In March of 1999, Dr. Ron Petersen and his colleagues published a paper proposing criteria for a diagnosis of Mild Cognitive Impairment. The paper was simply meant to describe what they were seeing in their clinic, he says, and to propose a diagnostic template as a starting point. The resulting discussion has been intense, with over 2100 published papers citing his original paper.
The term Mild Cognitive Impairment (MCI) is used to describe a mild level of memory loss that is somewhere between normal aging and dementia. It does not specify what might be causing that memory loss. Scientists believe that potential treatments to prevent Alzheimer’s and other dementias will be most effective at this stage (or even earlier), so there is a lot of interest in improving our understanding of MCI.
Ten years after publication of his original paper, Dr. Petersen, who is Director of the Mayo [Mayo Clinic] Alzheimer’s Disease Research Center, gave the first day’s keynote address at the 7th annual Mild Cognitive Impairment Symposium. Dr. Petersen’s talk was a comprehensive overview of the progress towards understanding MCI, and an assessment of the work still to be done. Here’s a summary of his presentation:
Diagnosis of MCI
In a 2003 conference, researchers agreed on revisions to Dr. Petersen’s original criteria for a diagnosis of Mild Cognitive Impairment. But debate on those criteria continues. Do patterns on brain scans indicate MCI? Which neuropsychological tests are best? What cutoff scores should be used? Can agreement be reached on a quantitative step-by-step procedure doctors can use to reliably diagnose MCI?
A standard diagnostic procedure would help ensure uniformity in clinical trials of treatments for people with MCI. For individual patients, results from any standard procedure should be considered along with other information, rather than interpreted as a definitive diagnosis.
How many people have MCI?
Estimates of how many people over age 65 have MCI vary, but on average, studies have shown the percentage to be in the teens. As the world’s population ages, these estimates are becoming more important.
Do people with MCI develop dementia?
It’s unclear how many people with MCI go on to develop Alzheimer’s and other dementias. Some diagnosed with MCI stay about the same, and some improve instead of getting worse. At Mayo, between 10 and 15 percent of patients diagnosed with MCI develop dementia each year, but in the general population, the rate is between 7 and 10 percent.
Researchers are investigating ways to predict which MCI patients will develop dementia. Patients may be at increased risk if they carry the APOE4 gene variation. The levels of certain proteins in spinal fluid or rapid shrinkage in certain areas of the brain may also be indicators, along with the type and severity of memory decline. Unusual brain activity patterns seen on functional MRIs are linked to the risk of developing dementia.
Finally, the amount of the amyloid protein associated with Alzheimer’s, as shown by new PET scans of the brain, may be helpful in predicting who will develop dementia. About 40 percent of people with MCI don’t have a large amyloid buildup, though, maybe because their memory problems are caused by a non-Alzheimer’s condition such as vascular disease or Lewy body disease.
Studies underway now will provide evidence about how well these factors can predict cognitive decline. They include:
- The Alzheimer’s Disease Neuroimaging Initiative, a study tracking some of these indicators for 200 people with Alzheimer’s, 400 with MCI and 200 with “normal” memory
- A Mayo Clinic study measuring memory loss and collecting the results of MRI scans, blood tests, genetic information and other data for two to three thousand residents of Olmsted County, Minnesota, age 70-89.
Can treating people with MCI prevent dementia?
Multiple trials of treatments for MCI over the past few years have had negative results. Most of these trials involved Alzheimer’s drugs. MCI patients taking the drugs did no better on cognitive tests than those taking placebos.
In some of these studies, the memory and thinking of people taking placebos did not decline as much as expected, making it harder to show that a treatment was effective. Perhaps efforts to standardize diagnostic criteria and better estimate how many people with MCI will develop dementia will reduce this problem in future trials.
The flurry of studies and papers in the last ten years has improved scientists’ understanding of mild memory loss, but a lot of questions remain. Researchers still face significant challenges before the goal of early diagnosis and treatment can be met.