Fran Lowry

July 17, 2011

July 17, 2011 (Paris, France) — Falls in older adults who are otherwise physically and cognitively healthy might be an early sign of Alzheimer's disease, according to research presented here at the Alzheimer's Association International Conference 2011.

"The results of our study indicate the importance of understanding not only the cognitive impairments associated with Alzheimer's disease, but also the motor changes that appear to come before the cognitive changes," presenting author Susan Stark, PhD, from Washington University, St. Louis, Missouri, told Medscape Medical News.

Dr. Susan Stark

"I study falls in older adults, and we know that the fall rate among older adults who have Alzheimer's disease is much higher than in adults who do not," Dr. Stark said.

There are potential cures for Alzheimer's disease, but by the time they are started, the brain has become so damaged that they are ineffective. That is why discovering the disease as early as possible is paramount, she said.

To explore whether falls come before cognitive changes in people who eventually develop symptomatic Alzheimer's disease, Dr. Stark and her colleagues examined the rate of falls in a group of healthy older volunteers who participate in the Knight Alzheimer's Disease Research Center (ADRC) at Washington University.

Researchers at the ADRC are "trying to understand what happens in the preclinical phase of Alzheimer's disease. We are fortunate to have a dedicated group of normal volunteers who, like us, want to find a cure," Dr. Stark said.

Marked Difference

The researchers followed 125 volunteers for 8 months. The mean age of the participants was 74.5 years, 63.9% were female, and most were white. All of the study subjects had been tested for the presence of amyloids, a sign of preclinical Alzheimer's, using positron emission tomography with Pittsburgh compound B (PiB).

The participants recorded the number of falls, defined as unintentional movement to the floor, the ground, or an object below knee level, every month in a journal that they sent to the researchers by mail.

The researchers controlled for factors that are known to increase the risk for falls in older individuals, including alcoholism, years of education, age, numbers of medications, and ability to perform activities of daily living.

The study showed that the fall rate among the volunteers who did not have a substantial amyloid burden was about 30% — similar to what would be seen in the general population.

But among the PiB-positive volunteers who have preclinical Alzheimer's disease, the fall rate was about 66%, Dr. Stark said.

"There was a statistically significant marked difference in the fall rates between the 2 groups," she said.

Observation of the participants is ongoing and will conclude in a year, she added.

Cognitively Normal

"These are all cognitively normal, healthy, aging people who otherwise do not look any different from us, so this hints to us that there are probably things other than the changes in the brain that are occurring that are affecting other things.

"We are trained to look for cognitive changes, but in fact there probably are other changes that are happening. In this case, it's the motor changes that are making a fall occur," Dr. Stark said.

The next step will be to increase the size of the study sample and to look at other types of imaging to learn more about falls and why they occur, she added.

"We think that there are probably other systemic issues. For example, we know that people lose a lot of weight right before they convert to having the cognitive changes we see in Alzheimer's disease, so there are other things that are probably happening. We need to understand them better so we can really see what this preclinical phase of Alzheimer's disease looks like," Dr. Stark said.

Commenting on the findings for Medscape Medical News, Maria Carrillo, PhD, senior director of medical and scientific affairs at the Alzheimer's Association, said that understanding the early signs of Alzheimer's disease is important because there might be treatments that are more effective if they are started early.

"The goal of the revised National Institute of Aging/Alzheimer's Association guidelines for the diagnosis of Alzheimer's disease is...the ability to diagnose the disease earlier and apply therapeutic interventions at that early stage to prevent dementia," she said.

Falls May Serve as a Prompt

This study is important because we now understand more fully that underlying symptoms can occur much earlier than the official diagnosis of dementia. It is really important to understand that falls may be one of those early symptoms, Dr. Carrillo added.

"Falls may trigger physicians to do other types of examinations in their patients, including psychological evaluation for potential memory issues."

Dr. William Klunk

Also commenting on the study for Medscape Medical News, William E. Klunk, MD, from the Western Psychiatric Institute and Clinic, University of Pittsburgh, Pennsylvania, said the study might lead to a better understanding of Alzheimer's disease pathology and, ultimately, facilitate earlier diagnosis.

"The thing to keep in mind is that not everyone with Alzheimer's disease presents with memory problems. Even though a patient shows up as 'asymptomatic' on cognitive testing, this study suggests that pathology is already active and that it may not be completely silent," he said in an interview.

"As a physician, these findings suggest to me that when I see a 70-year-old who has no cognitive symptoms, maybe I should be focusing more carefully on whether they've had any falls — even though these falls may not have been considered that significant — and add that to the patient's history, [which would] potentially prompt me to look a little harder for cognitive findings," said Dr. Klunk.

Dr. Stark and Dr. Carrillo have disclosed no relevant financial relationships. Dr. Klunk is coinventor of the PiB technology that is licensed to GE Healthcare by the University of Pittsburgh.

Alzheimer's Association International Conference (AAIC) 2011: Abstract 13426. Presented July 17, 2011.

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