Identifying an Optimal Cut-off Value and if Sex Differences Exist in Nigrostriatal Dopamine Transporter Binding of 123I-FP-CIT SPECT in Autopsy Confirmed Lewy Body Disease and/or Alzheimer’s Disease
Toji Miyagawa1, Scott Przybelski1, Cynthia Vernon1, Paul Min1, Leah Forsberg1, Julie Fields1, Stuart McCarter1, Tanis Ferman2, Vijay Ramanan1, Jonathan Graff-Radford1, David Jones1, Rodolfo Savica1, Ross Reichard1, Joseph Parisi1, Aivi Nguyen1, Dennis Dickson1, Melissa Murray1, Gregory Day1, Neill Graff-Radford2, Erik St. Louis1, Manoj Jain1, Kejal Kantarci1, Val Lowe1, Bradley Boeve1
1Mayo Clinic, 2Mayo Clinic Jacksonville
Objective:
To assess 123I-FP-CIT SPECT (DaT-SPECT) in autopsy confirmed Lewy body disease (LBD) and/or Alzheimer’s disease (AD) patients, and to identify if sex differences exist.
Background:
Identifying optimal cut-off value for DaT-SPECT in detecting LBD is essential in LBD clinical trials and research. Effects of sex in nigrostriatal dopamine transporter (DaT) binding of the DaT-SPECT in autopsy confirmed LBD is not well known.
Design/Methods:
Autopsy confirmed neocortical or limbic LBD and/or AD patients who underwent DaT-SPECT were included. Nigrostriatal DaT binding and z-scores were assessed using DaTQUANT2.0 software (GE Healthcare).
Results:
Thirty-three patients had LBD pathology [19 without AD (L+/A-) and 14 with AD (L+/A+); 30 neocortical and 3 limbic LBD; 26 male and 7 female] and 12 had AD pathology without LBD (L-/A+). A cut-off value of -0.98 for the DaTQUANT putamen z-score yielded 94% sensitivity and 100% specificity in detecting LBD. Age at death, age at DaT-SPECT, MMSE, UPDRS part III, and DaTQUANT z-score of putamen (-3.55±0.97 vs -2.94±1.71) or caudate (-2.77±1.18 vs -2.46±1.48) did not differ between the L+/A- and L+/A+. Males were more frequent in L+/A- (95%) than in L+/A (57%). Age at death, age at DaT-SPECT, interval between DaT-SPECT and death, and MMSE did not differ between the L+ males and females. The L+ females had more frequent AD co-pathology (86% vs 31%), more AD dementia clinical diagnosis (29% vs 0%), lower UPDRS part-III (11.4±12.3 vs 23.2±13.0), and higher DaTQUANT putamen (-2.17±1.98 vs -3.60±0.97) and caudate (-1.65±1.64 vs -2.90±1.08) z-scores. All L+ females had neocortical LBD, and the two L+ females with AD clinical diagnosis had normal DaT-SPECT and L+/A+ pathology.
Conclusions:
DaTQUANT using cut-off putamen z-score value of -1 showed excellent discriminatory power in detecting LBD pathology. Though limited by relatively few females, there were potential sex differences observed in DaT-SPECT as well as in clinical and pathological findings.
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