Sep 252013
 

British scientists recently reported finding signs of the gum-disease bacterium toothbrush (P. gingivalis) in the brains of Alzheimer’s patients. The new study is being widely reported as adding to a growing body of evidence linking periodontal (gum) disease to an increased risk for Alzheimer’s disease.

However, such data needs to be considered very carefully.

In fact, what the study found was that substances on the surface of the bacterium (lipopolysaccharides) were present in the brain tissue of four out of 10 recently deceased people who had Alzheimer’s. It was found in zero out of 10 age-matched patients who did not have Alzheimer’s. The bacteria itself was not found in the brain tissue of any people.

The theory behind linking gum disease with Alzheimer’s is that the presence of gum bacteria lipopolysaccharides in the brain may cause inflammation. This in turn could trigger a biological cascade that may be linked to the brain changes associated with Alzheimer’s disease.

We already know that P. gingivalis is commonly found in chronic periodontal (gum) disease, and, if there is significant dental disease, it can enter the bloodstream through such everyday activities as eating, brushing teeth and invasive dental treatments. While in the bloodstream, the bacteria can settle on heart valves and damage them. Hence, patients with mitral valve prolapse and other heart anomalies often take an antibiotic before dental procedures to prevent the bacteria from depositing within the heart. However, no bacteria have been reported in the brains of patients with gum disease, as the brain is an immunologically, well-protected organ, more so than any other.

It is important for readers to know that these types of studies show an association between gum disease and Alzheimer’s disease, but do not prove causation. For example:

  • The number of subjects is extremely small to make a definitive conclusion, and the finding could have occurred simply by statistical chance.
  • Only four out of 10 subjects with Alzheimer’s had such changes, not 10 out of 10. If the gum disease was causative, one would expect more than just a minority of patients exhibiting the lipopolysaccharides.
  • Finally, what if very early stage dementia caused people to actually brush their teeth less often, or altered their dietary intake? They would be at risk of developing gum disease. But the gum disease would have resulted from the early dementia, not vice versa.

It is also important to note that previous studies have shown links between gum disease and other illnesses, including heart disease and certain forms of cancer; these findings are not specific to Alzheimer’s.

The study is important and should be followed up with larger sample sizes, but given the above limitations, the study does not show that “brushing teeth reduces the risk of dementia” or that “gum disease can lead to dementia.”

Thanks for reading.

Michael S. Rafii, M.D., Ph.D.

Director, Memory Disorders Clinic
Associate Medical Core Director, Alzheimer’s Disease Cooperative Study
University of California San Diego

This post originally appeared in Alzheimer’s Insights, an ADCS Blog.

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Nov 152011
 
AB Plaque

Gantenerumab, an antibody that binds to beta-amyloid, clears plaques in a matter of months, report scientists at F. Hoffmann-La Roche Ltd., Basel, Switzerland, in a study published online in Archives of Neurology.

The Phase I study of 16 Alzheimer’s patients tested gantenerumab at two doses against a placebo over six months of treatment. Senior author Luca Santarelli and colleagues used positron emission tomography (PET) scans to visualize and compare levels of amyloid plaques in the brain before and after intravenous antibody treatments, and found the decreases. The current study did not evaluate cognition. Many researchers suspect the build-up of such plaques may be a cause of this memory robbing disease.

There are, in fact, almost a dozen anti-beta-amyloid antibodies in clinical testing, including solanezumab, developed by Eli Lilly and Company, Indianapolis, Indiana, which, along with bapineuzumab, is furthest along in clinical development.

An earlier small study of the Elan Pharmaceuticals/Wyeth antibody bapineuzumab (now developed by Janssen Alzheimer Immunotherapy, Dublin, Ireland) also used PET scans to compare plaque levels in the brain before and after intravenous antibody treatment. This antibody lowered brain amyloid levels in Alzheimer’s patients by an average of 8.5 percent over 18 months, compared with a 16.9 percent increase in untreated patients.

In the current study, 18 patients, aged 50-90, who had mild to moderate Alzheimer’s disease, received either placebo or gantenerumab (60 mg or 200 mg) in up to seven monthly intravenous infusions. At the end of the study, PET scans indicated that the six patients in the low-dose group lost 15.9 percent of their plaques, while the six in the high-dose group dispatched 35.7 percent. If this holds up, it would indicate faster amyloid removal than reported for bapineuzumab.

It is unclear whether beta-amyloid clearance by gantenerumab prevents or slows cognitive decline. We await results of Phase 3 trials of solanezumab and bapineuzumab next year, which will reveal whether clearance of beta-amyloid provides any cognitive benefit in mild to moderate Alzheimer’s. Of course, studies are being planned for prodromal Alzheimer’s disease. Prodromal Alzheimer’s is a condition in which a person’s memory loss is worse than can be expected by the normal aging process, while their ability to engage in daily activities is not affected to the extent that dementia would be diagnosed. Research sites around the world are preparing to enroll patients for the SCarlet RoAD study, to evaluate efficacy and safety of gantenerumab in patients with prodromal AD.

Ostrowitzki S, Deptula D, Thurfjell L, Barkhof F, Bohrmann B, Brooks DJ, Klunk WE, Ashford E, Yoo K, Xu Z, Loetscher H, Santarelli L. Mechanism of Amyloid Removal in Patients With Alzheimer Disease Treated With Gantenerumab. Arch Neurol. 2011 Oct 10

Michael S. Rafii, M.D., Ph.D.

Director, Memory Disorders Clinic
Associate Medical Core Director, Alzheimer’s Disease Cooperative Study
University of California San Diego

This post originally appeared in Alzheimer’s Insights, an ADCS Blog.

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