Effects of telmisartan on cognition and regional cerebral blood flow in hypertensive patients with Alzheimer's disease

Department of Geriatric Medicine, Tokyo Medical University, Tokyo, Japan.
Geriatrics & Gerontology International (Impact Factor: 2.19). 09/2011; 12(2):207-14. DOI: 10.1111/j.1447-0594.2011.00746.x
Source: PubMed


Recent studies have shown that some antihypertensive medications are associated with a significant reduction in the incidence of Alzheimer's disease (AD). However, it remains uncertain whether antihypertensive drugs may have a preventive effect on cognitive decline in patients with AD. We investigated the effects of telmisartan, an angiotensin II type 1 receptor blocker with peroxisome proliferator-activated receptor γ-stimulating activity, on cognition and regional cerebral blood flow (rCBF) in elderly hypertensive patients with AD.
A total of 20 patients with probable AD and essential hypertension were randomly assigned to the telmisartan group (n = 10, 40-80 mg daily) or the amlodipine group (n = 10, 5-10 mg daily) for 6 months.
The groups had a similar significant reduction in systolic and diastolic blood pressure after treatment. The telmisartan group did not show any changes in cognitive function test scores, while the amlodipine group showed significantly higher scores on the AD Assessment Scale-Cognitive Subscale (Japanese version). Analysis of covariance to analyze treatment effect revealed that the telmisartan group showed increased rCBF in the right supramarginal gyrus, superior parietal lobule, cuneus, and lingual gyrus compared with the amlodipine group, while the amlodipine group showed increased rCBF only in the right cingulate gyrus compared with the telmisartan group at 6 months.
These findings suggest that telmisartan may have additional benefits and be useful for the treatment of elderly hypertensive patients with AD.

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    • "Of interest are the results of a small Japanese study investigating the effect of telmisartan on cognition and regional cerebral blood flow in hypertensive patients with AD. Compared to amlodipine, treatment with telmisartan was not associated with cognitive decline (measured by the ADAS-Jcog test) after 6 months of treatment and, furthermore, improved cerebral blood flow in several brain subregions [119]. "
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    ABSTRACT: Loss of cognitive function is one the most devastating manifestations of ageing and vascular disease. Cognitive decline is rapidly becoming an important cause of disability worldwide and contributes significantly to increased mortality. There is growing evidence that hypertension is the most important modifiable vascular risk factor for development and progression of both cognitive decline and dementia. High blood pressure contributes to cerebral small and large vessel disease resulting in brain damage and dementia. A decline in cerebrovascular reserve capacity and emerging degenerative vascular wall changes underlie complete and incomplete brain infarcts, haemorrhages and white matter hyperintensities. This review discusses the complexity of factors linking hypertension to brain functional and structural changes, and to cognitive decline and dementia. The evidence for possible clinical markers useful for prevention of decreased cognitive ability, as well as recent data on vascular mechanism in the pathogenesis of cognitive decline, and the role of antihypertensive therapies in long-term prevention of late-life cognitive decline will be reviewed.
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    • "Pretreatment with a low dose of olmesartan completely prevented beta-amyloidinduced vascular dysregulation and partially attenuated the impairment of hippocampal synaptic plasticity in young Alzheimer's disease model transgenic mice (APP23 mice) with cerebrovascular dysfunction [160]. AT(1) blocker, telmisartan, administered to hypertensive patients with probable Alzheimer's disease showed increased region cerebral blood flow in the right supramarginal gyrus, superior parietal lobule, cuneus, and lingual gyrus, without any changes in cognitive function test scores [161]. In normotensive young adults, acute administration of losartan improved performance on a task of prospective memory and reversed the detrimental effects of scopolamine in a standard lexical decision paradigm with the incorporation of a prospective memory component, highlighting the cognitive enhancing potential of losartan on compromised cognitive systems in normotensive subjects [162]. "
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    ABSTRACT: Angiotensin II represents a key molecule in hypertension and cerebrovascular pathology. By promoting inflammation and oxidative stress, enhanced Ang II levels accelerate the onset and progression of cell senescence. Sustained activation of RAS promotes end-stage organ injury associated with aging and results in cognitive impairment and dementia. The discovery of the angiotensin-converting enzyme ACE2-angiotensin (1–7)-Mas receptor axis that exerts vasodilator, antiproliferative, and antifibrotic actions opposed to those of the ACE-Ang II-AT1 receptor axis has led to the hypothesis that a decrease in the expression or activity of angiotensin (1–7) renders the systems more susceptible to the pathological actions of Ang II. Given the successful demonstration of beneficial effects of increased expression of ACE2/formation of Ang1–7/Mas receptor binding and modulation of Mas expression in animal models in containing cerebrovascular pathology in hypertensive conditions and aging, one could reasonably hope for analogous effects regarding the prevention of cognitive decline by protecting against hypertension and cerebral microvascular damage. Upregulation of ACE2 and increased balance of Ang 1–7/Ang II, along with positive modulation of Ang II signaling through AT2 receptors and Ang 1–7 signaling through Mas receptors, may be an appropriate strategy for improving cognitive function and treating dementia.
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    • "Corroborating the hypothesis that ARBs could be beneficial in reducing the onset of AD, Kume et al. [128] recently observed that AD hypertensive patients treated with telmisartan presented no decrease in cognitive functions test scores, but an increased cerebral blood flow, suggesting that treatment with this ARB could reduce AD progression. Altogether, studies conducted using various models of cognitive disorders have reported improved memory and cognitive processes and/or attenuation of Aβ1–42 oligomerization following treatment with ARBs, particularly valsartan [129], losartan [130], telmisartan [128] [131], and olmesartan [132] (now called metabosartans for ARBs with a PPARγ agonistic effect) (review in [11] [14] [49] [133]). More recently, a study using direct stimulation of the AT 2 receptor with the selective agonist C21/M024 demonstrated similar effects in an AD mouse model [134]. "
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