Not So Fast: Signs of Lewy body dementia not seen by dopamine SPECT

For patients suspected to have dementia with Lewy bodies (DLB), SPECT brain imaging of the dopamine transporter (DAT) system has been considered a possible means of evaluating classic symptoms of the disease—hallucinations, cognitive fluctuations, dementia and parkinsonism—and disease-specific changes in striatal dopaminergic function, but researchers have found no such positive connection, according to a study published May 1 by the Journal of Nuclear Medicine.

Morten Ziebell, MD, from the neurobiology research unit at University of Copenhagen in Denmark, and colleagues observed that DAT availability was not a clear marker for major symptoms of DLB in newly diagnosed patients.

This study focused on SPECT imaging using the radiotracer 123I-N-(3-iodoprop-2E-enyl)-2-beta-carbomethoxy-3beta-(4-methylphenyl) nortropane (123I-PE2I) as a binding agent to the dopamine transporter system providing information about dopamine transporter availability and therefore striatal dopaminergic function, which was thought to be intrinsically involved in Lewy body illnesses, not just Parkinson's disease (PD) but also DLB. However, findings of this retrospective controlled study showed that binding of I-123 PE21 to the dopamine transporter system does not correlate with symptoms of DLB.

“Since more than half of DLB patients clinically and neuropathologically show overlap with both Alzheimer disease patients and idiopathic PD patients, we were interested in determining whether the cognitive dysfunction [assessed with Mini Mental State Examination] in DLB patients correlated with striatal dopaminergic function,” wrote Ziebell et al. “Our results suggest that the general level of cognitive impairment in DLB patients is not influenced by striatal dopaminergic dysfunction.”

A total of 280 patients were given a battery of neurological evaluations and cognitive testing according to Yahr and Hoehn grading and Mini Mental State Examination to indicate presence of DLB and were then referred to undergo SPECT imaging to gauge dopamine transporter with I-123 PE21. At follow up a minimum of three months later, but averaging about 16 months, DLB was diagnosed in 51 of these subjects based on clinical guidelines. Patients were not pharmacologically influenced and ranged from having barely any symptoms to being extremely symptomatic. Scans from this key cohort were matched with SPECT I-123 PE21 scans of 28 healthy controls to observe the correlation. There was no significant connection found between results of the Mini Mental State evaluation and DAT binding in the putamen, caudate nucleus and striatum regions of interest.

“Even though we should be careful about drawing any major conclusions from data based on the present group of DLB patients, the results overall suggest that DLB in its early stages is more similar to Alzheimer disease with cortical dysfunction than to striatal dysfunction expressed as decreased DAT density [as it is in Parkinson’s disease], and this possibility may explain the symptomatology,” wrote the authors. “Most likely, however, the cortical dysfunction is more related to a cortical distribution of Lewy bodies than to Alzheimer disease pathology alone.”

These results indicated that for those with DLB, striatal dopaminergic function may not be related at all, as previously thought, since neither outcomes of cognitive testing nor major symptoms of the disease were found to match SPECT I-123 PE21 binding of DAT systems. Further studies will need to be conducted with larger patients populations and prospectively to replicate these findings and make final conclusions about DAT imaging with SPECT for the evaluation of DLB, the researchers concluded.