Striatal dopamine transporters and cognitive function in Parkinson’s disease

Abstract

Background Idiopathic Parkinson’s disease (PD) is characterized by clinical motor symptoms including hypokinesia, rigidity and tremor. In addition to the movement disorder, cognitive deficits are commonly described. In the present study, we applied FP‐CIT SPECT to investigate the impact of nigrostriatal dopaminergic degeneration on cognitive function in PD patients. Methods Fifty‐four PD patients underwent [123I]FP‐CIT SPECT and CERAD (Consortium to Establish a Registry for Alzheimer’s Disease) testing. FP‐CIT SPECT visualized the density of presynaptic dopamine transporters in both striata, each subdivided into a limbic, executive and sensorimotor subregion according to the atlas of Tziortzi et al (Cereb Cortex 24, 2014, 1165). CERAD testing quantified cognitive function. Results In the CERAD testing, PD patients exhibited deficits in the domains of semantic memory, attention, visuospatial function, non‐verbal memory and executive function. After correction for multiple testing, the performance of the subtests Figure Recall and Trail‐Making Test A correlated significantly with FP‐CIT uptake into the ipsilateral executive subregion. The performance of the subtest Figure Saving correlated significantly with FP‐CIT uptake into the contralateral executive subregion. Conclusions The significant correlation between cognitive function and density of nigrostriatal dopamine transporters, as assessed by FP‐CIT SPECT, indicate that striatal dopaminergic pathways—primarily the executive striatal subregion—are relevant to cognitive processing in PD.

Dopamine-Related Reduction of Semantic Spreading Activation in Patients With Parkinson’s Disease

“…In addition, a more heterogeneous picture of cognition in PD has emerged, as other cognitive domains may be impaired in PD in addition to executive functions: this includes impairments in semantic processing (MacDonald et al, 2019 ; Stögbauer et al, 2020 ), as well as a variety of language functions including pragmatic abilities such as metaphor comprehension (Monetta and Pell, 2007 ; Baraldi et al, 2021 ), syntactic processing (Johari et al, 2019 ), verb use (Holtgraves et al, 2010 ; Salmazo-Silva et al, 2017 ), and lexico-semantic retrieval (Foster et al, 2008 ; Salmazo-Silva et al, 2017 ; Silveri et al, 2018 ; Wagner et al, 2020 ). The most consistent finding with respect to language functions, however, is a significantly reduced verbal fluency (VF) in PD patients (e.g., Gotham et al, 1988 ; Raskin et al, 1992 ; Flowers et al, 1995 ; Troyer et al, 1998 ; Obeso et al, 2012 ; El-Nazer et al, 2019 ).…”

A mind in motion: Exercise improves cognitive flexibility, impulsivity and alters dopamine receptor gene expression in a Parkinsonian rat model

“…The importance of the striatum in EF, also termed the basal ganglia (BG) or caudate nucleus-putamen (CPu), is based on a large rodent and human literature (see review ( Macdonald and Monchi, 2011 )). For example, in individuals with PD, resting state functional magnetic resonance imaging, as well as positron emission tomographic neuroimaging, have demonstrated hypo-activation in a number of cortical and sub-cortical (basal ganglia) regions impacting the EF network ( Kim et al, 2019 ; Apostolova et al, 2020 ; Stögbauer et al, 2020 ; Hirano, 2021 ).…”