TY - JOUR
T1 - Bidirectional Correlations Between Dopaminergic Function and Motivation in Parkinson’s Disease
AU - Hinkle, Jared T.
AU - Mills, Kelly A.
AU - Perepezko, Kate
AU - Pontone, Gregory M.
N1 - Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: J.H.: Receives tuition and stipend support through the Medical Scientist Training Program at the Johns Hopkins School of Medicine (NIH/NIGMS T32GM007309) and through the National Institute on Aging (F30AG067643). K.P.: No disclosures to report. K.M.: Dr. Mills receives funding through the NIH/NINDS (K23NS101096). G.P.: Dr. Pontone receives funding through the NIH/NIA (K23AG044441). He is also co-sponsored by Acadia Pharmaceuticals, Inc., for writing a book on psychosis in Parkinson’s that was co-written by the National Parkinson’s Foundation. PPMI financial relationships statement: PPMI – a public-private partnership – is funded by the Michael J. Fox Foundation for Parkinson’s Research and funding partners, including Abbvie, Allergan, Amathus Therapeutics, Avid Radiopharmaceuticals, Biogen, Biolegend, Bristol-Myers Squibb, Celgene, Denali, GE Healthcare, Genentech, GlaxoSmithKline, Janssen Neuroscience, Lilly, Lundbeck, Merck, Meso Scale Discovery, Pfizer, Piramal, Prevail Therapeutics, Roche, Sanofi Genzyme, Servier, Takeda, Teva, UCB, Verily, and Voyager Therapeutics. Golub Capital is a philanthropic funding partner.
Funding Information:
Supplemental material for this article is available online. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: J.H.: Receives tuition and stipend support through the Medical Scientist Training Program at the Johns Hopkins School of Medicine (NIH/NIGMS T32GM007309) and through the National Institute on Aging (F30AG067643). K.P.: No disclosures to report. K.M.: Dr. Mills receives funding through the NIH/NINDS (K23NS101096). G.P.: Dr. Pontone receives funding through the NIH/NIA (K23AG044441). He is also co-sponsored by Acadia Pharmaceuticals, Inc., for writing a book on psychosis in Parkinson?s that was co-written by the National Parkinson?s Foundation. PPMI financial relationships statement: PPMI ? a public-private partnership?? is funded by the Michael J. Fox Foundation for Parkinson?s Research and funding partners, including Abbvie, Allergan, Amathus Therapeutics, Avid Radiopharmaceuticals, Biogen, Biolegend, Bristol-Myers Squibb, Celgene, Denali, GE Healthcare, Genentech, GlaxoSmithKline, Janssen Neuroscience, Lilly, Lundbeck, Merck, Meso Scale Discovery, Pfizer, Piramal, Prevail Therapeutics, Roche, Sanofi Genzyme, Servier, Takeda, Teva, UCB, Verily, and Voyager Therapeutics. Golub Capital is a philanthropic funding partner.
Publisher Copyright:
© The Author(s) 2021.
PY - 2022/5
Y1 - 2022/5
N2 - Objective: To test the hypothesis that striatal dopamine function influences motivational alterations in Parkinson disease (PD), we compared vesicular monoamine transporter 2 (VMAT2) and dopamine transporter (DaT) imaging data in PD patients with impulse control disorders (ICDs), apathy, or neither. Methods: We extracted striatal binding ratios (SBR) from VMAT2 PET imaging (18F-AV133) and DaTscans from the Parkinson’s Progression Markers Initiative (PPMI) multicenter observational study. Apathy and ICDs were assessed using the Movement Disorders Society-revised Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease (QUIP), respectively. We used analysis of variance (ANOVA) and log-linear mixed-effects (LME) regression to model SBRs with neurobehavioral metrics. Results: Among 23 participants (mean age 62.7 years, mean disease duration 1.8 years) with VMAT2 imaging data, 5 had apathy, 5 had an ICD, and 13 had neither. ANOVA indicated strong groupwise differences in VMAT2 binding in right anterior putamen [F(2,20) = 16.2, p < 0.0001), right posterior putamen [F(2,20) = 16.9, p < 0.0001), and right caudate [F(2,20) = 6.8, p = 0.006)]. Post-hoc tests and repeated-measures analysis with LME regression also supported right striatal VMAT2 elevation in the ICD group and reduction in the apathy group relative to the group with neither ICD nor apathy. DaT did not exhibit similar correlations, but normalizing VMAT2 with DaT SBR strengthened bidirectional correlations with ICD (high VMAT2/DaT) and apathy (low VMAT2/DaT) in all striatal regions bilaterally. Conclusions: Our findings constitute preliminary evidence that striatal presynaptic dopaminergic function helps describe the neurobiological basis of motivational dysregulation in PD, from high in ICDs to low in apathy.
AB - Objective: To test the hypothesis that striatal dopamine function influences motivational alterations in Parkinson disease (PD), we compared vesicular monoamine transporter 2 (VMAT2) and dopamine transporter (DaT) imaging data in PD patients with impulse control disorders (ICDs), apathy, or neither. Methods: We extracted striatal binding ratios (SBR) from VMAT2 PET imaging (18F-AV133) and DaTscans from the Parkinson’s Progression Markers Initiative (PPMI) multicenter observational study. Apathy and ICDs were assessed using the Movement Disorders Society-revised Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease (QUIP), respectively. We used analysis of variance (ANOVA) and log-linear mixed-effects (LME) regression to model SBRs with neurobehavioral metrics. Results: Among 23 participants (mean age 62.7 years, mean disease duration 1.8 years) with VMAT2 imaging data, 5 had apathy, 5 had an ICD, and 13 had neither. ANOVA indicated strong groupwise differences in VMAT2 binding in right anterior putamen [F(2,20) = 16.2, p < 0.0001), right posterior putamen [F(2,20) = 16.9, p < 0.0001), and right caudate [F(2,20) = 6.8, p = 0.006)]. Post-hoc tests and repeated-measures analysis with LME regression also supported right striatal VMAT2 elevation in the ICD group and reduction in the apathy group relative to the group with neither ICD nor apathy. DaT did not exhibit similar correlations, but normalizing VMAT2 with DaT SBR strengthened bidirectional correlations with ICD (high VMAT2/DaT) and apathy (low VMAT2/DaT) in all striatal regions bilaterally. Conclusions: Our findings constitute preliminary evidence that striatal presynaptic dopaminergic function helps describe the neurobiological basis of motivational dysregulation in PD, from high in ICDs to low in apathy.
KW - PPMI
KW - Parkinson’s disease
KW - VMAT2
KW - apathy
KW - biomarkers
KW - dopamine
KW - dopamine transporter
KW - geriatric psychiatry
KW - impulse control disorders
KW - motivation
KW - movement disorder
KW - neuropsychological testing
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U2 - 10.1177/0891988721996802
DO - 10.1177/0891988721996802
M3 - Article
C2 - 33622073
AN - SCOPUS:85101608839
SN - 0891-9887
VL - 35
SP - 353
EP - 362
JO - Journal of Geriatric Psychiatry and Neurology
JF - Journal of Geriatric Psychiatry and Neurology
IS - 3
ER -