Early identification and phenotyping of prodromal dementia with Lewy bodies via established and novel biomarkers: PRO-DLB

• Applicant: Privatdozent Dr. Niels Hansen
• Subject Area: Biological Psychiatry
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 530229798

Prodromal dementia with Lewy bodies (DLB) is difficult to diagnose, as it differs in how it is differentiated from psychiatric disorders or mild cognitive impairment (MCI) having other etiologies. There is a genuine need for improving the early diagnosis of prodromal DLB. Our goal is to evaluate and validate potentially novel clinical (neuropsychology and psychopathology) and molecular biomarkers (monoaminergic markers, and markers of alpha-synuclein in serum exosomes) to optimize the diagnosis of prodromal stage DLB along with subtypes of MCI-, psychiatric- and delirium-onset, and early DLB compared to disease controls (MCI due to Alzheimer´s disease (AD), delirium and psychiatric episode) in an age- and sex-matched case-control study design. All patients with suspected prodromal DLB will be stratified using established biomarkers such as (123)-I-2-ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane single photon emission computed tomography (123I-FP-CIT SPECT), [123I] Metaiodobenzylguanidine (MIBG) cardiac scintigraphy, and polysomnography. We will investigate monoaminergic blood biomarkers in DLB at the prodromal stage compared to controls. We expect to find more monoaminergic markers in the blood and CSF of DLB patients at the prodromal stage than in controls. In addition, we will investigate alpha-synuclein in serum exosomes as a proxy for alpha-synucleinopathy in prodromal stage DLB. We will correlate our biomarker results with psychopathological and neuropsychological performance data between patient DLB subgroups (psychiatric-onset, MCI-onset, delirium-onset) and controls. Taken together, first, through our study we will evaluate biomarkers by which to stratify DLB patients with a psychiatric- or MCI-onset and differentiate them from early AD patients. Second, our understanding of prodromal DLB will be elucidated.

• DFG Programme: Research Grants