Severity of neuropsychiatric symptoms and dopamine transporter levels in dementia with Lewy bodies: A ¹²³I‐FP‐CIT SPECT study

Abstract

Neuropsychiatric symptoms are frequent in dementia with Lewy bodies (DLB). Dopamine transporter (DAT) imaging with (123)I-labeled ligand N-delta-(fluoropropyl)-2 beta-carbomethoxy-3beta-(4-iodophenyl)tropene ((123)I-FP-CIT), which reliably measures midbrain dopaminergic dysfunction, has provided important evidence on the neurobiological substrate of some of these symptoms including apathy and depression. However, little is known on DAT levels and other distressing symptoms such as delusions and hallucinations. Therefore, (123)I-FP-CIT imaging was performed in 18 well-characterized patients with DLB, and striatal DAT levels were correlated with the frequency/severity ratings of several neuropsychiatric symptoms. A wide range of neuropsychiatric symptoms could be observed in the sample. Significant correlations were observed between decreased striatal DAT levels and visual hallucinations. Although there were no correlations between striatal DAT levels and other neuropsychiatric symptoms, when considering the putamen and the caudate nucleus separately, delusions, depression, and apathy were inversely correlated to decreased caudate DAT levels. The seresults provide intriguing evidence on the involvement of the mesocortical dopaminergic pathways in neuropsychiatric symptoms in DLB.

Striatal Dopamine Transporter Binding Does Not Correlate with Clinical Severity in Dementia with Lewy Bodies

“…We did not confirm the findings of Roselli et al (12), as we found no correlation between low striatal binding and the presence of hallucinations. There are some differences between our study and the study by Roselli et al Primarily, 123 I-FP-CIT binds not only to DAT but also to the serotonin transporter, which also is present in the striatum (13), and this factor is not discussed by Roselli et al (13).…”

“…Roselli et al showed a high inverse correlation between the degree of hallucinations and striatal function assessed with 123 I-FP-CIT (12). This finding is somewhat contradictory to the literature regarding the pathophysiology for hallucinations in DLB patients.…”

“…The frontal hypoperfusion is interesting, since the dorsolateral circuit involved in planning and attention connects the frontal cortex with the striatum and thus attentional fluctuations are also greatly influenced by the striatum and the dopamine system (11). One study that included 18 patients with well-defined DLB and used 123 I-FP-CIT as the radioligand found a correlation between SPECT DAT and visual hallucinations (12). However, this study would be interesting to replicate.…”

Neuroimaging Findings in Dementia with Lewy Body: A Review

“…In particular, in a phase III multicentre study among a large cohort of subjects, McKeith and co-workers determined the effectiveness of FP-CIT SPECT to distinguish DLB from other dementias (principally AD), revealing a sensitivity and specificity of respectively 78% and 90% respectively. So far, there have been published many studies that investigated DLB by dopaminergic SPECT (Colloby et al, 2005;David et al, 2008;Lim et al, 2009;O'brien et al, 2009;Roselli et al, 2009;Walker et al, 2007). All these works consistently show the diagnostic value of dopaminergic SPECT as applied to DLB, through the evaluation of the striatal dopaminergic innervations reduction, also in the distinction from other dementias (Soret et al, 2006).…”

Dopamine receptor D4 promoter hypermethylation increases the risk of drug addiction

“…Heroin addicts have lower levels of striatal dopamine transporter and more depressive symptoms compared with healthy controls (32,33). A previous study on genome-wide DNA methylation profiling identified that DNA methylation levels were lower in patients with major depressive disorder compared with controls and that the majority of the methylated sites (85.7%) were located on the promoter CpG islands (34).…”