Dementia with Lewy bodies (DLB) is a chronic deterioration of mental abilities associated with the presence of Lewy bodies in the cytoplasm of cortical neurons. Lewy bodies are likewise present in the brains of patients with Parkinson's disease, Alzheimer disease and other forms of dementia.
The onset of cognitve degeneration in DLB is similar to that of other dementias in which extrapyramidal symptoms occur. However, in DLB (compared to Parkinson's disease) cognitive and extrapyramidal manifestations occur one year apart from each other. Thus, extrapyramidal symptoms differ between these two dementias.
DLB is characterized by fluctuating cognitive function, whereby periods of alertness, coherence, and normal orientation alternate with periods of confusion and unresponsiveness to questions, lasting for days or weeks but sometimes during the same interview. Impaired memory results from diminished alertness and attention rather than from loss of memory. Short-term recall is less vulnerable than digit span memory (as tested by the ability to repeat 7 digits forward and 5 backward). Patients may stare blankly into space and experience frequent daytime drowsiness. Visuospatial and visuoconstructional abilities (as tested by exercises such as figure copying, clock drawing or block design) are adversely affected more than other cognitive deficits. Rule out delirium in these patients.
Visual hallucinations are often alarming in contrast to the benign hallucinations of Parkinson's disease. Auditory, olfactory, and tactile hallucinations are less frequently encountered in DLB patients. Delusions in 50 to 65% of patients are more bizarre than the simple persecutory ideation in Alzheimer's disease. Autonomic dysfunction and unexplained syncope may accompany the onset of cognitive deficits. DLB patients are very sensitive to antipsychotics. Rapid eye movement (REM) sleep behavior disorder, a parasomnia, is characterized by vivid dreams that may be acted out, sometimes to the detriment of the patient's companion in bed.
Although DLB can not be distinguished from other forms of dementias on the basis of laboratory examinations alone, nevertheless these should be done as a matter of procedure e.g., routine screening for depression, hypothyroidism, vitamin B12 deficiency, and syphilis for persons with previous history of infection. CT scan is part of the workup for dementia . MRI in dementia with Lewy bodies will reveal preservation of hippocampal and medial temporal lobe volume in contrast with Alzheimer disease while SPECT will detect occipital hypoperfusion . Sophisticated neuroimaging procedures may be useful in the future since current technics are wanting in sensitivity and specificity to clearly diagnose dementia with Lewy bodies .
The management of DLB entails differential diagnosis within a wide spectrum of LB-associated dementias. In this premise depends the choice of appropriate pharmacologic and non-pharmacologic interventions. Evaluation of the patient's initial cognitive, psychiatric and motor disabilities and confirmation by the family can help prioritize target symptoms for treatment. Some relevant indicators are slow movement, tremors, fluctuations in alertness and attention, hallucinations, depression, sleep disorder, behavioral changes, daytime drowsiness, and autonomic dysfunction. Treatment can focus on the most severe symptoms taking into consideration possible contraindications. An example of this is the use of cholinesterase inhibitors for dementia which causes drooling and postural instability in Parkinson's disease.
The usefulness of nonpharmacologic interventions in dementia with Lewy bodies has nor been evaluated , although these modalities have benefited patients with Alzheimer’s disease and other forms of dementia . Treatment should be based on the particular needs of the patient and orientation of caregivers. These include supportive treatment with glasses and hearing aids for sensory impairment, promoting rapport between patient and caregivers, and providing a restful but conducive environment. Hallucinations may be managed by careful tolerance, providing visibility and wholesome company.
Pharmacologic management of DLB requires special considerations in dealing with patients with acute psychotic symptoms while excluding other causes of symptoms such as pain, subdural hematoma, intercurrent infection, or adverse drug reaction . There is need to differentiate pseudodelirium in DLB from a superimposed delirium with any abrupt increase in confusion . DLB patients respond better to treatment with cholinesterase inhibitor than patients with other forms of dementia. Results have shown lessening of fluctuations in cognitive abilities, hallucinations, anxiety, apathy, and sleep disturbances.
The clinical course and subsequent recovery from dementia with Lewy bodies remain to be clearly understood. The presumption is that progression of the disease and mortality in DLB is similar to Alzheimer disease ; however, shorter survival has been observed in DLB patients. Predictive indicators of a more severe clinical decline or decreased survival have yet to be identified .
The precise etiology of DLB remains to be identified. One probable cause is the disruption of the two-way relay of information from the striatum to the neocortex in the frontal lobe which is multifactorial in origin. As it were, the function of neuronal circuits is affected by changes in levels of neuromodulators and/or neurotransmitters such as ACh and dopamine. Nonpyramidal cells in layers V and VI of the neocortex serve to process information and relay data to subcortical regions. This function appears to be impaired in DLB. The cause of fluctuations in mental abilities in DLB is currently not known .
In the study of Nagahama et al, perfusion changes in the brain correlated with psychotic symptoms in patients with DLB. Observations based on single-photon emission computed tomography (SPECT) in 145 DLB patients confirmed the following :
Hereditary DLB, though rare, may occur. For instance, apolipoprotein E subtype 4 (ApoE4) genotype has been associated with DLB in patients with concomitant Alzheimer disease .
Postmortem studies attribute DLB to 10-20% of dementias. However, precise epidemiologic data on the true incidence or prevalence of DLB is unavailable due to lack of reliable clinical assessment tools.
The frequency of DLB in autopsy studies in Europe, Japan and the United States shows a similar trends. A prospective, cohort-study of persons over 65 years of age in southwestern France resulted in an incidence rate of 112 per 100,000 person-years for suspected DLB . In addition, the study showed that the incidence of DLB increased with age, in contrast to Parkinson's disease which decreased after age 85 years. DLB affects people of Asian, African, and European origin but data on its relative frequency among races is wanting. DLB is slightly more common in men than in women and occurs in late middle age and older.
DLB is a progressive deterioration of cognitive function distinguished by the presence of characteristic Lewy bodies in brain parenchyma. First described in idiopathic Parkinson's disease, Lewy bodies are also found in Alzheimer disease and other dementias. The pathology of DLB and that of idiopathic Parkinson's disease have common features.
Lewy body inclusions consist mainly of the protein alpha-synuclein, a cytoplasmic protein associated with synaptic vesicles , which is involved in the transportation of synaptic vesicles and synaptic plasticity. Lewy bodies include other proteins, i.e., neurofilament and ubiquitin. The clinical manifestation of DLB correlate with the distribution and density of Lewy bodies in the CNS whereas the disposition of Lewy bodies in Alzheimer disease is determined by phenotype .
Amyloid pathology is evident in both DLB and Alzheimer disease (AD). Neurofibrillary tangles are less complicated in DLB than in Alzheimer disease . The disorder is less likely to be DLB if neurofibrillary pathology is severe . DLB pathology is characterized by focal vacuolization in the temporal lobe and Lewy neurites. Cholinergic and dopaminergic deficits are more prominent in DLB than in AD.
Ability to recognize the signs and symptoms of dementia with Lewy bodies can facilitate prompt diagnosis and treatment. Timely and appropriate interventions can alleviate symptoms or at least minimize the progression of the degenerative effects of the disorder.
Frederick Lewy in 1914 first described cellular inclusions in the substantia nigra in the brain of patients with idiopathic Parkinson's disease, which he called Lewy bodies. Henceforth, Lewy bodies (LBs) became a diagnostic feature of progressive, degenerative dementia. In the 1960s, pathologists have already found LBs in the neocortex of patients with dementia. It was only in the mid-1980s, with the development of more precise immunochemical methods for detecting Lewy bodies, that Dementia with Lewy bodies (DLB) was recognized as a distinct clinical entity.
There appears to be a spectrum of LB-associated disorders since DLB may coexist with Parkinson's disease and Alzheimer disease. In 1996, clinical diagnostic features for DLB was first proposed . These have undergone modifications in successive DLB consortium reports. Clinicopathologic studies aim to establish the reliability (i.e., the sensitivity and specificity) of these criteria .
A third report of the DLB Consortium, headed by Ian McKeith, proposed a tentative one-year rule on distinguishing DLB from Parkinson's disease with dementia . If dementia is not manifested within 12 months or longer in a Parkinson patient, the disorder is called Parkinson's disease with dementia; otherwise, it is called DLB. This rule is not without drawbacks in clinical practice. When visual hallucinations and reduced alertness precede motor signs, the diagnosis of DLB should be considered.
Dementia is a gradual deterioration of brain function affecting memory, mental alertness, thought, speech, behavior and movements. One type of dementia is that which is characterized by the presence of abnormal clumps of proteins in the brain cells called Lewy bodies. Hence, the condition is known as dementia with Lewy bodies or DLB.
Lewy bodies are eosinophilic intracytoplasmic inclusions bodies in the brainstem and neocortex. However, it is not clear if these protein clumps actually damage the brain cells or whether some other destructive process is involved. These are found in other dementias such as Alzheimer disease and Parkinson's disease thus, necessitating careful consideration of signs and symptoms of each for differential diagnosis and appropriate treatment.
Although symptoms may vary among DLB patients, all are vulnerable to progressive loss of mental abilities that impede normal daily activities. This may include loss of recent memory, alertness and attention, inability for rational thinking and problem solving, and disorientation with time and space. Fluctuations in mental functions from better to worse is prominent in DLB, alternating with episodes of being confused and apathetic. Other symptoms that may occur as in other dementia are:
DBL patients are sensitive to "neuroleptic" drugs which are given to control hallucinations and delusions. People with dementia with Lewy bodies, however, often manifest symptoms of Alzheimer and Parkinson's disease within 1 year of each other.
Diagnosis entails clinical evaluation of signs and symptoms, routine laboratory examinations, and confirmatory tests with specialized diagnostic equipment.
Cofirmatory diagnostic procedures, to distinguish from other dementias:
Chemotherapy is prescribed for DLB as in other dementia. Acetylcholinesterase inhibitors decrease confusion and cognitive fluctuations, agitation and hallucinations but do not affect motor symptoms. Mild symptoms do not require treatment.
An atypical neuroleptic (antipsychotic) drug is indicated for hallucinations and agitation which can cause unsafe behavior and injuries. However, haloperidol (Haldol) is not recommended for DBL patients.
Drugs that increase levels of the neurotransmitter dopamine may be used in DBL as in Parkinson's disease to alleviate the motor symptoms. Motor function is improved in some patients. These drugs have no effect on cognitive symptoms and may even worsen the condition, especially hallucinations.
Depression in DLB may result from brain damage and/or impaired psychological function. The drugs of choice for this condition are serotonin reuptake inhibitors (SSRIs) and monoamine oxidase-B inhibitor (MAOI). Combinations are not recommended because of possible severe side effects, especially in older people.