What is the clinical evidence from this study?

Study design: Cohort. Population: Adults aged 45 years and older with hypertension initiating antihypertensive treatment (ARB or ACEI) (n=51574). Intervention: Angiotensin II receptor blockers (ARB) vs. Angiotensin-converting enzyme inhibitors (ACEI). Primary outcome: Incident dementia diagnosed via linked administrative datasets and self-report (HR 0.72, 95% CI 0.65-0.80, p=<0.001).

What question did this study set out to answer?

To assess whether angiotensin II receptor blockers (ARBs) affect the long-term risk of dementia differently than angiotensin-converting enzyme inhibitors (ACEIs) in hypertensive patients.

March 1, 2026Open Access

Long-term risk of dementia with angiotensin receptor blockers versus angiotensin-converting enzyme inhibitors in hypertensive patients: A 15-year follow-up using the 45 and Up Study

Q: What are the key findings of this study?

ARB use reduced the risk of incident dementia by 28% compared to ACEI use in hypertensive adults over 11 years (HR 0.72; 95% CI: 0.65-0.80; p<0.001).

Q: What does this research mean for the field?

Angiotensin receptor blocker (ARB) use reduces the risk of incident dementia by 28% compared to angiotensin-converting enzyme inhibitor (ACEI) use in hypertensive adults. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To assess whether angiotensin II receptor blockers (ARBs) affect the long-term risk of dementia differently than angiotensin-converting enzyme inhibitors (ACEIs) in hypertensive patients.

Key Result

ARB use reduced the risk of incident dementia by 28% compared to ACEI use in hypertensive adults over 11 years (HR 0.72; 95% CI: 0.65-0.80; p<0.001).

Key Points

To assess whether angiotensin II receptor blockers (ARBs) affect the long-term risk of dementia differently than angiotensin-converting enzyme inhibitors (ACEIs) in hypertensive patients.
Conducted a prospective cohort study in patients aged ≥ 45 with hypertension beginning ARB or ACEI therapy.
Defined ARB/ACEI exposure based on a supply covering at least 80% of the follow-up period.
Applied propensity score matching to balance baseline characteristics.
Utilized the Cox proportional hazards model to estimate dementia risk.
ARB use linked to a 28% reduced risk of dementia compared to ACEI use (HR = 0.72).
Specific ARBs showed significantly lower risks compared to lisinopril, with olmesartan showing the greatest reduction (HR = 0.32).
Captopril was associated with a significantly increased risk of dementia (HR = 4.9).
Results consistent across various subgroup and sensitivity analyses.

Study Design

Type

Cohort (n=51,574)

Multicenter

Yes

Structured PICO

Does angiotensin II receptor blocker (ARB) use reduce the risk of incident dementia compared with angiotensin-converting enzyme inhibitor (ACEI) use in hypertensive patients?

Population

51,574 adults aged ≥ 45 years with hypertension (mean age 66.3, 48.2% women) from the 45 and Up Study Cohort in New South Wales, Australia.

Intervention

Angiotensin II receptor blockers (ARBs) with a supply covering at least 80% of the follow-up period.

Comparator

Angiotensin-converting enzyme inhibitors (ACEIs) with a supply covering at least 80% of the follow-up period.

Outcome

Incident dementia (identified via multiple linked data sources including hospital admissions, emergency presentations, mental health data, death records, self-report, and anti-dementia medication dispensing).hard clinical

In hypertensive patients, long-term use of ARBs is associated with a significantly lower risk of incident dementia compared to ACEIs.

Main Result

Effect estimate: HR 0.72 (95% CI 0.65-0.80)

Absolute Event Rate: 6.5% vs 8.5%

p-value: p=<0.001

Limitations

Observational design limits causal inference and potential residual confounding may persist.
Medication adherence assessed by prescription coverage may not reflect actual intake.
Lack of blood pressure measurements and treatment intensity data precludes adjustment for BP control differences.
Low event counts limited precision for some individual drug analyses.
Dementia subtypes could not be reliably classified.
Exposure classification may be subject to immortal time bias due to using cumulative post-baseline medication information.
Comorbidities and medication use assessed only at baseline, missing changes over time.
Results may not generalize to younger populations or those outside Australia.

Abstract

Abstract It is still unclear whether hypertensive patients using angiotensin II receptor blockers (ARBs) have a different risk of developing dementia compared with those taking angiotensin-converting enzyme inhibitors (ACEIs). We conducted a prospective cohort study using the 45 and Up Study Cohort in patients aged ≥ 45 years with hypertension who initiated ARB or ACEI therapy between 2004 and June 30, 2022. ARB/ACEI exposure was defined as having a supply that covered at least 80% of their follow-up period. Propensity score matching was used to balance baseline characteristics. We used the Cox proportional hazards model to estimate the risk of incident dementia. We included 51,574 patients with hypertension (mean age 66.3 (9.0) years; 48.2% women), with a mean follow-up of 11.3 (5.2) years. After controlling for major modifiable lifestyle factors such as diet and physical activity, ARB use was linked to a significantly reduced risk of dementia compared with ACEI use (hazard ratio HR = 0.72; 95% confidence interval CI: 0.65–0.80, p < 0.001). In exploratory agent-level analyses, compared with lisinopril, olmesartan (HR = 0.32; 95% CI: 0.16–0.62), candesartan (HR = 0.41; 95% CI: 0.24–0.69), telmisartan (HR = 0.42; 95% CI: 0.25–0.71), irbesartan (HR = 0.45; 95% CI: 0.27–0.75), and perindopril (HR = 0.52; 95% CI: 0.31–0.87) were associated with a significantly lower risk of dementia, while captopril showed a significantly increased risk (HR = 4.9; 95% CI: 1.04–23.4). The findings were consistent across subgroup analyses (sex, head-to-head ARBs vs ACEIs) and sensitivity analyses (excluding hypertension defined only by antihypertensive medication use, adjusting for competing risk of death or inverse probability of treatment weighting analysis). Among hypertensive patients, ARB use was linked to a reduced risk of dementia compared with ACEI treatment, regardless of diet and physical activity, and the effect varied across specific agents. These findings highlight the potential role of ARBs in dementia prevention; however, further randomised controlled trials are needed to confirm them.

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