Extrastriatal dopaminergic and serotonergic pathways in Alzheimer’s disease: A ¹²³I‐FP‐CIT study

Abstract

Background Pathological reports suggest that dopaminergic and serotonergic pathways are early involved in Alzheimer’s disease (AD). 123I‐FP‐CIT SPECT imaging allows the evaluation of both dopamine transporter (DAT) and serotonin transporter (SERT) in several brain regions. Method Alzheimer’s disease patients were included in a multicenter study and underwent a standardized neurological examination, structural imaging and CSF, amyloid and metabolism imaging in order to reach a biomarker diagnosis of AD (i.e. A+T+N+ classification). Each patient underwent 123I‐FP‐CIT SPECT imaging and the bindings of extrastriatal regions of interests were calculated from spatially normalized images. The occipital‐adjusted specific to non‐displaceable binding (SBR) in the different regions was compared between AD and controls adjusting for the effect of age, sex, disease duration and serotonergic/dopaminergic treatment. Result 52 AD patients A+T+N+ and 75 controls entered in the study. AD patients showed lower 123I‐FP‐CIT SPECT SBR in cingulate (p=0.001) and temporal lobe (p=0.007) as well as in insula (p=0.01) and thalamus (p=0.025) compared to controls. When dividing AD according to severity, MCI due to AD (n=17) showed significantly lower parietal SBR compared to controls (p=0.002) and significantly higher SBR in insula (p=0.01), thalamus (p=<0.001) and temporal lobe (p=0.008) compared to AD dementia (n=35). Conclusion We demonstrated extrastriatal dopaminergic and serotonoergic impairment in Alzheimer’s disease. In the parietal cortex the alterations was present already at MCI stage, while in the temporal regions, thalamus and insula alterations appeared later in the AD dementia stage. Longitudinal studies will be necessary in order to evaluate the clinical value of extrastriatal 123I‐FP‐CIT SPECT assessment for possible different pattern of progression and response to treatment in AD patients.

Clinical and Dopamine Transporter Imaging Trajectories in a Cohort of Parkinson's Disease Patients with GBA Mutations

“…Kaasinen et al reported decreased SUVr in the olfactory cortex, thalamus, and anterior cingulate cortex in PD compared to controls 24 . Pilotto et al recently reported a significant SUVr reduction in the thalamus and insula in PD compared to controls 35 . Of note, our study is the first attempt to explore this issue in a group of well‐characterized newly diagnosed GBA‐PD and compare them with two groups of iPD patients.…”

“…24 Pilotto et al recently reported a significant SUVr reduction in the thalamus and insula in PD compared to controls. 35 Of note, our study is the first attempt to explore this issue in a group of wellcharacterized newly diagnosed GBA-PD and compare them with two groups of iPD patients. Alterations of extra-striatal 123 I-FP-CIT SUVr are involved in different phenotypes of iPD 36 and are associated with the severity of motor symptoms and decline of cognitive performance.…”