Lewy body dementias

Abstract

The broad importance of dementia is undisputed, with Alzheimer's disease justifiably getting the most attention. However, dementia with Lewy bodies and Parkinson's disease dementia, now called Lewy body dementias, are the second most common type of degenerative dementia in patients older than 65 years. Despite this, Lewy body dementias receive little attention and patients are often misdiagnosed, leading to less than ideal management. Over the past 10 years, considerable effort has gone into improving diagnostic accuracy by refining diagnostic criteria and using imaging and other biomarkers. Dementia with Lewy bodies and Parkinson's disease dementia share the same pathophysiology, and effective treatments will depend not only on successful treatment of symptoms but also on targeting the pathological mechanisms of disease, ideally before symptoms and clinical signs develop. We summarise the most pertinent progress from the past 10 years, outlining some of the challenges for the future, which will require refinement of diagnosis and clarification of the pathogenesis, leading to disease-modifying treatments.

Figure 1. Hypothetical model of prodromal dementia with Lewy bodies

Shows dynamic changes in biomarkers associated with the progression of Alzheimer’s disease and dementia with Lewy bodies. Based on retrospective data, which used similar concepts and assumptions to the original model by Jack and colleagues for Alzheimer’s disease. (A) In patients with Alzheimer’s disease, the progression of amyloid β deposition is detectable by changes in the concentrations of amyloid β 42 in cerebrospinal fluid or on PET imaging. These alterations precede changes in structural MRI and ¹⁸F-fluorodeoxyglucose PET and other disease biomarkers, such as tau-mediated neuron injury and dysfunction (detected by cerebrospinal fluid concentrations of tau). (B) By contrast, in patients who have dementia with Lewy bodies (which is associated with α-synuclein-mediated neuronal dysfunction), altered sleep and arousal behaviour is often the earliest detectable change, followed by alterations in cognition and motor or clinical function. Reproduced from Fields and colleagues. MCI=mild cognitive impairment.

Figure 2. Representative neuroimaging in dementia with Lewy bodies and dementia in Alzheimer’s disease

FDG-PET=¹⁸F-fluorodeoxyglucose PET. FP-CIT SPECT=¹²³I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane single photon emission CT. Note the lack of hippocampal atrophy on MRI, presence of occipital hypometabolism on FDG-PET, and reduced striatonigral uptake on FP-CIT SPECT in dementia with Lewy bodies, compared with the findings in Alzheimer’s disease. Images courtesy of Clifford Jack, Kejal Kantarci, and Val Lowe.