Detecting the Earliest Signs of Alzheimer’s

People who complain of memory problems, yet still perform normally on cognitive tests, show significant degeneration in some parts of their brains, according to new research from Dartmouth College in Hanover NH. These intriguing findings might just point to a very early form of Alzheimer’s disease, and could also help identify those who would most benefit from protective therapies currently in development.

“We eventually want to be able to detect changes in the brain 5, 10, or 20 years before anyone shows any symptoms,” says Sam Gandy, director of the Farber Institute for Neurosciences at Thomas Jefferson University in Philadelphia and chief scientific adviser to the Alzheimer’s Association. “Then we can try to prevent dementia from ever starting.”

In the aging process, the brain’s grey matter, which is composed of neural cell bodies, slowly shrinks as these cells weaken and die. That shrinkage is much worse in people with Alzheimer’s disease, especially in brain areas involved in memory. Past research has shown that people with mild cognitive impairment, a lesser memory disorder that often precedes Alzheimer’s, have an intermediate level of brain degeneration.

Now Andrew Saykin and colleagues at Dartmouth have identified even earlier evidence of damage to the brain’s memory centers. The study, published today in the journal Neurology, focused on a relatively little-studied population: people who complain of memory problems but show no signs of memory impairment on cognitive tests.

The researchers used magnetic resonance microscopy (MRI) to study the brain structure of 120 volunteers, age 65 to 85, who were either cognitively normal, complained of memory problems, or had mild cognitive impairment. To detect very fine-scale changes in the brain, the team used a method known as voxel-based morphometry, a tool that has only recently been applied to detecting brain changes in neurological disease. (A voxel is the three-dimensional equivalent of a pixel.) Individual brain scans are mapped onto a standard brain template, voxel by voxel, creating a more robust average brain image. The averaged images are then compared among groups.

While previous studies have detected changes in the volume of grey matter structures in patients with mild cognitive impairment and Alzheimer’s, the voxel-based method was able to detect changes in grey matter density–a more subtle sign of the degeneration of brain tissue. Volunteers who complained of memory problems showed a three-percent loss in grey matter density, compared with healthy volunteers, while those with mild cognitive impairment showed a four-percent loss.

“We think that patients with Alzheimer’s disease and mild cognitive impairment, who show a loss in brain volume, have already lost neurons and probably other components of brain tissue,” says Saykin. “But in people with memory complaints, the decrease in density suggests an abnormality that may precede tissue loss…and suggests a promising way of using MRI in early diagnosis.”

Saykin cautions that the findings will need to be confirmed in other studies and that it’s not yet clear if those in the study with cognitive complaints will go on to develop Alzheimer’s disease. To answer this question, the researchers plan to follow the people in the study for the next five years.

Finding a way to diagnose Alzheimer’s or to assess a person’s risk of developing the disease is crucial. Several novel types of neuroprotective medicines are currently in clinical trials for the disease, and experts believe these remedies will probably be most effective as a protective measure, rather than as a treatment after significant brain damage has occurred.

The ultimate goal is for doctors to use brain imaging to monitor patients’ risk for Alzheimer’s disease (AD)–as they monitor blood pressure and cholesterol levels to prevent heart attacks. But before that’s possible, studies such as Saykin’s are needed to characterize the normal pattern of aging in the brain and the features that distinguish those who will likely develop dementia.

In the mean time, though, people shouldn’t worry if they have the occasional “senior moment.”

“Memory problems are very common as you age, so elderly people who have some memory complaints should not take this to mean that they have early AD,” says Michael Weiner, professor of radiology and medicine and an imaging expert at the University of California, San Francisco. “I don’t remember as well as I used to, and I don’t have early AD.”