Article
Clinical Neurology
Julia Schumacher, Nicola J. Ray, Calum A. Hamilton, Paul C. Donaghy, Michael Firbank, Gemma Roberts, Louise Allan, Rory Durcan, Nicola Barnett, John T. O'Brien, John-Paul Taylor, Alan J. Thomas
Summary: Patients with dementia with Lewy bodies and Alzheimer's disease exhibited early degeneration of the cholinergic nucleus basalis of Meynert. However, it remains unknown how white matter projections between the nucleus basalis of Meynert and the cortex are affected in neurodegenerative diseases. This study utilized diffusion-weighted imaging to investigate the white matter pathways originating from the nucleus basalis of Meynert in patients with different cognitive conditions. The results demonstrated that the integrity of these pathways is associated with cognition and attention, and might serve as an early indicator for the risk of dementia conversion in individuals with mild cognitive impairment.
Article
Clinical Neurology
Claire Andre, Marie-eve Martineau-Dussault, Veronique Daneault, Helene Blais, Sonia Frenette, Dominique Lorrain, Carol Hudon, Celyne Bastien, Dominique Petit, Alexandre Lafreniere, Cynthia Thompson, Jacques Montplaisir, Nadia Gosselin, Julie Carrier
Summary: This study investigated the associations between the volume of basal forebrain nuclei and REM sleep characteristics, and the impact of cognitive status on these links. The findings suggest that REM sleep disturbances may be an early manifestation of the degeneration of the basal forebrain cholinergic system, especially in participants with mild memory deficits.
ALZHEIMERS RESEARCH & THERAPY
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Piao Zhang, Siming Rong, Chentao He, Yan Li, Xiaohong Li, Zhenzhen Chen, Kun Nie, Limin Wang, Lijuan Wang, Yuhu Zhang
Summary: This study investigated the cholinergic basal forebrain pathology in Parkinson's disease with mild cognitive impairment (PD-MCI) and found that functional connectivity changes are frequency-specific, providing new insights into the functional alterations within the cholinergic system in cognitive impairment.
QUANTITATIVE IMAGING IN MEDICINE AND SURGERY
(2023)
Article
Clinical Neurology
Julia Schumacher, Nicola J. J. Ray, Calum A. A. Hamilton, Maurizio Bergamino, Paul C. C. Donaghy, Michael Firbank, Rosie Watson, Gemma Roberts, Louise Allan, Nicola Barnett, John T. T. O'Brien, Alan J. J. Thomas, John-Paul Taylor
Summary: This study used a diffusion tensor imaging model to study the degeneration of cholinergic projection pathways in Alzheimer's disease and dementia with Lewy bodies. The results showed an increased free water content in the cortical cholinergic pathways in both diseases, which was associated with cognitive performance. The cholinergic pathway from the pedunculopontine nucleus to the thalamus showed increased free water content only in dementia with Lewy bodies, and this was related to visual hallucinations.
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Michel J. Grothe, Miguel A. Labrador-Espinosa, Silvia Jesus, Daniel Macias-Garcia, Astrid Adarmes-Gomez, Fatima Carrillo, Elena Iglesias Camacho, Pablo Franco-Rosado, Florinda Roldan Lora, Juan Francisco Martin-Rodriguez, Miquel Aguilar Barbera, Pau Pastor, Sonia Escalante Arroyo, Berta Solano Vila, Anna Cots Foraster, Javier Ruiz Martinez, Francisco Carrillo Padilla, Mercedes Pueyo Morlans, Isabel Gonzalez Aramburu, Jon Infante Ceberio, Jorge Hernandez Vara, Oriol de Fabregues-Boixar, Teresa de Deus Fonticoba, Berta Pascual-Sedano, Jaime Kulisevsky, Pablo Martinez-Martin, Diego Santos-Garcia, Pablo Mir
Summary: Early cognitive deficits in PD without dementia are more closely related to structural MRI measures of CBF degeneration than hippocampal degeneration.
PARKINSONISM & RELATED DISORDERS
(2021)
Article
Neuroimaging
Christine Kindler, Neeraj Upadhyay, Zeynep Bendella, Franziska Dorn, Vera C. Keil, Gabor C. Petzold
Summary: This study explored the influence of white matter hyperintensities on the degeneration of cholinergic basal forebrain structures in Alzheimer's disease (AD). The results showed that the volumes of cholinergic basal forebrain structures were significantly smaller in AD patients compared to controls, but there was no clear correlation between white matter hyperintensity burden and cholinergic basal forebrain structure volumes.
NEUROIMAGE-CLINICAL
(2023)
Article
Clinical Neurology
Milan Nemy, Martin Dyrba, Frederic Brosseron, Katharina Buerger, Peter Dechent, Laura Dobisch, Michael Ewers, Klaus Fliessbach, Wenzel Glanz, Doreen Goerss, Michael T. Heneka, Stefan Hetzer, Enise I. Incesoy, Daniel Janowitz, Ingo Kilimann, Christoph Laske, Franziska Maier, Matthias H. Munk, Robert Perneczky, Oliver Peters, Lukas Preis, Josef Priller, Boris-Stephan Rauchmann, Sandra Roeske, Nina Roy, Klaus Scheffler, Anja Schneider, Bjorn H. Schott, Annika Spottke, Eike J. Spruth, Michael Wagner, Jens Wiltfang, Renat Yakupov, Maria Eriksdotter, Eric Westman, Olga Stepankova, Lenka Vyslouzilova, Emrah Duezel, Frank Jessen, Stefan J. Teipel, Daniel Ferreira
Summary: Nemy et al. investigate cholinergic white matter projections along the Alzheimer's disease continuum, finding that alterations in these pathways are present in individuals with subjective cognitive decline. These alterations precede the more widespread changes seen in mild cognitive impairment and Alzheimer's disease dementia. The study highlights the potential of using cholinergic white matter pathways as markers for the early stages of Alzheimer's disease.
Article
Neuroimaging
Julia Schumacher, John-Paul Taylor, Calum A. Hamilton, Michael Firbank, Ruth A. Cromarty, Paul C. Donaghy, Gemma Roberts, Louise Allan, Jim Lloyd, Rory Durcan, Nicola Barnett, John T. O'Brien, Alan J. Thomas
Summary: The study found that cholinergic degeneration in the MCI-LB stage is related to cognitive impairment severity. Early EEG slowing in MCI-LB might be partly cholinergically driven. These findings suggest an early cholinergic deficit in MCI-LB.
NEUROIMAGE-CLINICAL
(2021)
Article
Biochemistry & Molecular Biology
Elisabetta Coppi, Federica Cherchi, Erica Sarchielli, Irene Fusco, Giulia Guarnieri, Pasquale Gallina, Renato Corradetti, Felicita Pedata, Gabriella B. Vannelli, Anna Maria Pugliese, Annamaria Morelli
Summary: This study characterized cholinergic effects in human NBM neurons, showing that acetylcholine can modulate ion channels by enhancing K currents, reducing Na currents, and activating different receptors. Spontaneous acetylcholine release from neuroblasts in the human fetal NBM may play a key role in brain development.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Clinical Neurology
Nicola J. Ray, Rachael A. Lawson, Sarah L. Martin, Hilmar P. Sigurdsson, Joanna Wilson, Brook Galna, Sue Lord, Lisa Alcock, Gordon W. Duncan, Tien K. Khoo, John T. O'Brien, David J. Burn, John-Paul Taylor, River C. Rea, Maurizio Bergamino, Lynn Rochester, Alison J. Yarnall
Summary: Free-water imaging can predict dopamine system degeneration in Parkinson's disease and enhance the sensitivity of traditional DTI metrics. However, it has not been applied to investigate cholinergic system degeneration. Free-water imaging, free-water-corrected DTI, and volumetry were used to extract structural metrics from the cholinergic basal forebrain and pedunculopontine nucleus in people with Parkinson's disease.
Article
Biochemistry & Molecular Biology
Zhao-yi Chen, Yao-lian Yang, Mai Li, Lu Gao, Wei-min Qu, Zhi-li Huang, Xiang-shan Yuan
Summary: The cholinergic neurons in the nucleus basalis of Meynert (NBM) play a crucial role in cognition and are associated with various neurological disorders. This study used a transgenic mouse model and tracing techniques to investigate the neural connectivity of NBM cholinergic neurons. The results revealed specific inputs from the caudate putamen and the posterior limb of the anterior commissure, as well as widespread axon projections to the cortex mantle. Interestingly, while NBM cholinergic neurons received input projections from certain regions, they sparsely sent axon projections back to these areas. Furthermore, specific cortical regions received abundant inputs from the NBM but sent few outputs back. These findings provide important insights into the connectivity and function of cholinergic neurons in the NBM.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Clinical Neurology
Dorothee Kuebler, Sophie Katharina Wellmann, Jakob Kaminski, Cornelia Skowronek, Gerd-Helge Schneider, Wolf-Julian Neumann, Kerstin Ritter, Andrea Kuehn
Summary: NBM volume can be used as a simple non-invasive predictor for cognitive outcome after DBS in Parkinson's disease, especially when combined with other clinically relevant parameters.
PARKINSONISM & RELATED DISORDERS
(2022)
Article
Multidisciplinary Sciences
Panna Hegedus, Katalin Sviatko, Balint Kiraly, Sergio Martinez-Bellver, Balazs Hangya
Summary: Basal forebrain cholinergic neurons have an important role in associative learning and processing stimuli that predict future outcomes. This study used calcium imaging and spiking recordings to investigate the impact of outcome probabilities on these neurons in mice. The results showed that the cholinergic neurons responded more strongly to sensory cues that were often paired with reward, and reward delivery activated the neurons, with surprising rewards generating a stronger response. The findings suggest that the cholinergic neurons differentially weigh predictions of positive and negative reinforcement, reflecting the relative salience of appetitive and aversive outcomes.
Article
Clinical Neurology
Jolien Schaeverbeke, Sandra O. Tome, Alicja Ronisz, Simona Ospitalieri, Christine A. F. von Arnim, Markus Otto, Rik Vandenberghe, Dietmar Rudolf Thal
Summary: This study quantitatively assessed neuronal density and pathology in the nucleus basalis of Meynert (nbM) of 47 cases, including different variants of primary progressive aphasia (PPA) and Alzheimer's disease (AD). The results showed that reduced nbM neuronal density was only found in AD. PPA patients with underlying AD pathology exhibited lower neuronal densities, while those with frontotemporal lobar degeneration (FTLD) were unaffected.
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Chen-Pei Lin, Irene Frigerio, Baayla D. C. Boon, Zihan Zhou, Annemieke J. M. Rozemuller, Femke H. Bouwman, Menno M. Schoonheim, Wilma D. J. van de Berg, Laura E. Jonkman
Summary: Cognitive deficits in Alzheimer's disease, especially memory decline, are associated with cholinergic degeneration in the basal forebrain. This study used a combination of post-mortem in situ MRI and histopathology to investigate the pathophysiology of nucleus basalis of Meynert atrophy in Alzheimer's disease. The results showed that Alzheimer's disease donors had reduced volume and altered microstructural integrity of the nucleus basalis of Meynert, which was associated with decreased cholinergic cell density and damaged cortical projections, leading to cognitive deterioration.
Article
Neuroimaging
Rok Berlot, Zvezdan Pirtosek, Simon Brezovar, Blaz Koritnik, Stefan J. Teipel, Michel J. Grothe, Nicola J. Ray
Summary: The study found that in patients with Parkinson's disease, visuospatial memory is associated with hippocampal volume and the subregions of the cholinergic basal forebrain, mediated by the integrity of CA2-3. This implies a relationship between the integrity of the cholinergic basal forebrain and regional hippocampal volume in Parkinson's disease patients.
BRAIN IMAGING AND BEHAVIOR
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Catharina Lange, Anja Maurer, Per Suppa, Ivayla Apostolova, Ingo G. Steffen, Michel J. Grothe, Ralph Buchert
Summary: The aim of this study was to evaluate the predictive ability of brain FDG PET for cognitive decline, need for assisted living, and survival in acutely hospitalized geriatric patients with newly detected CUCI. The study found that FDG PET can predict further cognitive/functional decline and the need for assisted living within 1 to 2 years in patients with newly detected CUCI.
CLINICAL NUCLEAR MEDICINE
(2022)
Article
Clinical Neurology
Stefan J. Teipel, Michel J. Grothe
Summary: This study compared the atrophy of the cholinergic basal forebrain in cases with limbic TDP-43 pathology and pure Alzheimer disease (AD) using MRI. The findings suggest that the atrophy of the cholinergic basal forebrain is similarly pronounced in both TDP-43 and AD cases, indicating a potential need for clinical trials of cholinesterase inhibitors in amyloid-negative cases with amnestic dementia and an imaging signature of TDP-43 pathology.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Neurosciences
Nils Richter, Lara-Sophia David, Michel J. Grothe, Stefan Teipel, Markus Dietlein, Marc Tittgemeyer, Bernd Neumaier, Gereon R. Fink, Oezguer A. Onur, Juraj Kukolja
Summary: The study aimed to investigate if the extent of cholinergic deficit in non-demented AD patients could be predicted from the volume of cholinergic basal forebrain nuclei. Results showed that greater volumes of anterior basal forebrain nuclei and younger age were associated with a more significant cholinergic deficit in MCI due to AD. Further research is needed to explore if individual response to cholinomimetics can be inferred from these measures.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Clinical Neurology
Michel J. Grothe, Alexis Moscoso, Jesus Silva-Rodriguez, Catharina Lange, Kwangsik Nho, Andrew J. Saykin, Peter T. Nelson, Michael Scholl, Ralph Buchert, Stefan Teipel
Summary: This study investigated the clinical utility of an autopsy-derived FDG-PET signature for differential diagnosis of amnestic dementia patients. The study found that an FDG-PET pattern resembling LATE-NC can identify older patients with clinical features consistent with underlying LATE-NC. These patients exhibit a memory-predominant profile and a slower disease course.
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Frederic Sampedro, Saul Martinez-Horta, Andrea Horta-Barba, Michel J. Grothe, Miguel A. Labrador-Espinosa, Silvia Jesus, Astrid Adarmes-Gomez, Fatima Carrillo, Arnau Puig-Davi, Florinda Roldan-Lora, Miquel Aguilar-Barbera, Pau Pastor, Sonia Escalante Arroyo, Berta Solano Vila, Anna Cots-Foraster, Javier Ruiz-Martinez, Francisco Carrillo-Padilla, Mercedes Pueyo-Morlans, Isabel Gonzalez-Aramburu, Jon Infante-Ceberio, Jorge Hernandez-Vara, Oriol de Fabregues-Boixar, Teresa de Deus Fonticoba, Asuncion Avila, Juan Carlos Martinez-Castrillo, Helena Bejr-Kasem, Antonia Campolongo, Berta Pascual-Sedano, Pablo Martinez-Martin, Diego Santos-Garcia, Pablo Mir, Pedro J. Garcia-Ruiz, Jaime Kulisevsky
Summary: This study explores the neural correlates of reduced facial expression and its relationship with other non-motor symptoms in Parkinson's disease. The severity of hypomimia was found to be closely associated with rigidity and bradykinesia, and significantly related to the severity of apathy. At the neural level, hypomimia was related to several brain regions involved in the recognition and production of facial expressions.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
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.
Editorial Material
Clinical Neurology
Joseph Therriault, Michel J. Grothe
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
Clinical Neurology
Laura Munoz-Delgado, Miguel Angel Labrador-Espinosa, Daniel Macias-Garcia, Silvia Jesus, Belen Benitez Zamora, Paula Fernandez-Rodriguez, Astrid D. Adarmes-Gomez, Maria Isabel Reina Castillo, Sandra Castro-Labrador, Jesus Silva-Rodriguez, Fatima Carrillo, David Garcia Solis, Michel J. Grothe, Pablo Mir
Summary: Two independent studies found that peripheral immune responses are associated with dopaminergic degeneration in Parkinson's disease (PD), with a main correlation found with lymphocyte count.
MOVEMENT DISORDERS
(2023)
Article
Computer Science, Artificial Intelligence
Hangfan Liu, Michel J. Grothe, Tanweer Rashid, Miguel A. Labrador-Espinosa, Jon B. Toledo, Mohamad Habes
Summary: In this paper, a method is proposed to improve clustering of subjects in neuroimaging applications by exploiting the underlying clusters of features and suppressing noise through nonnegative matrix tri-factorization and adaptive regularization. Experimental results on synthetic data and real magnetic resonance imaging (MRI) data demonstrate the superiority of the proposed method.
IEEE TRANSACTIONS ON EMERGING TOPICS IN COMPUTATIONAL INTELLIGENCE
(2023)
Article
Clinical Neurology
Julia Schumacher, Prabesh Kanel, Martin Dyrba, Alexander Storch, Nicolaas Bohnen, Stefan Teipel, Michel J. Grothe
Summary: The study aimed to investigate the relationship between basal forebrain degeneration and cortical acetylcholinesterase activity in Parkinson’s disease, as well as their contribution to cognitive impairment. The findings demonstrated that the hypo-cholinergic Parkinson’s group had significantly reduced posterior basal forebrain volume compared to both the normo-cholinergic Parkinson’s group and the control group. Furthermore, the volume of posterior basal forebrain was significantly associated with cortical acetylcholinesterase activity in Parkinson’s patients, and both cholinergic markers were independently associated with multi-domain cognitive deficits.
Article
Psychiatry
Julia Schulz, Felix Brandl, Michel J. Grothe, Matthias Kirschner, Stefan Kaiser, Andre Schmidt, Stefan Borgwardt, Josef Priller, Christian Sorg, Mihai Avram
Summary: This study used VBM technology and different stages of schizophrenia patients to find that the volumes of basal-forebrain cholinergic nuclei were smaller in patients with schizophrenia and were correlated with attentional deficits. However, it is unclear if and how these changes and their link to cognitive symptoms extend across the schizophrenia spectrum.
SCHIZOPHRENIA BULLETIN
(2023)
Article
Clinical Neurology
Laura Munoz-Delgado, Miguel Angel Labrador-Espinosa, Daniel Macias-Garcia, Silvia Jesus, Belen Benitez Zamora, Paula Fernandez-Rodriguez, Astrid D. Adarmes-Gomez, Maria Isabel Reina Castillo, Sandra Castro-Labrador, Jesus Silva-Rodriguez, Fatima Carrillo, David Garcia Solis, Michel J. Grothe, Pablo Mir
Summary: The findings from two independent cohorts suggest a relationship between systemic inflammation and dopaminergic degeneration in patients with PD, primarily driven by lymphocyte count.
MOVEMENT DISORDERS
(2023)
Article
Clinical Neurology
Jon B. Toledo, Hangfan Liu, Michel J. Grothe, Tanweer Rashid, Lenore Launer, Leslie M. Shaw, Haykel Snoussi, Susan Heckbert, Michael Weiner, John Q. Trojanwoski, Sudha Seshadri, Mohamad Habes
Summary: This study evaluated the associations between magnetic resonance imaging (MRI) atrophy and flortaucipir positron emission tomography (PET) clusters across the Alzheimer's disease (AD) spectrum. The results showed that different clusters were associated with the apolipoprotein E genotype and white matter hyperintensity volumes. Moreover, only the hippocampal sparing atrophy cluster showed a specific association with brain aging imaging index. Tau clusters had stronger clinical associations than atrophy clusters. Tau and atrophy clusters were partially associated.
ALZHEIMERS & DEMENTIA-TRANSLATIONAL RESEARCH & CLINICAL INTERVENTIONS
(2022)
