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Dementia with Lewy Bodies

Dementia Lewy Body

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.


Presentation

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 diseaseAutonomic 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.

Falling
  • Associated symptoms included visual hallucinations, excessive daytime drowsiness, recurrent falls, orthostatic hypotension and urinary incontinence.[ncbi.nlm.nih.gov]
  • Other common symptoms include syncope, falls, sleep disorders, and depression.[ncbi.nlm.nih.gov]
  • From a review of five cases of dementia with Lewy bodies with supranuclear gaze palsy including this case, the absence of falls in the early stage of the disease, fluctuation of cognition, hallucination and vertical gaze palsy with a more severe defect[ncbi.nlm.nih.gov]
  • Lewy body dementia (consisting of dementia with Lewy bodies and Parkinson's disease dementia) is a common neurodegenerative disease characterised by visual hallucinations, fluctuating attention, motor disturbances, falls, and sensitivity to antipsychotics[ncbi.nlm.nih.gov]
  • INTRODUCTION: People with Parkinson's disease (PD) are at risk of falling and have an increased risk of complications and prolonged recovery during hospitalisation.[ncbi.nlm.nih.gov]
Muscle Rigidity
  • The neuropsychiatric manifestations tend to precede the onset of bradykinesia, muscle rigidity, and other extrapyramidal signs. Delusions and visual hallucinations are relatively frequent in this condition.[icd9data.com]
  • Side effects include motor related symptoms, loss of cognitive function and/or development of muscle rigidity. Click here to download PDF[dementia.ie]
  • A person with LBD may be an unsafe driver early in the course of the illness due to visual hallucinations, muscle rigidity or slow reaction times, and fluctuating cognition.[lbda.org]
  • Movement disorders: Parkinson’s-like movement issues, such as muscle rigidity, tremors, falls, or a shuffling gait or way of walking, may occur.[hopkinsmedicine.org]
  • Negative reactions to antipsychotic medications can include a worsening of symptoms, extreme muscle rigidity, or even catatonia - which can take the form of apathy and complete motionlessness or constant overexcitement.[mentalhelp.net]
Facial Numbness
  • At 78 years of age, he consulted a neurologist with complaints of facial numbness and irritability. Neurological examination revealed no overt abnormality, and he scored 21 points on the Mini-Mental State Examination.[ncbi.nlm.nih.gov]
Visual Hallucination
  • BACKGROUND: Complex visual hallucinations occur in 70%-80% of dementia with Lewy bodies patients and significantly affect well-being.[ncbi.nlm.nih.gov]
  • Considering several hypotheses of visual hallucinations implicating dysfunctional attention toward external stimuli, these findings may provide evidence of pathologic changes that contribute to the manifestation of visual hallucinations in DLB.[ncbi.nlm.nih.gov]
  • To describe the assessment and treatment of an elderly woman with parkinsonism, progressive memory and cognitive deficits, and visual hallucinations.[ncbi.nlm.nih.gov]
  • However, visual hallucinations were significantly more frequent in the patients with hypermetabolism in all 3 areas (P 0.0018). Hypermetabolism is common in patients with DLB and may be related to visual hallucinations.[ncbi.nlm.nih.gov]
  • Memantine has been reported to have positive effects on visual hallucinations and cognition in patients with dementia with Lewy bodies (DLB).[ncbi.nlm.nih.gov]
Delusion
  • Delusion of other persons are stealing was the most common symptom (35.3%).[ncbi.nlm.nih.gov]
  • The delusion resolved spontaneously, coincident with worsening of the dementia.[ncbi.nlm.nih.gov]
  • We reported on a female patient affected by DLB who presented with an unusual delusion of duplication.[ncbi.nlm.nih.gov]
  • However, psychotic symptoms, such as visual hallucinations, delusions, and stupor, may complicate the clinical diagnosis of DLB.[ncbi.nlm.nih.gov]
  • Three patients with probable dementia with Lewy bodies (DLB) experienced worsening delusions and visual hallucinations as a result of memantine therapy. Significant resolution occurred once treatment was discontinued.[ncbi.nlm.nih.gov]
Tremor
  • The patient presented with a 10-year history of hand tremors, an 8-year history of short-term memory problems, and a 3-4-year history of visual hallucinations.[ncbi.nlm.nih.gov]
  • Furthermore, patients exhibit resting tremor, unstable gait, and impaired balance, which may be associated with cerebellar dysfunction. Therefore, we screened the cerebella of 12 patients with alpha-synucleinopathies for neuropathological changes.[ncbi.nlm.nih.gov]
  • , it’s Parkinson’s, and if dementia appears before or at the same time as the tremors, it’s DLB.[qz.com]
  • As such, medical treatment aims to control the symptoms of the dementia, such as the muscle stiffness, tremor and psychiatric disturbances.[myvmc.com]
  • Core clinical features include: recurrent visual hallucinations; cognitive fluctuations; REM sleep behaviour disorder; and one or more spontaeous cardinal features of parkinsonism: bradykinesia, rest tremor, or rigidity.[bestpractice.bmj.com]
Bradykinesia
  • He showed bradykinesia and small step gait with supranuclear vertical gaze palsy, especially upward gaze palsy. He was started on levodopa therapy but without response. A diagnosis of progressive supranuclear palsy was clinically suspected.[ncbi.nlm.nih.gov]
  • Core clinical features include: recurrent visual hallucinations; cognitive fluctuations; REM sleep behaviour disorder; and one or more spontaeous cardinal features of parkinsonism: bradykinesia, rest tremor, or rigidity.[bestpractice.bmj.com]
  • The neuropsychiatric manifestations tend to precede the onset of bradykinesia, muscle rigidity, and other extrapyramidal signs. Delusions and visual hallucinations are relatively frequent in this condition.[icd9data.com]
  • Postural instability and bradykinesia is noted on physical exam.[medbullets.com]
  • Parkinson’s symptoms in LBD: loss of spontaneous movement (bradykinesia) rigidity (muscles feel stiff and resist movement) tremor (less common in LBD than in Parkinson’s disease) shuffling walk face has a flat, unexpressive look Alzheimer's disease symptoms[med.emory.edu]
Memory Impairment
  • This result indicates that CA1 may be more functionally relevant than CA2 in the context of memory impairment in DLB.[ncbi.nlm.nih.gov]
  • She also developed episodic memory impairment. Her condition progressed to dementia with behavioral changes. Magnetic resonance imaging showed early left perisylvian and bitemporal atrophy. The patient died shortly afterward from colon cancer.[ncbi.nlm.nih.gov]
  • On neuropsychological tests, sub-cortical frontal syndrome is frequent, visual memory impairment, visuospatial impairment and visuo-constructive difficulties are also characteristics. On brain MRI, isolated diminished insula is to look for.[ncbi.nlm.nih.gov]
  • Dementia with Lewy bodies (DLB) tends to exhibit greater visuoperceptual, attentional and executive impairment and less pronounced memory impairment than AD.[ci.nii.ac.jp]
  • These include: Changes in thinking and reasoning Short term memory impairments Parkinson's symptoms, such as rigid and stiff muscles, tremors, loss of dexterity, stooped posture and shuffling movement.[dementia.ie]
Postural Instability
  • Postural instability and bradykinesia is noted on physical exam.[medbullets.com]
  • Supportive clinical features include sensitivity to antipsychotic agents, postural instability and falls, syncope, autonomic dysfunction, delusions and non-visual hallucinations, apathy, anxiety, and depression.[bestpractice.bmj.com]
  • The main symptoms of Parkinson's disease involve motor control, such as tremor (hands, arms, legs, jaw and face), slowness of movement, stiffness of the limbs and trunk as well as postural instability.[asceneuron.com]
  • “Diagnosing dementia with Lewy bodies early is critical, and with this important tool, a clinician can assess whether the patient has bradykinesia, rigidity, postural instability, or rest tremor without having to grade each extremity,” said Galvin.[fau.edu]
Shuffling Gait
  • Symptoms Patients with DLB may have parkinsonian features such as slow or decreased amplitude of movements (akinesia), muscle stiffness (rigidity), tremor, and/or shuffling gait, or features similar to those of Alzheimer's disease such as loss of memory[neurosciences.ucsd.edu]
  • Movement disorders: Parkinson’s-like movement issues, such as muscle rigidity, tremors, falls, or a shuffling gait or way of walking, may occur.[hopkinsmedicine.org]
  • Other features include fluctuating cognition, visual hallucinations, and spontaneous features of Parkinsonism such as body stiffness, tremors, shuffling gait, emotionless facial features and/or decreased coordination.[medicinenet.com]
  • Other symptoms that may occur as in other dementia are: Visual and non-visual hallucinations (tactile, auditory, olfactory) Abnormal movements of Parkinson's disease(shuffling gait, tremor, muscle stiffness) Agitation Depression Delusion Unexplained fainting[symptoma.com]
  • gait Slowness of movement Cog-wheeling (smooth motions now jerky) Posture altered (stooping or leaning) Chronic runny nose Myoclonic jerking Comprehension issues Ability to learn new tasks affected Short term memory impacted Loss of initiative, interests[lewybodydementia.ca]

Workup

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 [10]. 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 [10]. 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 [11].

Lewy Bodies in the Brain
  • The outstanding pathological findings were as follows; 1. presence of senile plaques, neurofibrillary changes, Pick bodies, Hirano bodies, granulovacuolar degeneration of neurons, etc. 2. numerous Lewy bodies in the brain stem and diencephalon, 3. peculiar[doi.org]
  • “If we see Lewy bodies in someone’s brain during an autopsy, that’s considered a ‘pathologic certainty’ of Parkinson’s disease,” she says.[hopkinsmedicine.org]
  • Regardless of the initial symptoms, over time people with LBD often develop similar symptoms due to the presence of Lewy bodies in the brain. But there are some differences.[nia.nih.gov]
  • Furthermore, at autopsy patients with PDD and DLB can have very similar findings of Lewy bodies throughout the brain, in addition to varying degrees of Alzheimer’s disease–associated plaque and tangles.[ftd.med.upenn.edu]

Treatment

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.

Non-pharmacologic treatment

The usefulness of nonpharmacologic interventions in dementia with Lewy bodies has nor been evaluated [10], although these modalities have benefited patients with Alzheimer’s disease and other forms of dementia [11]. 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 treatment 

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 [12]. There is need to differentiate pseudodelirium in DLB from a superimposed delirium with any abrupt increase in confusion [13]. 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.

Prognosis

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 [9]; 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 [10].

Etiology

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 [4].

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 [5]:

  • Hypoperfusion of the parietal and occipital association cortices correlated with visual hallucinations.
  • Hypoperfusion of the limbic-paralimbic structures coincided with misidentifications.
  • Hyperperfusion of the frontal cortices was associated with delusions.

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 [6].

Epidemiology

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 [7]. 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.

Sex distribution
Age distribution

Pathophysiology

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 [4], 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 [8].

Amyloid pathology is evident in both DLB and Alzheimer disease (AD). Neurofibrillary tangles are less complicated in DLB than in Alzheimer disease [4]. The disorder is less likely to be DLB if neurofibrillary pathology is severe [8]. 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.

Prevention

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.

Summary

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 [1]. 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 [2].

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 [3]. 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.

Patient Information

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.

Symptoms

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

Diagnosis entails clinical evaluation of signs and symptoms, routine laboratory examinations, and confirmatory tests with specialized diagnostic equipment.

Basic dementia screen includes: Hematology, ferritin, vitamin B12, folate, blood chemistry, thyroid function tests, and urinalysis. 

Cofirmatory diagnostic procedures, to distinguish from other dementias:

  • CT scan or MRI
  • Dopaminergic iodine-123-radiolabelled 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (FP-CIT) SPECT, to detect decreased dopamine transporter uptake.
  • Metaiodobenzylguanidine (MIBG) scintigraphy, to differentiate from Alzheimer and Parkinson's syndromes and other motor impairment. 

Treatment

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.

Vitamin E, an antioxidant, shown to lessen progression of Alzheimer disease, has been tried in DLB with inconclusive result.

References

Article

  1. McKeith IG, Galasko D, Kosaka K, et al. Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology. 1996 Nov; 47(5):1113-24.
  2. McKeith IG, Ballard CG, Perry RH, et al. Prospective validation of consensus criteria for the diagnosis of dementia with Lewy bodies. Neurology. 2000 Mar 14; 54(5):1050-8.
  3. McKeith IG, Dickson DW, Lowe J, et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology. 2005 Dec 27; 65(12):1863-72.
  4. Serra L, Cercignani M, Basile B, et al. White Matter Damage along the Uncinate Fasciculus Contributes to Cognitive Decline in AD and DLB. Curr Alzheimer Res. 2012 Jan 23; 326-33.
  5. Nagahama Y, Okina T, Suzuki N, et al. Neural correlates of psychotic symptoms in dementia with Lewy bodies. Brain. 2009 Nov 17.
  6. Galasko D, Saitoh T, Xia Y, et al. The apolipoprotein E allele epsilon-4 is overrepresented in patients with the Lewy body variant of Alzheimer's disease. Neurology. 1994; 44: 1950-1951.
  7. Perez F, Helmer C, Dartigues JF, et al. A 15-year population-based cohort study of the incidence of Parkinson's Disease and dementia with Lewy bodies in an elderly French cohort. J Neurol Neurosurg Psychiatry. 2009 Dec 3.
  8. McKeith IG, Dickson DW, Lowe J, et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology. 2005; 65:1863-1872.
  9. 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; 16:499–503.
  10. McKeith I, Mintzer J, Aarsland D, et al. Dementia with Lewy bodies. Lancet Neurol. 2004; 3:19–28.
  11. Mosimann UP, McKeith IG. Dementia with Lewy bodies—diagnosis and treatment. Swiss Med Wkly. 2003; 133:131–42.
  12. Burn DJ, McKeith IG. Current treatment of dementia with Lewy bodies and dementia associated with Parkinson’s disease. Mov Disord. 2003; 18(suppl 6):S72–9.
  13. Kalra S, Bergeron C, Lang AE. Lewy body disease and dementia. A review. Arch Intern Med. 1996; 156:487–93.

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Last updated: 2019-07-11 20:30