Search

Although epidemiological data associate hypertension with a strong predisposition to develop Alzheimer disease, no mechanistic explanation exists so far. We developed a model of hypertension, obtained by transverse aortic constriction, leading to alterations typical of Alzheimer disease, such as amyloid plaques, neuroinflammation, blood-brain barrier dysfunction, and cognitive impairment, shown here for the first time. The aim of this work was to investigate the mechanisms involved in Alzheimer disease of hypertensive mice. We focused on receptor for advanced glycation end products (RAGE) that critically regulates Aβ transport at the blood-brain barrier and could be influenced by vascular factors. The hypertensive challenge had an early and sustained effect on RAGE upregulation in brain vessels of the cortex and hippocampus. Interestingly, RAGE inhibition protected from hypertension-induced Alzheimer pathology, as showed by rescue from cognitive impairment and parenchymal Aβ deposition. The increased RAGE expression in transverse aortic coarctation mice was induced by increased circulating advanced glycation end products and sustained by their later deposition in brain vessels. Interestingly, a daily treatment with an advanced glycation end product inhibitor or antioxidant prevented the development of Alzheimer traits. So far, Alzheimer pathology in experimental animal models has been recognized using only transgenic mice overexpressing amyloid precursor. This is the first study demonstrating that a chronic vascular insult can activate brain vascular RAGE, favoring parenchymal Aβ deposition and the onset of cognitive deterioration. Overall we demonstrate that RAGE activation in brain vessels is a crucial pathogenetic event in hypertension-induced Alzheimer disease, suggesting that inhibiting this target can limit the onset of vascular-related Alzheimer disease.

The Tower of London (ToL) is a problem-solving task, which is a valuable tool for the neuropsychological examination of a patient with a possible cognitive decline. The aim of the present study was to evaluate the ToL in comparison to the Mini Mental State Examination (MMSE) in a group of older people with or without dementia.Seventy outpatients of both sexes, 30 with low-moderate dementia and 40 with apparently normal cognition were evaluated with the MMSE and the ToL task in the same day. The ToL score was calculated according to the Krikorian method and also the execution time was measured. The differences between groups were assessed with the unpaired t-test, and the relationship between two parameters was assessed with the analysis of the coefficient of linear regression. The results were adjusted for age and education.The evaluation of cognitive impairment by MMSE showed a significant difference in the two groups (p0.001). The mean scores (p0.001) and execution times (p0.05) of the ToL, resulted significantly lower in the patients affected by dementia. However, seven participants with dementia had a normal score in the ToL test, indicating that the executive neuropsychological tasks could be preserved notwithstanding the cognitive decline and nine participants with normal MMSE obtained a low ToL score, suggestive of the higher sensibility of the ToL for the executive task that reveals an unknown cognitive deficit.The correlation between MMSE and ToL is good, but ToL test provides complementary information to the MMSE and vice versa.