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Even Mild Infections Hasten Decline With Alzheimer's

They speed memory loss as much as 10-fold, researchers find,,

MONDAY, Sept. 7 (HealthDay News) -- For people with Alzheimer's disease, even a minor infection can double the rate of memory loss, British researchers report.

In this new study, researchers found that Alzheimer's patients who had respiratory, gastrointestinal or other infections -- even minor bumps and bruises -- can have high levels of tumor necrosis factor-alpha (TNF-a), in their blood. TNF-a is a protein linked to inflammation, and has been associated with memory loss or other types of cognitive decline.

"Illnesses that we normally consider to be of little consequence in the healthy aged person need to be taken more seriously in patients with Alzheimer's disease," said lead researcher Clive Holmes, from the Clinical Neurosciences Research Division at the University of Southampton in the U.K.

"Short-lived illnesses or conditions that cause inflammation outside the brain are associated with a marked decline in memory function in patients that have Alzheimer's disease. This decline is not a temporary effect, and remains after the illness has resolved," he added.

The report is published in the Sept. 8 issue of Neurology.

For the study, Holmes and colleagues looked at blood tests and cognitive ability in 222 Alzheimer's patients. The researchers measured these factors at the start of the study and three more times during the trial.

In addition, caregivers reported any infections or accidental injuries suffered by the patients during that time.

Over the six months of the study, 110 people had an infection or injury that resulted in inflammation. These people had memory loss at twice the rate of those who did not have infections or injuries, the researchers found.

Memory loss among patients with high TNF-a levels at the start of the study was four times greater than among patients with low TNF-a levels.

"The effect of these illnesses on memory function is most marked in subjects who also have existing chronic inflammatory conditions," Holmes said. "Here, the rate of memory decline is 10-fold. We believe the signal is coming from these illnesses and being sent to the brain by TNF-a, a protein known to be associated with a range of inflammatory conditions," he said.

For those whose TNF-a levels were high at the start of the study, an infection increased their memory loss 10 times over those who had low TNF-a levels, the study authors found.

Greater care is needed to prevent these conditions occurring in people with Alzheimer's disease, Holmes said.

"Thus the use of influenza vaccinations should be encouraged, and early treatment of infections may reduce the deleterious effect of these infections," he said.

"Finally, the development of drugs or lifestyle changes, such as moderate exercise that has been shown to reduce TNF-a in patients with Alzheimer's disease, are worth examining for their beneficial effects on slowing down the disease process," Holmes said.

Greg M. Cole, associate director of the Alzheimer's Disease Research Center at UCLA David Geffen School of Medicine, said this is a very interesting study associating episodes of infectious disease with increases in a pro-inflammatory molecule in blood and rates of cognitive decline in people who already have Alzheimer's disease.

"Like all association studies, it does not prove causal relationships," Cole said. "However, it makes some sense because the molecule they measure in blood, TNF-a, is known to traffic from the blood to trigger increased brain inflammation in animal models, and has been a candidate target for disease intervention," he said.

However, common anti-inflammatory medications, such as Celebrex or Aleve, have generally failed to slow disease progression in clinical trials, Cole said.

"This study raises the question of whether or not anti-inflammatory drugs in previous and perhaps future trials may have been or may be more helpful in the subset of dementia patients with other conditions causing inflammation outside the brain," he said. "If this is true, it might help explain why people taking anti-inflammatory drugs for systemic inflammatory diseases appear to have less risk for getting Alzheimer's."

Maria Carrillo, director of medical and scientific relations at the Alzheimer's Association, noted that TNF-a is not the only protein involved in inflammation and cognition.

"This study tells us that inflammatory processes are involved in cognition," Carrillo said. "TNF-a could be a therapeutic target, but there are other neuromodulators out there that are therapeutic targets," she said.

More information

For more information on Alzheimer's disease, visit the Alzheimer's Association.

SOURCES: Clive Holmes, MRCPsych, Ph.D., Clinical Neurosciences Research Division, University of Southampton, U.K.; Greg M. Cole, Ph.D., neuroscientist, Greater Los Angeles VA Healthcare System, and associate director, Alzheimer's Disease Research Center, UCLA David Geffen School of Medicine; Maria Carrillo, Ph.D., director, medical and scientific relations, Alzheimer's Association; Sept. 8, 2009, Neurology

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