npj Parkinsons Dis: Dynamic network impairments underlie cognitive fluctuations in dementia with Lewy bodies

Dementia with Lewy bodies, including dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), is a common neurodegenerative disorder with higher morbidity, socioeconomic cost, and caregiver burden compared with other dementias

Figure 1 Title map of the paper

Although cognitive fluctuations are common and clinically significant in DLB, objective biomarkers are lacking, and our understanding of their neuroanatomical substrate remains limited

Indeed, previous approaches in DLB that have relied solely on structural markers or time-averaged functional imaging measurements have yielded variable findings on the contribution of individual regions or networks

Specifically, acetylcholine and norepinephrine, which promote wakefulness and alertness, respectively, have also been implicated in the interaction between efficient network-level segregation and integration, and the involvement of these systems is thought to be an important part of the pathophysiology of cognitive fluctuations in DLB.

Figure 2 Brain fMRI changes

Compared with healthy age-matched controls, DLB patients exhibited functional features of reduced network integration and low temporal variability, which may be directly related to subjective and objective measures of cognitive fluctuations

Compared with controls, DLB patients had less structural integration (higher dissociation) of functional networks, with integration observed in dorsal and ventral attention, sensorimotor, visual, dentate, and dentate parietal networks area of ​​reduced severity

Correlating topological measures with neurotransmitter/neuroregulator receptor gene expression maps, we found that regions of reduced integration and destabilization of module assignments were associated with noradrenergic and cholinergic receptor subtypes throughout the cerebral cortex The expression patterns of the classes are clearly related

Taken together, these findings suggest that cognitive fluctuations are associated with imaging features of dynamic network impairment and are associated with specific neurotransmitters/neurodulators in the ascending arousal system, highlighting new potential diagnostic and therapeutic approaches for this symptom.

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