Neuroimaging Markers Predict Cognitive Decline in PD
MJFF Research Grant, 2012
This grant builds upon the research from a prior grant:
Promising Outcomes of Original Grant:
Excessive amounts of amyloid in brain tissue are believed to be toxic and cause the neuronal damage that results in dementia.† Amyloid deposits can be detected in life using brain scans with the agent PiB.† Using PiB brain scans, we found that ~30% of non-demented PD patients have increased amyloid deposits, and that high PiB uptake was associated with declines on some cognitive, but not motor, tests. †Data analyses suggested that amyloid burden predicted risk of developing severe cognitive impairments and even dementia, but this trend was not statistically significant.† To reach a final conclusion therefore, additional years of research are required to supplement the original 3 year study.
Objectives for Supplemental Investigation:
In order to strengthen the conclusion that amyloid burden is a major factor contributing to cognitive decline and dementia in PD, we plan to follow and test on an annual basis our enrolled cohort of subjects (n=36). †The neurological examination (Hoehn & Yahr, UPDRS) and neuropsychological assessments are the same as weíve administered during the first 3 years of the study; no additional neuroimaging is required.
Importance of This Research for the Development of a New PD Therapy:††††
Linking amyloid beta deposits in brain to the risk of cognitive impairments and dementia has the potential for opening up an entirely new avenue of treatment in PD.† Amyloid toxicity is an acknowledged early event in Alzheimerís disease, and is hypothesized to trigger a cascade of changes leading to synaptic dysfunction and neuronal death that underlies the clinical signs of dementia.† Anti-amyloid therapies are being actively developed and tested by numerous pharmaceutical companies throughout the world.† Should any of these approaches prove successful in Alzheimerís disease, such treatments would become immediately applicable to PD, with the expectation that they would slow the onset and progression of cognitive impairments in those with amyloid beta deposits in the brain, and possibly prevent end-stage dementia.
Based on positron emission tomography (PET) brain scans that detect amyloid, we found high accumulation in ~40% of non-demented individuals with Parkinsonís disease (PD). Contrary to our expectation, these deposits did not distinguish people with PD with impaired cognition from those with normal mental abilities, whereas different PET scans that measure glucose metabolism revealed deficits that correlated with cognitive impairments. Amyloid accumulation in the brain is not benign; however; those people with PD who at baseline had above normal levels of amyloid progressed to cognitive impairment and dementia over 3-5 years faster than those with low level of amyloid. This result implies that treatments under development for treating Alzheimerís disease by reducing amyloid-beta toxicity will have direct application for PD as well.
Presentations & Publications
Gomperts SN et al.† Aβ deposits are common in brains of non-demented PD patients.† World Federation of Neurology World Congress on PD.† Dec. 12-13, 2009.† Miami, FL.
Bruck A, et al.† Patterns of amyloid deposition distinguish non-demented PD from normal aging.†† Human Amyloid Imaging meeting.† April 9, 2010.† Toronto, CN.
Gomperts SN et al.† Regional burden of Aβ relates to cognitive function in PD.† Human Amyloid Imaging meeting.† April 9, 2010.† Miami, FL.
Growdon JH et al.† Amyloid and α-synuclein in PD dementias.† 7th University of Zurich Winter Brain Conference.† February 28-March 3, 2011.† Sils Maria, Switzerland.
Growdon JH et al.† Brain amyloid and cognition in PD.†† 10th International Conference on Alzheimerís and Parkinsonís Diseases.† March 9-13, 2011.† Barcelona, Spain.
Gomperts SN et al.† Brain amyloid and cognition in Lewy body diseases. Movement Disorders 2012;27:965-973.
Gomperts SN et al.† Neuroimaging markers predict cognitive decline in PD.† Human Amyloid Imaging meeting.† January 12-13, 2012.† Miami, FL.
Marquie M et al.† Glucose metabolism, but not amyloid deposition, differentiates PD-MCI from PD without cognitive mpairment.† Human Amyloid Imaging meeting.† January 12-13, 2012.† Miami, FL.
Gomperts SN et al.† Amyloid is linked to cognitive decline in patients with Parkinson disease without dementia.† Neurology 2013;80:85-91.
Growdon JH et al.† Amyloid, FDG and dopamine transporter imaging in Lewy body diseases.† 11th International Conference of Alzheimerís and Parkinsonís diseases.† March 6-10, 2013.† Florence, Italy.
Marquie M. et al.† Striatal and extrastriatal dopamine transporter levels relate to cognition in Lewy body diseases.† Human Amyloid Imaging meeting.† January 15-17, 2014.† Miami, FL. & also presented at the 66th Annual American Academy of Neurology meeting.† April 29, 2014.† Philadelphia, PA.† (A manuscript on this material has been submitted for publication in Movement Disorders).
Growdon JH et al.† PET radioligands reveal the bases of dementia in parkinsonian diseases.† 12th International Conference on Alzheimerís and Parkinsonís diseases.† March 17-22, 2015.† Nice, France.
Massachusetts General Hospital, Harvard Medical School
Location: Boston, Massachusetts
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