Changes in gray matter volume and functional connectivity in dementia with Lewy bodies compared to Alzheimer’s disease and normal aging: implications for fluctuations

Abstract

Background: Fluctuations 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. Methods: Structural 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). Results: At 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.

Microstructural changes in prodromal dementia with Lewy bodies compared to normal ageing: Multiparametric quantitative MRI evidences

“…In DLB, considering the minimal atrophy compared to AD, especially in the prodromal stage, these microstructural changes may reflect a reduced synaptic density, or neurodegenerative changes in axons and myelin in GM fibers, rather than neuronal loss. The location of diffusivity alterations in our DLB group is in accordance with previous studies (Chabran et al, 2020; Schumacher et al, 2018) highlighting early functional connectivity changes in fronto‐parietal attentional networks in DLB patients. It is thus possible that microstructural changes may parallel the functional disturbances occurring in these regions at the prodromal stage (although further studies would be required to determine if such changes have a causative/contributing or a consecutive role regarding functional troubles).…”

Prevalence of Severe Neurocognitive Impairment and Its Association with Socio-Demographics and Functionality Among Ugandan Older Persons: A Hospital-Based Study

“…38 This relationship may be because of severe neurocognitive impairment, such as Alzheimer's dementia causing loss of significant areas in the brain, which is responsible for operating daily life activities. 39 Hence, the increasing odds for neurocognitive impairment as the functional dependence increases. This makes decreasing functional independence a sensitive marker for early detection of neurocognitive impairment, similar to other studies.…”

Large-scale network dysfunction in α-Synucleinopathy: A meta-analysis of resting-state functional connectivity

“…This study included 72 publications, 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , …”