Dementia with Lewy bodies: a comparison of clinical diagnosis, FP-CIT single photon emission computed tomography imaging and autopsy

Background

Dementia with Lewy bodies (DLB) is a common form of dementia. The presence of Alzheimer''s disease (AD) pathology modifies the clinical features of DLB, making it harder to distinguish DLB from AD clinically during life. Clinical diagnostic criteria for DLB applied at presentation can fail to identify up to 50% of cases. Our aim was to determine, in a series of patients with dementia in whom autopsy confirmation of diagnosis was available, whether functional imaging of the nigrostriatal pathway improves the accuracy of diagnosis compared with diagnosis by means of clinical criteria alone.

Methods

A single photon emission computed tomography (SPECT) scan was carried out with a dopaminergic presynaptic ligand ¹²³I]‐2beta‐carbometoxy‐3beta‐(4‐iodophenyl)‐N‐(3‐fluoropropyl) nortropane (FP‐CIT; ioflupane) on a group of patients with a clinical diagnosis of DLB or other dementia. An abnormal scan was defined as one in which right and left posterior putamen binding, measured semiquantitatively, was more than 2 SDs below the mean of the controls.

Results

Over a 10?year period it was possible to collect 20 patients who had been followed from the time of first assessment and time of scan through to death and subsequent detailed neuropathological autopsy. Eight patients fulfilled neuropathological diagnostic criteria for DLB. Nine patients had AD, mostly with coexisting cerebrovascular disease. Three patients had other diagnoses. The sensitivity of an initial clinical diagnosis of DLB was 75% and specificity was 42%. The sensitivity of the FP‐CIT scan for the diagnosis of DLB was 88% and specificity was 100%.

Conclusion

FP‐CIT SPECT scans substantially enhanced the accuracy of diagnosis of DLB by comparison with clinical criteria alone.Distinguishing patients with dementia with Lewy bodies (DLB) from those with Alzheimer''s disease (AD) can be challenging, in some cases even after repeated follow‐up observation. Imaging modalities which assess the integrity of the nigrostriatal pathway have detected impaired function of this pathway in patients with clinically diagnosed DLB but preserved function in patients with clinically diagnosed AD.^{1,2,3,4,5,6,7,8} Such imaging is potentially of considerable value in supporting a diagnosis of DLB. However, the accuracy of the clinical diagnosis of DLB is imperfect,^9,10 meaning that estimation of the diagnostic accuracy of the imaging investigation needs to be done against neuropathological findings.We have been following a cohort of patients with dementia whose initial dementia diagnosis was made on the basis of standard clinical criteria (for AD,¹¹ for DLB¹²). These patients underwent a single photon emission computed tomography (SPECT) scan using ¹²³I]‐2beta‐carbometoxy‐3beta‐(4‐iodophenyl)‐N‐(3‐fluoropropyl) nortropane (FP‐CIT; ioflupane), a ligand that binds to the presynaptic dopamine transporter, demonstrating the integrity of the nigrostriatal projection pathway. Scanning was undertaken at the time of presentation to our service—that is, directly after the clinical diagnosis was made. Autopsies are now available for 20 patients, enabling us to report what abnormal FP‐CIT scans actually equate to in pathological terms. Furthermore, this autopsy series allows a more robust assessment of the role of FP‐CIT SPECT scanning in the diagnosis of DLB than can be made using clinical diagnoses only.