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Alzheimers Dement (N Y). 2018 Oct 14;4:542-555. doi: 10.1016/j.trci.2018.09.001. eCollection 2018.

Synergism of antihypertensives and cholinesterase inhibitors in Alzheimer's disease.

Author information

1
Department of Pharmaceutical Sciences and Computational Chemical Genomics Screening Center, School of Pharmacy; NIDA National Center of Excellence for Computational Drug Abuse Research, University of Pittsburgh, Pittsburgh, PA, USA.
2
Department of Clinical Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, China.
3
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
4
Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA.
5
Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.

Abstract

Introduction:

We investigated the effect of antihypertensive (aHTN) medications and cholinesterase inhibitors (ChEIs) on the cognitive decline in patients with Alzheimer's disease (AD) and analyzed synergism by chemogenomics systems pharmacology mapping.

Methods:

We compared the effect of aHTN drugs on Mini-Mental State Examination scores in 617 AD patients with hypertension, and studied the synergistic effects.

Results:

The combination of diuretics, calcium channel blockers, and renin-angiotensin-aldosterone system blockers showed slower cognitive decline compared with other aHTN groups (Δβ = +1.46, P < .0001). aHTN medications slow down cognitive decline in ChEI users (Δβ = +0.56, P = .006), but not in non-ChEI users (Δβ = -0.31, P = .53).

Discussion:

aHTN and ChEI drugs showed synergistic effects. A combination of diuretics, renin-angiotensin-aldosterone system blockers, and calcium channel blockers had the slowest cognitive decline. The chemogenomics systems pharmacology-identified molecular targets provide system pharmacology interpretation of the synergism of the drugs in clinics. The results suggest that improving vascular health is essential for AD treatment and provide a novel direction for AD drug development.

KEYWORDS:

Alzheimer's disease; Antihypertensive medications; Cholinesterase inhibitors; Clinical data mining; Cognitive decline; Combination therapy; Systems pharmacology

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