"Dynamic network impairments underlie cognitive fluctuations in Lewy body dementia" Elie Matar, Kaylena A. Ehgoetz Martens, Joseph R. Phillips, Gabriel Wainstein, Glenda M. Halliday, Simon J. G. Lewis, 2 and James M. Shine NPJ Parkinsons Dis. 2022; 8: 16 doi: 10.1038/s41531-022-00279-x (2022)

Cognitive fluctuations are one of the most common and characteristic symptoms of Dementia with Lewy bodies (DLB) and are marked by significant variation in attention, consciousness (wakefulness) and cognitive abilities over time. Despite being an important ‘core’ diagnostic feature, we don’t have a good mechanistic understanding of cognitive fluctuations and objective biomarkers of this symptom are lacking. In this study, we used dynamic functional MRI to study the potential neural correlates of fluctuations. In the resting state, the brains of healthy consciousness are usually characterized at the network level by integration (many parts of the brain connected to each other over long distances) and temporal variability (the connection patterns re-arranging themselves frequently to accommodate fluid and changing brain states). In this study, we found that patients with fluctuations tend to display whole-brain network characteristics of reduced integration and reduced temporal variability compared to controls. Using the Allen’s brain atlas we found regions with especially less integration overlapped with areas that express specific cholinergic and noradrenergic receptors. These results provide us with an avenue to investigate dynamic imaging as a biomarker of fluctuations and also suggest possible therapeutic options (cholinergic and noradrenergic promoting agents).

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