VALIDATION BY NEUROPATHOLOGY OF FP-CIT NEUROIMAGING IN DEMENTIA WITH LEWY BODIES

Abstract

Dementia with Lewy bodies (DLB) is the second commonest neurodegenerative cause of dementia. In the absence of synuclein imaging indirect detection of synuclein pathology may be achieved through agents binding to the dopamine transporter, measuring loss of dopaminergic neurones in the substantia nigra leading to a loss of striatal dopamine transporter. Such dopaminergic imaging, e.g. using 123I-FP-CIT SPECT, is a suggestive diagnostic feature in the current consensus diagnostic criteria for DLB. Studies using FP-CIT with clinical diagnosis as the standard have reported very good accuracy (sensitivity 78%, specificity 90%). However, there has been little neuropathology validation of FP-CIT imaging. We conducted an autopsy validation study of FP-CIT imaging for the diagnosis of DLB. All subjects over 60 with dementia who had donated their brain tissue to the Newcastle Brain Bank and who had had FP-CIT imaging in research studies were included. Subjects came from studies in London and Newcastle. Clinical diagnoses were applied by consensus panels using international diagnostic criteria. All subjects had a baseline FP-CIT scan which was rated by blinded panels as normal or abnormal and were reviewed in prospective studies until death. They then underwent autopsy and final neuropathological diagnoses were applied. 55 patients were included in this analysis (33 DLB, 22 AD). Against autopsy diagnosis FP-CIT had a balanced diagnostic accuracy of 86% (sensitivity 80%, specificity 92%), compared with clinical diagnosis whose accuracy was 79% (sensitivity 87%, specificity 72%). 10% of patients with clinical DLB met pathological criteria for Lewy body disease but had had normal FP CIT imaging. Such cases had high neocortical and limbic synucleinopathy but minimal brainstem involvement This autopsy study found FP-CIT to be a valid and accurate biomarker of DLB in the context of dementia. The specificity of FP-CIT diagnosis was 20% higher than clinical diagnosis which is important when selecting ‘pure’ groups for interventional studies. The finding that a normal dopaminergic scan occurs in about 10% of DLB is consistent with not all DLB patients developing parkinsonism. It is important to remember that a normal FP-CIT scan does not exclude Lewy body disease.