Abstract
BackgroundFluctuations are one of the core clinical features characterizing dementia with Lewy bodies (DLB). They represent a determining factor for its diagnosis and strongly impact the quality of life of patients and their caregivers. However, the neural correlates of this complex symptom remain poorly understood. This study aimed to investigate the structural and functional changes in DLB patients, compared to Alzheimer’s disease (AD) patients and healthy elderly subjects, and their potential links with fluctuations.MethodsStructural and resting-state functional MRI data were collected from 92 DLB patients, 70 AD patients, and 22 control subjects, who also underwent a detailed clinical examination including the Mayo Clinic Fluctuation Scale. Gray matter volume changes were analyzed using whole-brain voxel-based morphometry, and resting-state functional connectivity was investigated using a seed-based analysis, with regions of interest corresponding to the main nodes of the salience network (SN), frontoparietal network (FPN), dorsal attention network (DAN), and default mode network (DMN).ResultsAt the structural level, fluctuation scores in DLB patients did not relate to the atrophy of insular, temporal, and frontal regions typically found in this pathology, but instead showed a weak correlation with more subtle volume reductions in different regions of the cholinergic system. At the functional level, the DLB group was characterized by a decreased connectivity within the SN and attentional networks, while the AD group showed decreases within the SN and DMN. In addition, higher fluctuation scores in DLB patients were correlated to a greater connectivity of the SN with the DAN and left thalamus, along with a decreased connectivity between the SN and DMN, and between the right thalamus and both the FPN and DMN.ConclusionsFunctional connectivity changes, rather than significant gray matter loss, could play an important role in the emergence of fluctuations in DLB. Notably, fluctuations in DLB patients appeared to be related to a disturbed external functional connectivity of the SN, which may lead to less relevant transitions between different cognitive states in response to internal and environmental stimuli. Our results also suggest that the thalamus could be a key region for the occurrence of this symptom.
Highlights
Fluctuations are one of the core clinical features characterizing dementia with Lewy bodies (DLB)
Fluctuations in DLB patients appeared to be related to a disturbed external functional connectivity of the salience network (SN), which may lead to less relevant transitions between different cognitive states in response to internal and environmental stimuli
In the cohort used for the functional analysis, the Alzheimer’s disease (AD) group was older than the control group but not the DLB group, and the latter were comparable in age
Summary
Fluctuations are one of the core clinical features characterizing dementia with Lewy bodies (DLB). Defined as spontaneous alterations in cognition with pronounced variations in attention and alertness, they occur in 80–90% of DLB patients [1, 2] and have a significant impact on patients’ autonomy and quality of life [3,4,5] In daily life, they result in substantial changes in patients’ mental status and behavior over time, alternating between periods of poorer task performance, incoherent speech and behavior, excessive daytime somnolence and episodes of altered consciousness (described by caregivers as sudden “switching off”), and periods of greater lucidity and cognitive performance [1, 6, 7]. Fluctuations in DLB patients seem to be internally driven, while those in AD patients may be more related to environmental triggers [9]
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