Objective: Because of the time course of detecting DLB symptoms and signs, DLB is poorly diagnosed and hardly differentiate from AD, especially in early stage of dementia without the core clinical features of DLB.

Background: We investigated patients with a clinical diagnosis of amnestic mild cognitive impairment (MCI) and early AD whether they had cardiac sympathetic denervation, detected by cardiac 123I-MIBG scintigraphy. And we also assessed presynaptic nigrostriatal dopaminergic system by 18F FP-CIT-PET imaging to distinguish between DLB and AD.

Method: Thirty patients (72±9.0 yrs old: M:F 17:13) with a clinical diagnosis of  amnestic MCI and early AD (CDR 0.5/SOB 3) who have been had visual hallucination and/or suspicious fluctuating cognition history without parkinsonism (n=20, prodromal DLB group, pDLB) and who have not been had visual hallucination and/or suspicious fluctuating cognition

history (n=10, early AD group, eAD) enrolled in this study. 23I-Metaiodobenzylguanidine (MIBG) uptake was assessed using the ratio of the heart to the upper mediastinum (H/M ratio), and we also assessed presynaptic nigrostriatal dopaminergic system by 18F FP-CIT-PET imaging to distinguish between pDLB and eAD. Autonomic function tests and orthostatic vital signs were recorded.

Results: The H/M ratio were decreased in pDLB group, and the mean H/M ratio was significantly lower(early/delayed uptake:1.72±0.61/1.65±0.63) compared with eAD group (early/delayed uptake:2.36±0.50/2.15±0.29) in 123I-MIBG scintigraphy (p<0.05). Presynaptic nigrostriatal dopaminergic deficits were founded in 18F FP CIT PET and orthostatic hypotension was evident only in pDLB group regardless of spontaneous Parkinsonism (n=17, 85%).

Conclusion: Myocardial postganglionic sympathetic denervation and autonomic dysfunctions especially orthostatic hypotension can be good biomarkers to predict DLB before core clinical symptoms appear, and may useful to distinguish from AD even in early stage. This study is under long term follow up.

References: 1. Sympathetic noradrenergic before striatal dopaminergic denervation: relevance to Braak staging of synucleinopathy.
Goldstein DS, Holmes C, Sewell L, Park MY, Sharabi Y. Clin Auton Res. 2012 Feb;22(1):57-61. doi: 10.1007/s10286-011-0136-4. Epub 2011 Jul 28.
2.Roles of cardiac sympathetic neuroimaging in autonomic medicine.
Goldstein DS, Cheshire WP Jr. Clin Auton Res. 2018 Aug;28(4):397-410. doi: 10.1007/s10286-018-0547-6. Epub 2018 Jul 30.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/myocardial-sympathetic-denervation-biomarkers-for-early-detection-of-prodromal-dlb/