High BDNF Levels May Offer Protection Against Alzheimer’s

It appears that higher blood levels of brain-derived neurotrophic factor (BDNF) may be able to protect people against development of Alzheimer’s disease and other types of dementia, according to a study published online November 25 in JAMA Neurology .

BDNF is widely expressed throughout the central nervous system, especially in the cerebral cortex and in the brain’s memory seat—the hippocampus. Moreover, researchers found a link between low blood levels of BDNF and a smaller hippocampus and poorer memory in older dementia-free adults. In light of these previous findings, Sudha Seshadri, M.D., a professor of neurology at Boston University, and colleagues conducted a study to see whether blood levels of BDNF might influence the risk for Alzheimer’s or other types of dementia.

Their study included more than 2,000 individuals aged 60 or older (average age 72) in whom blood levels of BDNF were measured. Subjects were then followed for a decade to determine whether any of them developed Alzheimer’s disease or another type of dementia.

A total of 117 subjects developed Alzheimer’s, while 23 developed another type of dementia. The researchers then assessed whether there were any correlations between subjects’ BDNF levels and their risk for Alzheimer’s or other types of dementia, while taking potential confounders—for example, age, gender, education, blood pressure, history of cardiovascular disease, diabetes, smoking status, and APOE-e4 status—into consideration.

Such correlations did in fact appear. Each standard-deviation increment in BDNF was associated with a 33 percent lower risk for developing Alzheimer’s or another dementia. Compared with the bottom quintile, BDNF levels in the top quintile were associated with less than half the risk for Alzheimer’s or dementia. However, these links were restricted to men and women over age 80, women under age 80, and individuals with a college education or graduate degree.

Thus, the researchers concluded, “Higher serum BDNF levels may protect against future occurrence of dementia and Alzheimer’s.”

“This is a potentially important study from the perspective of reducing the risk of dementia,” Dilip Jeste, M.D., chair in aging at the University of California, San Diego, and immediate past APA president, told Psychiatric News. “BDNF has been previously shown to be related to lifestyle factors and interventions. One study even reported an increase in BDNF in individuals with schizophrenia who received cognitive enhancement therapy. Continued research on BDNF and related neurotrophic factors in people at risk of dementia is necessary to help develop interventions to treat and prevent cognitive deficits in older adults,” Jeste said.

“This study highlights the beneficial neuroprotective effects of BDNF, especially for women, individuals with college degrees, or those who have lived past 80 years, and the possibility that serum BDNF could one day be a ‘blood test’ biomarker for the risk for developing dementia and Alzheimer’s disease,” geriatric psychiatrist Mohit Chopra, M.D., a lecturer in psychiatry at Harvard Medical School, said in an interview.

This is indeed an eventuality, Seshadri agreed. Giving BDNF to older people might prevent or counter Alzheimer’s symptoms, she suggested. “We need to study the benefits and potential side effects of giving BDNF to people. Ways of doing this—such as using agonists that would cross the blood-brain barrier into the brain—are being studied. “

Interestingly, lithium, long used in the treatment of bipolar disorder, has been found to increase BDNF levels in individuals with Huntington’s disease, Seshadri pointed out. So there is reason to believe that if lithium increases BDNF levels, then it might also possess some effectiveness against Alzheimer’s, she indicated. Preliminary evidence reported in the May 2012 Drugs and Aging bolsters this possibility.

Finally, there is something that people can do on their own to increase their BDNF levels and possibly, as a result, lower their risk for Alzheimer’s, Seshadri and colleagues suggested in their study report. And that is to exercise, because “BDNF levels can be elevated through simple lifestyle measures such as increased physical activity.”

She and her team will continue to conduct research in this domain, Seshadri said. “We plan to look at BDNF in younger individuals, average age 45, to see if it affects cognition at that age as well. And we will explore the mechanisms, genetic and otherwise, that may underlie BDNF’s impact on Alzheimer’s and dementia.”

The study was funded by the National Institutes of Health. ■

An abstract of “Serum Brain-Derived Neurotrophic Factor and the Risk for Dementia” is posted at http://archneur.jamanetwork.com/article.aspx?articleid=1779513.