Molecular Imaging of the Cholinergic System in Parkinson's Disease

Abstract

One of the first identified neurotransmitter in the brain, acetylcholine is an important modulator that drives changes in neuronal and glial activity. For more than two decades, the main focus of molecular imaging of the cholinergic system in Parkinson’s disease (PD) has been on cognitive changes. Studies have shown that degeneration of the cholinergic system is a major determinant of dementia in PD. Within the last decade, the focus is expanding to studying cholinergic correlates of mobility impairments, dyskinesias, olfaction, sleep, visual hallucinations and risk taking behavior in this disorder. These studies increasingly recognize that the regional topography of cholinergic brain areas associates with specific functions. In parallel with this trend, more recent molecular cholinergic imaging approaches are investigating cholinergic modulatory functions and contributions to large-scale brain network functions. A novel area of research is imaging cholinergic innervation functions of peripheral autonomic organs that may have the potential of future prodromal diagnosis of PD. Finally, emerging evidence of hypercholinergic activity in prodromal and symptomatic LRRK2 PD may reflect neuronal cholinergic compensation versus a response to neuro-inflammation. Molecular imaging of the cholinergic system has led to many new insights in the etiology of many dopamine non-responsive symptoms of PD and is poised to guide and evaluate future cholinergic drug development in PD.

Resting-State Cerebello-Cortical Dysfunction in Parkinson's Disease

“…Paracentral lobules, SMA, frontal gyrus, superior parietal, and occipital lobules have all been identified as areas with abnormal metabolism, connectivity, and/or neurotransmission ( 2 ). While occipital dysfunction is not observed consistently, alterations in cholinergic activity that are hypothesized to drive memory deficits are present in the occipital lobe in early PD ( 31 , 32 ). This is consistent with our finding that there is decreased FC to occipital lobule in our early stage (duration = 7.7 ± 4.2 years) PD cohort.…”

Cognitive tests that identify high risk of conversion to dementia in Parkinson’s disease

“…Genetic variation, for example in the microtubule-associated protein tau gene, alpha synuclein gene and glucocerebrosidase gene, also influences the risk of dementia 54,60,61 . Degenerating cholinergic pathways, white matter hyperintensities and cortical thinning are among brain correlates that influence the course of cognitive decline [62][63][64][65][66][67][68] . Another interesting question is whether more fundamental changes in visual perception, including poor visual acuity, contrast sensitivity and color vision, also associate with the risk of dementia 14,69 .…”

Clinical Perspectives of Parkinson's Disease for Ophthalmologists, Otorhinolaryngologists, Cardiologists, Dentists, Gastroenterologists, Urologists, Physiatrists, and Psychiatrists

“… 31 32 The cholinergic changes in the brainstem and brainstem-subcortical circuits have been implicated in the development of parasomnias in patients with PD. 31 33 Certain drugs that include selective serotonin reuptake inhibitor, serotonin-norepinephrine reuptake inhibitor, and tricyclic antidepressant can trigger both RBD and non-REM parasomnias. 34 RLS, characterized by uncomfortable sensations in the legs, an urge to move, and a transitory decrease after moving, as well as PLMS, rhythmical extension of the big toe and dorsiflexion of the ankle, have been reported in 15%–20% of patients with PD.…”