TY - JOUR
T1 - Regional brain amyloid-β accumulation associates with domain-specific cognitive performance in Parkinson disease without dementia
AU - Akhtar, Rizwan S.
AU - Xie, Sharon X.
AU - Chen, Yin J.
AU - Rick, Jacqueline
AU - Gross, Rachel G.
AU - Nasrallah, Ilya M.
AU - Van Deerlin, Vivianna M.
AU - Trojanowski, John Q.
AU - Chen-Plotkin, Alice S.
AU - Hurtig, Howard I.
AU - Siderowf, Andrew D.
AU - Dubroff, Jacob G.
AU - Weintraub, Daniel
N1 - Funding Information:
This study was partially funded by Avid Radiopharmaceuticals, a wholly-owned subsidiary of Eli Lilly and Company, who manufactures F-florbetapir A.D.S. is an employee of Avid Radiopharmaceuticals, a wholly-owned subsidiary of Eli Lilly and Company. J.Q.T. may accrue revenue in the future on patents (Kung, H.F., et. al. “Amyloid plaque aggregation inhibitors and diagnostic imaging agents.” U.S. Patent 6,696,039, February 24, 2004, and 6,946,116, September 20, 2005) submitted by the University of Pennsylvania wherein he is co-Inventor and he received revenue from the sale of Avid Radiopharmaceuticals to Eli Lilly and Company as co-Inventor on imaging related patents submitted by the University of Pennsylvania. This does not alter our adherence to PLOS ONE policies on sharing data and materials. 18
Publisher Copyright:
© 2017 Akhtar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2017/5
Y1 - 2017/5
N2 - Parkinson disease patients develop clinically significant cognitive impairment at variable times over their disease course, which is often preceded by milder deficits in memory, visuospatial, and executive domains. The significance of amyloid-β accumulation to these problems is unclear. We hypothesized that amyloid-β PET imaging by 18F-florbetapir, a radiotracer that detects fibrillar amyloid-β plaque deposits, would identify subjects with global cognitive impairment or poor performance in individual cognitive domains in non-demented Parkinson disease patients. We assessed 61 non-demented Parkinson disease patients with detailed cognitive assessments and 18F-florbetapir PET brain imaging. Scans were interpreted qualitatively (positive or negative) by two independent nuclear medicine physicians blinded to clinical data, and quantitatively by a novel volume-weighted method. The presence of mild cognitive impairment was determined through an expert consensus process using Level 1 criteria from the Movement Disorder Society. Nineteen participants (31.2%) were diagnosed with mild cognitive impairment and the remainder had normal cognition. Qualitative 18F-florbetapir PET imaging was positive in 15 participants (24.6%). Increasing age and presence of an APOE ϵ4 allele were associated with higher composite 18F-florbetapir binding. In multivariable models, an abnormal 18F-florbetapir scan by expert rating was not associated with a diagnosis of mild cognitive impairment. However, 18F-florbetapir retention values in the posterior cingulate gyrus inversely correlated with verbal memory performance. Retention values in the frontal cortex, precuneus, and anterior cingulate gyrus retention values inversely correlated with naming performance. Regional cortical amyloid-β amyloid, as measured by 18F-florbetapir PET, may be a biomarker of specific cognitive deficits in non-demented Parkinson disease patients.
AB - Parkinson disease patients develop clinically significant cognitive impairment at variable times over their disease course, which is often preceded by milder deficits in memory, visuospatial, and executive domains. The significance of amyloid-β accumulation to these problems is unclear. We hypothesized that amyloid-β PET imaging by 18F-florbetapir, a radiotracer that detects fibrillar amyloid-β plaque deposits, would identify subjects with global cognitive impairment or poor performance in individual cognitive domains in non-demented Parkinson disease patients. We assessed 61 non-demented Parkinson disease patients with detailed cognitive assessments and 18F-florbetapir PET brain imaging. Scans were interpreted qualitatively (positive or negative) by two independent nuclear medicine physicians blinded to clinical data, and quantitatively by a novel volume-weighted method. The presence of mild cognitive impairment was determined through an expert consensus process using Level 1 criteria from the Movement Disorder Society. Nineteen participants (31.2%) were diagnosed with mild cognitive impairment and the remainder had normal cognition. Qualitative 18F-florbetapir PET imaging was positive in 15 participants (24.6%). Increasing age and presence of an APOE ϵ4 allele were associated with higher composite 18F-florbetapir binding. In multivariable models, an abnormal 18F-florbetapir scan by expert rating was not associated with a diagnosis of mild cognitive impairment. However, 18F-florbetapir retention values in the posterior cingulate gyrus inversely correlated with verbal memory performance. Retention values in the frontal cortex, precuneus, and anterior cingulate gyrus retention values inversely correlated with naming performance. Regional cortical amyloid-β amyloid, as measured by 18F-florbetapir PET, may be a biomarker of specific cognitive deficits in non-demented Parkinson disease patients.
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U2 - 10.1371/journal.pone.0177924
DO - 10.1371/journal.pone.0177924
M3 - Article
C2 - 28542444
AN - SCOPUS:85019839083
SN - 1932-6203
VL - 12
JO - PloS one
JF - PloS one
IS - 5
M1 - e0177924
ER -