Treating Vascular Risk Factors Slows Cognitive Decline in Alzheimer's Disease

Pauline Anderson

September 03, 2009

September 3, 2009 — Treating vascular risk factors such as high blood pressure, diabetes, and dyslipidemia slows cognitive decline in patients with Alzheimer's disease who don't have cerebrovascular disease, according to new research.

The observational study showed that patients who had all their vascular risk factors (VRFs) treated experienced the slowest rate of cognitive decline, followed by those who had only some risk factors treated, and then by those who had no risk factors treated. This, say the authors, suggests a causal relation.

These results should encourage doctors to pay more attention to somatic problems of patients with dementia, said lead author Florence Pasquier, MD, PhD, from Université Lille Nord de France. As it stands, doctors may not see the need to treat vascular risk factors in demented patients.

"For example, if general practitioners find high blood pressure in an elderly patient who is demented, they may think it's not too important — the patient is already demented, so why bother him or her with another pill," she told Medscape Psychiatry.

The study is published in the September 1 issue of Neurology.

Slowest Decline in Treated Patients

For the study, investigators used the computerized database at the Université Lille Nord de France outpatient memory clinic. Patients in this database have had a clinical examination, cerebral imaging, and laboratory investigations. The database includes information on patient demographics, medical and treatment history, and the results of clinical examination, including the Mini Mental State Examination (MMSE).

The study included 301 patients with a mean age of 71.7 years who had a definite, probably, or possible diagnosis of Alzheimer's disease according to National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria. The patients' first clinic visit was between 1997 and 2003 and they had a minimum of 2 MMSEs at least 6 months apart. Mean follow-up for patients in the study was 2.3 years.

Researchers recorded the presence of high blood pressure, dyslipidemia, diabetes, tobacco smoking, and atherosclerotic disease. Each of these VRFs was considered to have been treated if the patient received a medication at the first evaluation.

The 21 patients who did not have any VRFs to begin with were excluded from the analysis, leaving 280 patients (93.0%) with at least 1 VRF. These participants were divided into 3 groups: no VRFs treated (25.7%), some VRFs treated (42.5%), and all VRFs treated (31.8%).

To assess cognition, the Dementia Rating Scale was performed at baseline, and MMSE scores were recorded at each visit. At the start of the study, the mean MMSE score of patients was 21.6. During the study period, the mean annual decline on MMSE was 1.6 points. The decline was slowest for patients with all VRFs treated.

Mechanism Unclear

When VRFs were analyzed individually, dyslipidemia treatment was significantly associated with cognitive decline. Patients whose dyslipidemia was treated with either a statin or a fibrate had a slower decline than those without dyslipidemia.

This, said Dr. Pasquier, suggests that in addition to lowering cholesterol, these drugs have some effect on amyloid protein deposits in the brain.

When looking at atherosclerosis, a risk factor for vascular brain lesions, researchers found that patients with untreated disease declined faster than patients with no disease. In terms of preserving cognition, "it might be better if your blood vessels are in good shape or you have a good metabolism of the brain," said Dr. Pasquier.

It's not clear from the study whether VRF treatment slowed cognitive decline by reducing the appearance of new vascular brain lesions or by some other mechanism.

Good for the Brain

Researchers did not find a significant effect for hypertension, diabetes, or tobacco-smoking treatments, but Dr. Pasquier said this could be because the study did not include enough subjects.

During the study, 24 patients died. After adjustment, the risk for mortality was similar for patients with some or all VRFs treated, compared with patients with no VRFs treated.

The results suggest that addressing vascular risk factors is "not worthless" said Dr. Pasquier. "Treating vascular risk factors is good for the brain. It prevents stroke, it prevents ischemic myocardial infarct, and it's also good for Alzheimer's disease."

It might also provide cardiologists with evidence to help convince patients to accept treatment, she said. "If doctors can convince patients that treating their hypertension could prevent Alzheimer's disease, or at least slow the decline of cognitive function, patients would be more prone to accept treatment," said Dr. Pasquier.

In 2003, it was estimated that dementia affected 27.7 million people worldwide. Dementia prevalence is expected to double within the next 20 years, as the population ages.

Findings Surprising

Asked by Medscape Psychiatry to comment on the findings, David S. Knopman, MD, professor of neurology, Mayo Clinic in Rochester, Minnesota, stressed that the study was observational and not a controlled clinical trial.

The finding that treating risk factors delayed mental decline, even in people who already had Alzheimer's disease, was somewhat surprising, he said. "One might have expected that at this stage of illness, treatment wouldn't make much difference."

But the finding that dyslipidemia treatment slows cognitive decline should be viewed in the context of a somewhat confusing background. Although several observational studies have shown that statins reduce the likelihood of dementia, there are soon-to-be-published clinical trials involving patients with Alzheimer's disease who have normal cholesterol that show these medications "have no benefit whatsoever" in slowing cognitive decline, said Dr. Knopman.

Almost every elderly Alzheimer's disease patient has some degree of cerebrovascular disease that will contribute to cognitive impairment. Although patients in this study didn't have overt cerebrovascular disease, "there is an enormous literature showing that vascular risk factors are associated with later-life cognitive impairment and dementia, even in the absence of overt infarct, so the explanation is that microvascular disease is playing a role."

Dr. Pasquier has served on scientific advisory boards and has received funding for travel from Bayer Healthcare (International), Eisai, Janssen-Cilag (National: French), and Ipsen; and receives research support from the University Research Group EA 2691. Details about the relevant financial relationships for the other researchers can be found in the paper. Dr. Knopman was the handling editor at Neurology for this paper.

Neurology. 2009;73:674-680. Abstract