Prognosis and treatment of dementia with Lewy bodies
- Martin R Farlow, MD
Martin R Farlow, MD
- Professor of Neurology
- Indiana University School of Medicine
Dementia with Lewy bodies (DLB) is increasingly recognized clinically as the second most common type of degenerative dementia after Alzheimer disease (AD). In addition to dementia, distinctive clinical features include: visual hallucinations, parkinsonism, cognitive fluctuations, dysautonomia, sleep disorders, and neuroleptic sensitivity.
First described in the 1960s, DLB has a varied clinical presentation that shares features with other degenerative dementias. It was often overlooked pathologically because of the difficulty in identifying cortical Lewy bodies. With the advent of immunohistochemical stains for constituents of Lewy bodies, the prevalence of this disorder began to be recognized. However, challenges remain in defining this as a distinct entity from other degenerative dementias.
There is some clinical imperative to diagnose DLB, as optimal treatment choices – for best efficacy and limitation of significant side effects – are specific to DLB. However, DLB continues to be under recognized, and the clinical diagnostic criteria continue to be refined to improve specificity and sensitivity.
This article will describe the prognosis and treatment of dementia with Lewy bodies. The epidemiology, neuropathology, pathogenesis, clinical features, and diagnosis are discussed separately. (See "Epidemiology, pathology, and pathogenesis of dementia with Lewy bodies" and "Clinical features and diagnosis of dementia with Lewy bodies".)
The treatment of other dementia syndromes and the treatment of dementia in general are discussed separately. (See "Cholinesterase inhibitors in the treatment of dementia" and "Treatment of dementia" and "Management of neuropsychiatric symptoms of dementia" and "Cognitive impairment and dementia in Parkinson disease" and "Frontotemporal dementia: Treatment" and "Treatment and prevention of vascular dementia".)
- Ballard CG, O'Brien JT, Swann AG, et al. The natural history of psychosis and depression in dementia with Lewy bodies and Alzheimer's disease: persistence and new cases over 1 year of follow-up. J Clin Psychiatry 2001; 62:46.
- Ballard C, O'Brien J, Swann A, et al. One year follow-up of parkinsonism in dementia with Lewy bodies. Dement Geriatr Cogn Disord 2000; 11:219.
- Hamilton JM, Salmon DP, Galasko D, et al. Visuospatial deficits predict rate of cognitive decline in autopsy-verified dementia with Lewy bodies. Neuropsychology 2008; 22:729.
- McKeith IG. Dementia with Lewy bodies. Br J Psychiatry 2002; 180:144.
- Ballard C, O'Brien J, Morris CM, et al. The progression of cognitive impairment in dementia with Lewy bodies, vascular dementia and Alzheimer's disease. Int J Geriatr Psychiatry 2001; 16:499.
- Walker Z, Allen RL, Shergill S, et al. Three years survival in patients with a clinical diagnosis of dementia with Lewy bodies. Int J Geriatr Psychiatry 2000; 15:267.
- O'Brien JT, Paling S, Barber R, et al. Progressive brain atrophy on serial MRI in dementia with Lewy bodies, AD, and vascular dementia. Neurology 2001; 56:1386.
- Stavitsky K, Brickman AM, Scarmeas N, et al. The progression of cognition, psychiatric symptoms, and functional abilities in dementia with Lewy bodies and Alzheimer disease. Arch Neurol 2006; 63:1450.
- Olichney JM, Galasko D, Salmon DP, et al. Cognitive decline is faster in Lewy body variant than in Alzheimer's disease. Neurology 1998; 51:351.
- Del Ser T, Hachinski V, Merskey H, Munoz DG. Clinical and pathologic features of two groups of patients with dementia with Lewy bodies: effect of coexisting Alzheimer-type lesion load. Alzheimer Dis Assoc Disord 2001; 15:31.
- Williams MM, Xiong C, Morris JC, Galvin JE. Survival and mortality differences between dementia with Lewy bodies vs Alzheimer disease. Neurology 2006; 67:1935.
- Lopez OL, Wisniewski S, Hamilton RL, et al. Predictors of progression in patients with AD and Lewy bodies. Neurology 2000; 54:1774.
- Graff-Radford J, Aakre J, Savica R, et al. Duration and Pathologic Correlates of Lewy Body Disease. JAMA Neurol 2017; 74:310.
- Graff-Radford J, Lesnick TG, Boeve BF, et al. Predicting Survival in Dementia With Lewy Bodies With Hippocampal Volumetry. Mov Disord 2016; 31:989.
- Rolinski M, Fox C, Maidment I, McShane R. Cholinesterase inhibitors for dementia with Lewy bodies, Parkinson's disease dementia and cognitive impairment in Parkinson's disease. Cochrane Database Syst Rev 2012; :CD006504.
- Wang HF, Yu JT, Tang SW, et al. Efficacy and safety of cholinesterase inhibitors and memantine in cognitive impairment in Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies: systematic review with meta-analysis and trial sequential analysis. J Neurol Neurosurg Psychiatry 2015; 86:135.
- Stinton C, McKeith I, Taylor JP, et al. Pharmacological Management of Lewy Body Dementia: A Systematic Review and Meta-Analysis. Am J Psychiatry 2015; 172:731.
- Simard M, van Reekum R. The acetylcholinesterase inhibitors for treatment of cognitive and behavioral symptoms in dementia with Lewy bodies. J Neuropsychiatry Clin Neurosci 2004; 16:409.
- Lanctôt KL, Herrmann N. Donepezil for behavioural disorders associated with Lewy bodies: a case series. Int J Geriatr Psychiatry 2000; 15:338.
- Beversdorf DQ, Warner JL, Davis RA, et al. Donepezil in the treatment of dementia with lewy bodies. Am J Geriatr Psychiatry 2004; 12:542.
- Edwards K, Royall D, Hershey L, et al. Efficacy and safety of galantamine in patients with dementia with Lewy bodies: a 24-week open-label study. Dement Geriatr Cogn Disord 2007; 23:401.
- McKeith IG, Grace JB, Walker Z, et al. Rivastigmine in the treatment of dementia with Lewy bodies: preliminary findings from an open trial. Int J Geriatr Psychiatry 2000; 15:387.
- Ikeda M, Mori E, Kosaka K, et al. Long-term safety and efficacy of donepezil in patients with dementia with Lewy bodies: results from a 52-week, open-label, multicenter extension study. Dement Geriatr Cogn Disord 2013; 36:229.
- McKeith I, Del Ser T, Spano P, et al. Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study. Lancet 2000; 356:2031.
- Mori E, Ikeda M, Kosaka K, Donepezil-DLB Study Investigators. Donepezil for dementia with Lewy bodies: a randomized, placebo-controlled trial. Ann Neurol 2012; 72:41.
- Ikeda M, Mori E, Matsuo K, et al. Donepezil for dementia with Lewy bodies: a randomized, placebo-controlled, confirmatory phase III trial. Alzheimers Res Ther 2015; 7:4.
- Samuel W, Caligiuri M, Galasko D, et al. Better cognitive and psychopathologic response to donepezil in patients prospectively diagnosed as dementia with Lewy bodies: a preliminary study. Int J Geriatr Psychiatry 2000; 15:794.
- Onofrj M, Thomas A. Severe worsening of parkinsonism in Lewy body dementia due to donepezil. Neurology 2003; 61:1452.
- Morita S, Miwa H, Kondo T. [A patient with probable dementia with Lewy bodies, who showed catatonia induced by donepezil: a case report]. No To Shinkei 2004; 56:881.
- Sheffrin M, Miao Y, Boscardin WJ, Steinman MA. Weight Loss Associated with Cholinesterase Inhibitors in Individuals with Dementia in a National Healthcare System. J Am Geriatr Soc 2015; 63:1512.
- Ballard CG, Chalmers KA, Todd C, et al. Cholinesterase inhibitors reduce cortical Abeta in dementia with Lewy bodies. Neurology 2007; 68:1726.
- Aarsland D, Ballard C, Walker Z, et al. Memantine in patients with Parkinson's disease dementia or dementia with Lewy bodies: a double-blind, placebo-controlled, multicentre trial. Lancet Neurol 2009; 8:613.
- Emre M, Tsolaki M, Bonuccelli U, et al. Memantine for patients with Parkinson's disease dementia or dementia with Lewy bodies: a randomised, double-blind, placebo-controlled trial. Lancet Neurol 2010; 9:969.
- Ridha BH, Josephs KA, Rossor MN. Delusions and hallucinations in dementia with Lewy bodies: worsening with memantine. Neurology 2005; 65:481.
- Sabbagh MN, Hake AM, Ahmed S, Farlow MR. The use of memantine in dementia with Lewy bodies. J Alzheimers Dis 2005; 7:285.
- Stubendorff K, Larsson V, Ballard C, et al. Treatment effect of memantine on survival in dementia with Lewy bodies and Parkinson's disease with dementia: a prospective study. BMJ Open 2014; 4:e005158.
- Kurlan R, Cummings J, Raman R, et al. Quetiapine for agitation or psychosis in patients with dementia and parkinsonism. Neurology 2007; 68:1356.
- Walker Z, Grace J, Overshot R, et al. Olanzapine in dementia with Lewy bodies: a clinical study. Int J Geriatr Psychiatry 1999; 14:459.
- Cummings JL, Street J, Masterman D, Clark WS. Efficacy of olanzapine in the treatment of psychosis in dementia with lewy bodies. Dement Geriatr Cogn Disord 2002; 13:67.
- Leopold NA. Risperidone treatment of drug-related psychosis in patients with parkinsonism. Mov Disord 2000; 15:301.
- Tariot PN, Ismail MS. Use of quetiapine in elderly patients. J Clin Psychiatry 2002; 63 Suppl 13:21.
- Rasmussen KG Jr, Russell JC, Kung S, et al. Electroconvulsive therapy for patients with major depression and probable Lewy body dementia. J ECT 2003; 19:103.
- Olson EJ, Boeve BF, Silber MH. Rapid eye movement sleep behaviour disorder: demographic, clinical and laboratory findings in 93 cases. Brain 2000; 123 ( Pt 2):331.
- Boeve BF, Silber MH, Ferman TJ. Melatonin for treatment of REM sleep behavior disorder in neurologic disorders: results in 14 patients. Sleep Med 2003; 4:281.
- Gagnon JF, Postuma RB, Montplaisir J. Update on the pharmacology of REM sleep behavior disorder. Neurology 2006; 67:742.
- Molloy S, McKeith IG, O'Brien JT, Burn DJ. The role of levodopa in the management of dementia with Lewy bodies. J Neurol Neurosurg Psychiatry 2005; 76:1200.
- Bonelli SB, Ransmayr G, Steffelbauer M, et al. L-dopa responsiveness in dementia with Lewy bodies, Parkinson disease with and without dementia. Neurology 2004; 63:376.
- Lucetti C, Logi C, Del Dotto P, et al. Levodopa response in dementia with lewy bodies: a 1-year follow-up study. Parkinsonism Relat Disord 2010; 16:522.
- Kato K, Wada T, Kawakatsu S, Otani K. Improvement of both psychotic symptoms and Parkinsonism in a case of dementia with Lewy bodies by the combination therapy of risperidone and L-DOPA. Prog Neuropsychopharmacol Biol Psychiatry 2002; 26:201.
- Yamauchi K, Takehisa M, Tsuno M, et al. Levodopa improved rapid eye movement sleep behavior disorder with diffuse Lewy body disease. Gen Hosp Psychiatry 2003; 25:140.
- Fernandez HH, Wu CK, Ott BR. Pharmacotherapy of dementia with Lewy bodies. Expert Opin Pharmacother 2003; 4:2027.
- Drugs to treat autonomic dysfunction in Parkinson's disease. Mov Disord 2002; 17 Suppl 4:S103.
- Thaisetthawatkul P, Boeve BF, Benarroch EE, et al. Autonomic dysfunction in dementia with Lewy bodies. Neurology 2004; 62:1804.
- General strategies
- Cognition and neuropsychiatric disturbances
- - Cholinesterase inhibitors
- - Memantine
- - Neuroleptics
- - Other psychotropic medications
- REM sleep behavior disorder
- Parkinsonian symptoms
- Orthostatic hypotension
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS