Dementia with Lewy Bodies (Diffuse Lewy Body Disease)
Dementia (from Latin "de" meaning apart and "mentis" meaning mind) is a gradual decline of cognitive functions, including memory, language abilities and problem solving skills, severe enough to interfere with normal daily functioning. There are many causes of dementia, the most common form being Alzheimer's disease, where memory loss is the most prominent feature.
Dementia with Lewy bodies (DLB) is the second most common cause of dementia in the general population. The name comes from deposits, called Lewy bodies, of an abnormal protein (synuclein) in the brain neurons. DLB consists of a combination of symptoms: dementia, parkinsonism (slowness, stiffness, problems walking) and visual hallucinations (seeing things that are not real). Patients with DLB may not have significant memory problems in the beginning, but almost always suffer from attention deficits, difficulties organizing and carrying tasks to completion, and problems with their visuospatial abilities. The symptoms usually fluctuate with "good days" and "bad days." The hallucinations in DLB are usually visual, such as anonymous people, family members, animals or machines. They tend to be in color, very detailed and nonthreatening. Insight is usually retained, especially in the beginning. Many patients with DLB also have repeated falls, faintness and marked sensitivity to certain psychiatric drugs (neuroleptics). Besides hallucinations, other psychiatric symptoms include delusions, depression and apathy. They also tend to act out their dreams and become quite agitated and combative during sleep, condition known as REM sleep behavior disorder (RBD), which may precede the onset of any other symptom of DLB by several years. On examination, besides cognitive impairment and parkinsonian features, many patients with DLB have jerk-like movements (myoclonus).
Cognitive, particularly memory, impairment, may also be present in Parkinson's disease (PD), called Parkinson's disease dementia (PDD). It occurs in about a third of all PD patients, particularly in advanced stages. Severe dementia may be associated with agitation, disorientation, confusion, and hallucinations. These and other psychiatric symptoms often necessitate close supervision by caretakers. DLB and PDD probably represent the two clinical entities on a spectrum of Lewy body disease. The time course of the clinical symptoms differentiates these two conditions. In PDD, dementia develops within the context of an already established diagnosis of Parkinson's disease. In DLB, dementia precedes or coincides with the development of parkinsonian signs for at least one year.
The cause of DLB is unknown, but problems with cellular processing of abnormally folded proteins in certain brain cells have been suspected to cause the neurodegeneration in brain cortex and in the basal ganglia, the deep portion of the brain involved in motor control. Although few families with DLB have been described, the disorder is almost always sporadic (not genetic). Analysis of the genetic forms of this disorder allows researchers to work on identifying particular proteins involved in the disease process. About one third of Alzheimer's disease patients develop signs of parkinsonism, such as tremor, rigidity, slowed movement, and postural instability, and patients with PD have a slightly higher risk for Alzheimer's disease than those without PD, but the dementia that is seen in advanced stages of PD appears to be due to progression of PD rather than a co-existent Alzheimer's disease. A gene called APOE4, thought to increase risk of Alzheimer's dementia, has been found increase risk of DLB as well.
Although DLB patients usually do not respond as well to levodopa as those with typical PD, many do obtain satisfactory improvement with levodopa and benefit from chronic treatment. The treatment of hallucinations, delusions, agitation and other psychiatric symptoms may be challenging. The traditional anti-psychotic drugs (also called typical neuroleptics), such as thioridazine (Mellaril) or haloperidol (Haldol), can worsen parkinsonian symptoms, and should not be used. The newer, atypical antipsychotic drugs, such as clozapine (Clozaril), olanzapine (Zyprexa), quetiapine (Seroquel), ziprasidone (Geodon), and aripiprazole (Abilify) can suppress hallucinations and treat other psychiatric problems without worsening parkinsonian symptoms. However, clozapine can cause loss of infection-fighting white blood cells in 1-2 percent of cases, a serious side effect which limits the usefulness of this drug. Also, medications used for dementia and behavioral problems associated Alzheimer's disease, such as donepezil (Aricept), rivastigmine (Exelon), and memantine (Namenda), may be helpful in DLB.
©2011 Joseph Jankovic, M.D.
Boeve BF, Silber MH, Parisi JE, et al. Synucleinopathy pathology and REM sleep behavior disorder plus dementia or parkinsonism. Neurology. 2003;61:40-5.
Bogaerts V, et al. A novel locus for dementia with Lewy bodies: a clinically and genetically heterogeneous disorder. Brain. 2007;130(9):2277-91.
Bonelli SB, Ransmayr G, Steffelbauer M, et al. L-dopa responsiveness in dementia with Lewy bodies, Parkinson disease with and without dementia. Neurology. 2004;63:376-8.
Burn DJ. Cortical Lewy body disease. J Neurol Neurosurg Psychiatry. 2004;75:175-8.
Emre M, Aarsland D, Brown R, et al. Clinical diagnostic criteria for dementia associated with Parkinson's disease. Mov Disord. 2007;22(12):1689-1707.
Fahn S, Jankovic J. Principles and Practice of Movement Disorders, Churchill Livingstone, Elsevier, Philadelphia, PA, 2007:1-652. (Accompanied by a DVD of movement disorders.)
Jankovic J, Shannon KM. Movement disorders. In: Bradley WG, Daroff RB, Fenichel GM, Jankovic J, eds. Neurology in Clinical Practice, 5th ed., Butterworth-Heinemann (Elsevier), Philadelphia, PA, 2008.
Jankovic J, Tolosa E, eds. Parkinson's Disease and Movement Disorders, 5th ed., Lippincott Williams and Wilkins, Philadelphia, PA, 2007:1-720. (Accompanied by a CD video atlas.)
Lippa CF, Duda JE, Grossman MD, et al. DLB and PDD boundary issues. Diagnosis, treatment, molecular pathology, and biomarkers. Neurology. 2007;68:812-9.
Lopez OL, Becker JT, Kaufer DI, et al. Research evaluation and prospective diagnosis of dementia with Lewy bodies. Arch Neurol. 2002;59:43-6.
McKeith IG, Dickson DW, Lowe J, et al. Diagnosis and management of dementia with Lewy bodies. Third report of the DLB consortium. Neurology. 2005;64:1863-72.
Ohtake H, Limprasert P, Fan Y, et al. Beta-synuclein gene alterations in dementia with Lewy bodies. Neurology. 2004;63:805-11.
Thomas M, Jankovic J. Parkinson-plus syndromes. In: Noseworthy J, editor-in-chief, Neurological Therapeutics: Principles and Practice, 2nd ed., Informa Healthcare, Milton Park, Abingdon, Oxon, UK, 2006:2803-26.