New Research Could Lead to Early Diagnosis, Better Treatments to Help Slow Alzheimer's Progression
Jun 4, 2004
Subtle but profound changes in blood flow within the brain may be among the earliest signs of Alzheimer's disease, according to a review of recent research conducted by Dr. Costantino Iadecola, Chief of the Division of Neurobiology at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, in New York City.
"These vascular changes are very early markers of disease, and can be used very effectively to diagnose patients early on", said Dr. Iadecola, who is the George C. Cotzias Distinguished Professor of Neurology and Neuroscience at Weill Cornell Medical College, and Attending Neurologist at NewYork-Presbyterian/Weill Cornell. "Early diagnosis is important", he said, "because the earlier you start treatment, the better you're going to be." His review of more than 150 published studies on Alzheimer's-linked vascular changes appeared in the May issue of Nature Reviews/Neuroscience.
Over the past few decades, research into the causes of Alzheimer's has focused primarily on the activity of the brain's neural cells. Alois Alzheimer at the beginning of the 20th century uncovered two hallmarks of the disease that bears his name: The buildup in the brain of plaques made of amyloid, a kind of protein, as well as masses of neuro-fibers called "tangles."
But what about the role of neurovascular changes in Alzheimer's development?
Dr. Iadecola believes it's time to put the spotlight back on this aspect of the disease. First of all, he said, studies in mice genetically modified to develop an Alzheimer's-like illness are revealing changes in brain blood flow as among the first detectable signs of disease. What's more, those changes appear to be linked to very small levels of amyloid, previously believed to be of no consequence. "One of the things amyloid does is it has a profound effect on blood vessels," Dr. Iadecola explained. "So although the patient is functioning in a normal state, that amyloid is already affecting the reactivity of the blood vessels."
Indeed, using special functional MRI brain scans, scientists can already distinguish the brains of cognitively normal patients with a familial predisposition to Alzheimer's from those with no genetic predisposition simply by noting changes in brain blood flow.
"It's the first stage," Dr. Iadecola said.
Other studies suggest that amyloid increases cerebrovascular atherosclerosis – hardening of the cerebral arteries – through its effects on cholesterol deposition."This hasn't been definitively proven", Dr. Iadecola stressed. However, one study noted increased atherosclerosis in the cerebral blood vessels of Alzheimer's patients versus patients unaffected by the disease. "You could almost tell them apart," he said.
About a third of patients with Alzheimer's disease are also thought to suffer from a concurrent form of dementia linked to either stroke or smaller, more subtle "mini-strokes". Now, research is suggesting amyloid raises stroke risk in patients with Alzheimer's.
As Dr. Iadecola explained, as amyloid builds up in the brain, it impairs the ability of nearby blood vessels to constrict or dilate. "If vessels aren't reacting very well, the brain is more susceptible to stroke," he said. Unfortunately, when stroke damage occurs, then the brain starts making more amyloid at a greater rate, setting up a kind of "vicious circle" that inevitably speeds progression of the disease.
While these findings may seem grim, there is a silver lining. Because changes in the brain's vascular activity appear to be a very early sign of Alzheimer's, doctors might someday use brain scan technology to detect the illness much earlier on, when treatment is most effective.
Amyloid has also been linked to increased production of "free radicals" – rogue molecules that can damage cells and have long been implicated in cardiovascular disease. According to Dr. Iadecola, this could mean that free radical-fighting antioxidants, such as Vitamin E, might prove useful in slowing Alzheimer's. The findings might also bring neurologists and cardiovascular specialists closer together as they battle a common enemy. "The fact that risk factors for Alzheimer's disease and stroke are the same suggests that we have to aggressively treat those factors," Dr. Iadecola said. "Traditionally, those fields have been separate, but now we need to get together and address them. The National Institutes of Health is developing new initiatives to encourage scientists to study the interaction between brain cells and blood vessels."