Did you know symptoms of Alzheimer’s disease (AD) can appear nearly 20 years before the disease can be clinically diagnosed? One of those symptoms, which seems harmless and may be commonly overlooked, is getting lost, according to new research published in the April issue of the Journal of Alzheimer’s Disease.

Researchers from Washington University in St. Louis recruited 71 people to complete a virtual maze designed to assess cognitive map skills. Participants were divided into one of the three groups: people with preclinical AD or Alzheimer-related changes in the brain; people with brain and spinal fluid changes associated with AD; and people with early-stage AD. Then, they were tested on how well they could learn and follow a pre-set route, and how well they could form and use a mental map of the environment. They were given 20 minutes to either learn a specified route, or to study and explore the maze with a navigation joystick. They were then tested on their ability to recreate the route or find their way to specific landmarks in the environment.

Results showed participants with increasing difficulties navigating new surroundings was an early sign of the progressive, neurodegenerative disease.

“These findings suggest that navigational tasks designed to assess a cognitive mapping strategy could represent a powerful new tool for detecting the very earliest Alzheimer’s disease-related changes in cognition,” senior author Denise Head, associate professor of psychological and brain sciences in Arts & Sciences said in a statement.

The findings are in tune with previous studies that have shown that people with Alzheimer’s have had navigation problems early on, and are consistent with where in the brain the effects of AD first surface: the hippocampus. This is a region of the brain that plays a role in memory forming, organizing and storing, as well as the creation of mental maps.

“People with cerebrospinal markers for preclinical Alzheimer’s disease demonstrated significant difficulties only when they had to form a cognitive map of the environment — an allocentric, place-learning navigation process associated with hippocampal function,” Head said. “This same preclinical Alzheimer’s disease group showed little or no impairment on route learning tasks — an egocentric navigation process more closely associated with caudate function.”

Alzheimer’s reportedly affects more than five million Americans. It is also the sixth-leading cause of death in the U.S., according to the Alzheimer’s Association. Starting at age 65, the risk of developing the disease doubles every five years.

Beyond its small size, study limitations include lack of direct information about brain regions and networks beyond the hippocampus that play a part in spatial navigation and wayfinding. Researchers also warn that the presence of cerebrospinal fluid markers doesn’t guarantee that a person will develop full-blown Alzheimer’s later.

“Future research should examine whether cognitive mapping deficits in individuals in preclinical Alzheimer’s are associated with an increased risk of developing symptomatic Alzheimer’s,” they said.

Source: Allison S, Fagan A, Morris J, Head D. Spatial Navigation in Preclinical Alzheimer’s Disease. Journal of Alzheimer’s Disease. 2016.

This article originally incorrectly stated that Alzheimer's was the leading cause of death in the United States. It is the sixth-leading cause of death in the United States.