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Identifying Cut-off Values, Effects of AD Co-pathology, Sex Differences, and Temporal Changes of 123I-FP-CIT SPECT in Autopsy-proven LBD

T. Miyagawa, S. Przybelski, C. Cynthia, HK. Minmin, L. Forsberg, J. Fields, S. Mccarter, T. Ferman, V. Ramanan, J. Graff-Radford, D. Jones, R. Savica, D. Knopman, R. Petersen, R. Reichard, A. Nguyen, D. Dickson, M. Murray, G. Day, N. Graff-Radford, C. Lachner, E. St Louis, M. Jain, K. Kantarci, V. Lowe, B. Boeve (ROCHESTER, USA)

Meeting: 2025 International Congress

Keywords: Dementia with Lewy bodies (DLB), Lewy bodies, Single-photon emission computed tomography(SPECT)

Category: Parkinson's disease: Neuroimaging

Objective: We analyzed autopsy-proven Lewy body disease (LBD) and/or Alzheimer’s disease (AD) dementia patients with 123I-FP-CIT SPECT to investigate previously unclarified detailed aspects of 123I-FP-CIT SPECT.

Background: Autopsy confirmation has been the gold standard for definite diagnosis of dementia with Lewy bodies (DLB). Due to frequent concomitant AD pathology, it is sometimes difficult to clinically differentiate DLB from AD dementia. The 123I-FP-CIT SPECT is an important biomarker in detecting LBD. Understanding optimal cut-off values, effects of AD co-pathology and sex, and temporal change in nigrostriatal binding of 123I-FP-CIT SPECT in LBD are essential for its use in LBD clinical trials.

Method: Forty-four dementia patients with autopsy-proven neocortical or limbic LBD and/or AD who had 123I-FP-CIT SPECT were assessed retrospectively, including eight patients with two or more longitudinal scans. Striatal binding ratio (SBR) and z-scores were semi-quantitatively assessed with DaTQUANT 2.0 software (GE Healthcare).

Results: Thirty-three patients had LBD pathology [19 without AD (LBD) and 14 with AD (LBD+AD); 30 neocortical and 3 limbic; 26 male and 7 female] and 11 patients had AD pathology without LBD. A cut-off z-score value of -1 for the DaTQUANT putamen showed 94% sensitivity and 100% specificity in detecting LBD pathology. There was no difference in DaTQUANT values between LBD and LBD+AD. Males were more common in LBD (95%) than in LBD+AD (57%) patients and 86% of the females with LBD pathology also had AD pathology. In the patients with LBD pathology, females had higher DaTQUANT putamen and caudate z-scores and lower MDS-UPDRS part III scores than males. Eight LBD patients had 2.5±0.7 longitudinal scans, and all had DaTQUANT putamen z-score <-1 at initial scan and eventually presented putamen z-score <-2 at last scan.

Conclusion: DaTQUANT using cut-off putamen z-score of -1 showed excellent discriminatory power in detecting LBD pathology and enabled detection of early stages of LBD in symptomatic patients. AD co-pathology did not affect 123I-FP-CIT SPECT features. Female patients had higher putamen and caudate z-scores with less motor impairment than male patients with LBD pathology. Nigro-striatal dopamine transporter binding tended to decline over time.

To cite this abstract in AMA style:

T. Miyagawa, S. Przybelski, C. Cynthia, HK. Minmin, L. Forsberg, J. Fields, S. Mccarter, T. Ferman, V. Ramanan, J. Graff-Radford, D. Jones, R. Savica, D. Knopman, R. Petersen, R. Reichard, A. Nguyen, D. Dickson, M. Murray, G. Day, N. Graff-Radford, C. Lachner, E. St Louis, M. Jain, K. Kantarci, V. Lowe, B. Boeve. Identifying Cut-off Values, Effects of AD Co-pathology, Sex Differences, and Temporal Changes of 123I-FP-CIT SPECT in Autopsy-proven LBD [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/identifying-cut-off-values-effects-of-ad-co-pathology-sex-differences-and-temporal-changes-of-123i-fp-cit-spect-in-autopsy-proven-lbd/. Accessed October 5, 2025.
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MDS Abstracts - https://www.mdsabstracts.org/abstract/identifying-cut-off-values-effects-of-ad-co-pathology-sex-differences-and-temporal-changes-of-123i-fp-cit-spect-in-autopsy-proven-lbd/

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