Reduced volume, or atrophy, in parts of the brain known as the amygdala and hippocampus may predict which cognitively healthy elderly people will develop dementia over a six-year period, according to a study in the January issue of Archives of General Psychiatry, one of the JAMA/Archives journals.

New strategies may be able to prevent or delay the onset of Alzheimer's disease (AD), the most common cause of dementia among older adults, according to background information in the article. Accurate methods of identifying which people are at high risk for dementia in old age would help physicians determine who could benefit from these interventions. There is evidence that adults with AD and mild cognitive impairment, a less severe condition that is considered a risk factor for AD, have reduced hippocampal and amygdalar volumes. However, previous research has not addressed whether measuring atrophy using magnetic resonance imaging (MRI) can predict the onset of AD at an earlier stage, before cognitive symptoms appear.

Tom den Heijer, M.D., Ph.D., of the Erasmus Medical Center, Rotterdam, the Netherlands, and colleagues used MRI to assess the brain volumes of 511 dementia-free elderly people who were part of the Rotterdam Study, a large population-based cohort study that began in 1990. They screened the participants for dementia at initial visits in 1995 and 1996 and then in follow-up visits between 1997 and 2003, during which they asked about memory problems and performed extensive neuropsychological testing. The authors also monitored the medical records of all participants. During the follow-up, 35 participants developed dementia and 26 were diagnosed with AD.

People with severe amygdalar or hippocampal atrophy had the highest risk of developing dementia or AD over the course of the study, which followed participants for an average period of six years. "Concerning the extent of atrophy, we found in those destined to develop dementia volume reductions between 17 percent and 5 percent, depending on how long before the diagnosis of dementia the MRI was conducted," the authors report. "In persons with mild to moderate Alzheimer disease, volume reductions compared with healthy elderly persons are between 25 percent and 40 percent, suggesting that atrophy rates accelerate in patients with Alzheimer disease."

"Our study suggests that structural brain imaging can help identify people at high risk for developing dementia, even before they have any memory complaints or measurable cognitive impairment," they write. "However, we must bear in mind that most people with atrophy did not develop dementia, even after six years. Further prospective population studies are therefore required to find additional biomarkers, including other brain imaging parameters, that alone or in combination with clinical and genetic characteristics can help separate those who are at risk for developing dementia from those who are not."

(Arch Gen Psychiatry. 2006;63:57-62)

Editor's Note: This research was financially supported by the Netherlands Organisation for Scientific Research and the Health Research and Development Council, The Hague, the Netherlands.

Monique M. B. Breteler
m.breteler@erasmusmc.nl
JAMA and Archives Journals
www.jamamedia.org