The use of blockers of receptors of angiotensin and the risk of dementia

The reasons for the development of dementia, particularly Alzheimer’s, is complex, but evidence increasingly point to three major risk factors: age, the accumulation of -amyloid in the brain and the natural deterioration of the cardiovascular system.

Cardiovascular dysfunctionis also very closely connected with other forms of dementia. Studies have shown that cardiovascular risk factors that arise in mid-life, such as hypercholesterolemia, arterial hypertension and diabetes mellitus, contribute to the development of dementia. Drugs used to treat these risk factors can also reduce the incidence of dementia.

Numerous studies have shown that angiotensin converting enzyme inhibitors (aceis) prevent the action of angiotensin II and are the most effective means to lower blood pressure. Due to its effectiveness of this class of drugs is used as the primary treatment of hypertension. Their use is also associated with lower levels of indicators of congestive heart failure, myocardial ischemia, renal failure and death than the use of antihypertensive drugs with a different mechanism of action. In two small studies it was shown that aceis reduce the rate of deterioration of cognitive functions.

The role of the renin-angiotensin system in Alzheimer’s disease and the impact on cognitive function of drugs that inhibit the renin-angiotensin system discussed in comprehensive reviews [32, 33]. Based on these data must be made evaluation of the effect of ARBS and aceis on outcomes of dementia.

For analysis of disease progression we studied the period before enrolment of the patient in a nursing home or to death. Previous clinical studies have successfully used new medical diagnoses, or the presence of events as indicators of the progression of Alzheimer’s disease. Time until the patient has been in a nursing home, for example, was used as a criterion to assess the clinical efficacy of the alleged treatment of Alzheimer’s disease in numerous clinical trials.

Death was also a reliable measure of progression of Alzheimer’s disease. Identifying the usefulness of the time before patient admission to special institutions of social security gives a good basis for using this criterion as an indicator of the progression of Alzheimer’s disease in this study.

The outcomes of progressive disease was based on well documented and approved dossier database Beneficiary Identification and Records Locator Subsystem in relation to the deaths, which included information about its registration, and records nursing homes system Veteran Affairs according to the data obtained from the social security institutions.

All the files were merged by unique reference designators using encrypted personal numbers of the social insurance system, and then deprived of these identifiers to maintain confidentiality.


We used Cox proportional hazards models, considering time to event, to obtain risk indicators in the group of BRA and the comparison drugs. Censoring was defined according to three criteria:

  • the end of the study (30 September 2006);
  • loss of contact for monitoring patients mounted on the basis of three dossiers database for attendance by patients, diagnoses, and procedures;
  • death.

For all statistical calculations we used SAS software version 9.01. Covariates of the Cox proportional hazard models were age, the presence in the patient of stroke, hypertension, cardiovascular disease and diabetes. We have completed processing the data for missing values for covariates and outcomes variables (time before event). During the main study period (20032006 financial) we have identified 6 867 768 patients diagnosed on the basis of the database. Only 6630 (0,1%) were missing date of birth. In the selection of persons aged 65 years and over on 1 October 2002, those who were missing date of birth were automatically excluded from the study. Covariates were coded as is the presence (1) or not available (0) on the basis of diagnoses in the study period.

If the codes for a particular disease condition was absent, we regarded the condition as absent (0). Outcomes were defined as time to occurrence of the event and the missing event could be denoted as time, censored or at the end of the study, either due to the fact that patients were lost contact for observation or death (except for the study of progression, where death is defined as the event).

Point estimate and 95% confidence intervals in Cox proportional hazard models are reports adjusted risk ratios. Outcomes for each cohort were plotted on a graph with logarithmic coordinates. Curves were generated in parallel and validated regarding the application of Cox proportional hazards models. In addition, we tested the Weibull model for sensitivity analysis and obtained similar results.

After excluding for the study was the access to governmental 819 491 the case of Alzheimer’s disease and 799 069 cases of dementia. Number of participants with Alzheimer’s disease to study disease progression (admissions in a nursing home) was 12 574 (476 in the group WALL, 3227 in the lisinopril group, and 8871 in cardiovascular the comparison group, and participants with dementia 44 601 (1920 in the ARBS group, 12 064 in the lisinopril group, and 30 617 in the cardiovascular group).

Overall, 12 879 participants with Alzheimer’s disease (491 group BRA, 3333 group lisinopril and cardiovascular 9055 in the comparison group) and 45 724 participants with dementia (1980 in the group of SCONCES, 12 483 in the group of lisinopril and 31 261 cardiovascular in the comparison group) were included in the study of mortality. The average period of observation are described in supplementary table 3 online. The characteristics of the groups used in the analysis of Alzheimer’s disease and dementia were similar. The average age in each group was 74 years, and participants were predominantly male (98%).

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The prevalence of General cardiovascular disease and stroke in groups of ARBS and lisinopril was lower than in cardiovascular comparison groups, however, the prevalence of diabetes in groups of ARBS and lisinopril was higher than in cardiovascular comparison groups. These groups of drugs in daily practice of medical care, as would be expected, persons with diabetes often prescribe. Each of the differences in comorbidity was also statistically significant (P0,001) due to the large number of persons in each group. Average systolic and diastolic blood pressure in the groups was similar.

The data of this study suggest that the use of ARBS is associated with a decrease in the number of new cases and a decrease in the progression of Alzheimer’s disease and dementia compared with other drugs for the treatment of cardiovascular diseases and hypertension. One of the events with the progression of the disease, were patients in a nursing home. Reliable reduction in the frequency of such hospitalizations associated with the use of LAMPS, is an extremely important observation, which could have a significant impact on the health of the population, if confirmed in future studies. The intensity and persistence of the effect when using several different tests confirms the validity of this conclusion.

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