Cognitive fluctuations in Lewy body dementia: towards a pathophysiological framework

Brain. 2020 Jan 1;143(1):31-46. doi: 10.1093/brain/awz311.

Abstract

Fluctuating cognition is a complex and disabling symptom that is seen most frequently in the context of Lewy body dementias encompassing dementia with Lewy bodies and Parkinson's disease dementia. In fact, since their description over three decades ago, cognitive fluctuations have remained a core diagnostic feature of dementia with Lewy bodies, the second most common dementia in the elderly. In the absence of reliable biomarkers for Lewy body pathology, the inclusion of such patients in therapeutic trials depends on the accurate identification of such core clinical features. Yet despite their diagnostic relevance, cognitive fluctuations remain poorly understood, in part due to the lack of a cohesive clinical and scientific explanation of the phenomenon itself. Motivated by this challenge, the present review examines the history, clinical phenomenology and assessment of cognitive fluctuations in the Lewy body dementias. Based on these data, the key neuropsychological, neurophysiological and neuroimaging correlates of cognitive fluctuations are described and integrated into a novel testable heuristic framework from which new insights may be gained.

Keywords: Lewy body dementia; Parkinson’s disease; arousal; attention; cognitive fluctuations.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Arousal*
  • Attention*
  • Brain / diagnostic imaging
  • Brain / physiopathology*
  • Cognitive Dysfunction / physiopathology*
  • Cognitive Dysfunction / psychology
  • Diffusion Magnetic Resonance Imaging
  • Electroencephalography
  • Evoked Potentials, Auditory
  • Functional Neuroimaging
  • Humans
  • Lewy Body Disease / physiopathology*
  • Lewy Body Disease / psychology
  • Magnetic Resonance Spectroscopy
  • Neuropsychological Tests
  • Periodicity*
  • Polysomnography
  • REM Sleep Behavior Disorder / physiopathology
  • Sleep Wake Disorders / physiopathology
  • Surveys and Questionnaires
  • Tomography, Emission-Computed, Single-Photon