Alzheimer's Unease
By Donald D. Hensrud, M.D.

(FORTUNE Magazine) – A common concern I hear from patients is that they're having trouble remembering names and dates. What they're really worried about is Alzheimer's disease. Anyone who's seen someone struggling with it understands their concern. Watching someone's memory fade over time, seeing the essence of that person being extinguished, can be devastating.

Occasional memory lapses are normal, as my wife can attest after I almost forgot our anniversary. But dementia--a much more severe, progressive loss of memory and other mental skills--is something else. Although various conditions can cause dementia, Alzheimer's is responsible for more than half the cases. Alzheimer's afflicts roughly 1% of people who have reached age 65, and up to 40% of people 85 or older.

Somewhere between normal brain function and Alzheimer's is mild cognitive impairment (MCI). People with MCI have short-term memory problems but no other manifestations of Alzheimer's. They're at least ten times more likely to develop Alzheimer's than others.

Early Alzheimer's symptoms might go unnoticed if you're around someone all the time. Also, people with early cognitive problems often develop excellent coping skills for their deficits--the covert only becomes obvious when they can't find their way home.

Depression and delirium often mimic dementia, so excluding them is important before making a diagnosis. Alzheimer's can be diagnosed with certainty only by a brain autopsy; characteristic findings include plaque (protein deposits between nerve cells) and neurofibrillary tangles (twisted protein fibers within nerve cells). Even so, if a patient's symptoms are consistent with Alzheimer's and if small strokes, tumors, and other causes of dementia have been ruled out, a diagnosis can be made.

Once we suspect Alzheimer's, we take a thorough patient history with a relative present; we ask about symptoms, changes over time, and medications that can cause a dementia-like picture. A mental status exam (oral or written questions assessing different areas of thinking) can reveal cognitive problems. If more investigation is necessary, neuropsychologic testing is the next step. A physical examination sometimes detects other conditions associated with dementia, such as Parkinson's disease. Appropriate lab tests are used to exclude other causes (hypothyroidism, vitamin B12 deficiency). A CT or MRI of the brain that shows brain atrophy is indicative of dementia. In some cases, a PET scan of the brain can lead to a more accurate diagnosis.

The plaque in the brain of Alzheimer's patients is made of a type of protein (amyloid beta-protein) that seems to be responsible for memory loss. Animal studies have demonstrated that the loss is reversible when the protein is attacked by an antibody, and researchers are hard at work on this area.

Despite all the studies done to date, we still don't know what causes Alzheimer's. Besides plaques and tangles, which are probably a result rather than a cause, suspects include inflammation and oxidative stress. We also know that high levels of homocysteine, a blood protein, increase the risk. (The same holds true for a history of head injuries.) Because 30% of Alzheimer's sufferers have a family history of the disorder, a great deal of genetic research is going on. People with a blood protein called APOE-e4 have increased risk. Mutations in the genes of other proteins have also been shown to be factors in the disease. Genetic screening isn't routinely performed, but testing may assist diagnosis in select situations.

Vitamin E, the drug selegiline, and the herb ginkgo biloba have antioxidant properties; while some studies have suggested they have a mild anti-Alzheimer's benefit, others suggest not. Homocysteine can be lowered by treatment with folic acid and possibly vitamins B6 and B12, but there have been no clinical trials that show that this regimen helps prevent or treat Alzheimer's. Antihypertensive drugs, statins (Lipitor, Zocor, and others), and nonsteroidal anti-inflammatories (ibuprofen, naprosyn, aspirin) may protect against developing Alzheimer's, but do little to treat it. Wine or fish consumption seems to decrease risk, so fish may be brain food after all.

Medications help some patients with mild to moderate Alzheimer's. Donepezil, rivastigmine, and galantamine are cholinesterase inhibitors that help stabilize cognitive function and sometimes improve behavior. A vaccine showed strong potential when it reversed memory deficits and anatomic changes in mice. Unfortunately, a human trial was stopped early when a dozen of the subjects developed encephalitis. Also being explored are protease inhibitors and neural stem cells. While depression, anxiety, and sleep problems are often associated with Alzheimer's--and, to a lesser extent, MCI--it's important to be aware that they're more treatable.

Some loss of brain cells is a part of aging, but cognitive decline doesn't always occur. It's been my experience that executives, used to functioning at high levels, often overreact to occasional memory lapses. If leaving the stove on all night becomes a recurrent theme, however, it may be time to see a physician. Until breakthroughs emerge from the labs, the best Alzheimer's strategy seems to be exercising your mind as well as your body. Play bridge and do crossword puzzles. Stay stimulated and keep on learning. And if you forget your next anniversary, don't try to blame it on Alzheimer's disease.

Donald D. Hensrud, M.D., is director of the Mayo Clinic Executive Health Program. For more on this topic, go to Mayo Clinic offers Executive Health Programs in Jacksonville, Fla.; Rochester, Minn.; and Scottsdale, Ariz.