 MCI patients were included and followed for a one-year period. Demographic characteristics, vascular risk factors, extent of cerebrovascular lesions, markers of carotid atherosclerosis investigated with an ultrasonographic assessment (plaque index and intima-media thickness) and cerebrovascular reactivity to apnea (breath-holding index) were considered as potential predictors of conversion. RESULTS 106 (26%) MCI patients showed a conversion to AD. Plaque index, intima-media thickness, and breath-holding index were relevant predictors of conversion (p = 0.042; p = 0.003; p < 0.001, multivariate logistic regression analysis). A simplified scoring system was devised based on the magnitude of the estimated multinomial logistic regression β coefficient results. A total score was calculated as the sum of each predictive factor which resulted in a 0-5 range. The optimal cut-off score was ≥3 (sensitivity, 23.6%, 95% CI 15.9%-32.8%; specificity, 97.7%, 95% CI 95.3%-99.1%; positive likelihood ratio, 10.1, 95% CI 4.5%-22.7%; negative likelihood ratio, 0.78, 95% CI 0.70%-0.87%). The AUC was 0.71 (95% CI, 0.65-0.77). CONCLUSIONS Our findings show the possibility to obtain a predictive indicator of the risk of conversion from MCI to dementia by considering the presence of both atherosclerotic changes in the carotid district and impairment of cerebral hemodynamics. Such an approach may allow us to formulate a correct prognosis in more than 70% of patients with amnesic MCI.

Visit-to-visit blood pressure variability in Alzheimer disease.

The aim of this study was to evaluate visit-to-visit blood pressure (BP) variability in a cohort of patients with Alzheimer disease (AD) and healthy controls. Patients with clinically diagnosed mild or moderate AD and cognitively normal controls matched for age and sex were recruited and followed up for 6 months. To characterize the BP status of each individual, mean, maximum and minimum values, SD, and coefficient of variation were obtained for both systolic BP (SBP) and diastolic BP (DBP). Seventy AD patients and 140 controls were enrolled. No meaningful differences were found in prevalence or treatments of various vascular risk factors. AD patients had higher maximum and lower minimum values and greater SD and coefficient of variation of both SBP and DBP. Group differences in mean values were significant only for SBP. In the multiple logistic regression analysis, adjusted for confounding variables, all the indices related to BP variability were significantly associated with AD. Our results show that AD patients have a greater variability of both SBP and DBP in comparison with age-matched cognitive normal controls, suggesting potential implication in the pathogenesis or progression of the disease.

Framingham risk score can predict cognitive decline progression in Alzheimer's disease

The role of vascular factors in influencing cognitive decline has been extensively investigated, and some difficulties in defining their weight in dementia pathogenesis have emerged. The aim of the study was to investigate the relevance of the Framingham cardiovascular risk profile (FCRP) in influencing cognitive deterioration in a population of Alzheimers disease (AD) patients. Two hundred eighty-four consecutive AD patients were enrolled. For each patient, FCRP score was calculated. We did a 1-year follow-up to quantify the cognitive decline by recording changes in the Clinical Dementia Rating score. The FCRP score predicted cognitive deterioration with an area under the curve of 0.63 (95% confidence interval: 0.57-0.69; p < 0.0001). In the subpopulation of patients with a genetic increased predisposition to develop cognitive deterioration and with an advanced vascular impairment, the FCRP predictive value significantly increased with an area under the curve of 0.77 (95% confidence interval: 0.52-0.93; p < 0.05). Our findings show that FCRP can predict the progression of deterioration in AD patients. This was particularly evident in patients with major genetic and atherosclerotic risk factors.

Neurocognitive functioning and cerebrovascular reactivity after carotid endarterectomy

Objective To evaluate in patients with TIA and ipsilateral high-grade internal carotid artery (ICA) stenosis whether changes in cognitive performance and cerebral hemodynamics occurred after carotid endarterectomy (CEA) and to explore their relationship. Methods Participants were patients who underwent CEA, had TIA within the last 6 months, and had an ipsilateral severe ICA stenosis. Coloured Progressive Matrices (CPM) plus Complex Figure Copy Test (CFCT) and phonemic (ph) plus categorical (ca) Verbal Fluency (VF) tests were performed to assess right and left hemisphere cognitive functions, respectively. Hemodynamics was assessed with transcranial Doppler ultrasonography by means of the cerebral vasomotor reactivity (CVR) to hypercapnia. Results A total of 137 patients were included. Before CEA, patients with right ICA obtained lower scores on the CPM and CFCT; patients with left ICA stenosis performed worse on the phonemic and categorical VF tests. The CVR was decreased on the side of the stenosis. At 6 months from CEA, CVR and cognitive performance were significantly improved. The performance change in cognitive tests exploring the revascularized hemisphere was positively associated with the ipsilateral CVR variation (CPM: R2 for linear regression = 0.759, adjR2 = 0.737; CFCT: R2 = 0.734, adjR2 = 0.710; (ph)VF: R2 = 0.774, adjR2 = 0.749; (ca)VF: R2 = 0.732, adjR2 = 0.703). Conclusion Cognitive performance was enhanced at 6 months since CEA, and the improvement was related to the CVR increase. Cerebral hemodynamics may be an independent and potentially reversible determinant of cognitive dysfunction in severe carotid artery disease.

Metabolic syndrome and cerebrovascular impairment in Alzheimer's disease

Metabolic Syndrome (MeS) has inconstantly been associated with cognitive impairment. The aim of this study was to investigate the influence of MeS on cerebrovascular reactivity and the possible consequences on cognitive impairment in patients with Alzheimers disease (AD).

Obstructive Sleep Apnea Syndrome: An Emerging Risk Factor for Dementia.

Epidemiological studies have suggested that obstructive sleep apnea syndrome (OSAS) may increase the risk of developing cognitive impairment. In patients with Alzheimers disease (AD), the prevalence of OSAS is much higher than that expected in cognitively healthy subjects. A deeper knowledge of the pathophysiological link between OSAS and AD and the demonstration that OSAS may directly influence the development of cognitive alterations, would increase prevention and treatment strategies for AD patients. In this article, we discuss the evidence of the association between OSAS and dementia. Moreover, we present data about the functional and anatomic cerebral changes induced by OSAS and the possible effects on cognitive activities and on AD pathogenesis. The possibility to positively influence cognitive impairment by OSAS treatment will be also discussed.

Framingham Risk Score and the Risk of Progression from Mild Cognitive Impairment to Dementia

BACKGROUND Mild cognitive impairment (MCI) often represents the clinical manifestation of cognitive deterioration preceding Alzheimers disease (AD). Currently, there are no reliable approaches for an objective evaluation of the risk of developing AD in MCI patients. OBJECTIVE The aim of this study was to verify whether the Framingham cardiovascular risk profile (FCRP) could be useful to identify patients at the highest risk of conversion from MCI to AD. METHODS Patients with amnestic MCI (aMCI) were carefully investigated to assess their vascular risk profile. They were also submitted to a comprehensive neuropsychological evaluation. The FCRP was calculated for each patient and the apolipoprotein E (ApoE) genotype was determined from peripheral blood cells. The main outcome was defined as a conversion to AD within 24 months after inclusion. RESULTS 385 consecutive aMCI subjects were included. Age, FCRP, and vascular age showed a fairly predictive value on conversion to AD. Selecting the subpopulation of ApoE ɛ4 carriers, we observed that FCRP had an increased performance in predicting the conversion. The rate of conversion increased from 12.5% in the FCRP low-risk group to 43.2% in the high-risk group (p < 0.0001). ApoE ɛ4 carriers had a 3.7-times increased probability of conversion with respect to the other subjects (p < 0.0001). CONCLUSIONS FCRP assessment could be considered a reliable approach to predict conversion to AD in aMCI subjects. The presence of ApoE ɛ4 increases significantly the risk of conversion. These data confirm the narrow relationship between genetic and vascular risk factors in influencing the evolution of cognitive impairment.