Distinguishing Lewy body dementias from Alzheimer’s disease

Abstract

Lewy body dementia (LBD) is the second most common dementia after Alzheimer’s disease (AD). LBD is characterized clinically by visual hallucinations, extrapyramidal symptoms, cognitive fluctuations and neuroleptic sensitivity. LBD and AD share many common features in pathology, genetics and biochemical alterations; however, correct clinical distinction between these disorders has prognostic and therapeutic implications. There are currently no definitive radiological or biological markers for LBD, but studies suggest that premorbid differences in cognitive domains and personality traits, differences in clinical presentation, and alterations in autonomic function and sleep may improve diagnosis. Cholinergic dysfunction plays a major role in both AD and LBD; however, dysfunction is greater in LBD. This may account for the more prominent hallucinations, and offers the possibility of a greater response to cholinesterase inhibitors in LBD. The treatment of LBD is symptomatic and is based on a limited number of clinical trials and extension of results from trials in AD. Current research is focused on the role of synuclein aggregation with possible roles for synuclein-derived peptides as aggregation inhibitors. Other approaches target amyloid, neuroinflammation, oxidative injury, proteolysis, lipid peroxidation and immunotherapies with variable results. Improved understanding of disease mechanisms may open new therapeutic avenues for LBD in the future.

Keywords::

• acetylcholinestrase inhibitors
• Alzheimer’s disease
• dementia
• dementia with Lewy bodies
• hallucinations
• Parkinson’s disease
• personality

Financial & competing interests disclosure

This review was supported by grants from the National Institute of Aging (AG20764, AG03991 and AG05681) and by a generous gift from the Alan A and Edith L Wolff Charitable Trust. JE Galvin is a paid consultant for Pfizer, Eisai, Novartis, Ortho-McNeil and Forest. In the past year, JE Galvin has received research support from Wyeth, Elan, Novartis, Eli Lilly, Merck and Martek. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.