Since vascular risk factors are likely to impact on dementia risk, we also examined the angiotensin-converting enzyme (ACE) and methylenetetrahydrofolate reductase (MTHFR) genes as candidates.
To discover whether polymorphism in either the apolipoprotein E (ApoE) or angiotensin-converting enzyme (ACE) genes is associated with leukoaraiosis, white matter lesions visible on neuroimaging of the brain, which is commonly seen in dementia as well as some normal elderly subjects.
In order to verify the association of Angiotensin converting enzyme (ACE) gene with different kinds of dementia, as well as its association with APO-E (genotype), we performed ACE genotyping in subjects with late-onset probable Alzheimer's disease (LOAD, n = 64), early-onset probable Alzheimer's disease (EOAD, n = 32), possible Alzheimer's disease (pAD, n = 44), vascular dementia (VD, n = 12), age-associated memory impairment (AAMI, n = 15) and 40 healthy age-matched controls, who were previously characterized for APO-E. After the principal component analysis ACE D and Apo-Eepsilon4 alleles disclosed the highest prevalence in the cognitively impaired groups of subjects, Apo-Eepsilon4 being more specific for LOAD and pAD.
Moreover, although inconsistent, several results of case-control studies tend to suggest that the ACE I/D genetic polymorphism may constitute a genetic susceptibility factor for dementia, reinforcing the hypothesis of a major implication of vascular risk factors in the occurrence of dementia.
Paraoxonase, ACE, and MTHFR polymorphisms were not associated with VD or LOAD; these common polymorphisms might have a marginal role in the pathogenesis of dementia in older subjects.
The involvement of the ACE D/I polymorphism in the pathogenesis of DWMHs in dementia (AD and VaD), by a mechanism that is independent of its association with cardiovascular risk factors, should be confirmed in a large population-based sample.
Variations among reports on the relationship between the ACE ID polymorphism and dementia may be due to lack of consideration for gene-gene and gene-phenotype associations.
The frequency of the ACE*ins allele was also greater in the groups with Alzheimer's disease and dementia in general (P = 0.022; P = 0.045), but genotype frequencies were only different in groups without the E*4/-317*ins haplotype (P = 0.012 for Alzheimer's disease; P = 0.04 for dementia).
This study suggests that the ACE I/D polymorphism does not have any genetic association with global or specific cognitive domain in aged men without dementia.
We screened 37 AD, 8 mild cognitive impairment (MCI), 3 AD and CVD (cerebrovascular disease), 3 MCI and CVD, 8 frontotemporal dementia (FTD) and 2 progressive supranuclear palsy (PSP) patients, and 28 normal controls (NCs).We sequenced PSEN1, PSEN2 and APP (EOAD risk factors), as well as MAPT, GRN and TARDBP for all cases and NCs, and analysed the APOE, CLU, CR1 and PICALM genotypes as well as the MAPT and ACE haplotypes (LOAD risk factors) for the AD (n = 37) and AD + MCI (n = 45) cases and NCs (n = 28).We identified variants in PSEN1, PSEN2 and TARDBP across a range of phenotypes (AD, AD and CVD, FTD and PSP), suggesting that screening of all known candidate genes of Alzheimer's and non-Alzheimer's forms of dementias in all dementia cases might be warranted.
Other covariates in the model that were independently associated with CINA included advanced age, diabetes mellitus (DM), use of angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB), history of dementia and living in a residential care facility.
Our results suggest that, ApoE ε4, ACE I and PON1-L55M T alleles are associated with dementia risk whether these polymorphisms were studied separately or gathered in haplotypes.
The Addenbrooke's Cognitive Examination III (ACE-III), an adaptation of the ACE cognitive screening test, has been demonstrated to have high sensitivity and specificity in detecting cognitive impairment in patients with dementia and other neurological and psychiatric disorders.