FDG Metabolism in Dementia With Lewy Body (DLB) Patients as Indicated by PET Dynamic Acquisition

Summary

Dementia with Lewy Body (DLB) is a common neurodegenerative disorder responsible to 15%-20% of the dementia cases in the elderly population.

Dementia with Lewy Body (DLB) is a common neurodegenerative disorder responsible to 15%-20% of the dementia cases in the elderly population . This disorder belongs to the family of synucleinopathies, which are diseases characterized by the abnormal accumulation of the protein α-synuclein (α-syn) in neuronal and non-neuronal cells in the brain. The clinical symptoms of DLB include dementia with the presence of fluctuations in attention or alertness, recurrent visual hallucinations, spontaneous extrapyramidal motor features and REM sleep behavior disorder (RBD). Supportive clinical symptoms are severe sensitivity to antipsychotic agents, postural instability, repeated falls, syncope or other transient episodes of unresponsiveness, severe autonomic dysfunction e.g. constipation, orthostatic hypotension, urinary incontinence, hypersomnia, hyposmia, hallucinations in other modalities, systematized delusions, apathy, anxiety and depression. DLB differs from PD by the order of appearance of clinical symptoms.

The diagnosis of DLB requires in addition to the clinical symptoms the existence biomarkers indicating the pathology. It is important to note that due to the complexity of DLB diagnosis, mainly due to the similarity of this syndrome to other dementia conditions, more than one biomarker is required to identify DLB \[6\]. The biomarkers contain indicative biomarkers and supportive biomarkers. Indicative biomarkers include a. Assessment of the integrity of dopaminergic system by either F-DOPA Positron Emission Tomography (PET) or by Ioflupane 123I (DaT) Single Photon Emission Tomography (SPECT) scans. b. Abnormal (low uptake) MIBG myocardial scintigraphy. c. Polysomnographic confirmation of REM sleep without atonia.

Supportive biomarkers are: a. MRI/CT scans showing neuronal structural modifications with relative preservation of medial temporal lobe structures. b. Generalized low uptake on SPECT/PET perfusion/metabolism scan with reduced occipital activity +/- the cingulate island sign on 18F-fludeoxyglucose (FDG) PET imaging. c. Prominent posterior slow wave activity on EEG with periodic fluctuations in the pre-alpha/theta range.

Biochemical biomarkers from the blood and spinal fluid were also investigated. These biomarkers include measurement of levels of Amyloid β, tau, and phospho-tau measurements. However, they do not allow differentiation between DLB and AD. α-syn was not proven as a biomarker.

Conditions

• Dementia With Lewy Bodies

Interventions

DIAGNOSTIC_TEST

PET-CT FDG brain scan

Scans will be performed in Discovery MI PET/CT scanner (by GE). Dynamic FDG PET scan start immediately after a bolus injection of 18F-FDG (0.1 mCi/kg) 5. Dynamic PET scan protocol of 30 min will be follow by a static scan protocol with a duration of 8 min combined with a low dose CT scan. The radiation exposure of the patients is equal to the radiation exposure during the routine PET-CT FDG brain scan. The only discomfort to the patient is a longer scan duration. After the scan is concluded the patient will be released with no restrictions. Each of the acquired PET images will undergo visual assessment. In addition, quantification of the image data using Standardized Uptake Values (SUV) and kinetic model. The correlation between the clinical information, visual assessment and quantitative parameters will be tested. Sensitivity and accuracy of the quantification methods will be calculated.

Sponsors & Collaborators

• Tel-Aviv Sourasky Medical Center

  lead OTHER_GOV

Study Design

Allocation

NA

Purpose

DIAGNOSTIC

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

120 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-12-14

Primary Completion

2020-01-14

Completion

2021-12-14