Biomedical subjects

Albert Hofman

Publications and source records attributed to Albert Hofman.

At least 91 records · Page 5Linked to original sources

PubMed2005

Methylenetetrahydrofolate reductase C677T genotype and PD.

In a prospective, population-based cohort study among 5,920 participants aged 55 years or older, we observed that the TT variant of the methylenetetrahydrofolate reductase C677T polymorphism is associated with an increased risk for Parkinson's disease in smokers. Both smoking and the TT genotype are known to induce hyperhomocystinemia, and synergistic effects on homocysteine levels have been reported. Increased plasma levels of homocysteine through direct neurotoxic effects might accelerate the selective dopaminergic cell death underlying Parkinson's disease. Our findings support the hypothesis that homocysteine plays a role in the pathogenesis of Parkinson's disease.

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PubMed2005

Serum uric acid levels and the risk of Parkinson disease.

In a prospective population-based cohort study among 4,695 participants aged 55 years and older, with repeated in-person examination and on average 9.4 years of follow-up, we observed that higher serum levels of uric acid were associated with a significantly decreased risk of Parkinson disease (adjusted hazard ratio per standard deviation increase 0.71 [95% confidence interval 0.51-0.98]), with evidence for a dose-effect relationship (p value for trend over quartiles 0.040). Our findings support the hypothesis that oxidative stress contributes to the risk of Parkinson disease and suggest a potential protective effect of the natural antioxidant and free radical scavenger uric acid.

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PubMed2005

Effect of baseline cognitive function and antihypertensive treatment on cognitive and cardiovascular outcomes: Study on COgnition and Prognosis in the Elderly (SCOPE).

BACKGROUND: We examined whether cognitive function at baseline affected cognitive and cardiovascular outcomes in the Study on COgnition and Prognosis in the Elderly (SCOPE), a blood pressure (BP)-lowering intervention trial. METHODS: SCOPE included 4937 patients, aged 70 to 89 years, with mild-to-moderate hypertension and Mini Mental State Examination (MMSE) score > or =24. Double-blind treatment was initiated with candesartan or placebo. Open-label therapy was added as needed to control BP, both in the candesartan (49%) and control (66%) groups. Mean follow-up was 3.7 years. Low cognitive function (LCF) at baseline was defined as MMSE score 24 to 28 (N = 2070), and high cognitive function (HCF) as MMSE score 29 to 30 (N = 2867). RESULTS: Mean BP reductions were approximately 20/10 mm Hg both in LCF and HCF patients, with greater reductions in the candesartan group than in the control group. The incidence of dementia was higher in LCF than in HCF patients. A higher cardiovascular event rate observed in LCF patients was explained by older age and other cardiovascular risk factors at baseline. In LCF patients, the MMSE score declined less in the candesartan than in the control group (mean difference 0.49, 95% confidence interval 0.02 to 0.97, P = .04). Nonfatal stroke was reduced in the candesartan group in the total sample (28%, P = .04), with no difference between LCF (27%) and HCF (29%) patients. CONCLUSIONS: Elderly patients with mild-to-moderate hypertension and slightly impaired cognitive function (MMSE 24 to 28) are at increased risk of dementia and cardiovascular events. This analysis indicates that effective antihypertensive therapy may reduce cognitive decline and stroke incidence in these patients.

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PubMed2005

The association between angiotensin-converting enzyme gene polymorphism and coronary calcification. The Rotterdam Coronary Calcification Study.

BACKGROUND: An insertion/deletion (I/D) polymorphism in the gene encoding angiotensin-converting enzyme (ACE) has been associated with serum ACE levels. The association between the ACE I/D polymorphism and coronary heart disease is unclear. Electron-beam-computed tomography (EBT) is a technique to non-invasively quantify the amount of coronary calcification. We investigated the association between the ACE I/D polymorphism and coronary calcification. METHODS AND RESULTS: The Rotterdam Coronary Calcification Study is a population-based study in subjects aged 55 years and over. EBT scanning was performed in 2013 participants. Coronary calcification was quantified according to the Agatston score. The ACE I/D polymorphism was available for 1976 subjects. Geometric mean calcium scores in men with the II, ID and DD genotype were 167, 207 and 219, respectively. However, the difference in calcium score (p=0.19 for ID versus II; p=0.15 for DD versus II) and the trend (ptrend=0.17) were not significant. Calcium scores in women with the II, ID and DD genotype were 44, 42 and 36, respectively. There were no significant differences in calcium score (p=0.78 for ID versus II; p=0.29 for DD versus II), neither was the trend (ptrend=0.27). After we stratified on cardiovascular risk factors, no associations were present. CONCLUSION: The present study failed to show an association between the ACE I/D polymorphism and coronary calcification in the general population. Also, no significant associations were present between the ACE I/D polymorphism and coronary calcification in strata of cardiovascular risk factors.

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PubMed2005

Allelic variants of cytochrome P450 2C9 modify the interaction between nonsteroidal anti-inflammatory drugs and coumarin anticoagulants.

INTRODUCTION: Cytochrome P450 (CYP) plays a key role in the metabolism of coumarin anticoagulants and nonsteroidal anti-inflammatory drugs (NSAIDs). Because CYP2C9 is a genetically polymorphic enzyme, genetic variability could play an important role in the potential interaction between NSAIDs and coumarins. We investigated whether NSAIDs were associated with overanticoagulation during therapy with coumarins and evaluated the effect of the CYP2C9 polymorphisms on this potential interaction. METHODS: We conducted a population-based cohort study among patients of an anticoagulation clinic who were treated with acenocoumarol or phenprocoumon between April 1, 1991, and May 31, 2003, and whose CYP2C9 status was known. Patients were followed up until an international normalized ratio (INR) of 6.0 or greater was reached or until the end of treatment, death, or the end of the study. Proportional hazards regression analysis was used to estimate the risk of an INR of 6.0 or greater in relation to concomitant use of a coumarin anticoagulant and NSAIDs after adjustment for several potentially confounding factors. To study effect modification by CYP2C9 genotype, stratified analyses were performed for wild-type patients and patients with a variant genotype. RESULTS: Of the 973 patients in the cohort, 415 had an INR of 6.0 or greater. Several NSAIDs increased the risk of overanticoagulation. The risk of overanticoagulation was 2.98 (95% confidence interval, 1.09-7.02) in coumarin-treated patients taking NSAIDs with a CYP2C9*2 allele and 10.8 (95% confidence interval, 2.57-34.6) in those with a CYP2C9*3 allele. CONCLUSIONS: Several NSAIDs were associated with overanticoagulation. For NSAIDs that are known CYP2C9 substrates, this risk was modified by allelic variants of CYP2C9. More frequent INR monitoring of patients taking NSAIDs is warranted.

Acenocoumarol↗

PubMed2005

Heterogeneity of the genetic risk in age-related macular disease: a population-based familial risk study.

OBJECTIVE: To assess the extent of heterogeneity of the genetic risk of age-related macular disease (AMD) among families. DESIGN: Case-controlled population-based familial aggregation study. PARTICIPANTS: Participants comprised 190 first-degree relatives of 65 case probands and 347 relatives of 100 control probands. All probands had been identified from the baseline phase of the Rotterdam Study in The Netherlands. METHODS: A family score was computed for each family based on the presence and type of macular disease, the expected risk of disease, and the number, extent of kinship, and age of all family members. MAIN OUTCOME MEASURES: Presence and stage of AMD as diagnosed on fundus photographs, family score, and logistic regression coefficient. RESULTS: The family score of case families showed a peak of approximately 0 with a skewed tail (14% of families) of higher than expected risks of disease toward a maximum of 2.9. The family score of control families centered on 0, apart from 1 outlier. The risk of AMD increased significantly with higher family scores (beta = 1.34; P<0.001). CONCLUSIONS: The heterogeneity of genetic risk among AMD families is considerable, and the proportion of high-risk families is relatively small. The family score method is relevant for genetic counseling as well as for implementation in studies of genetic dissection of AMD.

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PubMed2005

Retinal vessel diameters and the risk of incident age-related macular disease: the Rotterdam Study.

PURPOSE: To study the relationship between retinal vessel diameters and incident age-related macular disease (iAMD). DESIGN: Prospective population-based cohort study. PARTICIPANTS: Persons (55 years and older) from the Rotterdam Study, who participated at the baseline (1990-1993) and 1 of 2 follow-up examinations (1993-1994 and 1997-1999). METHODS: In the current analysis, 4345 participants who were free of AMD at baseline and had gradable macular transparencies at both baseline and follow-up examination were included. Also, arteriolar and venular diameters were measured on digitized baseline images. Stereoscopic transparencies of the macular region were graded according to the International Classification and Grading System for AMD. Incidence of AMD was defined as the development of soft distinct drusen with pigmentary changes or indistinct or reticular drusen with or without pigmentary changes (early iAMD) or atrophic or neovascular AMD (late iAMD). Logistic regression models were used to assess these associations, adjusting for age, gender, and follow-up time and, additionally, for smoking, body mass index, intima-media thickness, systolic blood pressure, and total and high-density lipoprotein cholesterol levels. MAIN OUTCOME MEASURE: Incidence of AMD. RESULTS: After a mean follow-up time of 5.2 years, a total of 374 persons developed early and late iAMD. Neither arteriolar nor venular diameters were related to the risk of iAMD. The odds ratio (OR) per standard deviation (SD) decrease in arteriolar diameter was 1.03 (95% confidence interval [CI], 0.93-1.15), and the OR per SD increase in venular diameter was 1.04 (95% CI, 0.93-1.16). After categorizing the retinal vessel diameters into quintiles, there was no trend. After stratifying on age, only persons 75 years and older with smaller arteriolar diameters were at a borderline significant increased risk of iAMD: OR/SD decrease in arteriolar diameters adjusted for age, gender, follow-up time, and other cardiovascular risk factors, 1.24 (95% CI, 0.94-1.63). CONCLUSION: Overall retinal vessel diameters were not related to the risk of iAMD in this general elderly population.

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PubMed2005

Incidence of open-angle glaucoma in a general elderly population: the Rotterdam Study.

PURPOSE: To determine the incidence of open-angle glaucoma (OAG) in a general elderly white population. DESIGN: Population-based cohort study. PARTICIPANTS: Participants 55 years and older from the Rotterdam Study, The Netherlands. METHODS: Participants at risk for incident OAG underwent at baseline (1990-1993) and follow-up (1997-1999) the same ophthalmic examination, including measurement of intraocular pressure, visual field testing, and stereo optic disc photography. The diagnosis of probable or definite OAG was made with an algorithm based on optic disc parameters and on visual field testing, independent of the intraocular pressure. MAIN OUTCOME MEASURES: Five-year risk and incidence rates of OAG. RESULTS: In total, 3842 participants were examined (participation rate at follow-up, 78%). After a mean follow-up time of 6.5 years, probable (n = 58) or definite OAG (n = 29) developed in 87 persons. The 5-year risk of probable OAG was 1.2% and that of definite OAG 0.6%, and the rate rose for both together from 1% at age 60 years to approximately 3% at age 80 years. Bilateral OAG occurred 5 times more often after than before age 75 years. In participants with prevalent OAG in 1 eye, the 5-year risk of OAG in the fellow eye was 5 times higher than in fellow eyes of non-OAG eyes. Only 37% of the incident cases received treatment for OAG at the time of the reexamination. CONCLUSIONS: The incidence of OAG rose significantly with age. Most of the patients with incident OAG were unaware of having OAG.

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PubMed2005

The Study on COgnition and Prognosis in the Elderly (SCOPE) - major CV events and stroke in subgroups of patients.

The Study on COgnition and Prognosis in the Elderly (SCOPE) assessed the effect of candesartan on cardiovascular outcomes in elderly patients with mild to moderate hypertension. Patients were randomized to candesartan 8-16 mg daily (n = 2477) or placebo (n =2460). Due to extensive add-on therapy, blood pressure reduction was only about 3/2 mmHg greater in the candesartan group than in the control group. Nevertheless, non-fatal stroke was reduced by 28% (p = 0.04) in the candesartan group compared to the control group, and there was a non-significant 11% reduction in major cardiovascular events (p = 0.19). This report provides results in pre-specified subgroups of patients (age, gender, diabetes, history of stroke, smoking and cardiovascular risk at randomization). Reductions in major cardiovascular events and stroke with candesartan-based therapy were indicated in all subgroups. A significant interaction between treatment and subgroups was found for one pair of subgroups only; the reduction in major cardiovascular events with candesartan was greater in patients with a previous stroke (64% reduction, p = 0.004) than in those without (5% reduction, p > 0.20). In conclusion, this analysis indicated consistent favourable effects of candesartan-based therapy on major cardiovascular events and stroke across the different subgroups of patients. However, the benefit was particularly pronounced in patients who entered the study with a previous stroke.

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PubMed2005

Moderate alcohol consumption is associated with reduced arterial stiffness in older adults: the Rotterdam study.

BACKGROUND: Light-to-moderate alcohol consumption has been associated with a lower risk of cardiovascular disease. The protective effect of alcohol could involve arterial properties as arterial stiffness and distensibility. METHODS: The relationship between alcohol and arterial stiffness was studied within the framework of the Rotterdam Study, a population-based study in individuals aged 55 and older. The present study included 3178 participants in the third examination phase. Arterial stiffness was measured by two different methods, i.e., the carotid-femoral pulse wave velocity and the DC of the common carotid artery. Categories of alcohol consumption were defined as follows: < or =3 glasses of alcohol per week, 4-10 glasses per week, 11-20 glasses per week, and > or =21 glasses per week. Linear regression analysis was used to investigate the association between alcohol consumption and measures of arterial stiffness. RESULTS: In multivariate-adjusted models, women drinking 4-10, 11-20, and > or =21 glasses of alcoholic beverage per week had a -0.07 (0.22 to -0.38), -0.18 (0.12 to -0.49), and 0.12 (0.19 to -0.43) m/s difference in mean pulse wave velocity compared to those drinking 0-3 glasses per week (reference group). Corresponding differences in the carotid DC were 0.68 (1.21 to 0.15), 0.28 (0.82 to -0.25), and 0.36 (0.91 to -0.18) 10(-3)/kPa. In men, the estimates were not statistically significant, although a similar trend was observed. CONCLUSIONS: Moderate alcohol consumption is associated with lower arterial stiffness in women independently of cardiovascular risk factors and atherosclerosis.

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PubMed2005

Patients with an ApoE epsilon4 allele require lower doses of coumarin anticoagulants.

OBJECTIVE: Vitamin K is an essential cofactor for the synthesis of several blood coagulation factors. It has been suggested that the apolipoprotein E (ApoE) genotype has profound effects on vitamin K status. Therefore, we investigated whether this common genetic polymorphism influenced dose requirements and effects of coumarin anticoagulants. METHODS: We did a cohort study in 1637 patients from an outpatient anticoagulation clinic treated with acenocoumarol or phenprocoumon. RESULTS: To attain the same level of anticoagulation, patients with genotype epsilon4/epsilon4 and genotype epsilon3/epsilon4 required respectively 3.4 mg (95%CI: -6.0 to -0.9) and 0.8 mg (95%CI: -1.6 to 0.1) acenocoumarol per week less than patients with genotype epsilon3/epsilon3. Patients homozygous for the epsilon2 allele required 3.5 mg (95%CI: 0.1 to 6.9) acenocoumarol per week more than patients with genotype epsilon3/epsilon3. The acenocoumarol maintenance dose showed a gene dose effect of the epsilon4 allele, but not of the epsilon2 allele. No significant dose difference was observed for phenprocoumon, possibly because of low numbers. CONCLUSION: The ApoE genotype affects the dose requirements of acenocoumarol.

Acenocoumarol↗

PubMed2005

Mortality in patients with hypertension on angiotensin-I converting enzyme (ACE)-inhibitor treatment is influenced by the ACE insertion/deletion polymorphism.

BACKGROUND: The response to angiotensin-I converting enzyme (ACE)-inhibitor therapy is highly variable. Residual ACE activity during treatment, potentially modified by the ACE insertion/deletion (I/D) polymorphism, may explain part of this variability. We studied the possible interaction between ACE-inhibitor therapy in patients with hypertension and the ACE I/D polymorphism in incident heart failure and death. METHODS: We studied 3365 hypertensive participants of the population-based Rotterdam Study, without heart failure at baseline for whom ACE-genotyping was successful. Incident heart failure was defined according to established criteria. In addition, total and cardiovascular mortality were studied as endpoints. A Cox regression model with use of ACE-inhibitors defined as time-dependent covariates was used for data-analysis. Interaction was tested in this model assuming an allele-effect relationship. RESULTS: Although we could not demonstrate a beneficial effect of ACE-inhibitors, there was significant interaction between the ACE I/D polymorphism (II-ID-DD) and ACE-inhibitor use in the prediction of total and cardiovascular mortality. Mortality risk associated with treatment increased with the number of D alleles present; e.g. for total mortality in the II genotype group: RR=0.95 (95% CI 0.63-1.45), in the ID genotype group: RR=1.08 (95% CI 0.84-1.38) and in the DD genotype group: RR=1.61 (95% CI 1.18-2.18). No statistically significant interaction was found for incident heart failure. CONCLUSION: The results of our study suggest a relative resistance to ACE-inhibitor therapy in subjects with hypertension and the DD genotype compared to the II genotype, with the ID genotype in an intermediate position.

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PubMed2005

Angiotensin-converting enzyme gene insertion/deletion polymorphism and breast cancer risk.

BACKGROUND: The renin-angiotensin system plays an important role in homeostasis and lately, its main effector, angiotensin II, has been attributed with angiogenic and growth factor actions in the breast tissue. Previous studies have shown that the insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene accounts for the variability of ACE plasma concentrations. The use of ACE inhibitors and the ACE I/D polymorphism may be linked to breast cancer risk. In this study, we evaluate the relationship of the ACE I/D polymorphism with breast cancer risk in Caucasian postmenopausal women. METHODS: The ACE I/D polymorphism was genotyped in 4,117 women participants in the Rotterdam Study. Baseline information was obtained through a questionnaire. We conducted a logistic regression and survival analysis to assess the risk of breast cancer by the ACE genotype. RESULTS: The DD carriers showed a significantly increased risk of developing breast cancer when compared with the II carriers (odds ratio, 1.86; 95% confidence interval, 1.06-3.27; P = 0.03). This association remained after adjusting for other risk factors, including body mass index, age at menarche, age at menopause, hormone replacement therapy, and hypertension. Our survival analysis showed that the cancer-free survival was significantly reduced in DD compared with II carriers (hazard ratio, 1.80; 95% confidence interval, 1.07-3.01; P = 0.03). CONCLUSIONS: Our results suggest that the ACE I/D polymorphism plays an important role in breast cancer risk and disease-free survival in Caucasian postmenopausal women.

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PubMed2005

Retinal vessel diameters and incident open-angle glaucoma and optic disc changes: the Rotterdam study.

PURPOSE: It remains unclear whether reduced retinal blood flow and smaller arterioles, reported to exist in patients with open-angle glaucoma (OAG), are a cause or a consequence of ganglion cell loss. We examined whether baseline retinal vessel diameters were related to incident (i)OAG or incident optic disc changes in a population-based sample. METHODS: In the prospective population-based Rotterdam Study, baseline diameters of retinal arterioles and venules (1990-1993) were measured in digitized images of 3469 persons (aged 55 years and older) at risk for OAG. The follow-up examinations took place from 1997 to 1999. iOAG was based on the presence of incident glaucomatous visual field loss and/or incident glaucomatous optic neuropathy. Changes in neuroretinal rim, cup area, or vertical cup-to-disc ratio were calculated with a semiautomated image analyzer in 2782 persons. RESULTS: After a mean follow-up time of 6.5 years, 74 participants had iOAG. At baseline, the mean arteriolar diameter was 147.5 +/- 14.2 microm (SD) and the venular, 222.9 +/- 20.0 microm. Neither arteriolar diameters (odds ratio [OR] per SD decrease: 0.82; 95% confidence interval [CI]: 0.66-1.03) nor venular ones (OR per SD increase: 1.20; 95% CI: 0.95-1.53) were significantly related to iOAG. Baseline retinal vessel diameters did not predict changes in the optic disc. Additional adjustment for cardiovascular risk factors did not alter these results. CONCLUSIONS: The data show that baseline retinal vessel diameters did not influence the risk of iOAG or incident optic disc changes. These data provide no evidence for a retinal vascular role in the pathogenesis of OAG.

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PubMed2005

A direct approach to the estimation of the origin of oestrogens and androgens in elderly men by comparison with hormone levels in postmenopausal women.

OBJECTIVE: The origin of oestrogens in men is only partly understood. From infusion studies with radioactively labelled hormones, we know that oestradiol (E2) and oestrone (E1) are either directly secreted by the testes and adrenal glands or peripherally produced from testicular or adrenal androgens. DESIGN AND METHODS: We determined E2, E1, androstenedione, testosterone and dehydroepiandroster-one sulphate (DHEAS) in 292 elderly men and 367 postmenopausal women. We considered post-menopausal women as men without testes, assuming that the postmenopausal ovary is not endocrinologically active and that the testes do not contribute to circulating levels of DHEAS. Subjects were stratified by DHEAS levels to adjust for differences in DHEAS levels between sexes. For men and women separately, mean levels of E2, E1, androstenedione and testosterone were calculated per DHEAS stratum. The relative direct and indirect contributions of the testes to steroid levels in men were calculated by the formula [(C(m) - C(f))/C(m)] x 100%, in which C(m) and C(f) represent the mean concentrations of the steroid in men and women respectively. RESULTS: The relative contributions (%) of the testes to hormone levels per DHEAS stratum (<2, 2-4, 4-6 and >6 micromol/l) respectively were, for E2, 72%, 60%, 52% and 44%; for E1, 54%, 47%, 35% and 34%; for androstenedione, 14%, 4%, 12% and 0%; and, for testosterone, 88%, 88%, 87% and 83%. CONCLUSIONS: We conclude that in elderly men dependent on DHEAS levels, 44-72% of E2 and 34-54% of E1 originate directly or indirectly from the testes.

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PubMed2005

Estrogen receptor alpha gene polymorphisms are associated with estradiol levels in postmenopausal women.

OBJECTIVE: Postmenopausal estradiol (E(2)) levels vary widely between individuals and this variation is an important determinant of diseases such as osteoporosis. It has been suggested that the estrogen receptor alpha (ESR1) gene may influence peripheral E(2) levels, but the role of common sequence variations in the ESR1 gene is unclear. METHODS: In 631 postmenopausal women and 528 men from the Rotterdam Study, a population-based, prospective cohort study of individuals aged 55 years and over, ESR1 PvuII-XbaI haplotypes were determined and correlated with plasma E2 levels. RESULTS: In women, haplotype 1 (T-A) was significantly associated with an allele-dose-dependent decrease in E(2). After adjusting for age, body mass index, years since menopause and testosterone levels, plasma E(2) levels decreased by 1.90 pmol/l per allele copy of this haplotype (P < 0.05). Extreme genotypes, representing 23 and 27% of the population, varied by 3.93 pmol/l. No association with plasma testosterone was observed. In a subset of 446 women, no association of genotype with plasma concentrations of dehydroepiandrosterone sulfate, androstenedione or estrone was seen. In men, none of the sex hormone levels was associated with the ESR1 PvuII-XbaI haplotypes. CONCLUSION: We have demonstrated a role for genetic variations in the ESR1 gene in determining post-menopausal E(2) levels in women.

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PubMed2004

Plasma levels of antioxidants are not associated with Alzheimer's disease or cognitive decline.

Antioxidants prevent oxidative stress that possibly causes neuronal loss in Alzheimer's disease (AD). We examined whether high plasma levels of the antioxidant vitamins A and E were associated with lower prevalence of AD or cognitive decline (CD). We performed a cross-sectional study within the Rotterdam Study. In an univariate model, higher levels of vitamins A and E were significantly associated with lower prevalence of AD. However, when additional adjustments were made for important confounders, such as age, gender and total cholesterol, the relation substantially weakened -- odds ratios per standard deviation increase were 0.87 (95% CI 0.64-1.19) for vitamin A and 0.94 (95% CI 0.60-1.48) for vitamin E. Antioxidants were not related to CD in non-demented subjects. Our findings suggest no association between plasma levels of vitamin A and E and AD or CD.

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PubMed2004

ACE gene is associated with Alzheimer's disease and atrophy of hippocampus and amygdala.

Despite biological support for a role of angiotensin converting enzyme (ACE) in Alzheimer's disease (AD), studies assessing the ACE I/D polymorphism in AD are conflicting. We re-evaluated this association in the Rotterdam Study, a population-based cohort study. The mechanism of association was further explored by adjusting for vascular factors, and by analysing atrophy, white matter lesions and infarcts on MRI in non-demented individuals. Genotypes were available for 6488 participants. During average follow-up of 6 years 250 subjects developed AD. MRI data were available for 494 non-demented participants. Homozygosity for the I-allele conferred a slightly increased risk of AD compared to carrying a D-allele (RR 1.12 (95% CI 0.99-1.25)). This increase was only significant in women, and independent of vascular factors (RR 1.39 (95% CI 1.14-1.69)). Non-demented women with the II genotype had smaller hippocampal and amygdalar volumes. Vascular pathology was not significantly associated with ACE. This suggests a modest but significant increase in risk of AD and early AD pathology in women homozygous for the ACE I-allele independent of vascular factors.

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