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

ABSTRACT 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.
    Current Hypertension Reports 10/2013; 15(6). DOI:10.1007/s11906-013-0398-4 · 3.44 Impact Factor
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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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    ABSTRACT: Angiotensin II (Ang II) is the main active product of the renin-angiotensin system (RAS), mediating its action via two major receptors, namely, the Ang II type 1 (AT(1)) receptor and the type 2 (AT(2)) receptor. Recent results also implicate several other members of the renin-angiotensin system in various aspects of brain functions. The first aim of this paper is to summarize the current state of knowledge regarding the properties and signaling of the AT(2) receptor, its expression in the brain, and its well-established effects. Secondly, we will highlight the potential role of the AT(2) receptor in cognitive function, neurological disorders and in the regulation of appetite and the possible link with development of metabolic disorders. The potential utility of novel nonpeptide selective AT(2) receptor ligands in clarifying potential roles of this receptor in physiology will also be discussed. If confirmed, these new pharmacological tools should help to improve impaired cognitive performance, not only through its action on brain microcirculation and inflammation, but also through more specific effects on neurons. However, the overall physiological relevance of the AT(2) receptor in the brain must also consider the Ang IV/AT(4) receptor.
    International Journal of Hypertension 12/2012; 2012:351758. DOI:10.1155/2012/351758
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    • "Recent clinical studies suggest that treatment of hypertensive patients with the renin angiotensin system (RAS) affecting drugs improve cognitive function independent of their blood pressure lowering effect (Saxby et al. 2008; Radaideh et al. 2011; Kume et al. 2012). Clinical findings are supported by animal studies which showed that RAS inhibition improves memory function and prevents memory impairment associated with cholinergic hypofunction, oxidative stress, and β-amyloid deposition (Hou et al. 2008; Tota et al. 2009, 2012a, b). "
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    ABSTRACT: RATIONAL: Studies have shown the involvement of angiotensin II (Ang II) in neurobehavioral aspects, but the exact role of Ang II in memory is still ambiguous. OBJECTIVE: This study explored the effect of central Ang II on spatial memory along with cholinergic neurotransmission, brain energy metabolism, cerebral blood flow (CBF), and brain-derived neurotrophic factor (BDNF) in rats. METHODS: Spatial memory was evaluated by Morris water maze (MWM) after Ang II (ICV) administration in male Sprague-Dawley rats. CBF was measured by laser Doppler flowmetry. Oxidative stress adenosine triphosphate (ATP), BDNF, acetylcholinesterase (AChE), and acetylcholine (ACh) were estimated in the cortex and hippocampus at 1, 24, and 48 h after Ang II administration. The effect of AT1 and AT2 receptor blocker (candesartan and PD123,319, respectively), AChE inhibitor (donepezil), and antioxidant melatonin was studied on memory, CBF, and biochemical parameters. RESULTS: Ang II caused spatial memory impairment by affecting acquisition, consolidation, and recall in the MWM test along with a significant reduction in CBF. Ang II significantly reduced ACh level and caused oxidative stress in the rat brain 1 h post-injection. No significant change was observed in BDNF, AChE, and ATP level. Candesartan and donepezil prevented Ang II-induced memory impairment, reduction in CBF and ACh level. However, PD123,319 and melatonin failed to prevent Ang II-induced memory impairment but improved CBF partially. CONCLUSION: This study suggests that Ang II, via the AT1 receptor, affects spatial memory formation, CBF, and ACh level while AT2 receptor has no significant role.
    Psychopharmacology 11/2012; 226(2). DOI:10.1007/s00213-012-2913-8 · 3.88 Impact Factor
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