American College of Physicians: Internal Medicine — Doctors for Adults ®


Do you know what to look for in Alzheimer’s patients?

Generalists rarely catch the diagnosis. Here are some tips to help identify—and treat—the disease.

From the June 2001 ACP-ASIM Observer, copyright © 2001 by the American College of Physicians-American Society of Internal Medicine.

By Phyllis Maguire

Atlanta—While Alzheimer’s disease is one of the leading causes of death in America’s seniors, most primary care physicians don’t do a very good job of detecting it in their patients.

At an Annual Session presentation on strategies for coping with dementia and Alzheimer’s, Allan Levey, MD, cited studies showing that primary care physicians recognize only 3% of patients with mild dementia and 25% of patients suffering from more advanced stages of the disease.

While he acknowledged that time con­straints leave many physicians wondering how they can do an exhaustive history and physical exam to find Alzheimer’s in the grind of daily practice, he said that a time-consuming workup is not always needed.

“The good news for all of us is that the simplest approaches are the most effective,” said Dr. Levey, professor of neurology at Emory University in Atlanta and director of the Emory Alzheimer’s Disease Center. “Taking a careful history and an examination are the hallmarks of diagnosis. It may sound silly, but they usually are not done in patients with dementia.”

Dr. Levey gave the following advice on how to diagnose patients with Alzheimer’s disease and treat the condition.


Four million Americans now suffer from Alzheimer’s disease, which is the most common form of dementia. By the middle of this century, Dr. Levey said, up to 14 million Americans may be diagnosed with the disease.

Dementia encompasses impairment of several types of intellectual functions. Memory problems are most common, but language, visual perception and abstract judgment are also typically affected.

While memory loss is a hallmark sign of Alzheimer’s, Dr. Levey says that patients also generally lose function in language, decision-making or future planning.

In diagnosing a patient with dementia or Alzheimer’s, Dr. Levey said, physicians must distinguish dementia from normal age-associated memory impairment. He acknowledged that this can be difficult when a patient is suffering from mild stages of the disease, particularly because physicians know that a history from the patient may not be reliable.

Talking to the patient’s family members, he said, is critical to making the right diagnosis. “Five minutes with a spouse really can tell you the diagnosis in many cases,” Dr. Levey explained. Talking to family members, for example, may tell you that a patient is experiencing problems that have worsened over time.

The hallmark cognitive symptom of Alzheimer’s is memory loss. “If someone comes in with cognitive problems but a good memory, they probably do not have Alzheimer’s disease, no matter how confused they are,” Dr. Levey said.

And Alzheimer’s patients usually experience loss of function in at least one other cognitive area. Typically, they have problems with language, decision-making, planning for the future or doing calculations. Families are frequently tipped off when a patient can no longer balance a checkbook or do taxes.

Risk factors

Age is the primary risk factor for Alzheimer’s disease, Dr. Levey said. Patients with Alzheimer’s disease are typically between 40 and 90 years of age. “Strikingly,” he said, “nearly 50% of people past the age of 85 have the disease.” Age as a risk factor begins to drop once people reach age 90.

Family genetics appears to be a key risk factor. In about 5% to 10% of cases, individuals have a very early onset of familial Alzheimer’s disease due to mutations in two genes known as presenilin 1 and presenilin 2. Much more commonly, there are normally occurring polymorphisms in the gene that controls the formation of the protein apoliproprotein E-IV. These polymorphisms are associated with about 40% to 50% of cases in which the disease appears late in life.

Researchers have recently identified head injury as a risk factor. Dr. Levey said that individuals who have had a head injury severe enough to cause a loss of consciousness for 30 minutes or more are at “very high risk” of developing Alzheimer’s disease decades later.

Physicians should also monitor their patients with depression and delirium, as those conditions are high-risk factors for dementia.

Education has emerged as a controversial risk factor. Dr. Levey noted that studies around the world suggest that the more highly educated patients are, the less likely they are to develop Alzheimer’s disease.


If you cannot conclusively assess your patient’s cognitive problems in areas like memory, language and orientation, consider sending the patient for neuropsychological testing.

Dr. Levey said that neuropsychological testing is often crucial in distinguishing dementia from other conditions like depression, a common cognitive complaint that is easily treated. He pointed out that delirium, which is often an unrecognized side effect of a number of prescription drugs, should also be ruled out. And he suggested checking that patients with language problems aren’t suffering small strokes.

Don’t omit routine blood tests, Dr. Levey cautioned. “Blood tests are necessary because many simple, reversible etiologies of dementia can be discovered and treated,” he said. Although it is rare to find dementias caused by syphilis, hypothyroidism or a vitamin B12 deficiency, it is important to make sure such causes are not contributing factors.

While simple imaging cannot lead yet to a diagnosis of Alzheimer’s disease, imaging can help identify other problems. “The No. 1 thing we look for is multi-infarcts,” Dr. Levey said. “Patients with degenerative diseases are often hard to distinguish from those with multi-infarcts except through careful history.”

A CT scan or an MRI will help with a multi-infarct diagnosis. Imaging studies can also help reveal other conditions such as normal pressure hydrocephalus and subdural hematomas.

Dr. Levey said that several companies are now marketing genetic tests to use in diagnosing or forecasting Alzheimer’s disease. But he added that he believes those tests are unreliable because many patients without Alzheimer’s disease also test positive.

He also discouraged physicians from using spinal fluid and urine tests that measure levels of abnormal proteins in making an Alzheimer’s disease diagnosis. None of the tests now available, he said, have yet proven to be useful as a diagnostic aid to community physicians for dementia evaluations.


Physicians need to think about treating both the intellectual and behavioral com­ponents of Alzheimer’s disease, Dr. Levey said.

The major structural changes brought about by dementia lead to the destruction of three major neurotransmitters: glutamate, acetylcholine and serotonin. Acetylcholine, which is crucial to learning and memory, is released across nerve synapses.

Because acetylcholine is degraded by the enzyme acetylcholinesterase, acetylcholinesterase inhibitors such as donepezil, rivastigmine and galantamine can improve cognitive symptoms in patients with Alzheimer’s.

Families of patients who begin acetylcholinesterase inhibitor treatment, however, often return in a month or two and claim that the drugs are not working. Dr. Levey said physicians should not be put off by what may seem like a lack of response.

While he acknowledged that improvements may be small, he explained that changes occur after one and even two years of the therapy. He said that the treatment allows patients to function better or maintain their ability to function even as their disease progresses.

While patients taking acetylcholinesterase inhibitors may continue to experience some cognitive decline, they become even more impaired when the medicines are discontinued. “Studies find that if you stop the medicine,” Dr. Levey said, “patients may fall off the cliff.” Studies have also shown that when patients stop taking the medicine and then restart it more than three or four weeks later, they don’t regain former benefits.

“When someone has progressed to later stages of the disease, you may wonder about the wisdom of continuing these expensive medications,” he said. “I’m increasingly influenced by the fact that the drugs help prevent behavioral problems. In addition, if patients have been on these drugs for a while and you take them off, their status may plummet and new behavioral problems develop.”

Dr. Levey also said that Alzheimer’s patients can benefit from therapeutic neuroprotection in an effort to slow down the progress of the disease. “Several years ago, we couldn’t really think of doing that realistically,” Dr. Levey said. “Now we have evidence that even very simple things like vitamin E can slow Alzheimer’s disease down.” New drugs for neuroprotection are now in research phases.

And while patients often suffer extensive cognitive problems, their families are typically more distressed by behavioral issues. Between 30% and 40% of Alzheimer’s patients experience psychiatric symptoms such as delusions, hallucinations and agitation, Dr. Levey explained.

Cholinesterase inhibitors can be used to address behavioral problems. While physicians used to use these treatments primarily to prevent the emergence of behavioral problems in patients with mild or moderate Alzheimer’s, he said that the drugs are now being used for patients in advanced stages of the disease when such problems become more prevalent.

Dr. Levey also pointed out that while traditional antipsychotics have been used extensively to treat Alzheimer’s patients, they are usually not effective and can cause side effects. Newer atypical antipsychotics appear to be more useful for psychosis in Alzheimer’s disease.


Finally, physicians need to play another critical role in treating Alzheimer’s patients: educating families and caregivers.

“In this disease,” Dr. Levey said, “education is as important and as effective as medicine in keeping people out of nursing homes.” He suggested referring patients and their caregivers to the national and local chapters of the Alzheimer’s Association (

Physicians should also remember that about half of Alzheimer’s caregivers—many of whom are also their patients—are going to experience clinically significant depression as a result of caring for someone with the disease.

Physicians need to treat their depression, he said, before their impairment compromises their ability to care for a loved one.


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