Few of us would be eager to have a future of dementia revealed to us while we are still sharp. But there are powerful arguments for knowing -- as early as possible -- if we are at risk.
True, there is currently no medication that can slow or reverse Alzheimer's disease. But more and more research suggests that long before dementia sets in, nearly imperceptible changes are happening in the brain. Researchers believe that the key to bending dementia's arc will be to intervene either before behavioral symptoms set in or when they are still very mild.
And if researchers are to find therapies for dementia that work, they will need clinical trial participants who are brave enough both to learn they are at risk early and to submit to experimental treatments.
A new study, published Wednesday in the journal Neurology, distills a way for physicians and their patients, in the course of a regular office visit, to measure an individual's risk of developing mild cognitive impairment, or MCI. In a population of 1,449 Minnesotans 70 to 89 years old, the resulting algorithm helped identify individuals whose scores were in the top 25% and who were more than seven times more likely to develop MCI than those in the bottom quartile of risk.
Patients diagnosed with MCI are at greatly increased risk for Alzheimer's disease: studies suggest that each year, 10% to 15% of those with MCI will progress to Alzheimer's. So knowing one's risk for developing MCI may be one of the earliest ways to detect future Alzheimer's patients at a point when still-experimental therapies might work.
"This risk scale may be an inexpensive and easy way for doctors to identify people who should undergo more advanced testing for memory issues or may be better candidates for clinical trials," said Dr. Ronald C. Petersen, a neurologist at the Mayo Clinic in Rochester, Minn., and lead author of the study.
Until now, the most powerful single marker for Alzheimer's disease risk has been whether an individual is a carrier of a specific variation of the APOE-4 gene. The current study finds that a person's APOE-4 carrier status can further refine his or her risk for mild cognitive impairment. But the risk measure devised here also takes into account other contributors to risk that can be easily gleaned during an office visit.
For men and women alike, a diagnosis of diabetes contributes powerfully to the risk of developing mild cognitive impairment, particularly if the individual is younger than 75 and has developed the metabolic condition already. Two other hefty contributors to MCI risk are high levels of agitation, anxiety or apathy, as measured by a patient's response to a battery of neuropsychiatric questions.
A history of alcohol problems, self-reported memory problems and failure to complete at least 12 years of education also contribute to a man or woman's risk of MCI. And a history of stroke or atrial fibrillation nudged risk scores up modestly.
Some risk factors are specific to a patient's gender.
For women, being a current smoker, or having had worrisome cholesterol numbers, high blood pressure or diabetes in midlife drive risk of MCI higher.
For men, being widowed or having never married raises MCI risk. And having been obese at anytime (body mass index of 30 or above) also drive up the likelihood of MCI. In men, walking carefully or unsteadily -- slow gait -- also raises risk.
When added to this constellation of risk measures, APOE-4 carrier status proved only to confer moderately increased risk of developing mild cognitive impairment.
In an accompanying editorial published in Neurology, Dr. Timo Grimmer and Alan B. Zonderman cautioned that, until the current findings have been replicated in a larger and more ethnically and educationally diverse sample, physicians would be "well advised to utilize the risk score with caution."
But Grimmer, an Alzheimer's disease researcher, and Zonderman, a cognitive neuroscientist at the National Institutes of Health, said the study offers physicians and their patients some key guidance on how to lower risk of dementia, starting in midlife: for women, avoid or stop smoking, and for men, stay trim.
For both sexes, the latest research underscores the importance of keeping alcohol consumption moderate or quitting altogether. And at all costs, head off the development of type 2 diabetes, a metabolic condition closely linked to obesity.