An investigation of ACE as a risk factor for dementia and cognitive decline in the general population

Dementia is the most common neurodegenerative condition affecting older people. It is estimated that around 550 000 subjects aged 65 years and over in England and Wales suffer from dementia of mild or greater severity.1 Prevalence increases exponentially with age, from around 1% of 65 year olds to approximately 30% of people aged 85 years and older.2 Most cases (60-70%) of incident dementia have clinical diagnoses of Alzheimer's disease, while 15-20% are accounted for by vascular dementia (VaD).3 However, Alzheimer-type and vascular pathology frequently occur in the same person, the neuropathological features associated with AD and VaD are present in many cognitively intact people, and some demented subjects do not have the neuropathological hallmarks of AD or VaD.4 Alzheimer's disease risk is unequivocally associated with polymorphisms in the apolipoprotein E ( APOE ) gene. However, APOE accounts for around half of the genetic risk for AD. Recent data suggest that the angiotensin-I converting enzyme or ACE gene (chromosome 17q23) may also be involved in genetic susceptibility to AD.6,7 ACE (OMIM *1061805) is a dipeptidyl carboxypeptidase that plays an important role in blood pressure regulation and electrolyte balance by hydrolysing angiotensin-I into angiotensin-II, a potent vasopressor and aldosterone stimulating peptide, and inactivating bradykinin, a potent vasodilator. An insertion (I)/deletion (D) polymorphism situated in intron 16 of the gene accounts for 50% of the interperson variability of plasma ACE concentration, and its links with myocardial infarction and other ischaemic heart disease and longevity have been studied extensively.5 There are few published studies on the association between the ACE I/D polymorphism and AD risk: Kehoe et al 6 reported increased risk for AD among I allele carriers; however, this result was not uniformly replicated in subsequent studies. Results from our pooled analysis suggest a slightly increased risk …