[123]FP-CIT SPECT scans initially rated as normal became abnormal over time in patients with probable dementia with Lewy bodies

Abstract

PurposeDecreased striatal dopamine transporter (DAT) binding on SPECT imaging is a strong biomarker for the diagnosis of dementia with Lewy bodies (DLB). There is still a lot of uncertainty about patients meeting the clinical criteria for probable DLB who have a normal DAT SPECT scan (DLB/S−). The aim of this study was to describe the clinical and imaging follow-up in these patients, and compare them to DLB patients with abnormal baseline scans (DLB/S+).MethodsDLB patients who underwent DAT imaging ([123I]FP-CIT SPECT) were selected from the Amsterdam Dementia Cohort. All [123I]FP-CIT SPECT scans were evaluated independently by two nuclear medicine physicians and in patients with normal scans follow-up imaging was obtained. We matched DLB/S-− patients for age and disease duration to DLB/S+ patients and compared their clinical characteristics.ResultsOf 67 [123I]FP-CIT SPECT scans, 7 (10.4 %) were rated as normal. In five DLB/S− patients, a second [123I]FP-CIT SPECT was performed (after on average 1.5 years) and these scans were all abnormal. No significant differences in clinical characteristics were found at baseline. DLB/S− patients could be expected to have a better MMSE score after 1 year.ConclusionThis study was the first to investigate DLB patients with the initial [123I]FP-CIT SPECT scan rated as normal and subsequent scans during disease progression rated as abnormal. We hypothesize that DLB/S− scans could represent a relatively rare DLB subtype with possibly a different severity or spread of alpha-synuclein pathology (“neocortical predominant subtype”). In clinical practice, if an alternative diagnosis is not imminent in a DLB/S− patient, repeating [123I]FP-CIT SPECT should be considered.

FDG PET, dopamine transporter SPECT, and olfaction: Combining biomarkers in REM sleep behavior disorder

“…In 2 of these cases, 18 F‐FDG‐PET was performed before DAT‐SPECT. It has been shown that some DLB patients may initially have unremarkable DAT scans 30. It is possible that RBD subjects with significant PDRP expression but normal DAT binding will eventually develop DLB.…”

Is dopamine transporter invariably impaired at the time of diagnosis in dementia with Lewy bodies?

“…However, the 88 % sensitivity found by Walker et al suggests that one in eight DLB patients with confirmed DLB pathology at autopsy might have a normal 123 I-ioflupane SPECT scan. The patient with a normal scan actually had an asymmetric presentation with right-sided parkinsonism resembling a corticobasal syndrome, with abnormal posterior left putamen uptake on visual analysis but normal average counts between the two putamina (the index considered in the paper).…”

“…The demonstration of nigrostriatal dopaminergic impairment by SPECT or PET was included in the diagnostic criteria published in 2005 merely as a supportive feature [3]. Still a head-to-head comparison between 123 Iioflupane SPECT and neuropathology was needed. This was performed by Walker et al [4] who found a specificity of 100 % and a sensitivity of 88 % with semiquantitative analysis of the posterior putamen.…”

“…In 2011 a neuropathological study conducted in patients with DLB, AD and Parkinson's disease dementia (PDD) showed that 123 I-ioflupane SPECT correlated fairly well with neuronal density in the SN but not with the amount of α-synuclein, tau or amyloid pathology in the SN on post-mortem examination [6], although the authors commented that the lack of correlation with the amount of nigral α-synuclein and tau pathology might have been due to the relatively low number of patients. In that neuropathological series 2 of the 19 patients with DLB or PDD actually had a normal scan and a normal or slightly reduced SN neuronal density.…”

“…The availability of 123 I-ioflupane SPECT for dopamine transporter (DAT) assessment in the early 2000s prompted a large European multicentre study published in 2007 whose conclusion was that 123 I-ioflupane SPECT has a good accuracy in detecting dopaminergic impairment both in probable and in possible DLB (with clinical diagnosis as the gold standard), achieving about 90 % specificity, similar to clinical diagnosis in previous studies, but a definitely higher sensitivity (77.7 %) thus pointing to this tool as a valuable support for the clinical diagnosis of DLB [2]. The demonstration of nigrostriatal dopaminergic impairment by SPECT or PET was included in the diagnostic criteria published in 2005 merely as a supportive feature [3].…”