Amyloid May Influence Parkinson's Status
2011; Elsevier BV; Volume: 12; Issue: 8 Linguagem: Inglês
10.1016/s1526-4114(11)60227-8
ISSN2377-066X
Autores Tópico(s)Parkinson's Disease Mechanisms and Treatments
ResumoBARCELONA – Preliminary evidence of brain amyloid-beta deposition in patients with Parkinson's disease and varying cognitive impairment suggests that the timing and amount of Alzheimer's pathology present may influence when and if dementia symptoms arise.“Accepting this model leads to some new directions for potential treatment,” said John Growdon, MD, director of the memory and movement disorders clinic at Massachusetts General Hospital, Boston. “If there is evidence of concomitant Alzheimer's pathology, as imaged … we should consider applying some of the antiamyloid treatments under development for Alzheimer's in our Parkinson's disease dementia patients.”Dr. Growdon presented the results of a longitudinal cohort study of 74 patients, which included 26 of 41 patients who were initially evaluated in a 2008 cross-sectional study, at an international conference on Alzheimer's and Parkinson's diseases. This original group of 41 patients included 8 with dementia with Lewy bodies (DLB), 7 with Parkinson's disease dementia, 11 Parkinson's disease patients with normal cognition, 15 with Alzheimer's disease, and 37 control subjects (Neurology 2008;71:903-10).He differentiated DLB and Parkinson's dementia by the timing of the onset of dementia symptoms.The initial cross-sectional study found that amyloid burden in the DLB group was similar to that in the Alzheimer's group. Amyloid burden in the Parkinson's dementia group was similar to that found in the cognitively normal Parkinson's patients and the normal controls.Imaging in the initial study also revealed that amyloid in the Parkinson's disease patients aggregated in the lateral parietal, precuneus, and posterior cingulate region and was related to visuospatial impairment.“There was an apparent clean separation of [amyloid-binding compound] uptake in Lewy body dementia and Parkinson's disease dementia, and we wondered whether amyloid burden might contribute in a meaningful way to both the behavior and cognitive problems seen in Lewy body dementia,.” Dr. Growdon said.He also said the investigators were “struck by the fact that half our nondemented Parkinson's patients had substantial [binding compound] uptake, raising the question that these individuals might be on the path to developing dementia.”In the current cohort of 74 patients (33 Parkinson's disease patients with normal cognition, 10 with Parkinson's disease and mild cognitive impairment [MCI], 12 with Parkinson's disease dementia, and 19 with DLB), the subjects have now been followed for a mean of 3.5 years, with annual Pittsburgh compound B (PiB)–PET imaging, and physical, cognitive, and neuropsychological testing.After the follow-up period of 2-5 years, Dr. Growdon found that 11 patients had cognitive declines. Of the 33 Parkinson's disease patients who had normal cognition, 6 now have MCI. Of the 10 who had Parkinson's and MCI, 5 have progressed to Parkinson's dementia. Although amyloid binding was not significantly related to that decline, people with minimalPamyloid burden at baseline remained relatively stable, while those with an initially high amyloid burden tended to lose their normal cognitive status.While treatment with an antiamyloid for patients who experience early amyloid deposition may someday be recommended, Dr. Growdon suggested that a different path might be appropriate for DLB patients, who show early alpha-synuclein deposition. “We need to think about ways to prevent this accumulation, whether by a chaperone for the molecule or antibodies aimed against alpha-synuclein oligomers and aggregates.”Dr. Growdon's study was sponsored by the National Institutes of Health and the Michael J. Fox Foundation for Parkinson's Research. He reported no relevant financial disclosures.Michele G. Sullivan is with the Mid-Atlantic bureau of Elsevier Global Medical News. BARCELONA – Preliminary evidence of brain amyloid-beta deposition in patients with Parkinson's disease and varying cognitive impairment suggests that the timing and amount of Alzheimer's pathology present may influence when and if dementia symptoms arise. “Accepting this model leads to some new directions for potential treatment,” said John Growdon, MD, director of the memory and movement disorders clinic at Massachusetts General Hospital, Boston. “If there is evidence of concomitant Alzheimer's pathology, as imaged … we should consider applying some of the antiamyloid treatments under development for Alzheimer's in our Parkinson's disease dementia patients.” Dr. Growdon presented the results of a longitudinal cohort study of 74 patients, which included 26 of 41 patients who were initially evaluated in a 2008 cross-sectional study, at an international conference on Alzheimer's and Parkinson's diseases. This original group of 41 patients included 8 with dementia with Lewy bodies (DLB), 7 with Parkinson's disease dementia, 11 Parkinson's disease patients with normal cognition, 15 with Alzheimer's disease, and 37 control subjects (Neurology 2008;71:903-10). He differentiated DLB and Parkinson's dementia by the timing of the onset of dementia symptoms. The initial cross-sectional study found that amyloid burden in the DLB group was similar to that in the Alzheimer's group. Amyloid burden in the Parkinson's dementia group was similar to that found in the cognitively normal Parkinson's patients and the normal controls. Imaging in the initial study also revealed that amyloid in the Parkinson's disease patients aggregated in the lateral parietal, precuneus, and posterior cingulate region and was related to visuospatial impairment. “There was an apparent clean separation of [amyloid-binding compound] uptake in Lewy body dementia and Parkinson's disease dementia, and we wondered whether amyloid burden might contribute in a meaningful way to both the behavior and cognitive problems seen in Lewy body dementia,.” Dr. Growdon said. He also said the investigators were “struck by the fact that half our nondemented Parkinson's patients had substantial [binding compound] uptake, raising the question that these individuals might be on the path to developing dementia.” In the current cohort of 74 patients (33 Parkinson's disease patients with normal cognition, 10 with Parkinson's disease and mild cognitive impairment [MCI], 12 with Parkinson's disease dementia, and 19 with DLB), the subjects have now been followed for a mean of 3.5 years, with annual Pittsburgh compound B (PiB)–PET imaging, and physical, cognitive, and neuropsychological testing. After the follow-up period of 2-5 years, Dr. Growdon found that 11 patients had cognitive declines. Of the 33 Parkinson's disease patients who had normal cognition, 6 now have MCI. Of the 10 who had Parkinson's and MCI, 5 have progressed to Parkinson's dementia. Although amyloid binding was not significantly related to that decline, people with minimalPamyloid burden at baseline remained relatively stable, while those with an initially high amyloid burden tended to lose their normal cognitive status. While treatment with an antiamyloid for patients who experience early amyloid deposition may someday be recommended, Dr. Growdon suggested that a different path might be appropriate for DLB patients, who show early alpha-synuclein deposition. “We need to think about ways to prevent this accumulation, whether by a chaperone for the molecule or antibodies aimed against alpha-synuclein oligomers and aggregates.” Dr. Growdon's study was sponsored by the National Institutes of Health and the Michael J. Fox Foundation for Parkinson's Research. He reported no relevant financial disclosures. Michele G. Sullivan is with the Mid-Atlantic bureau of Elsevier Global Medical News.
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