Observational Study of Brain Atrophy and Cognitive Decline Comparing a Sample of Community-Dwelling People Taking Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Over Time

Moran, Chris; Xie, Kenneth; Poh, Su; Chew, Sarah Ching Jern; Beare, Richard; Wang, Wei Chun; Callisaya, Michele L.; Srikanth, Velandai

doi:10.3233/jad-180943

Cited by 12 publications

(8 citation statements)

References 38 publications

(52 reference statements)

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“…152 A recent longitudinal analysis following non-demented subjects 55 to 90 years of age found that participants utilizing an ARB had slower brain atrophy rates compared to those taking ACEIs. 153 It was also demonstrated that AD patients utilizing ARBs exhibited a 9.4% slower decline in delayed recall performance compared to those who utilized ACEIs. ARB use was also associated with better performance over time on the Trail Making Test (TMT-A) and the Digit Symbol Substitution Test (DSST), both of which assess attention and psychomotor processing speed.…”

Section: 83mentioning

confidence: 98%

Hypertension and hyperhomocysteinemia as modifiable risk factors for Alzheimer's disease and dementia: New evidence, potential therapeutic strategies, and biomarkers

Carey

Fossati

2022

Alzheimer's & Dementia

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This review summarizes recent evidence on how mid-life hypertension, hyperhomocysteinemia (HHcy) and blood pressure variability, as well as late-life hypotension, exacerbate Alzheimer's disease (AD) and dementia risk. Intriguingly, HHcy also increases the risk for hypertension, revealing the importance of understanding the relationship between comorbid cardiovascular risk factors. Hypertension-induced dementia presents more evidently in women, highlighting the relevance of sex differences in the impact of cardiovascular risk. We summarize each major antihypertensive drug class's effects on cognitive impairment and AD pathology, revealing how carbonic anhydrase inhibitors, diuretics modulating cerebral blood flow, have recently gained preclinical evidence as promising treatment against AD. We also report novel vascular biomarkers for AD and dementia risk, highlighting those associated with hypertension and HHcy. Importantly, we propose that future studies should consider hypertension and HHcy as potential contributors to cognitive impairment, and that uncovering the underlying molecular mechanisms and biomarkers would aid in the identification of preventive strategies.

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Section: 83mentioning

confidence: 98%

Hypertension and hyperhomocysteinemia as modifiable risk factors for Alzheimer's disease and dementia: New evidence, potential therapeutic strategies, and biomarkers

Carey

Fossati

2022

Alzheimer's & Dementia

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“…Through successive analyses for different AHMs groups, the current study demonstrated that in patients with hypertension and MCI, ARBs were associated with a lower risk of progression to dementia compared with ACE inhibitors and other classes of AHMs, which was consistent with several studies in that ARBs provided more neuroprotection than ACE inhibitors. 13,14,[16][17][18]26 In an older study in the ADNI, 15 Hajjar et al found that ARBs were associated with a longitudinal decrease in CSF tau in patients with MCI. However, evidence based on biomarkers alone is insufficient, and there is a gap between these biomarkers and the clinical dementia outcome, especially when the underlying mechanisms are still not fully understood.…”

Section: Comparison With Other Studiesmentioning

confidence: 99%

Angiotensin Receptor Blockers Are Associated With a Lower Risk of Progression From Mild Cognitive Impairment to Dementia

et al. 2022

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Background: Previous studies found that antihypertensive medications (AHMs) acting on the renin-angiotensin system had the potential to reduce the progression from mild cognitive impairment to dementia. However, it remains unclear whether this association differs between ACE (angiotensin-converting enzyme) inhibitors and angiotensin receptor blockers. methods: We conducted a retrospective cohort study in the Alzheimer’s Disease Neuroimaging Initiative among 403 participants with hypertension and mild cognitive impairment at baseline. Information on AHMs received during the follow-up period, including angiotensin receptor blockers, ACE inhibitors, beta-blockers, calcium channel blockers, and diuretics, were self-reported. Cox proportional hazards models adjusted for potential confounders were used in the time to event analysis with progression to dementia as outcome. Results: Of the 403 participants, the mean (SD) age was 74.0 (7.3) years, 152 (37.7%) were female, 158 (39.2%) progressed to dementia over a median follow-up time of 3.0 years. Angiotensin receptor blockers were associated with a lower risk of progression to dementia as compared to ACE inhibitors (adjusted hazard ratio=0.45 [95% CI, 0.25–0.81]; P =0.023), other classes of AHMs (beta-blockers, calcium channel blockers, diuretics; adjusted hazard ratio, 0.49 [95% CI, 0.27–0.89]; P =0.037), and none of AHMs (adjusted hazard ratio, 0.31 [95% CI, 0.16–0.58]; P =0.001). Conclusions: In patients with hypertension and mild cognitive impairment, angiotensin receptor blockers were associated with a lower risk of progression to dementia compared with ACE inhibitors and other classes of AHMs. Our findings may have important implications for clinical practice but still warrant further investigations in larger prospective cohorts or clinical trials.

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“…The little data available suggest that cognitively intact individuals on ARB have slower atrophy rates and less cerebral amyloid-beta deposition than those on ACEI. 46,47 The "angiotensin hypothesis" ideally requires RCT testing. Trials comparing antihypertensive subclasses with dementia as primary outcome are however challenging,…”

Section: A C C E P T E Dmentioning

confidence: 99%

Association of Angiotensin II–Stimulating Antihypertensive Use and Dementia Risk

et al. 2021

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ObjectiveTo assess whether angiotensin-II stimulating antihypertensives (thiazides, dihydropyridine calcium channel blockers, and angiotensin-1 receptor blockers) convey a lower risk of incident dementia compared to angiotensin-II inhibiting antihypertensives (angiotensin-converting enzyme inhibitors, beta blockers, and non-dihydropyridine calcium channel blockers), in accordance with the “angiotensin hypothesis.”MethodsCox regression analyses of incident dementia (and/or mortality as competing risk) during 6–8 years of follow-up, in a population sample of 1909 non-demented community-dwelling individuals (54% women), aged 70–78 (mean: 74.5 ± 2.5) years.ResultsAfter a median of 6.7 years of follow-up, dementia status was available for 1,870 (98%) and mortality for 1,904 (>99%) participants. Dementia incidence was 5.6% (27/480) in angiotensin-II stimulating, 8.2% (59/721) in angiotensin-II inhibiting, and 6.9% (46/669) in both antihypertensive type users. Adjusted for dementia risk factors including blood pressure and medical history, angiotensin-II stimulating antihypertensive users had a 45% lower incident dementia rate (HR = 0.55, 95% CI = 0.34–0.89) without excess mortality (HR = 0.86, 95% CI = 0.64–1.16), and individuals using both types had a non-significant 20% lower dementia rate (HR = 0.80, 95% CI = 0.53–1.20) without excess mortality (HR = 0.97, 95% CI = 0.76–1.24), compared to angiotensin-II inhibiting antihypertensive users. Results were consistent for subgroups based on diabetes and stroke history, but may be specific for individuals without a history of cardiovascular disease.ConclusionsUsers of angiotensin-II stimulating antihypertensives had lower dementia rates compared to angiotensin-II inhibiting antihypertensive users, supporting the “angiotensin hypothesis.” Confounding by indication must be examined further, although sub-analyses suggest this did not influence results. If replicated, dementia prevention could become a compelling indication for older individuals receiving antihypertensive treatment.

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Observational Study of Brain Atrophy and Cognitive Decline Comparing a Sample of Community-Dwelling People Taking Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Over Time

Abstract: These results support the theory that ARB may be preferable to ACEi to reduce brain atrophy. The mechanisms underlying this differential association warrant further investigation.

Cited by 12 publications

References 38 publications

Hypertension and hyperhomocysteinemia as modifiable risk factors for Alzheimer's disease and dementia: New evidence, potential therapeutic strategies, and biomarkers

Hypertension and hyperhomocysteinemia as modifiable risk factors for Alzheimer's disease and dementia: New evidence, potential therapeutic strategies, and biomarkers

Angiotensin Receptor Blockers Are Associated With a Lower Risk of Progression From Mild Cognitive Impairment to Dementia

Association of Angiotensin II–Stimulating Antihypertensive Use and Dementia Risk

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