Cognitive fluctuations in Lewy body dementia: towards a pathophysiological framework

Area of Science:

• Neurology
• Neuroscience
• Geriatrics

Background:

• Cognitive fluctuations are a hallmark symptom of Lewy body dementias (LBD), including dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD).
• Accurate identification of cognitive fluctuations is crucial for diagnosing LBD and enrolling patients in clinical trials, yet the phenomenon remains poorly understood.
• A lack of cohesive clinical and scientific explanations hinders a deeper understanding of cognitive fluctuations in LBD.

Purpose of the Study:

• To review the history, clinical phenomenology, and assessment of cognitive fluctuations in Lewy body dementias.
• To describe the neuropsychological, neurophysiological, and neuroimaging correlates of cognitive fluctuations.
• To propose a novel, testable heuristic framework for future research into cognitive fluctuations.

Main Methods:

• Literature review examining the history and clinical features of cognitive fluctuations in LBD.
• Synthesis of existing data on neuropsychological, neurophysiological, and neuroimaging correlates.
• Development of a heuristic framework integrating these correlates.

Main Results:

• Cognitive fluctuations are a persistent, core diagnostic feature of DLB, the second most common dementia in the elderly.
• Despite diagnostic relevance, a comprehensive understanding of the underlying mechanisms of cognitive fluctuations is lacking.
• Key correlates across neuropsychological, neurophysiological, and neuroimaging domains have been identified.

Conclusions:

• A synthesized understanding of cognitive fluctuations in LBD is presented.
• A novel heuristic framework is proposed to guide future research and clinical understanding.
• Further investigation is needed to elucidate the complex mechanisms underlying cognitive fluctuations in LBD.