Years Before Alzheimer’s, the Brain Shows Signs of Change

April 17, 2007

April 17, 2007

Men and women who develop Alzheimer’s disease may show changes in the structures of their brains years before memory loss or other symptoms arise, researchers report. These brain changes may help to identify people at risk of developing mild cognitive impairment, or MCI, a transitional and moderate stage of memory loss that sometimes progresses to Alzheimer’s disease. The findings appeared in Neurology, the scientific journal of the American Academy of Neurology.

Researchers at the University of Kentucky College of Medicine in Lexington performed brain scans and memory tests on 136 seniors aged 65 and older. All had intact memory and brain function at the start of the study. Over the next five years, study participants were given annual nervous system exams and tests to measure mental status and memory. By the end of the study, 23 people had developed mild cognitive impairment, and nine of the 23 went on to be diagnosed with Alzheimer’s disease.

The brain scans of the 23 people who developed memory problems were then compared to the 113 people who remained mentally alert. Compared to the group that didn’t develop memory problems, the 23 people who developed mild cognitive impairment or Alzheimer’s disease had less gray matter in key areas of the brain that process memories. The brain changes were present even at the beginning of the study, when none of those tested appeared to be showing any memory loss or cognitive deficits.

“We found that changes in brain structure are present in clinically normal people an average of four years before MCI diagnosis,” said study author Charles D. Smith, MD. “We knew that people with MCI or Alzheimer’s disease had less brain volume, but before now we didn’t know if these brain structure changes existed, and to what degree, before memory loss begins.”

Problems Appear Early

The study also found that individuals destined to develop MCI had lower cognitive test scores at the beginning of the study compared to the group that didn’t develop memory problems, even though these scores were still within normal range.

“These findings of structural changes in cognitively normal people before memory loss begins aren’t surprising given [the idea that the precursors of] Alzheimer’s disease may be present for many years before symptoms of the disease begin to appear,” said Smith.

The findings are also consistent with earlier reports showing that brain changes and subtle signs of cognitive loss may develop years before a diagnosis of Alzheimer’s disease. In a study published last year, investigators at Dartmouth Medical School reported that some older men and women who complain of “senior moments” may be losing brain cells along with their memory. [See the article, “Memory Deficits Linked to Brain Loss.”] The researchers found that seniors who complained of memory loss, despite scoring normally on standard memory tests, showed a measurable decrease in the density of their gray matter, a part of the brain essential for thinking and memory.

In an earlier report, Swedish researchers found that subtle signs of memory loss may appear in men and women a decade before Alzheimer’s disease is officially diagnosed. [See the article, “Signs of Alzheimer’s May Be Present 10 Years Before Diagnosis.”]

The data support an emerging consensus among doctors that most people show subtle mental and memory deficits years before Alzheimer’s disease is diagnosed. It is important to recognize, however, that mental decline can be caused by many other conditions and circumstances unrelated to Alzheimer’s.

Still, further study of what goes wrong in the earliest stages of memory loss  might one day lead to diagnostic tests to identify impending Alzheimer’s at a very early stage. Currently, drugs used to treat Alzheimer’s may ease symptoms for a time but do nothing to stop the relentless downward spiral of underlying illness. Medications, including new ones on the horizon, may be most effective in the earliest stages of memory loss, before damage to healthy brain cells has become extensive, highlighting the need for new diagnostic tools.

The findings also highlight the importance of cognitive complaints in older adults, and suggest that those who complain of significant memory problems should be evaluated and closely monitored over time. Memory complaints, a cardinal feature of MCI, which confers high risk for Alzheimer’s disease, are reported in up to half of the older adult population.

The Fisher Center for Alzheimer’s Research Foundation has played a leading role in funding research into the underlying causes of Alzheimer’s disease. Only through continued research can we learn more about what goes wrong in the brain in Alzheimer’s disease, and what we can do to treat and cure it. To learn more, visit www.ALZinfo.org.

By www.ALZinfo.org, The Alzheimer’s Information Site. Reviewed by William J. Netzer, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.


C.D. Smith, MD; H. Chebrolu, MSEE; D.R. Wekstein, PhD; et al: “Brain Structural Alterations Before Mild Cognitive Impairment.” Neurology, Volume 68, April 17, 2007, pages 1268-1273.


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