Fluctuating cognition in the Lewy body dementias

Abstract

Fluctuating cognition is a core diagnostic feature of dementia with Lewy bodies and is also a key clinical feature of Parkinson's disease dementia. These dementias share common pathological features and are referred to as Lewy body dementias. Whilst highly prevalent in Lewy body dementia, with up to 90% of patients experiencing the symptom at some point in the disease trajectory, clinical identification of fluctuating cognition is often challenging. Furthermore, its underlying pathophysiological processes remain unclear. However, neuroimaging and neurophysiological techniques have recently provided insight into potential drivers of the phenomenon. In this update, we review data pertaining to clinical features and underlying mechanisms of fluctuating cognition in Lewy body dementia. We collate evidence for different proposed aetiologies: fluctuating cognition as an attentional disorder, as a consequence of loss of cholinergic drive, as a manifestation of failure in neuronal efficiency and synchrony, and as a disorder of sleep/arousal. We also review data relating to putative mechanisms that have received less attention to date. Increased understanding of fluctuating cognition may help to illuminate pathophysiological mechanisms in cognitive processing in Lewy body dementia, guide future research, and facilitate the design of targeted therapeutic approaches.

Keywords: Parkinson's disease dementia; alertness; attention; dementia with Lewy bodies; fluctuating cognition.