Covariant perfusion patterns provide clues to the origin of cognitive fluctuations and attentional dysfunction in Dementia with Lewy bodies

Abstract

Background:Fluctuating cognition (FC), particularly in attention, is a core and defining symptom in dementia with Lewy bodies (DLB) but is seen much less frequently in Alzheimer's dementia (AD). However, its neurobiological origin is poorly understood. The aim of our study was therefore to characterize perfusion patterns in DLB patients that are associated with the severity and frequency of FC as measured both clinically and using objective neuropsychological assessments.Methods:Spatial covariance analyses were applied to data derived from single photon emission computed tomography (SPECT) HMPAO brain imaging in 19 DLB and 23 AD patients. Patients underwent clinical assessment of their FC and cognitive function as well as objective testing of their attention.Results:Covariant perfusion principal components (PCs) were not associated with either FC or cognitive or attentional measures in AD. However, in DLB patients, the second PC (defined as DLB-cognitive motor pattern, DLB-PCI2) which was characterized by bilateral relative increases in cerebellum, basal ganglia, and supplementary motor areas and widespread bilateral decreases in parietal regions, positively correlated with poorer cognitive function, increased FC and worse attentional function measured both clinically and neurophysiologically (p < 0.05) as well as with the severity of bradykinesia (p = 0.04).Conclusions:FC in DLB appears distinct from those seen in AD, and likely to be driven by internal neurobiological perturbations in brain circuitry as evidenced using spatial covariance analyses of cerebral perfusion. FC and certain aspects of attentional dysfunction in DLB may, in part, depend upon both distributed motor and non-motor networks.

fMRI resting state networks and their association with cognitive fluctuations in dementia with Lewy bodies

“…However it is notable that thalamic involvement in the manifestation of fluctuations has not been noted in other perfusion studies which take a network perspective (Taylor et al, 2013). Further studies focussing on the structure–function role of the thalamus in DLB which include active attentional task comparisons with resting state may be helpful.…”

“…Similarly, relative decreases in cerebral perfusion in posterior parietal areas covariant with relative increases in perfusion in distributed motor networks have been observed in fluctuating DLB patients (Taylor et al, 2013). Another approach which may be sensitive to cortical network disturbances associated with cognitive fluctuations is resting state blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) as this allows the characterization of resting state networks (RSNs) that are task free and thus are not confounded by task dependent differences in cognitive or motor function which may be compromised in patients with dementia and/or parkinsonism.…”

Voxelwise meta-analysis of gray matter abnormalities in dementia with Lewy bodies

“…Atrophy in this region was similar to our previous meta-analysis of GM changes in Parkinson's disease with dementia. Prior evidence from SPECT study in DLB suggested that the putamen had a significant contribution to the cognitive motor pattern [47]. One recent resting state fMRI study further demonstrated that cognitive fluctuations in DLB were associated with dysfunctions of attention-executive networks including fronto-parietal, temporal, and sensory-motor networks, in which the putamen play an important role [30].…”

Cortical–Subcortical Interactions in Hypersomnia Disorders: Mechanisms Underlying Cognitive and Behavioral Aspects of the Sleep–Wake Cycle

“…Neuroimaging studies of DLB report metabolic and blood flow reductions in parietal, frontal, and occipital cortices together with gray matter atrophy that is predominant in parieto-temporal regions (203–209). Occipital lobe dysfunction identified using both emission tomography and functional magnetic resonance imaging techniques, has been associated with poor visuospatial performance and visual hallucinations in some studies (203, 207, 210).…”