More than the usual forgetfulness

Mild cognitive impairment often stays mild, but it can "progress" to Alzheimer's disease.

Some difficulty with remembering things (like names) and forgetting where you put things (like keys) is so typical that it's considered a normal part of aging. Just as hair thins and joints become less flexible, the brain processes information more slowly in our later years.

But some people experience a middle ground of cognitive impairment that's worse than normal age-related problems but not as bad as dementia from Alzheimer's disease or other brain diseases. Researchers labeled this intermediate state "mild cognitive impairment" in the 1980s, and the name stuck.

Mild cognitive impairment stays mild in many cases. At the same time, studies have shown that people with the condition are about three times more likely to develop full-blown dementia than those without it. The problem is that doctors really don't yet have a reliable way of predicting who is going to "progress" to dementia and who isn't. Moreover, memory impairment is a symptom of many conditions that affect older people that are unrelated to Alzheimer's disease. Depression is the prime example.

The FDA hasn't approved any medications for mild cognitive impairment. Controlling cardiovascular risk factors, like high blood pressure and cholesterol, is often recommended. It's an open question whether it helps to use visualization and other memory aid techniques. On the other hand, there's probably no harm in trying them. Getting more exercise is also a can't-hurt, might-help proposition.

Is this normal?

It's often difficult to distinguish normal age-related memory loss from mild cognitive impairment. In an article in The New England Journal of Medicine in 2011, Dr. Ronald C. Petersen, a Mayo Clinic neurologist and researcher, said that one way to tell the difference is that people with mild cognitive impairment increasingly have lapses about significant events and obligations that they would have previously remembered without difficulty. Appointments and telephone conversations slip their minds. The avid sports fan might not remember the outcome of a big game.

People with mild cognitive impairment are often aware of their memory problems, but self-reporting can be unreliable. Worriers may fret that they're impaired when they're experiencing completely normal forgetfulness, while others with true problems may try to bluff their way through them. A person's growing forgetfulness is often most apparent to those who know her or him well; those who are less familiar may not notice the subtle compensations a person makes.

Another complication is that experts have broadened the definition of mild cognitive impairment to include two types: the forgetting, or "amnestic," variety that's most common, but also "nonamnestic" impairment that affects cognitive abilities other than memory, including use of language, attention span, and spatial sense. Nonamnestic deficits may be early symptoms of degenerative brain diseases other than Alzheimer's disease.

By definition, people with mild cognitive impairment, regardless of their particular blend of deficits, are able to handle the tasks of day-to-day living (although perhaps with less efficiency than they used to) and, for the most part, live independently. If the deficits get so severe that the person can't manage activities like shopping, preparing meals, and paying bills, then cognitive impairment is no longer mild, and dementia is a possibility.

Evaluation

By briefly discussing current events or family matters with a patient, a doctor can sometimes get a sense of the person's memory and cognitive shortcomings. Information from family members and loved ones is extremely important. Doctors may also ask brief, standardized sets of questions for an assessment of a patient's deficits. The questions might require the patient to recall a short list of unrelated words, perform some simple mathematical calculations, identify the first and current presidents, and so on. More elaborate questionnaires, usually administered by specially trained psychologists, can be useful. But that kind of neuropsychological testing is usually reserved for a handful of patients.

If someone is having serious memory problems, a careful evaluation needs to consider the many possible (and often quite treatable) causes, including depression, side effects from medications, and thyroid problems. A CT or MRI scan may be ordered as part of a complete workup.

Will it become Alzheimer's?

The optimistic way of looking at the numbers is that over 50% of people with mild cognitive impairment do not develop Alzheimer's disease. In some, the pathological processes that cause Alzheimer's move slowly, or they have brains that still function relatively well in spite of them. Another possibility is that impairment reflects something besides Alzheimer's (depression, for example). Plus, a certain percentage of people are going to die from other causes before Alzheimer's fully develops.

But there are also gloomier ways to spin the numbers. About 1% to 2% of the general population develops dementia every year, but among those with mild cognitive impairment, it's 5% to 10%. A 2009 review paper estimated that 7% of those with mild cognitive impairment convert to Alzheimer's disease each year.

Treatment

High doses of vitamin E were proposed as a way to keep mild cognitive impairment from becoming full-blown dementia, but a major clinical trial showed this approach was no better than placebo. Donepezil (Aricept) and the other cholinesterase inhibitors have also foundered in clinical trials.

Controlling high blood pressure and other cardiovascular risk factors is suggested because diseased blood vessels and atherosclerosis are also responsible for a certain percentage of mild cognitive impairment and dementia. But there isn't clinical trial evidence yet that doing so translates into a lesser chance of dementia for mild cognitive impairment patients.

There are techniques for improving memory. Many involve conscious efforts to create mental associations between what you're trying to remember and other information. When these techniques and other "cognitive interventions" have been tested in people with mild cognitive impairment, the results have been uneven, but a review published in 2010 suggested they can perhaps help with memory and mood.

What's in store

If you could be sure that your shaky memory wasn't going to get much worse, would it bother you? Maybe not so much. It's the prospect of Alzheimer's disease, or some other type of dementia, that's frightening. Researchers (and private companies) are looking for tests that would, if not make a definite prediction, at least give some sense of the risk of developing Alzheimer's. PET scans that detect beta-amyloid protein deposits in the brain, which are believed to play a critical role in causing the disease, may be available soon. Tests that analyze proteins in the spinal fluid are another possibility.

But without treatment, even the best tests will be of limited use. Many people might prefer not to know that Alzheimer's is likely to be their fate if there's little, if any, chance of altering it. But the hope is that identifying high-risk individuals will reveal more about the underlying causes of Alzheimer's so effective treatments will, at last, be available.