Dopamine Distribution Tied to Parkinson’s Dyskinesia
NEW YORK, April 21 (Reuters Health)—A PET study supports the role of presynaptic dopamine alterations in the appearance of dyskinesias in patients with Parkinson’s disease, Canadian researchers reported in the April 7 issue of Neurology.
“Our findings suggest that the surviving dopaminergic neurons undergo changes that at the same time appear to enhance the availability of dopamine, but at the risk of facilitating the emergence of dyskinesias in the future,” lead investigator Dr. Andre R. Troiano told Reuters Health.
Dr. Troiano and colleagues, at the University of British Columbia, Vancouver, studied 36 patients with Parkinson’s disease and motor fluctuations. Twenty-seven had dyskinesias; the other nine did not.
The subjects underwent PET using [11C]-d-threo-methylphenidate (MP) and [11C]-(+) dihydrotetrabenazine (DTBZ), and the ratio of the two was used to estimate the expression of dopamine transporter relative to dopamine nerve terminal density.
There was no between-group difference in this ratio in the caudate. However, the putaminal MP/DTBZ ratio was decreased in patients with dyskinesias. This continued to be the case after correcting for age, treatment, and measures of disease severity.
Dopamine transporter downregulation, the researchers suggested, may minimize symptoms by contributing to increased synaptic dopamine levels in early disease, but may lead to oscillating levels, which “might ultimately facilitate the appearance of dyskinesias.”
In an accompanying editorial, Dr. Francois J. G. Vingerhoets, of Centre Hospitalier Universitaire Vaudois–Université de Lausanne, Switzerland, observed that the study has limitations but “provides insight into the possible mechanisms that amplify the synaptic dopamine oscillations induced by current levodopa therapy.”
Neurology. 2009;72(14):1202-1203, 1211-1216.
NSAIDS Do Not Prevent But May Delay Alzheimer’s Disease Dementia
NEW YORK, April 22 (Reuters Health)—A recent prospective study disproves earlier observations that NSAIDs prevent Alzheimer’s dementia (AD). At best, NSAIDs may delay its onset, according to a report in the April 22 online issue of Neurology.
“The NSAIDs-AD relationship has been evaluated in more than 30 observational studies. Most have confirmed the original observations” of a prophylactic effect of NSAIDS, the authors wrote, “although some well-designed studies have found different results.”
In the prospective Adult Changes in Thought (ACT) study, Dr. John C. S. Breitner, of the University of Washington School of Medicine in Seattle, and colleagues analyzed NSAID use and development of dementia or AD in 2,736 members of a large local health care plan who were dementia-free at enrollment.
Strengths of the study included “an electronic pharmacy dispensing database with prescription information available since 1977 ... and a large sample that enabled unusually detailed analyses,” the researchers noted. Screening and examinations for dementia started in 1994, with biennial follow-ups continuing for as long as 12 years.
Using pharmacy records, the investigators identified 351 subjects (12.8%) with a history of heavy NSAID use at enrollment and an additional 107 who became heavy users during follow-up.
Incident dementia developed in 476 subjects, including 356 with AD. The median age at onset of either dementia or AD was roughly 83 years.
“Contrary to the hypothesis that NSAIDs protect against AD, pharmacy-defined heavy NSAID users showed increased incidence of dementia and AD, with adjusted hazard ratios of 1.66 and 1.57,” the researchers reported. Patient-reported NSAID use did not affect the results, they added.
The authors believe their findings are “a truer representation of the association of NSAIDs and dementia risk” than results from earlier studies, not only because they used a community-based sample but also because of their regular assessments for dementia and AD, access to “rigorous exposure classification based on pharmacy dispensing records” dating back 17 or more years before enrollment, inclusion of self-reported exposure, and large numbers of incident dementia or AD cases “affording good statistical power.”
They explained that the observational results found elsewhere might reflect delayed onset of AD in NSAID users. “Conceivably, such delay could result in increased AD incidence in late old age.” Indeed, Dr. Breitner pointed out in a press release from the publishers of the journal that “our participants were older.”
If NSAIDs do delay the onset of AD, he added, “it would follow that studies looking at younger people who use NSAIDs would show fewer cases of Alzheimer’s, while in groups of older people there might be more cases, including those that would have occurred earlier if they had not been delayed.”
Nonetheless, Dr. Breitner concluded, “We must not ignore the fundamental finding, which is an increase in the risk of dementia in the NSAID users. We need further research to understand that result more clearly.”
Neurology. 2009 Apr 22; [Epub ahead of print].