Objective: To compare the clinical and imaging characteristics of those PRECEPT (Parkinson Research Examination of CEP-1347 Trial) subjects with a scan without evidence of dopaminergic deficit (SWEDD) to those with dopamine transporter (DAT) deficit scans at study baseline and during a 22-month follow-up.
Methods: Baseline (n = 799) and 22-month follow-up (n = 701) [(123)I] β-CIT SPECT scans were acquired. The percent change in [(123)I] β-CIT striatal binding ratio, the percentage of subjects requiring dopaminergic therapy, the change in Unified Parkinson's Disease Rating Scale (UPDRS) score, and the PRECEPT Study investigators' diagnosis at study termination were compared between SWEDD and DAT deficit subjects.
Results: SWEDD subjects (n = 91) compared with DAT deficit subjects (n = 708) showed reduced UPDRS score at baseline (18.7 [SD 8.5] vs 25.5 [SD 10.5], p < 0.05) and minimal change in both [(123)I] β-CIT striatal binding ratio (-0.2% [SD 12.2] vs -8.5% [SD 11.9], p < 0.0001) and UPDRS score (0.5 [SD 6.9] vs 10.5 [SD 8.9], p < 0.0001) at follow-up assessments. At PRECEPT termination, the diagnosis by study investigators was changed from Parkinson disease (PD) to other disorders not associated with DAT deficit in 44% (95% confidence interval 34.2, 54.7) of SWEDD subjects compared with 3.6% (95% confidence interval 2.3, 5.1) of DAT deficit subjects.
Conclusion: These results indicate that subjects identified as having a SWEDD, with DAT imaging within the normal range, have minimal evidence of clinical or imaging PD progression. These data strongly suggest that SWEDD subjects are unlikely to have idiopathic PD.
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http://dx.doi.org/10.1212/WNL.0000000000000424 | DOI Listing |
Biomedicines
November 2024
State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China.
Background/objectives: Levo-Stepholidine (-SPD), a compound extracted from Chinese herbs, has the potential to treat psychotic disorders where cognitive deficits are a critical challenge. -SPD displays a D1R agonism/D2R antagonism pharmacological profile, and its effect on cognitive function is still vague and lacks comprehensive study. Here, we investigated the impact of l-SPD on two core indexes of executive function, working memory and response inhibition, and learning and memory.
View Article and Find Full Text PDFWe examined DA activity in the medial prefrontal cortex (mPFC) and nucleus accumbens core (NAcc) in two Different Rat Models of Attention-Deficit/Hyperactivity Disorder: Spontaneously Hypertensive Rats (SHR) Versus Lphn3 Knockout Rats. We examined baseline stimulation-evoked phasic DA release, half-life, and DA autoreceptor (DAR) functioning in the mPFC and NAcc, as well as the response to nomifensine (10 mg/kg, IP), a DA transporter (DAT) blocker, on these measures in the NAcc. Both rat models were hypodopaminergic, with notable regional and mechanistic differences.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
December 2024
Department of Biochemistry, King George's Medical University, Lucknow, India.
Heliyon
December 2024
Experimental Research Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Background: Striatal dopamine transporter (DAT) binding is a sensitive and specific endophenotype for detecting dopaminergic deficits across Parkinson's disease (PD) spectrum. Molecular and clinical signatures of PD in asymptomatic phases help understand the earliest pathophysiological mechanisms underlying the disease. We aimed to investigate whether blood epigenetic markers are associated with inter-individual variation of striatal DAT binding among healthy elderly individuals.
View Article and Find Full Text PDFFEBS J
January 2025
Research Center for Pharmaceutical Development, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
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