What is the clinical evidence from this study?

Study design: Review. Population: Dementia and cognitive decline. Intervention: Angiotensin II receptor blockers (ARBs) vs. ACE inhibitors and other anti-hypertensive medications. Primary outcome: Cognitive outcomes and incident dementia.

September 21, 2023Current Hypertension Reports46 citationsOpen Access

Angiotensin Receptor Blockers and Cognition: a Scoping Review

ZZZhen Zhou SOSuzanne G. Orchard MNMark Nelson

Key Result

Angiotensin II receptor blockers may provide greater neuroprotection and lower the risk of dementia and cognitive decline compared to other anti-hypertensive classes, particularly ACE inhibitors.

Structured PICO

Does angiotensin II receptor blocker use prevent cognitive decline and dementia in adults with hypertension or cardiovascular disease?

Population

Adults and elderly patients with hypertension, cardiovascular disease, or at risk of cognitive decline and dementia

Intervention

Angiotensin II receptor blockers (ARBs) as a class

Comparator

Other anti-hypertensive classes (including ACE inhibitors), placebo, or no anti-hypertensive medication

Outcome

Cognitive outcomes including incident dementia, Alzheimer's disease, vascular dementia, and cognitive decline

ARBs may offer superior neurocognitive protection compared to other antihypertensives like ACE inhibitors, highlighting their potential as an adjunctive approach for neuroprotection.

Limitations

Inconsistency of historical evidence from observational studies and early randomized trials
Much of the mechanistic evidence comes from animal and laboratory studies
Lack of high-quality evidence from large-scale, long-term prospective randomized controlled trials

Abstract

PURPOSE OF REVIEW: To provide an overview of the association between angiotensin II receptor blocker (ARB) use and cognitive outcomes. RECENT FINDINGS: ARBs have previously shown greater neuroprotection compared to other anti-hypertensive classes. The benefits are primarily attributed to the ARB's effect on modulating the renin-angiotensin system via inhibiting the Ang II/AT1R pathway and activating the Ang II/AT2R, Ang IV/AT4R, and Ang-(1-7)/MasR pathways. These interactions are associated with pleiotropic neurocognitive benefits, including reduced β-amyloid accumulation and abnormal hyperphosphorylation of tau, ameliorated brain hypo-fusion, reduced neuroinflammation and synaptic dysfunction, better neurotoxin clearing, and blood-brain barrier function restoration. While ACEis also inhibit AT1R, they simultaneously lower Ang II and block the Ang II/AT2R and Ang IV/AT4R pathways that counterbalance the potential benefits. ARBs may be considered an adjunctive approach for neuroprotection. This preliminary evidence, coupled with their underlying mechanistic pathways, emphasizes the need for future long-term randomized trials to yield more definitive results.

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