Dynamic network impairments underlie cognitive fluctuations in Lewy body dementia
Abstract Cognitive fluctuations are a characteristic and distressing disturbance of attention and consciousness seen in patients with Dementia with Lewy bodies and Parkinson’s disease dementia. It has been proposed that fluctuations result from disruption of key neuromodulatory systems supporting st...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-02-01
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| Series: | npj Parkinson's Disease |
| Online Access: | https://doi.org/10.1038/s41531-022-00279-x |
| _version_ | 1797642965221376000 |
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| author | Elie Matar Kaylena A. Ehgoetz Martens Joseph R. Phillips Gabriel Wainstein Glenda M. Halliday Simon J. G. Lewis James M. Shine |
| author_facet | Elie Matar Kaylena A. Ehgoetz Martens Joseph R. Phillips Gabriel Wainstein Glenda M. Halliday Simon J. G. Lewis James M. Shine |
| author_sort | Elie Matar |
| collection | DOAJ |
| description | Abstract Cognitive fluctuations are a characteristic and distressing disturbance of attention and consciousness seen in patients with Dementia with Lewy bodies and Parkinson’s disease dementia. It has been proposed that fluctuations result from disruption of key neuromodulatory systems supporting states of attention and wakefulness which are normally characterised by temporally variable and highly integrated functional network architectures. In this study, patients with DLB (n = 25) and age-matched controls (n = 49) were assessed using dynamic resting state fMRI. A dynamic network signature of reduced temporal variability and integration was identified in DLB patients compared to controls. Reduced temporal variability correlated significantly with fluctuation-related measures using a sustained attention task. A less integrated (more segregated) functional network architecture was seen in DLB patients compared to the control group, with regions of reduced integration observed across dorsal and ventral attention, sensorimotor, visual, cingulo-opercular and cingulo-parietal networks. Reduced network integration correlated positively with subjective and objective measures of fluctuations. Regions of reduced integration and unstable regional assignments significantly matched areas of expression of specific classes of noradrenergic and cholinergic receptors across the cerebral cortex. Correlating topological measures with maps of neurotransmitter/neuromodulator receptor gene expression, we found that regions of reduced integration and unstable modular assignments correlated significantly with the pattern of expression of subclasses of noradrenergic and cholinergic receptors across the cerebral cortex. Altogether, these findings demonstrate that cognitive fluctuations are associated with an imaging signature of dynamic network impairment linked to specific neurotransmitters/neuromodulators within the ascending arousal system, highlighting novel potential diagnostic and therapeutic approaches for this troubling symptom. |
| first_indexed | 2024-03-11T14:07:49Z |
| format | Article |
| id | doaj.art-0108549a050b4014bd8934c74a298ba7 |
| institution | Directory Open Access Journal |
| issn | 2373-8057 |
| language | English |
| last_indexed | 2024-03-11T14:07:49Z |
| publishDate | 2022-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Parkinson's Disease |
| spelling | doaj.art-0108549a050b4014bd8934c74a298ba72023-11-02T01:00:25ZengNature Portfolionpj Parkinson's Disease2373-80572022-02-01811910.1038/s41531-022-00279-xDynamic network impairments underlie cognitive fluctuations in Lewy body dementiaElie Matar0Kaylena A. Ehgoetz Martens1Joseph R. Phillips2Gabriel Wainstein3Glenda M. Halliday4Simon J. G. Lewis5James M. Shine6Central Clinical School, Faculty of Medicine and Health, University of SydneyForefront Parkinson’s Disease Research Clinic, Brain and Mind Centre, University of SydneyForefront Parkinson’s Disease Research Clinic, Brain and Mind Centre, University of SydneyForefront Parkinson’s Disease Research Clinic, Brain and Mind Centre, University of SydneyCentral Clinical School, Faculty of Medicine and Health, University of SydneyCentral Clinical School, Faculty of Medicine and Health, University of SydneyCentral Clinical School, Faculty of Medicine and Health, University of SydneyAbstract Cognitive fluctuations are a characteristic and distressing disturbance of attention and consciousness seen in patients with Dementia with Lewy bodies and Parkinson’s disease dementia. It has been proposed that fluctuations result from disruption of key neuromodulatory systems supporting states of attention and wakefulness which are normally characterised by temporally variable and highly integrated functional network architectures. In this study, patients with DLB (n = 25) and age-matched controls (n = 49) were assessed using dynamic resting state fMRI. A dynamic network signature of reduced temporal variability and integration was identified in DLB patients compared to controls. Reduced temporal variability correlated significantly with fluctuation-related measures using a sustained attention task. A less integrated (more segregated) functional network architecture was seen in DLB patients compared to the control group, with regions of reduced integration observed across dorsal and ventral attention, sensorimotor, visual, cingulo-opercular and cingulo-parietal networks. Reduced network integration correlated positively with subjective and objective measures of fluctuations. Regions of reduced integration and unstable regional assignments significantly matched areas of expression of specific classes of noradrenergic and cholinergic receptors across the cerebral cortex. Correlating topological measures with maps of neurotransmitter/neuromodulator receptor gene expression, we found that regions of reduced integration and unstable modular assignments correlated significantly with the pattern of expression of subclasses of noradrenergic and cholinergic receptors across the cerebral cortex. Altogether, these findings demonstrate that cognitive fluctuations are associated with an imaging signature of dynamic network impairment linked to specific neurotransmitters/neuromodulators within the ascending arousal system, highlighting novel potential diagnostic and therapeutic approaches for this troubling symptom.https://doi.org/10.1038/s41531-022-00279-x |
| spellingShingle | Elie Matar Kaylena A. Ehgoetz Martens Joseph R. Phillips Gabriel Wainstein Glenda M. Halliday Simon J. G. Lewis James M. Shine Dynamic network impairments underlie cognitive fluctuations in Lewy body dementia npj Parkinson's Disease |
| title | Dynamic network impairments underlie cognitive fluctuations in Lewy body dementia |
| title_full | Dynamic network impairments underlie cognitive fluctuations in Lewy body dementia |
| title_fullStr | Dynamic network impairments underlie cognitive fluctuations in Lewy body dementia |
| title_full_unstemmed | Dynamic network impairments underlie cognitive fluctuations in Lewy body dementia |
| title_short | Dynamic network impairments underlie cognitive fluctuations in Lewy body dementia |
| title_sort | dynamic network impairments underlie cognitive fluctuations in lewy body dementia |
| url | https://doi.org/10.1038/s41531-022-00279-x |
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