Effects of telmisartan on the level of Aβ1-42, interleukin-1β, tumor necrosis factor α and cognition in hypertensive patients with Alzheimer's disease

Abstract

To explore the effects of telmisartan, an angiotensin II type 1 receptor blocker with peroxisome proliferator-activated receptor γ-stimulating activity, on the levels of Aβ1-42, interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α) and cognition in elderly hypertensive patients with Alzheimer's disease (AD). A total of 48 patients with probable AD and essential hypertension were randomly assigned into telmisartan group (n = 24, 40 - 80 mg qd) or amlodipine group (n = 24, 5 - 10 mg qd) for 6 months at Henan Provincial People's Hospital during 2008 - 2011. Cognitive evaluations were assessed at pre-treatment and 24 weeks post-treatment by clinical assessment, rating scales and neuropsychological tests while the cerebrospinal fluid (CSF) levels of Aβ1-42, IL-1β and TNF-α by enzyme-linked immunosorbent assay (ELISA). After 6 months, mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) significantly decreased compared with baseline values to a similar extent in both groups. No significant differences existed between two groups in SBP or DBP. The patients displayed significantly higher Aβ1-42 and greatly lower levels of IL-1β and TNF-α in the telmisartan group versus the amlodipine group (P < 0.05). At 24 weeks, the patients in the telmisartan group had better mini-mental state examination (MMSE) (22.0 ± 3.4) and Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog) (15 ± 5) scales scores than those taking amlodipine (MMSE (19.5 ± 2.8) and ADAS-cog (18 ± 5). Patients treated with telmisartan had better improvement on the MMSE (P < 0.05) and ADAS-cog (P < 0.05) scales compared with the amlodipine group by the end of study week 24. Telmisartan may delay the decreased level of Aβ1-42 and reduce the levels IL-1β and TNF-α in CSF so as to improve the cognitive function of elderly hypertensive patients with AD. With additional benefits in comparison with common antihypertensive drugs, it may offer a novel therapeutic strategy of AD.