Objective/Rationale:
Isolated cognitive impairments are common in PD; they increase in number and severity with advancing age and motor disability but their relation to the risk of developing dementia remains unknown. This project seeks 1) to determine whether these cognitive impairments signal the onset of a dementing process and 2) whether brain scans that display anatomy, measure brain energy and detect excessive deposits of a protein called amyloid that is toxic to neurons will identify those PD patients who will eventually develop dementia.
Project Description:
We will enroll 40 non-demented men and women with moderate stages ofPD and conduct comprehensive neurological and neuropsychological examinations at entry into the study. These individuals will then undergo three brain scans: a magnetic resonance image to display anatomic structures, and two positron emission tomography scans -one to measure energy metabolism and another scan to detect amyloid deposits. These individuals will then be followed longitudinally with annual neurological and neuropsychological assessments to determine the incidence of cognitive impairments and dementia. Changes in these clinical measures will be analyzed in relation to the features on the initial brain scans to determine the value of neuroimaging in predicting cognitive decline.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Demonstrating that cognitive impairments signal increased risk ofdeveloping dementia would be a major conceptual advance and heighten awareness for assessing cognition in all PD patients. By examining the role ofimpaired energy and amyloid toxicity our data will provide new insights into the underlying problems that account for cognitive impairments and dementia in PD. Results from this study will have an immediate impact on clinical care in terms ofdiagnosis (the scans as reliable biomarkers), prognosis (confidence in predicting the course of illness) and potential treatment (refocus drug development on restoring energy and reducing amyloid).
Anticipated Outcome:
Impaired thinking and dementia are among the least understood but most feared consequences ofadvanced PD. Our project will clarify the relation between mild cognitive impairments and dementia, and determine whether abnormalities detected on brain scans in non-demented PD patients predict subsequent cognitive decline and dementia
Final Outcome
Excessive amounts of amyloid in brain tissue are believed to be toxic and cause Alzheimer’s disease. Amyloid can be detected in life using brain scans (the PiB scan) and is found in normal non-demented individuals as well as those with PD. Brain amyloid burden increases with increasing age, and is strongly linked to the APOE ε4 genotype. We found that ~40% of non-demented PD patients had positive PiB scans, but that the amount of amyloid did not distinguish between normal PD subjects and those with cognitive impairments. However, when followed for 3 years, high PiB uptake was associated with significant declines on some cognitive tests and possibly influenced emerging dementia. In contrast to the effects on cognition, amyloid burden did not influence changes in the motor signs of PD.
Presentations & Publications
1. Gomperts SN, Rentz DM, Bruck A, Johnson KA, Growdon JH. Aβ amyloid deposits are common in brains of non-demented PD patients. Presented at the World Federation of Neurology World Congress on PD and Related Disorders. Miami, FL. Dec. 13-16, 2009.
2. Bruck A, Locascio JJ, Gomperts SN, Rentz DM, Becker JA, Memole L, Carmasin J, Maye J,
Growdon JH, Sperling RA, Johnson KA. Patterns of amyloid deposition distinguish non-demented PD from normal aging. Presented at the Human Amyloid Imaging meeting. Toronto, Canada. April 9-10, 2010.
3. Gomperts SN, Bruck A, Locascio JJ, Rentz DM, Becker JA, Memole L, Carmasin J, Sperling
Growdon JH, Johnson KA. Regional burden of Aβ-amyloid relates to cognitive function in PD. Presented at the Human Amyloid Imaging meeting, Toronto, Canada. April 9-10, 2010.
4. Growdon JH. Amyloid and Alpha-Synuclein PD Dementias. Presented at the 7th Winter
Brain Symposium. Sils Maria, Switzerland. February 28-March 3, 2011.
5. Growdon JH, Gomperts SN, Locascio JJ, Rentz DM, Marquie-Sayagues M, Santarlasci A,
Johnson KA. Brain Amyloid and Cognition in PD. Presented at the 10th International Conference on Alzheimer’s and Parkinson’s Diseases. Barcelona, Spain. March 9-13, 2011.