Investigating attentional function and cognitive fluctuations in Lewy body dementia

Abstract

Lewy body dementias (LBD), which include dementia with Lewy bodies (DLB) and Parkinson’s disease with dementia (PDD), are characterised by attentional dysfunction and fluctuating cognition. The underlying aetiology of these clinical features is poorly understood, yet such knowledge is essential for developing effective management strategies. The aim of this project was to determine the specific facets of attention affected in LBD patients, and to use high-density electroencephalography (EEG) to delineate the underlying pathophysiology and how this relates to cognitive fluctuations. Methods: Attentional network efficiency was investigated in LBD patients (n = 32), Alzheimer’s disease (AD) patients (n = 27), and age-matched healthy controls (n = 21) by using a modified version of the Attention Network Test (ANT). The ANT, a visual attention task, probes the efficiency of three anatomically defined attentional networks: alerting, orienting and executive conflict. Participants completed the ANT whilst undergoing EEG recordings (128 channels). In a subsample of the participants (22 DLB, 24 AD, 19 controls), time-frequency wavelet analyses were conducted to investigate event-related spectral perturbations (ERSP), between 4-90 Hz, in the 500 ms post-stimuli presentation. Attentional network ERSP was calculated by contrasting the oscillatory reactivity following relevant stimuli. Results: Overall mean reaction time was slower in the dementia groups (AD and LBD) relative to the controls, and the LBD group were slower than the AD group. Behaviourally, there were no group differences regarding the orienting effect. However, both dementia groups exhibited reduced executive conflict processing efficiency, and a lack of an alerting effect. Electrophysiologically, the DLB group exhibited a profound lack of post-stimulus oscillatory reactivity below 30 Hz, irrespective of stimulus condition. For the alerting network, the DLB group exhibited attenuated reactivity in the lower frequencies (< 30 Hz); in the theta range (4-7 Hz) the controls and AD group showed global synchronisation (across all regions), peaking at approximately 300 ms, which was absent in the DLB group. Lack of DLB theta synchronisation between 200-450 ms over the right parietal cortex was associated with a ii higher total score on the Clinical Assessment of Fluctuation scale. Orienting and executive conflict network reactivity was comparable across all groups; primarily intermittent synchronisation, of reduced power relative to the alerting network, diffuse across the time and frequency domains in all regions. Conclusions: Attenuated global oscillatory reactivity in the DLB group specific to the alerting network (the network associated with the ability to maintain an alert state) is indicative of this fractionated aspect of attention being differentially affected in the DLB patients relative to the AD and control groups. Lack of theta reactivity in the parietal regions may contribute to the underlying pathophysiology of cognitive fluctuations in DLB.