Adjustment for the Age-and Gender-Related Metabolic Changes Improves the Differential Diagnosis of Parkinsonism

Age and gender are the important factors for brain metabolic declines in both normal aging and neurodegeneration,and the confounding effects may influence early and differential diagnosis of neurodegenerative diseases based on the[^(18)F]fluorodeoxyglucose positron emission tomography([^(18)F]FDG PET).We aimed to explore the potential of the adjustment of age-and gender-related confounding factors on[^(18)F]FDG PET images in differentiation of Parkinson’s disease(PD),multiple system atrophy(MSA)and progressive supra-nuclear palsy(PSP).Eight hundred and seventy-seven clinically definitely diagnosed Parkinsonian patients from a benchmark Huashan Parkinsonian PET imaging database were included.An age-and gender-adjusted Z(AGAZ)score was established based on the gender-specific longitudinal metabolic changes on healthy subjects.AGAZ scores and standardized uptake value ratio(SUVR)values were quantified at regional-level and support vector machine-based error-correcting output codes method was applied for classification.Additional references of the classifications based on metabolic pattern scores were included.The feature-based AGAZ score showed the best performance in classification(accuracy for PD,MSA,PSP:93.1%,96.3%,94.8%).In both genders,the AGAZ score con-sistently achieved the best efficiency,and the improvements compared to the conventional SUVR value for PD,MSA,and PSP mainly laid in specificity(Male:5.7%;Female:11.1%),sensitivity(Male:7.2%;Female:7.3%),and sensitivity(Male:7.3%;Female:17.2%).Female patients benefited more from the adjustment on[^(18)F]FDG PET in MSA and PSP groups(absolute net reclassification index,p<0.001).Collectively,the adjustment of age-and gender-related confounding factors may improve the differential diagnosis of Parkinsonism.Particularly,the diagnosis of female Parkinsonian population has the best improvement from this correction.

Kallikrein-related peptidases 6 and 10 are elevated in cerebrospinal fluid of patients with Alzheimer’s disease and associated with CSF-TAU and FDG-PET

Background:Alterations in the expression of human kallikrein-related peptidases(KLKs)have been described in patients with Alzheimer’s disease(AD).We elucidated the suitability of KLK6,KLK8 and KLK10 to distinguish AD from NC and explored associations with established AD biomarkers.Methods:KLK levels in cerebrospinal fluid(CSF),as determined by ELISA,were compared between 32 AD patients stratified to A/T/(N)system with evidence for amyloid pathology and of 23 normal controls with normal AD biomarkers.Associations between KLK levels and clinical severity,CSF and positron emission tomography(PET)based AD biomarkers were tested for.Results:Levels of KLK6 and KLK10 were significantly increased in AD.KLK6 differed significantly between AD A+/T+/N+and AD A+/T−/N+or NC with an AUC of 0.922.CSF pTau and tTau levels were significantly associated with KLK6 in AD.Conclusions:KLK6 deserves further investigations as a potential biomarker of Tau pathology in AD.