Article
Clinical Neurology
Nicola J. J. Ray, Prabesh Kanel, Nicolaas I. I. Bohnen
Summary: Structural imaging of the cholinergic basal forebrain may provide a biomarker for cholinergic system integrity in Parkinson's disease. This study validates the correlation between cholinergic basal forebrain morphometry and vesicular acetylcholine transporter in a large Parkinson's sample.
ANNALS OF NEUROLOGY
(2023)
Review
Biochemistry & Molecular Biology
Rachid Mahmoudi, Jean Luc Novella, Sarah Laurent-Badr, Sarah Boulahrouz, David Tran, Isabella Morrone, Yacine Jaidi
Summary: Cholinergic antagonists interfere with synaptic transmission in the central nervous system and are involved in pathological processes in patients with neurocognitive disorders (NCD), such as behavioral and psychological symptoms of dementia (BPSD). In this commentary, we review the impact of cholinergic burden on BPSD in NCD patients, including the main pathophysiological mechanisms. Given the lack of consensus on symptomatic management of BPSD, attention should be paid to this preventable, iatrogenic condition in NCD patients, and de-prescription of cholinergic antagonists should be considered for patients with BPSD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Nira Cedres, Daniel Ferreira, Milan Nemy, Alejandra Machado, Joana B. Pereira, Sara Shams, Lars-Olof Wahlund, Anna Zettergren, Olga Stepankova, Lenka Vyslouzilova, Maria Eriksdotter, Stefan Teipel, Michel J. Grothe, Kaj Blennow, Henrik Zetterberg, Michael Scholl, Silke Kern, Ingmar Skoog, Eric Westman
Summary: This study aimed to determine the contribution of amyloid, tau, and cerebrovascular biomarkers to the degeneration of cholinergic white matter projections in cognitively unimpaired individuals. The results showed that WM lesion burden played a central role in the degeneration of cholinergic pathways, while levels of A beta(38) and p-tau also contributed to degeneration. These findings are important for the development of prevention programs for neurodegeneration and cognitive impairment.
Article
Clinical Neurology
Niels Okkels, Jacob Horsager, Miguel Labrador-Espinosa, Pernille L. Kjeldsen, Malene F. Damholdt, Janne Mortensen, Karsten Vestergard, Karoline Knudsen, Katrine B. Andersen, Tatyana D. Fedorova, Casper Skjaerbaek, Hanne Gottrup, Allan K. Hansen, Michel J. Grothe, Per Borghammer
Summary: Cholinergic changes are highly relevant in the progression of dementia with Lewy bodies. This study found significant loss of cholinergic terminals in newly diagnosed patients with dementia with Lewy bodies, which correlated with atrophy of cholinergic cell clusters in the basal forebrain. The study also suggests that cholinergic system degeneration is linked with brain metabolism and degeneration of other neurotransmitter systems.
Article
Nutrition & Dietetics
Ji-Hye Choi, Eun-Byeol Lee, Hwan-Hee Jang, Youn-Soo Cha, Yong-Soon Park, Sung-Hyen Lee
Summary: Allium hookeri (AH) is a medicinal food used in Southeast Asia with positive effects in relieving memory impairment induced by scopolamine, especially the root extracts. AH improves cognitive effects by enhancing the cholinergic system, inhibiting neuroinflammation, and providing neuroprotective effects.
Review
Neurosciences
Alexandre Iarkov, Cristhian Mendoza, Valentina Echeverria
Summary: Parkinson's disease is characterized by the loss of dopaminergic neurons in the midbrain, triggered by genetic and environmental factors causing inflammation and mitochondrial dysfunction. This leads to oxidative stress, proteinopathy, and reduced viability of dopaminergic neurons.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Behavioral Sciences
Balazs Knakker, Vilmos Olah, Attila Trunk, Balazs Lendvai, Gyorgy Levay, Istvan Hernadi
Summary: The study found that the acetylcholinesterase inhibitor donepezil partially rescued the scopolamine-induced impairments of visual working memory (VWM) performance, while scopolamine-induced impairments of VWM maintenance are delay-dependent, especially affecting the time range of 15 to 33 seconds.
BEHAVIOURAL BRAIN RESEARCH
(2021)
Article
Multidisciplinary Sciences
Serena Becchi, Billy Chieng, Laura A. Bradfield, Roberto Capellan, Beatrice K. Leung, Bernard W. Balleine
Summary: The loss of neurons in the parafascicular thalamus and their inputs to dorsomedial striatum in Lewy body disease and Parkinson's disease dementia have been associated with neuroinflammation. The effects of this neuroinflammation on the function of striatal cholinergic interneurons and the encoding of action-outcome associations necessary for goal-directed action were investigated in rats. The study found that the neuroinflammation inhibited the activity of cholinergic interneurons and disrupted goal-directed control, but these effects could be rescued by administration of selegiline, which enhances the activity of adenosine triphosphatase in cholinergic interneurons.
Article
Clinical Neurology
Matthew J. Barrett, Justin M. Murphy, Jeffrey Zhang, Jamie C. Blair, Joseph L. Flanigan, Huma Nawaz, W. Alex Dalrymple, Scott A. Sperling, James Patrie, T. Jason Druzgal
Summary: In early Parkinson's disease patients, impaired olfaction is associated with degeneration of the cholinergic basal forebrain and multiple brain regions, and cognitive decline may be mediated by atrophy of the cortex and hippocampus.
PARKINSONISM & RELATED DISORDERS
(2021)
Article
Biochemistry & Molecular Biology
Christopher Simon, Tomoko Soga, Nafees Ahemad, Saatheeyavaane Bhuvanendran, Ishwar Parhar
Summary: This study discovers a neuropeptide, KP-10, that can alleviate the damage caused by amyloid-beta and alpha-synuclein in cholinergic neurons. KP-10 mitigates alpha-synuclein-induced toxicity in cholinergic neurons through preferential binding. Moreover, in vitro and in silico experiments support this observation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Behavioral Sciences
Isabella F. Orlando, James M. Shine, Trevor W. Robbins, James B. Rowe, Claire O'Callaghan
Summary: Noradrenergic and cholinergic systems play a crucial role in neuropsychiatric diseases of aging like Alzheimer's disease and Parkinson's disease. However, their contribution to symptoms is not well understood, and pharmacological interventions targeting these systems have had mixed success. This review addresses these challenges, outlining the roles of these systems in cognition and behavior and discussing their influence on neuropsychiatric symptoms in disease. Bridging across levels of analysis, the review emphasizes opportunities for improving drug therapies and personalized medicine strategies.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2023)
Review
Clinical Neurology
Prabesh Kanel, Marc-Andre Bedard, Meghmik Aghourian, Pedro Rosa-Neto, Jean-Paul Soucy, Roger L. Albin, Nicolaas I. Bohnen
Summary: This study reviewed brain cholinergic denervation in AD and DLB patients using molecular imaging, revealing distinct cortical and subcortical cholinergic lesions that can differentiate between the two types of dementia. The differential vulnerability of specific cholinergic projections may be associated with specific clinical features of these disorders, offering potential for symptomatic therapies through improved understanding of cholinergic deficits in the brain region.
CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS
(2021)
Article
Multidisciplinary Sciences
Ying Jiang, John J. Alam, Stephen N. Gomperts, Paul Maruff, Afina W. Lemstra, Ursula A. Germann, Philip H. Stavrides, Sandipkumar Darji, Sandeep Malampati, James Peddy, Cynthia Bleiwas, Monika Pawlik, Anna Pensalfini, Dun-Sheng Yang, Shivakumar Subbanna, Balapal S. Basavarajappa, John F. Smiley, Amanda Gardner, Kelly Blackburn, Hui-May Chu, Niels D. Prins, Charlotte E. Teunissen, John E. Harrison, Philip Scheltens, Ralph A. Nixon
Summary: The study found that Rab5 is closely related to BFCN degeneration, and inhibiting Rab5 activity may be a method for treating related diseases. The use of neflamapimod reduced Rab5 activity, reversed endosomal pathology, and restored the number and morphology of BFCNs. The clinical trial in DLB patients showed that neflamapimod did not affect cognitive function, but there were improvements in functional mobility and dementia rating-scale, confirming its effect on BFCN function.
NATURE COMMUNICATIONS
(2022)
Review
Clinical Neurology
Jacopo Pasquini, David J. Brooks, Nicola Pavese
Summary: The central cholinergic system plays a crucial role in regulating various functions of human behavior. In Parkinson's disease, disruptions in central cholinergic transmission are associated with cognitive decline, movement issues, and other symptoms. Studies suggest that degeneration of basal forebrain nuclei is linked to cognitive decline, while pathology in the pontine nuclei may precede the onset of motor symptoms.
MOVEMENT DISORDERS CLINICAL PRACTICE
(2021)
Article
Biochemistry & Molecular Biology
Shi Yu Yang, Jan-Willem Taanman, Matthew Gegg, Anthony H. Schapira
Summary: Cognitive impairment is a common complication of Parkinson's disease, and GBA1 gene variants are an important risk factor for PD and dementia with Lewy bodies. This study found that GBA1 mutations interfere with the metabolism of alpha-synuclein and tau proteins, leading to higher levels of these proteins in cholinergic neurons. Enhancing GCase activity can reduce the levels of these proteins, providing a potential therapeutic target for neurodegenerative disorders associated with pathological accumulation of alpha-synuclein or tau proteins.
HUMAN MOLECULAR GENETICS
(2022)