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59/100

✓ Peer-reviewed alzhub usefulness score 59 out of 100. Prevention and risk

Topic: Risk, prevention and care in population studies

Background Hypertension (HTN) is a risk factor for dementia, and animal studies suggest that centrally active angiotensin-converting enzyme (ACE) inhibitors (those that cross the blood-brain barrier) may protect against dementia beyond HTN control. Methods Participants in the Cardiovascular Health Study Cognition Substudy with treated HTN and no diagnosis of congestive heart failure (n = 1054; mean age, 75 years) were followed up for a median of 6 years to determine whether cumulative exposure to ACE inhibitors (as a class and by central activity), compared with other anti-HTN agents, was associated with a lower risk of incident dementia, cognitive decline (by Modified Mini-Mental State Examination [3MSE]), or incident disability in instrumental activities of daily living (IADLs). Results Among 414 participants who were exposed to ACE inhibitors and 640 who were not, there were 158 cases of incident dementia. Compared with other anti-HTN drugs, there was no association between exposure to all ACE inhibitors and risk of dementia (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.88-1.15), difference in 3MSE scores (-0.32 points per year; P = .15), or odds of disability in IADLs (odds ratio [OR], 1.06; 95% CI, 0.99-1.14). Adjusted results were similar. However, centrally active ACE inhibitors were associated with 65% less decline in 3MSE scores per year of exposure (P = .01), and noncentrally active ACE inhibitors were associated with a greater risk of incident dementia (adjusted HR, 1.20; 95% CI, 1.00-1.43 per year of exposure) and greater odds of disability in IADLs (adjusted OR, 1.16; 95% CI, 1.03-1.30 per year of exposure) compared with other anti-HTN drugs. Conclusions While ACE inhibitors as a class do not appear to be independently associated with dementia risk or cognitive decline in older hypertensive adults, there may be within-class differences in regard to these outcomes. These results should be confirmed with a randomized clinical trial of a centrally active ACE inhibitor in the prevention of cognitive decline and dementia.

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APA 7th

Sink, K. M., Leng, X., Williamson, J., Kritchevsky, S. B., Yaffe, K., Kuller, L., et al. (2009). Angiotensin-converting enzyme inhibitors and cognitive decline in older adults with hypertension: results from the Cardiovascular Health Study. Archives of internal medicine. https://doi.org/10.1001/archinternmed.2009.175

Vancouver

Sink KM, Leng X, Williamson J, Kritchevsky SB, Yaffe K, Kuller L, et al. Angiotensin-converting enzyme inhibitors and cognitive decline in older adults with hypertension: results from the Cardiovascular Health Study. Archives of internal medicine. 2009. doi:10.1001/archinternmed.2009.175. PMID: 19597068.

BibTeX

@article{sink2009-19597068,
  author  = {Sink, K. M. and Leng, X. and Williamson, J. and Kritchevsky, S. B. and Yaffe, K. and Kuller, L. and Yasar, S. and Atkinson, H. and others},
  title   = {{Angiotensin-converting enzyme inhibitors and cognitive decline in older adults with hypertension: results from the Cardiovascular Health Study}},
  journal = {Archives of internal medicine},
  year    = {2009},
  doi     = {10.1001/archinternmed.2009.175},
  pmid    = {19597068},
  url     = {https://doi.org/10.1001/archinternmed.2009.175}
}

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Key findings

Background Hypertension (HTN) is a risk factor for dementia, and animal studies suggest that centrally active angiotensin-converting enzyme (ACE) inhibitors (those that cross the blood-brain barrier) may protect against dementia beyond HTN control.
Methods Participants in the Cardiovascular Health Study Cognition Substudy with treated HTN and no diagnosis of congestive heart failure (n = 1054; mean age, 75 years) were followed up for a median of 6 years to determine whether cumulative exposure to ACE inhibitors (as a class and by central activity), compared with other anti-HTN agents, was associated with a lower risk of incident dementia, cognitive decline (by Modified Mini-Mental State Examination [3MSE]), or incident disability in instrumental activities of daily living (IADLs).
Results Among 414 participants who were exposed to ACE inhibitors and 640 who were not, there were 158 cases of incident dementia.
Compared with other anti-HTN drugs, there was no association between exposure to all ACE inhibitors and risk of dementia (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.88-1.15), difference in 3MSE scores (-0.32 points per year; P = .15), or odds of disability in IADLs (odds ratio [OR], 1.06; 95% CI, 0.99-1.14).
However, centrally active ACE inhibitors were associated with 65% less decline in 3MSE scores per year of exposure (P = .01), and noncentrally active ACE inhibitors were associated with a greater risk of incident dementia (adjusted HR, 1.20; 95% CI, 1.00-1.43 per year of exposure) and greater odds of disability in IADLs (adjusted OR, 1.16; 95% CI, 1.03-1.30 per year of exposure) compared with other anti-HTN drugs.

Why it matters

In this cohort of 1054 older adults with treated hypertension, use of all ACE inhibitors was not associated with risk of dementia, though centrally active ACE inhibitors were linked to less cognitive decline. The study reports associations and does not show that these drugs treat, cure, or prevent Alzheimer's disease.

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Study details

Participants1,054
Evidence strengthHigh

How this study scored 59/100

Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.

Component	Points	Why
Journal tier	7 / 10	Tier 3 — peer-reviewed journal (Archives of internal medicine)
Journal's citation record	3 / 4	Archives of Internal Medicine: journal h-index 462 (OpenAlex, 2026-10-29)
Study design	0 / 12	No study design recorded — scores zero, not guessed (not stated in the record — scored 0)
Strength of evidence	5 / 5	Rated “high” in our summary
Peer-review validation	10 / 10	Peer-reviewed. Published as an article in a named peer-reviewed journal.
How recent	1 / 5	2009 — within 20 year(s) of the newest study here
Sample size	3 / 4	1,054 participants
Effect reported	0 / 3	No effect size reported — scores zero (not stated in the record — scored 0)
Studied in people	3 / 3	Studied in people (participant count stated)
Randomised / blinded	0 / 2	No randomisation or blinding stated — scores zero (not stated in the record — scored 0)
Times cited	5 / 7	Cited 238 times (OpenAlex, 2026-10-10)
Citations per year	3 / 5	12.5 citations a year over 19 year(s) since 2009
Impact for its field and year	4 / 6	Cited 13.0× the average for papers of its field and year (OpenAlex FWCI)
Cited by studies here	2 / 6	Cited by 3 other studies in this library
Still being cited	2 / 4	Cited 29 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	4 / 4	Last-listed author David Calvin Goff: h-index 101 (OpenAlex, whole career)
Institution's track record	3 / 3	University of Washington: institution h-index 3,540 (OpenAlex)
Multi-centre collaboration	2 / 3	OpenAlex lists 5 institution(s) in 1 country
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 19597068)
Free to read	0 / 2	Behind a paywall — scores zero
Total	59 / 100	—

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