Re: Antibiotics for Alzheimer's?
William_at_Occam.com
Date: 06/13/04
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Date: Sat, 12 Jun 2004 23:51:26 -0400
Thanks for the abstract. It's good to see that at least one group
feels secure enough to essentially rule out C. pneumoniae as a
potential causative agent in AD. My money's on the metal chelating
abilities of the antibiotics (especially doxy) but I suppose only time
will tell.
How did you come across the article? In a search for doxy?
>Antibiotics for Alzheimer's?
>
>
>>From <http://www.ahcpub.com/ahc_root_html/products/newsletters/na.html>
>Neurology Alert | May 2004
>
>
>Abstract & Commentary
>
>
>Source: Loeb MB, et al. A randomized, controlled trial of doxycycline and
>rifampin for patients with Alzheimer's disease. J Am Geriatr Soc.
>2004;52:381-387.
>
>Although infectious agents are not widely believed to be the primary cause
>of Alzheimer's disease (AD), some evidence implicates certain neurotrophic
>viruses and bacteria as possible contributing factors. Canadian
>investigators Loeb and colleagues suggest that Chlamydia pneumonia infection
>might play a role in AD. They carried out a randomized, blinded, and
>placebo-controlled trial testing whether antichlamydial antibiotics
>(rifampin/doxycycline) could serve as a potential therapy for patients with
>mild-to-moderate AD.
>
>In this multicenter study, 51 mild-to-moderate AD patients were randomized
>to receive 3 months of treatment with rifampin 300 mg daily plus doxycycline
>200 mg daily. Fifty other age- and severity-matched AD patients received a
>placebo. The primary outcome measure was the standardized form of the
>ADAS-Cog, a test commonly used in AD drug trials. Additional measures of
>cognition, behavior, and daily function were obtained at 3 months, 6 months,
>and 12 months from the start of therapy. The majority of patients in the
>trial were on stable doses of cholinesterase inhibitors during the study
>period. Blood tests for C pneumonia, including PCR and immunoglobulins, were
>evaluated before and after antibiotic treatment.
>
>Approximately 84% of the subjects completed the trial, with relatively equal
>numbers of dropouts from the treatment and placebo arms. There was no
>significant difference in adverse events between groups. The primary outcome
>variable measured was ADAS-Cog. There was no significant difference between
>antibiotic-treated patients and placebo controls at 3 or 12 months. However,
>there was a statistically significant effect favoring antibiotic treatment
>at 6 months. A significant difference favoring antibiotic treatment was
>found on the Mini-Mental State Examination at 12 months and measures of
>function, behavior, and mood at 3 months.
>
>The PCR and immunoglobin tests did not indicate irradication of C pneumonia
>infection in those treated with antibiotics. Loeb et al suggested that the
>putative beneficial effects of these antibiotics observed in this trial were
>probably not mediated through any action against chlamydia. Instead, they
>postulate an anti-amyloid effect based on in vitro studies using antibiotics
>such as rifampin. Since amyloid levels were not measured in this study, this
>hypothesis could not be confirmed.
>
>
>Commentary
>
>
>The successful treatment of some forms of peptic ulcer disease (PUD) with
>antibiotics after the realization that Helicobacter pylori played a role in
>the pathogenesis of PUD provides a rationale for examining whether other
>diseases once thought to be unrelated to infection can be treated more
>effectively through antimicrobial therapies. However, the evidence
>supporting bacterial infection as a cause of AD is considerably less
>convincing than the associations between H pylori and PUD. If chlamydial
>infection does promote AD, however, relatively little is known about the
>mechanism. This lack of knowledge undoubtedly handicapped Loeb et al, whose
>study was otherwise well designed and executed despite the uncertainties
>inherent in a first attempt to use antibiotics to treat a neurodegenerative
>dementia. An attractive feature of the experimental design was the
>assessment of outcome several months after completing a 3-month treatment
>period. This reduces the likelihood that the effects observed were mediated
>through treatment of acute infections that are common in dementia patients,
>such as UTIs and pneumonias.
>
>In this study, the primary cognitive outcome measure at 12 months was
>negative, although results at an interim time point (6 months) suggested
>possible benefit with antibiotic treatment. Positive results in other
>domains, such as behavior and function, did not temporally correlate with
>improvement in cognition. This study, therefore, neither proves nor
>disproves a role for antimicrobial therapy in the treatment of AD. Before
>additional trials with antimicrobials are undertaken, more research should
>be carried out examining the possible association between infections and AD,
>including studies of the mechanisms involved and their relationship to known
>aspects of the AD pathogenesis. - Norman R. Relkin
>
>Dr. Relkin, Associate Professor of Clinical Neurology and Neuroscience, New
>York Presbyterian Hospital-Cornell Campus, is Assistant Editor of Neurology
>Alert.
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