SAN FRANCISCO —Cerebrovascular disease and Alz­heimer’s disease often coexist and interact, posited Vladimir Hachinski, MD, at the 2007 International Stroke Conference. The conditions share similar risk factors, such as high blood pressure and elevated cholesterol levels, and research has revealed that one in three North Americans will experience a stroke, dementia, or both. “It is quite obvious that cerebrovascular lesions are just as common as Alzheimer’s pathology to explain cognitive impairment in the elderly,” said Dr. Hachinski, of the University of Western Ontario in London. He noted that vascular cognitive impairment can occur alone or in association with Alzheimer’s disease, and therefore, a proactive approach to treating risk factors that are shared by both conditions is critical to preserving cognition.

EVIDENCE FOR TREATING RISK FACTORS

Dr. Hachinski cited a number of studies which have demonstrated that treating risk factors for both cardiovascular and Alzheimer’s disease during the “brain-at-risk” stage—before clinical manifestations appear—could reduce the likelihood of vascular cognitive impairment.

In 2005, he and his colleagues David Cechetto, PhD, and Shawn Whitehead used a rat model to show that stroke and Alzheimer’s disease interact and that treating risk factors early may benefit behavioral and pathologic outcomes of concomitant stroke and Alzheimer’s disease.

“What we did is take rats and have them learn a task by finding a hole in a platform,” explained Dr. Hachinski. After a number of trials, the rats learned the task and were able to remember it when tested again weeks later. When the investigators created a small striatal stroke in the rats’ brains, they found that learning and memory were not affected. However, when an Alzheimer’s-like condition was created in the rats’ brains by injecting Abeta (25-35) in the cisterns, the rats displayed difficulty with learning and memory. When both stroke and an Alzheimer’s-like condition were induced, the rats demonstrated increased difficulty with learning and memory. The investigators then found that if the rats were pretreated with an anti-inflammatory agent, some of the behavioral and histologic deficits that are seen with concomitant stroke and Alzheimer’s disease could be avoided.

Dr. Hachinski also noted that a number of studies have shown that treating hypertension seems to decrease likelihood of cognitive impairment, including Alzheimer’s disease. “And some of the data clearly show that the longer the treatment of hypertension, the greater the benefit,” he said.

In addition, the Honolulu Heart Program has shown a clear correlation between treating high blood pressure and a reduction in the likelihood that individuals would develop cognitive impairment later in life, Dr. Hachinski noted.

THE HARMONIZATION STANDARDS

Research on vascular cognitive impairment has been hindered due to a lack of satisfactory diagnostic criteria for the condition. “Stroke doctors don’t have time to do cognition assessments, and the people who are interested in cognition tend to be Alzheimer’s doctors who really are looking at an end stage of a particular process,” said Dr. Hachinski.

In 2005, he and his colleagues Gabrielle Leblanc, PhD, and Constantino Iadecola, MD, organized a workshop, that was held in Washington, DC, by the NINDS and the Canadian Stroke Network. Working groups in the areas of clinical/epidemiology, neuropsychology, imaging, neuropathology, experimental models, biomarkers, genetics, and clinical trials convened to develop screening questions that could be used to identify patients with possible cognitive and behavioral impairment. The objectives of the meeting were to establish a data set that would be useful in common clinical practice or large-scale research studies of vascular cognitive impairment—so that data could be pooled from different studies for comparison and cross-validation—and to develop an “ideal” data set for studies focused on particular research issues. Their findings represent a first step toward advancing diagnostic criteria for vascular cognitive impairment.

Dr. Hachinski reported that neuropsychologists who participated in the workshop were able to produce a five-minute battery comprising selected subtests from the Montreal Cognitive Assessment. If patients tested positive for cognitive impairment, a standard 30- or 60-minute battery could be used. It is likely that the five-minute battery will be recommended for funding from the NINDS and the Canadian Stroke Network, he noted.

Additional findings and recommendations made by the working groups were published in the September 2006 Stroke. “Using the same standards will help identify individuals in the early stages of cognitive impairment, will make studies comparable, and by integrating knowledge, will accelerate the pace of progress,” said the authors. Additional studies focusing on reducing the likelihood of cognitive impairment are needed, said Dr. Hachinski.            

NR