This essay has been submitted by a student. This is not an example of the work written by our professional essay writers.
Lewy Body Dementia (LBD) is the second leading cause of dementia after Alzheimer's Disease (AD). The core symptoms of LBD including cognitive fluctuations, visual hallucinations, and parkinsonism may not always be present and clinicians may be unaware of associated symptoms. Thus, this diagnosis is often missed by primary care providers. Often LBD is misdiagnosed as AD, Parkinson's Disease, or a primary psychiatric illness. Distinguishing between these disorders has important treatment implications.
Lewy Body Dementia (LBD) is the second leading cause of dementia after Alzheimer's Disease. It accounts for 15-35 percent of cases (1-2). This disorder presents several difficulties both regarding diagnosis and management. Many patients initially present to their primary care physician. Thus, the ability to diagnosis and differentiate LBD from other types of dementia and initiate evidence based treatment often falls on primary care providers. The purpose of this review is to summarize the diagnostic criteria and clinical features, radiographic features, pathology, and treatment of this disorder to aide primary care physicians in caring for this population.
Seeing as LBD is the second most common cause of dementia after Alzheimer's Disease, accurate recognition is crucial. Diagnostic criteria (Table 1) was initially established in 1996 and subsequently revised to improve sensitivity (3,4). However, despite the revised diagnostic criteria, the recognition of LBD remains poor with a reported sensitivity of less than 50 percent (5). One reason for the low recognition of LBD is the difficulty associated with recognizing the diagnostic criteria. A high index of clinical suspicion is needed along with collateral information from family and caretakers.
The diagnosis of dementia requires a gradual decline of cognitive function that impedes daily activities. The pattern of dementia in LBD differs from that observed in Alzheimer's Disease. Memory impairments may not be present until the latter stages of LBD. Standard bedside tests such as the Mini Mental Status exam cannot reliably discriminate between LBD and other forms of dementia (3). Neuropsychological testing reveals several specific deficits. When matched for age, education, and MMSE score, patients with LBD tend to demonstrate more deficits in visuoperceptive tasks, visuoconstructive tasks, nonverbal reasoning, attention, and executive function compared to patients with Alzheimer's disease (6-12). Additionally, LBD patients may show greater impairments in functional abilities earlier in the disease than AD patients (13). Deficits in neuropsychological testing demonstrated in LBD patients are similar to that seen in patients with Parkinson's Disease Dementia (PDD) (3, 14).
The detection of fluctuating cognition has ranged considerably from 30 - 89 percent (15, 16). The intensity and duration of fluctuations is variable. Some occur rapidly lasting minutes to hours while others are slower occurring weekly or monthly. The variable temporal profile makes these features difficult to detect by physicians who do not see the patient for prolonged periods of time. History from family members and caregivers is essential in determining the presence of altering mental status. Clinicians are encouraged to ask about lethargy, daytime somnolence, staring into space for sustained periods, periods of increased attention, periods with improved memory, and episodes of disorganized speech (4).
Recurrent Visual Hallucinations
The presence of recurrent complex visual hallucinations is a critical feature in differentiating between AD and LBD. Hallucinations in other sensory modalities also occur but with decreased frequency. Visual hallucinations are present earlier in the course of disease in LBD while memory may be relatively preserved. Although their presence is highly specific, the sensitivity of visual hallucinations has ranged from 39-77 percent (13, 15, 16). Typical images include people and animals. Although the patient is aware that the images are not real,emotional responses are common (4). One caveat is that antiparkinsons drug which are commonly administered to this population because of the presence of extrapyramidal symptoms (EPS) may exacerbate or cause hallucinations. Thus, the presence of visual hallucinations with concurrent medication administration may not be as significant as hallucinations in drug naÃ¯ve patients. Persistent hallucinations after antiparkinson medications have been withdrawn in a patient with EPS may be a warning of impending dementia. The role of medications in precipitating and perpetuating visual hallucinations in this population has not been systematically studied.
Differentiating the visual hallucinations that occur with LBD from those occurring during delirium can be difficult particularly with the cognitive fluctuations that occur in LBD. Hallucinations secondary to delirium will resolve with the treatment of the underlying medical problem. Additionally, unlike in delirium, hallucinations in the setting of LBD recur over long periods of time independent of changes in cognitive status.
The presence of parkinsonism has ranged from 60-92 percent (15,16). The severity of extrapyramidal symptoms is similar to that observed in age matched patients with Parkinson's Disease. Given the high rate of dementia in Parkinson's Disease patients, differentiating LBD from PDD can be difficult. It is suggested that if the onset of dementia is greater than 12 months after the onset of motor symptoms than PDD is the appropriate label. However, if cognitive deficits appear within 12 months of motor symptoms LBD is more likely. Key differences between LBD and Parkinson's include a lower prevalence of rest tremor, more postural instability, stooped posture, hypophonic speech, ataxia, and facial immobility in LBD compared to Parkinson's. Additionally, the responsiveness to levodopa has been reported to be less in LBD patients compared to Parkinson's (3, 4). Although parkinsonism occurs in AD, it tends to appear later in the course of illness than in LBD or PDD.
REM Sleep Behavior Disorder (RBD)
RBD is a parasomnia characterized by the presence of vivid dreams during REM sleep without muscle atonia. It predominately occurs in males and has an onset after the age of fifty. The patient will thus act out their dreams through speech and movement often shouting or talking with accompanying limb flailing and/or falling out of bed. Violent behavior can also occur. Iranzo, Santamaria, & Tolosa reported on a series of seventeen patients with RBD and LBD. Self awareness of behaviors was present in 29 percent and the recollection of unpleasant dreams by 82 percent. Unpleasant dreams most frequently involved being attached by someone, arguing with someone, and being chased by someone. The most frequently reported behaviors in descending order were talking, shouting, falling out of bed, punching, and laughing (17). Forty percent of patients reported sustaining injuries and six percent injured their bed partner (17). Often the history is obtained from a bed partner, and symptoms can be present for decades before the onset of dementia (18, 19). Idiopathic RBD can be a harbinger of a subsequent neurodegnerative disease namely one of the Î±-synucleinopathies, Parkinson's, multiple system atrophy, and LBD. The prevalence of polysomnogram confirmed RBD in patients with Î±-synucleinopathies is 39 percent versus 0 percent in patients with nonsynucleinopathies (AD, frontotemporal dementia, corticobasal degeneration, progressive supranuclear palsy, mild cognitive impairment, primary progressive aphasia, and posterior cortical atrophy) (20). The frequency of probable RBD in PD and LBD patients compared to those with AD and MCI was 56 percent versus 2 percent (20). In 10 autopsied patients with clinically diagnosed RBD, 9 had Lewy Body Disease (20). The estimated 10 year risk of developing a neurodegenerative disease has been reported to be 40 percent (21). The reported risk of development of LBD has ranged from 7-14 percent in patients presenting with idiopathic RBD (19,21). The exact prevalence of RBD in patients with LBD is unknown. However, studies have suggested rates of 50-83 percent (17).
Neuroleptics are frequently used in this population for psychotic symptoms. However, the decision to utilize these medications is not without significant risk. In a series of 20 patients with LBD, McKeith et al reported that 80 percent received neuroleptics. Of those, 46 percent developed EPS for the first time after neuroleptic administration. Additionally, 81 percent of patients receiving antipsychotics developed a neuroleptic sensitivity syndrome ranging from mild (54 percent) to severe (46 percent). A mild syndrome was characterized by increased tone, rigidity, or bradykinesia. Severe reactions were characterized by sudden onset of sedation, immobility, fever, and confusion at times resembling neuroleptic malignant syndrome. Patients suffering severe reactions did not differ in age, sex, presence of psychosis, EPS at presentation, or syncopal episodes from those not suffering severe reactions. Severe reactions were also associated with a two fold increase in mortality (22). In a follow up study, Ballard, Grace, McKeith, & Holmes found that 29 percent of LBD patients receiving neuroleptics had severe reactions, half of whom died within two months (23).
As highlighted in Table 1, there are several features that support a diagnosis of LBD, but are not specific enough to have diagnostic significance. Autonomic instability is also present in other Î±-synucleopathies and may predispose patients to falling or syncope. In turn, patients may come to clinical attention because of repeated falls or syncopal episodes. McKeith, Fairbairn, Perry, Thompson, & Perry found that on presentation 35 percent of LBD patients reported repeated unexplained falls while twenty five percent endorsed syncopal episodes (22). In patients presenting with frequent falls or loss of consciousness, cognitive deficits may only be elicited through careful questioning. Psychiatric symptoms including depression, anxiety, and psychosis are common. In a series of 92 LBD patients, Borroni, Agosti, & Padovani found that 67 percent reported anxiety, 62 percent endorsed depression, 58 percent complained of apathy, and psychotic symptoms were present in half the sample. Psychotic symptoms including delusions, hallucinations, and anxiety worsened with disease progression although depression remained stable (24). No relationship between neuropsychiatric symptoms and motor symptoms was observed. McKeith et al found that 45 percent of LBD patients endorsed auditory hallucinations while 80 percent had delusions at some point during their illness (22).
Clinically, differentiating LBD and other dementia subtypes such as PDD and AD can be difficult. Considering poor sensitivity of the diagnostic criteria it is important to look at additional distinguishing investigations to improve diagnostic precision(5). The AAN (American Academy of Neurology) recommends structural neuroimaging with either a noncontrast head CT or MRI in the routine initial evaluation of all patients with dementia to rule out neoplasms, normal pressure hydrocephalus, and subdural hematomas as possible causes (25).
An MRI is more sensitive than a CT scan for studying regional changes in tissue volume in the brain. AD is characteristically defined by diffuse cerebral atrophy with a disproportionate amount of atrophy in the medial temporal lobes with relative sparing of subcortical structures. Ventricular enlargement also is present as the disease progresses (26). Conversely, LBD and PDD have similar changes on MRI consisting of atrophy of subcortical structures including the basal ganglia with relative preservation of medial temporal lobe structures. (3). Additionally, LBD shows slower rates of cerebral atrophy and ventricular enlargement compared to AD (26).
Of increasing interest in differentiating AD from LBD are functional neuroimaging studies which examine cerebral perfusion and cerebral metabolism utilizing single-photon emission computed tomography (SPECT) or positron emission tomography (PET) respectively. This stems from the hypothesis that even LBD without parkinsonism will have degeneration in the nigralstriatal system whereas those with AD will not. Using molecules that bind to the dopamine reuptake and transporter molecule found in presynaptic membranes of dopamine producing neurons in the caudate and putamen, SPECT can be used to measure the density of dopaminergic neurons in the nigralstriatal system. Thus, reduced dopamine transporter (DAT) binding can be used to differentiate between LBD and AD (27). In a series of 23 patients with dementia, Walker et al found the sensitivity and specificity for diagnosing LBD via SPECT was 100 percent and 92 percent respectively (27). Other studies have reported that abnormal dopamine transporter scans have been shown to have a sensitivity of over 75% and a specificity of over 90% for LBD (28-30) .
Both SPECT and PET scanning appeared useful for the diagnosis of LBD, but SPECT provided more robust results than PET (31).
Although an EEG is not routinely done in evaluation of dementia, several investigators have examined its diagnostic utility. Bonnani et al identified slow activities (pre-alpha) in posterior derivations of all LBD patients which notably differentiated these patients from those with AD. (32) Intermittent Delta and sharp transients also occur more in patients with LBD than those with AD although their frequency may be too small to aide in diagnosis (3, 32).
The role of biomarkers including cerebrospinal fluid tau and amyloid Î² 42 concentrations in diagnosing dementia has garnered increased clinical attention recently and may have some diagnostic relevance. However, its routine use is not recommended at this time by the American Academy of Neurology (25, 33).
Pathological assessment of LBD reveals aggregates of Î±-synuclein referred to as Lewy Bodies (LB) found in neurons and glia. They are hypothesized to stem from abnormal protein processing giving rise to cytoplasmic inclusions identifiable by immunohistochemistry (34). Their presence is required for the diagnosis at autopsy. Brainstem involvement is nearly universal, and there are variable amounts of Lewy Body burden found in the limbic system and neocortex (3, 35). In addition to central nervous system involvement, lewy bodies are also found in the peripheral nervous system and autonomic nervous system and are thought to account for symptoms like orthostasis (35). There is some sense that the location of LB relates to neural dysfunction. Brainstem lesions are thought to account for EPS while cognitive and neuropsychiatric symptoms are attributed to neocortical and limbic involvement. However, despite the intuitive nature of this hypothesis, the burden of LB in specific brain regions has not been conclusively demonstrated to correlate with clinical symptoms. Whether LB are involved in neurodegeneration directly, a cellular defense mechanism, or by products of an as of yet identified degenerative process is unknown (35).
Additionally, the mere presence of LB is not in itself enough to cause clinical symptoms. In fact, an estimated 24-55 percent of neuropsychiatrically healthy elderly adults are found to have significant LBs (35). Confounding the pathologic picture is the high incidence of comorbid Alzheimer's pathology present in 35-90 percent of cases (36).
Similar to AD, LBD is also associated with deficiencies in cholinergic transmission. Additionally, relative to patients with AD, those with LBD have lower choline acetyltransferase activity (ChAT) (37-39). It has been hypothesized that the increased prevalence of psychotic symptoms and visuospatial dysfunction in LBD patients may be secondary to the greater deficits in cholinergic transmission. Reduced activity of ChAT in the temporal and parietal neocortex has been observed in LBD patients and correlated to the presence of visual hallucinations while upregulation of M1 postsynaptic receptors in the temporal lobe has been correlated with delusional thinking (40, 41). Relative to AD, LBD is also associated with reductions in dopamine in the basal ganglia and norepinephrine in the putamen (38) . Abnormalities in glutamate receptors and second messenger signaling have also been demonstrated (42).
The marked decrease in cholinergic functioning observed in LBD patients relative to AD patients lead to speculation that cholinesterase inhibitors (ChEI) may have a greater potential of improvement in LBD than AD. Additionally, the observation that there is less neuronal loss in LBD than AD suggests that cortical neurons in LBD are more viable than those in AD and could be more responsive to cholinergic stimulation (43).
Patients with LBD who are treated with ChEI have shown improvement. In a placebo controlled, double blind study done in 120 patients with Lewy body dementia, McKeith et al found significant improvements in measures of attention as well as reductions in psychotic symptoms (44). There was no observed mortality benefit. In a prospective, randomized, double blind, placebo controlled trial involving 92 LBD patients treated with rivastigmine, Wesnes et al observed improvements in measures of attention, working memory, and episodic memory (45). Grace et al observed improvements in Mini Mental Status exam scores and neuropsychiatric symptoms over 24 weeks, a finding that has been observed by others (46,47). The study was extended over 96 weeks and neither MMSE or NPI scores significantly differed from baseline suggesting that ChEIs may attenuate degeneration. This hypothesis is further supported by findings by Ballard et al who observed a 70 percent reduction in AÎ² pathology in autopsies of 12 patients with LBD receiving ChEI therapy versus patients not receiving such therapy. Groups were matched for age as well as duration and severity of dementia (48).
Galantamine has also been reported to be helpful. It is not only a CHEI but also allosterically modulates neuronal nicotinic receptors. In patients with LBD there is a selective loss of the alpha7 nictotinic receptors in the hippocampus, suggesting possible added benefits of galatamine for cognition and behaviour due to its selective nicotinic receptor modulation. One study showed substantial benefits in visual hallucinations and fluctuating cognitive deficits. (49). Finally, donepazil has also shown positive results in measures of cognition and neuropsychiatric symptoms (50, 51). Differences between ChEI have not been found although head to head trials are lacking (52).
Thus, it appears that all ChEIs can be effective in this population. However, results should be viewed cautiously as the number of trials is small with few being placebo controlled and the number of patients limited.
Given the observed aberrations observed in glutaminergic transmission, it seems intuitive that the NMDA antagonist namenda may have a role in treatment. Namenda has been shown to neuropsychiatric symptoms including aggressivity and disinhibition, as well as Clinical Global Impression of Change scores and MMSE scores(53-55).
LBD patients suffer from a variety of neuropsychiatric symptoms as discussed previously including anxiety, depression, and psychosis. Comorbid anxiety and depression is best addressed with SSRIs and SNRIs (3). Tricyclics and other antidepressants with anticholinergic properties are best avoided. Efforts should also be made to avoid benzodiazepines as they can worsen cognition and predispose this vulnerable population to falls. However, at times they may be necessary particularly for RBD. In these cases, very low doses can be administered prior to bedtime. Other agents showing effectiveness in RBD include melatonin and very small doses of quetiapine. The former should be used with caution, however, because of enhanced neuroleptic sensitivity (3). Apathy and aggression may respond noorotropics as mentioned above. Psychotic symptoms may improve with cholinesterase inhibitors. However, in cases where they are refractory to this and cause significant impairment and burden to care givers, second generation antipsychotics like quetiapine and clozapine can be used in lower doses with extreme caution and attention to neuroleptic sensitivity. First generation antipsychotics should be avoided (3).
Motor symptoms can be particularly disabling for patients and are often exacerbated by medications used for cognitive symptoms such as cholinesterase inhibitors and neuroleptics used for psychotic symptoms. Dopaminergic agents are typically administered for parkinsonism, but their use must be balanced against the risk of exacerbation of psychotic symptoms. Additionally, patients with LBD show a lower response than those with Parkinson's Disease, and it has been suggested that this be a distinguishing diagnostic feature (3). In a series of 14 patients with LBD, Molloy et al found only 36 percent demonstrated a response to L-dopa after an acute challenge defined as a 20 percent or greater improvement in two of three tests of motor function on Unified Parkinson's Disease Rating Scale (UPDRS). Seventy percent and fifty seven percent of PDD and PD patients were classficied as responders respectively. Medication dosage did not differ significantly between groups (56). Bonelli et al found a greater than 20 percent improvement in UPDRS scores in fifty percent of LBD patients compared to 65 percent and 90 percent of PDD and PD patients respectively. Adverse events were not reported(57). Goldman et al reported improvement in motor symptoms in 6/19 LBD patients. Of the responders, 2 developed worsening hallucinations. Thus, only 22 percent of the cohort was able to obtain improvement in motor symptoms without exacerbation of psychosis (58).
Further research is required to determine the pathophysiological mechanisms underlying these results, but they suggest a fundamental difference in disease process. Hypothesis put forward to explain these differences include intrinsic Î±-synuclein pathology in the striatal system, loss of DA receptors in the caudate and putamen, and loss of DA receptors on corticostriate projections (56). Other antiparkinsonian medications apart from levodopa, including selegeline, amantadine,COMT inhibitors, anti cholinergics and dopamine agonists should be used with extreme caution in view of concerns about inducing confusion and psychosis. (58).
Thus, the decision to use dopaminergic agents must be undertaken with caution. Clinicians are advised to start with low doses and titrate slowly with constant monitoring for worsening cognition and psychosis.
A summary to clinical studies involving treatment is presented in Table 2.
The prognosis of LBD is poor. Jellinger, Wenning, & Seppi (2007) found a median time of survival of 5 years from symptom onset in a series of 243 autopsy confirmed cases of LBD and Parkinson's Disease(59). Williams, Xiong, Morris & Galvin found a median survival of 7.3 years after onset of dementia(60). Relative to AD, LBD is associated with increased overall mortality and reduced survival after onset of dementia in some but not all studies. The time to institutionalization and rate of cognitive decline is similar between the two illnesses. These effects are independent of baseline cognitive status, comorbidities and medications. Male gender has been reported to be a risk factor for increased mortality in some but not all studies (60-62).
LBD is a common cause of dementia in the elderly. It's diagnosis is often missed because of the difficulty in obtaining core symptoms. Often patients are not forthcoming with psychiatric symptoms and may only endorse cognitive impairment or motor symptoms leading to a misdiagnosis of AD or Parkison's. Additionally, patients presenting with psychotic symptoms may be misdiagnosed with a primary psychotic disorder. Accurate diagnosis is critical to avoid using neuroleptics and antiparkinson's agents in this population. Patients presenting with motor symptoms or repeated falls should be carefully questioned about cognitive and psychiatric symptoms. Similarly, older patients presenting with new onset psychotic symptoms should have a thorough evaluation including neuropsychiatric testing prior to attributing their complaints to a late onset primary psychotic disorder. Additional history should be obtained from family members or caregivers as patients may not have insight into their symptoms. Education should be provided to family members about the overall prognosis and nature of psychotic symptoms as these can be particularly distressing to caregivers.
Conflicts of Interest: None
Table 1: Criteria for Diagnosis of Lewy Body Dementia (LBD)
Central Feature (mostbe present for possible or probable LBD): (reference?)
Dementia defined as progressive cognitive decline of sufficient amountto interfere with normal social or occupational function.
Prominent or persistent memory impairment may not necessarily occur in early stages but becomes evident with disease progression.
Deficits on tests of attention, executive function, and visuospatial ability may be especially prominent
Core Features (two core features are needed for probable LBD, one for possible LBD)
Recurrent visual hallucinations
Spontaneous features of parkinsonism
Suggestive Features (if one or more of these is present in addition to one or more core features, a diagnosis of probable DLB can be made. If no core features are present butand more than one suggestive feature is present than possible LBD can be diagnosed. Probable LBD cannot be diagnosed without the presence of core features)
REM sleep behavior disorder
Severe neuroleptic sensitivity
Low dopamine transporter uptake in basal ganglia demonstrated by SPECT or PET imaging
Supportive Features (commonly present but not proven to have diagnostic specificity)
Unexplained loss of consciousness
Preservation of medial temporal lobes on imagining
Low uptake MIBG myocardial scintigraphy
Slow wave activity on EEG with transient sharp waves in temporal lobe
A diagnosis of LBD is less likely if:
Presence of cerebral vascular disease evident by focal neurologic signs/imaging
Presence of other illness sufficient to account for symptoms
If parkinsonism only appears for first time at a stage of severe dementia
Table 2: Clinical Studies in Treatment
McKeith et al 2000 (44)
120 patients with lewy body dementia.
NPI, MMSE and CGC.
Trial with rivastigmine
With intent to treat no difference in two groups in NPI ,MMSE,CGC and mortality. However improvement in NPI of DLB patients was noted when analysis was restricted to observed cases.
Wesnes et al 2002 (45)
92 patients with LBD.
20 weeks with 3 week post treatment follow up.
Cognitive drug research comprehensive assessment system and NPI.
Trial of rivastigmine.
Improvement in attention episodes and working memory in rivastigmine compared to placebo. Three weeks after discontinuation of rivastigmine, cognitive performance returned to baseline.
Grace et al 2001 (46)
29 patients in 3 centers, randomized placebo controlled trial of rivastigmine in DLB.9 women and 20 men.
MMSE and NPI.
Treatment with rivastigmine.
After 24 weeks, MMSE and NPI scores were improved. At 96 weeks , neither MMSE nor NPI scores were worse than at baseline.
Rozzini et al 2007 (47)
30 AD and 30 DLB patients
MMSE,NPI and BPSD.
Treatment with rivastigmine
At baseline DLB compared to AD patients showed a greater number of EPS and were similar in cognitive symptoms and BPSD. After treatment both groups showed a comparable cognitive improvement in both groups with significant behavioral effect in DLB but not AD patients in hallucinations and sleep disorders.
Ballard et al 2007 (48)
Autopsy of 12 patients with LBD treated with donepezil, rivastigmine,
tacrine, and galantamine and an additional 12 untreated patients.
Mean duration of treatment of 24.8 months
Cortical beta amyloid and tau pathologies on autopsy
6 patients treated with donepezil,4 with rivastigmine and 1 each with tacrine and galantamine.
Treated patients with DLB had significantly 70 % less parenchymal amyloid beta deposition compared to untreated patients.
Edwards et al 2007 (49)
50 patients with DLB
24 weeks open label
NPI, CGI, Cognitive Assessment System
Efficacy and safety of galantamine in DLB
Treatment resulted in significant improvements in NPI scores and CGI scores.
Adverse events were mild and transient.
Shea et al 1998 (50)
9 patients with DLB
12 weeks open label
Neuropsych symptoms, MMSE
Treatment with donepazil
8/9 patients demonstrated improvement in hallucinations. Cognition improved in 7/9 patients.
Thomas et al 2005 (51)
70 patients, 30 with DLB and 40 with PDD.
MMSE, NPI, motor subsection of UPDRS-III
Open label treatment with donepezil.
After 20 weeks, each group showed significant improvements from baseline in NPI and MMSE but no between group differences noted. UPRS scores did not significantly differ from baseline.
Bhasin et al 2007 (52)
3 treatments at 12 and 20 weeks.
Thomas et al 2005- 29 patients treated with donepezil,
Edwards et al 2004- 42 patients treated with galantamine,
Mckeith et al 2000 -35 patiets treated with rivastigmine
12 and 20 weeks
NPI,MMSE and UPDRS-III
All acetylcholine esterase inhibitors significantly improved cognitive and neuropsychiatric measures. No compelling evidence that anyone ChEI is better than the other in treatment of DLB
Emre et al 2010 (53)
199 patients, 34 with DLB and 62 with PDD treated with memantine.41 patients with DLB and 58 with PDD treated with placebo
Efficacy and safety of memantine
Patients with DLB who received memantine showed greater improvement than placebo on NPI and CGI.
Aarsland et al 2009 (54)
40 patients with PDD and 32 with DLB
24 weeks randomized controlled trial.
Effect of memantine on Clinical global impression of change(CGIC)
Treatment with memantine in patients with PDD or DLB
Memantine group had better CGIC scores compared to placebo. No between group differences noted.
Levin et al 2009 (55)
23 patients in two groups. 14 treated with memantine and 9 control group.
16 week open label study
Mattis Dementia Scale (MDS)MMSE and Clinical Assessment of Fluctuation (CAF)Scale and behavioral impairment scales, UPDRS
Efficacy and safety of memantine in LBD.
Patient showed significant improvement on MMSE, MDS, CAF, aggression, lack of spontaneity, disinhibition. No change in severity of psychosis and motor disorder.
Molloy et al 2005 et al (56)
27 DLB patients, 33 PDD patients, 31 PD patients
UPDRS III scores
L-dopa treatment for EPS
Acute L-dopa challenge resulted in response in 36% DLB compared to 70% PDD and 57% PD patients.
Bonelli et al 2004 (57)
20 DLB patients, 20 PDD patients, 20 PD patients
L dopa challenge
UPDRS III scores
L-dopa treatment for EPS
Greater than 20 percent improvement noted in 50 percent DLB patients compared to 65 percent PDD patients and 90 percent PD patients.
Goldman et al 2008 (58)
19 subjects fulfilling probable DLB consensus criteria
Approximately 4 months
UPDRS III scores
Treatment with Levodopa
Motor benefit without exacerbation of psychosis was seen in only 4 (22%) DLB patients. Dopaminergic medication had limited benefit in DLB patients because of low likelihood of motor improvement and the risk of psychosis exacerbation.