Julia Schumacher1, John-Paul Taylor2, Calum A Hamilton2, Michael Firbank2, Ruth A Cromarty2, Paul C Donaghy2, Gemma Roberts2, Louise Allan3, Jim Lloyd4, Rory Durcan2, Nicola Barnett2, John T O'Brien5, Alan J Thomas2. 1. Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, United Kingdom. Electronic address: julia.schumacher@newcastle.ac.uk. 2. Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, United Kingdom. 3. Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, United Kingdom; Institute of Health Research, University of Exeter, Exeter, United Kingdom. 4. Nuclear Medicine Department, Newcastle upon Tyne Hospitals NFS Foundation Trust, Newcastle upon Tyne, United Kingdom. 5. Department of Psychiatry, University of Cambridge School of Medicine, Cambridge CB2 0SP, United Kingdom.
Abstract
OBJECTIVES: To investigate in vivo degeneration of the cholinergic system in mild cognitive impairment with Lewy bodies (MCI-LB), we studied nucleus basalis of Meynert (NBM) volumes from structural MR images and its relation to EEG slowing and cognitive impairment. METHODS: We studied the NBM using structural MR images in 37 patients with MCI-LB, 34 patients with MCI with Alzheimer's disease (MCI-AD), and 31 healthy control participants. We also tested correlations between NBM volumes and measures of overall cognition and measures of EEG slowing in the MCI groups. RESULTS: Overall NBM volume was reduced in MCI-LB compared to controls with no significant difference between MCI-AD and controls or between the two MCI groups. The voxel-wise analysis revealed bilateral clusters of reduced NBM volume in MCI-LB compared to controls and smaller clusters in MCI-AD compared to controls. There was a significant association between overall NBM volume and measures of overall cognition in MCI-LB, but not in MCI-AD. In both MCI groups, reduced NBM volume was correlated with more severe EEG slowing. CONCLUSIONS: This study provides in vivo evidence that early cholinergic degeneration in DLB occurs at the MCI stage and is related to the severity of cognitive impairment. Furthermore, the results suggest that early EEG slowing in MCI-LB might be in part cholinergically driven. Importantly, these findings suggest an early cholinergic deficit in MCI-LB that may motivate further testing of the effectiveness of cholinesterase inhibitors in this group.
OBJECTIVES: To investigate in vivo degeneration of the cholinergic system in mild cognitive impairment with Lewy bodies (MCI-LB), we studied nucleus basalis of Meynert (NBM) volumes from structural MR images and its relation to EEG slowing and cognitive impairment. METHODS: We studied the NBM using structural MR images in 37 patients with MCI-LB, 34 patients with MCI with Alzheimer's disease (MCI-AD), and 31 healthy control participants. We also tested correlations between NBM volumes and measures of overall cognition and measures of EEG slowing in the MCI groups. RESULTS: Overall NBM volume was reduced in MCI-LB compared to controls with no significant difference between MCI-AD and controls or between the two MCI groups. The voxel-wise analysis revealed bilateral clusters of reduced NBM volume in MCI-LB compared to controls and smaller clusters in MCI-AD compared to controls. There was a significant association between overall NBM volume and measures of overall cognition in MCI-LB, but not in MCI-AD. In both MCI groups, reduced NBM volume was correlated with more severe EEG slowing. CONCLUSIONS: This study provides in vivo evidence that early cholinergic degeneration in DLB occurs at the MCI stage and is related to the severity of cognitive impairment. Furthermore, the results suggest that early EEG slowing in MCI-LB might be in part cholinergically driven. Importantly, these findings suggest an early cholinergic deficit in MCI-LB that may motivate further testing of the effectiveness of cholinesterase inhibitors in this group.
Authors: Julia Schumacher; John-Paul Taylor; Calum A Hamilton; Michael Firbank; Paul C Donaghy; Gemma Roberts; Louise Allan; Rory Durcan; Nicola Barnett; John T O'Brien; Alan J Thomas Journal: J Neurol Date: 2021-04-29 Impact factor: 6.682
Authors: Kejal Kantarci; Zuzana Nedelska; Qin Chen; Matthew L Senjem; Christopher G Schwarz; Jeffrey L Gunter; Scott A Przybelski; Timothy G Lesnick; Walter K Kremers; Julie A Fields; Jonathan Graff-Radford; Rodolfo Savica; David Jones; Hugo Botha; David S Knopman; Val Lowe; Neill R Graff-Radford; Melissa M Murray; Dennis W Dickson; R Ross Reichard; Clifford R Jack; Ronald C Petersen; Tanis J Ferman; Bradley F Boeve Journal: Brain Commun Date: 2022-02-07
Authors: 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 Journal: Nat Commun Date: 2022-09-21 Impact factor: 17.694
Authors: 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 Journal: Brain Date: 2022-06-03 Impact factor: 15.255