Angiotensin-converting enzyme inhibitors and incidence of mild cognitive impairment. the Italian Longitudinal Study on Aging

Vincenzo Solfrizzi, Emanuele Scafato, Vincenza Frisardi, Davide Seripa, Giancarlo Logroscino, Patrick G. Kehoe, Bruno P. Imbimbo, Marzia Baldereschi, Gaetano Crepaldi, Antonio Di Carlo, Lucia Galluzzo, Claudia Gandin, Domenico Inzitari, Stefania Maggi, Alberto Pilotto, Francesco Panza

Research output: Contribution to journalArticlepeer-review


Midlife elevated blood pressure and hypertension contribute to the development of Alzheimer's disease (AD) and overall dementia. We sought to estimate whether angiotensin-converting enzyme inhibitors (ACE-Is) reduced the risk of developing mild cognitive impairment (MCI) in cognitively normal individuals. In the Italian Longitudinal Study on Aging, we evaluated 1,445 cognitively normal individuals treated for hypertension but without congestive heart failure from a population-based sample from eight Italian municipalities with a 3.5-year follow-up. MCI was diagnosed with current clinical criteria. Dementia, AD, and vascular dementia were diagnosed based on DSM-IIIR criteria, NINCDS-ADRDA criteria, and ICD-10 codes. Among 873 hypertension-treated cognitively normal subjects, there was no significant association between continuous exposure to all ACE-Is and risk of incident MCI compared with other antihypertensive drugs [hazard ratio (HR), 0.45, 95% confidence interval (CI), 0.16-1.28]. Captopril exposure alone did not significantly modify the risk of incident MCI (HR, 1.80, 95% CI, 0.39-8.37). However, the enalapril sub-group alone (HR, 0.17, 95% CI, 0.04 -0.84) or combined with the lisinopril sub-group (HR, 0.27, 95% CI, 0.08-0.96), another ACE-I structurally related to enalapril and with similar potency, were associated with a reduced risk of incident MCI. Study duration exposure to ACE-Is as a "class" was not associated with incident MCI in older hypertensive adults. However, within-class differences linked to different chemical structures and/or drug potencies may exist, with a possible effect of the enalapril and lisinopril sub-groups in reducing the risk of incident MCI.

Original languageEnglish
Pages (from-to)441-453
Number of pages13
Issue number2
Publication statusPublished - Apr 2013


  • Angiotensin-converting enzyme inhibitors
  • Antihypertensive drugs
  • Dementia
  • Mild cognitive impairment

ASJC Scopus subject areas

  • Ageing
  • Geriatrics and Gerontology


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