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Abstract: Epidemiological studies show that vascular risk factors (e.g. atherosclerosis, diabetes, homocysteine, hypertension or cholesterol) may play a role in the development of Alzheimer''s disease. Animal models may help to discover the role of vascular risk factors on cognition. In the present project we treated male Sprague Dawley rats with a diet containing homocysteine (hyperhomocysteinemia) or cholesterol (hypercholesterolemia) for 5months or exposed the rats to ethanol (20% in drinking water) or a combination of cholesterol + ethanol (mix) for 12months. Our experiments show that all 3 treatments (homocysteine, cholesterol, ethanol) declined spatial memory in the 8-arm radial maze, reduced the number of cholinergic neurons and induced blood–brain barrier leakage in the cortex. Rats treated with cholesterol also displayed markedly enhanced inflammation in the cortex. Levels of amyloid precursor protein, beta-amyloid(1–42), as well as tau and phospho-tau 181 were significantly enhanced in the cortex of cholesterol-fed rats. A combination of ethanol and cholesterol did not further potentiate the effects on spatial memory, cholinergic neurons and blood–brain barrier leakage. The data suggest that chronic mild vascular risk factors over months induce small lesions of the brain capillaries in the cortex, which may contribute to the development of vascular dementia or also Alzheimer''s disease. [Copyright &y& Elsevier]

Background: The fact that the allele &epsiv;4 of the Apolipoprotein E (APOE) gene could act like a risk factor not only in late-onset familial and sporadic Alzheimer''s disease (AD) but also in cerebrovascular disease (CVD) and vascular dementia (VaD) is still controversial. Methods: In order to study if &epsiv;4 allele is overrepresented not only in AD but also in CVD and VaD, APOE genotyping was undertaken in a series of 247 patients: 26 cases with VaD, 41 cases with CVD but without cognitive impairment (CVD-C), 83 cases with AD and 97 aged-matched “healthy controls” (HC). Results: Percentages of subjects bearing one or two copies of the &epsiv;4 allele was much higher in AD patients (54%) than in either CVD-C (29%) (p<0.05), VaD (15%) (p<0.001) or HC (13%) (p<0.001). Conclusions: These results strengthen the hypothesis that involves the APOE &epsiv;4 allele as a predisposing factor for AD, but not for CVD or VaD. [Copyright &y& Elsevier]

Hypertension is a risk factor for stroke and may also contribute to the development of vascular cognitive impairment (VCI) and vascular dementia (VaD). Cognitive complications of hypertension and the influence of anti-hypertensive treatment were underestimated until recently. In this paper, trials investigating the effect of anti-hypertensive treatment on cognitive function were evaluated. Analysis of these studies revealed that until approximately 1990–1995 investigations have assessed primarily if anti-hypertensive treatment impaired cognitive function. Only more recent studies have investigated positive effects on cognition of anti-hypertensive medication. Drugs more extensively evaluated were diuretics, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, sartanes and Ca2+ channel blockers. Available studies have confirmed that elevated diastolic blood pressure or pulse pressure and isolated systolic hypertension play an important role in the development of cognitive impairment. Randomized placebo-controlled trials have provided evidence that reduction of hypertension safely and effectively decreases morbidity and mortality rates and cognitive complications of hypertension. Ca2+ channel blockers and ACE inhibitors have been shown to be effective and probably better than diuretics and beta-blockers on cognitive domains of hypertension. More extensive investigations could contribute to establishing optimal choice and drug dosage for the treatment of cognitive complications of hypertension. [Copyright &y& Elsevier]

The existence of vascular dementia (VaD) was first identified by Marie, who described the etat lacunaire, and by Binswanger, who identified white matter lesions in demented individuals. The role of cortical lesions, while clear to clinicians, was highlighted only later by the pathological studies of Tomlinson and the clinical demonstrations of Hachinski et al., who have defined multi-infarct dementia. Lately, the emphasis shifted to pathogenic mechanisms with the identification of a multitude of processes, such as lipohyalinosis, cardiac dysfunction and genetic causes, to name only a few. Epidemiologic studies have demonstrated the high frequency of VaD, as well as the fact that vascular factors can contribute to Alzheimer''s disease (AD). All these considerations converge to the realization that VaD is an extremely important clinical entity and that its prevention and treatment are within reach. In fact, there is more data on how to prevent strokes (and presumably VaD) than on how to prevent AD. Moreover, many factors which were identified as contributing to cerebrovascular disease in general and VaD in particular are frequently suspected as predisposing to AD as well. These unexpected findings highlight the importance of mixed vascular-degenerative dementia as a disorder which has to be properly defined and has important implications on prevention and treatment. [Copyright &y& Elsevier]

Abstract: Arterial beta stiffness index is a potential risk factor for increased stroke occurrence. Vascular component appears to be significant in both Alzheimer''s disease (AD) and vascular dementia (VAD). We aimed to further explore vascular characteristics of patients with both types of cognitive decline using non-invasive neurosonological methods. There were 38 patients; 16 diagnosed with AD and 22 with VAD. Vascular risk factors were assessed and ultrasound measurements on common carotid artery (CCA) were performed using Aloka ProSound ALPHA 10 with 13 MHz linear probe. Among AD patients there were 5 with arterial hypertension (AH), 3 with atrial fibrillation (AF), 2 with diabetes mellitus (DM), 6 with hyper lipidemia and 1 smoker. Nineteen VAD patients had AH, 6 had AF, 12 had hyper lipidemia and one was diabetic. We found no statistically significant differences between groups regarding average body mass index (BMI), blood pressure, pulse pressure, intima–media thickness (IMT), CCA diameter or arterial beta stiffness indices. However, the trend of BMI increase, slight blood and pulse pressure decrease, CCA diameter increase and beta stiffness index increase was noted in VAD patients. Even though there was no significant difference found among two explored subgroups of patients with dementia, there was a tendency of greater systolic and diastolic diameters noted in VAD as well as greater stiffness, especially when measured in the right CCA. This indicates that VAD patients may have more prominent vascular changes that may help differentiate the type of dementia and further monitor these individuals. Further studies on a larger number of patients are needed support this evidence. [Copyright &y& Elsevier]