There’s no mistaking that Alzheimer’s disease poses a major threat: Some 5.3 million Americans live with the disorder—a number likely to double over the next 20 years as baby boomers age.

Well aware of that, a team of Johns Hopkins psychiatrists has spent years teasing out which early patient symptoms foreshadow an Alzheimer’s diagnosis. Certain signs of functional loss (problems driving, forgetting to pay bills) or slips in cognition (word loss, forgetfulness) seem most reliable.

Now, growing evidence suggests that psychiatric (behavioral) symptoms can also be Alzheimer’s predictors. “For many years, we’ve been working backward—treating Alzheimer’s as a purely cognitive disease,” says Paul Rosenberg, associate director of the Johns Hopkins Memory and Alzheimer’s Treatment Center. “But behavioral changes can be widespread and disabling,” and pose the greatest challenge to caregivers.

“So, when I hear a spouse say, ‘My husband has never been a worrier, and now he frets over everything,’ or, ‘He used to be interested in everything and now has no get-up-and-go,’ I have good reason to think Alzheimer’s is involved.”

The scenario is common enough that Johns Hopkins scientists, working with an international consortium, have coined the term “mild behavioral impairment” (MBI) to describe neuropsychiatric symptoms that can accompany, and possibly even predate, Alzheimer’s cognitive lapses.

In recent clinical studies, Rosenberg, Memory Center Director Constantine Lyketsos and colleagues used the Neuropsychiatric Inventory Questionnaire to reveal trends in several psychiatric symptoms. For example, they found newly irritable or apathetic seniors 30 to 40 percent more likely to develop Alzheimer’s. “It wasn’t so surprising seeing MBI in people already mildly cognitively impaired,” says Rosenberg, “but that risk also applies to those who appear cognitively fine.” 

The biology underlying Alzheimer’s behavioral symptoms is far from clear. But, surely, damage to specific nerve circuits is involved. And they likely overlap other, better-known Alzheimer’s pathways, Rosenberg adds, such as those for salience—the ability to judge something’s importance.

As for therapy, present research hopes to shed light on how behavioral interventions work. For now, to alleviate symptoms, Rosenberg favors lifestyle changes, like stress reduction programs, yoga and exercise, over traditional psychiatric approaches. 

Rosenberg’s “big-picture dream,” is to nail down who’s at risk for Alzheimer’s. “Our best chance of making a difference,” he says, “is to assess as early as possible.” The near future should bring far fewer expensive brain scans and pedigree searches. Instead, he says, “We expect to combine cognitive tests, gene assays and other low-tech ways to diagnose Alzheimer’s.”

Detecting mild behavioral impairment, of course, will be part of the mix.