Vascular Risk Factors Promote Conversion to Alzheimer's

Megan Brooks

April 13, 2011

April 13, 2011 — Effective management of vascular risk factors in older adults with mild cognitive impairment (MCI) may lower the risk for progression to Alzheimer's disease (AD), results of an observational study released today suggest.

The study shows a 2-fold increased risk for conversion from MCI to AD in those with hypertension, hypercholesterolemia, diabetes, or other vascular risk factors relative to those with MCI but no vascular risk factors. Treatment of vascular risk factors was associated with reduced risk for progression to AD.

The study is published online April 13 in Neurology.

This study highlights "the critical role of vascular risk factors in the development of AD," study author Yan-Jiang Wang, MD, PhD, deputy director of the Department of Neurology, Daping Hospital and Third Military Medical University, Chongqing, China, told Medscape Medical News.

Richard B. Lipton, MD, of Albert Einstein College of Medicine, New York City, who was not involved in the study, said the findings are "important because they suggest that managing vascular risk factors is important in AD prevention, not just in middle life, but later in life and even after amnestic MCI has developed."

Vascular Factors Hasten Cognitive Decline

Dr. Wang and colleagues investigated the impact of vascular risk factors, and their treatment, on conversion from MCI to AD in 837 Chinese adults with MCI at baseline who were followed up annually for 5 years. At last follow-up, 298 (35.6%) had developed AD dementia and 352 (42.1%) continued to have only MCI. The conversion rate from MCI to AD was 7.1% per year.

At baseline, 414 individuals had at least 1 vascular risk factor; during follow-up, a total of 199 vascular risk factors were found in the entire cohort. Hypertension was detected in 42 subjects, diabetes in 36, and hypercholesterolemia in 22. Eighteen subjects had myocardial infarction (MI), 10 had atrial fibrillation, and 71 had cardiovascular disease (CVD). A total of 46 subjects with no vascular risk factors at baseline developed one or more during follow-up.

The researchers found that subjects with vascular risk factors experienced "faster decline" in global cognition (P < .001) assessed via the Mini-Mental State Examination scores and in global functioning (P < .001) assessed using the Activities of Daily Living instrument.

Among the individual vascular risk factors, hypertension, diabetes, hypercholesterolemia, and CVD were associated with faster decline in cognition and function, as well as a higher risk for incident AD. The adjusted hazard ratio (aHR) for AD with the presence of vascular risk factors was 2.0 (95% confidence interval [CI], 1.3 – 3.1).

Treatment Makes a Difference

Dr. Wang and colleagues also found that subjects receiving full treatment for their vascular risk factors were 39% less likely to convert to AD than those whose vascular risk factors remained untreated (aHR, 0.614; 95% CI, 0.386 – 0.976).

Those receiving some treatment for vascular risk factors were 26% less likely to develop AD compared with those left untreated (aHR, 0.735; 95% CI, 0.579 – 0.933).

Dr. Wang noted that "currently, there are no disease-modifying prevention or treatment for AD, and the medicines approved to be used for patients with AD are mainly to relieve symptoms." Managing vascular risk factors may be a "practical way to prevent the development of AD," Dr. Wang added.

Unique Contribution to the Literature

Dr. Lipton noted that "substantial prior literature has shown that risk factors for vascular disease are also risk factors for AD. But prior studies do not tell us whether vascular risk factors have their effects early or late in the course of AD; nor do they tell us when intervention might be effective.

"Increasingly," Dr. Lipton explained, "the onset of AD is conceptualized as a 2-transition process. The first transition is from cognitive normality to amnestic MCI (aMCI). The second is from aMCI to dementia. This study shows that vascular risk factors play a role not just in the transition from normal to AD but, in the late stage, the transition from aMCI to AD."

Importantly, he said, it also suggests that treating vascular risk factors reduces the risk for AD onset in person with aMCI.

"Of course, these findings need to be assessed in randomized trials and not just observational studies, but while we await the randomized trials, in older adults with aMCI, this study would support managing vascular risk factors, not just to prevent MI and stroke, but also to delay the onset of AD," Dr. Lipton said.

The study was supported by the Science and Technology Committee of Chongqing, China. The study authors and Dr. Lipton have disclosed no relevant financial relationships.

Neurology. 2011;76:1485-1491.

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