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Dementia with Lewy bodies: a comprehensive review for nurses.

ABSTRACT

Much of the current nursing literature on dementia focuses on Alzheimer disease (AD), the dementia subtype most commonly diagnosed in the older adults. There is a paucity of nursing literature on dementia with Lewy bodies (DLB), the second most common subtype of dementia, which is closely associated with Parkinson disease with dementia (PDD), considered the third most common dementia subtype. Both are aging-related disorders attributed to Lewy bodies, abnormal protein aggregates or "clumps" found to cause cumulative neurodegeneration over time. DLB is defined as dementia onset that is preceded by Parkinsonian symptoms for 1 year or less, whereas in PDD, 2 or more years of Parkinsonian symptoms precede dementia onset. Although basic science knowledge of DLB has increased exponentially, the lack of nursing research on DLB indicates that this knowledge excludes the nursing perspective and its implications for nursing practice. The purpose of this article is to provide nurses with a comprehensive overview of DLB as it compares with PDD and Alzheimer disease and to propose key nursing interventions for clinical practice.

Keywords: dementia with Lewy bodies, Lewy bodies, Parkinson disease with dementia

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Today, 25 million people worldwide have some form of dementia; it afflicts 7% of the population over 65 years old and 25%-30% of those over 80 years old (Aarsland et al., 2009; Hanyu et al., 2006). Among these cases are seven million Americans, and of these, five million live with Alzheimer disease (AD), whereas two million have non-Alzheimer-related dementia (Aarsland et al., 2009; Gallagher & Long, 2011).

Dementia with Lewy bodies (DLB) and Parkinson disease with dementia (PDD) are the most common dementia types after AD, with a worldwide incidence rate of 15%-20% among dementia diagnoses (Aarsland et al, 2009; Ballard et al, 2010; Reilly, Rodriguez, Lamy, & Neils-Strunjas, 2010; Sauer, Ffytche, Ballard, Brown, & Howard, 2006). Both are aging-related disorders attributed to Lewy bodies, which are abnormal protein aggregates or "clumps" found to cause cumulative neurodegeneration over time. DLB is defined as dementia onset that is preceded by Parkinsonian symptoms for 1 year or less, whereas in PDD, 2 or more years of Parkinsonian symptoms precede dementia onset (Love, 2005; Maetzler-Baddeley, 2007; Mollenhauer et al, 2010; Robillard, 2007; Tsuboi, Uchikado, & Dickson, 2007). DLB first emerged as a distinct diagnosis in 1990, when Perry, Irving, Blessed, Fairbairn, and Perry (1990) identified a group of elderly patients who did not meet the criteria for AD or vascular dementia (VAD) but exhibited some mild Parkinsonian symptoms. Since then, studies have found that the mean age onset for DLB is comparable with AD at 68 years, whereas Parkinson disease (PD) has a mean age onset of 60 years. Of those with PD, 24%-31% eventually develop dementia (Johansen, White, Sando, & Aasly, 2010; Perry et al, 1990; Reilly et al, 2010). Several studies have also reported an increased risk for mortality and a shorter time course from onset or diagnosis to institutionalization or death for patients with DLB, compared with other AD and other dementia types (Hanyu et al, 2009; Matsui et al, 2009; Williams, Xiong, Morris, & Galvin, 2006).

Although basic science knowledge of DLB has increased exponentially, there is little, if any, nursing research on DLB. The purpose of this article is to provide nurses with a comprehensive overview of DLB as it compares with other dementia subtypes, particularly AD and PDD, and to propose nursing interventions for clinical practice. Neuropathological and clinical diagnosis of DLB will be reviewed, and nursing interventions for DLB will be proposed.

What Is Lewy Body Disease/DLB?

Lewy bodies are abnormal aggregates or "clumps" found in several areas of the brain and are composed primarily of an insoluble form of the protein alpha-synuclein ([alpha]-syn), which is known to regulate neuron differentiation, synaptic plasticity, and dopamine production; [alpha]-syn is also found in the amyloid-[beta] (protein or long chain peptide)-based plaques associated with AD (Ohrfelt et al., 2009; Tsuboi et al, 2007; Yokota et al, 2007). Lewy neurites, on the other hand, are similar protein clumps found within neurons (nerve cells). Lewy bodies and Lewy neurites are found in both symptomatic and asymptomatic individuals, and several studies show that their presence is an age-related feature that typically presents in the 60- to 90-year-old age range (Schulz-Schaeffer, 2010). Lewy body disease results from the damage caused by progressive spread of Lewy bodies and Lewy neurites to specific parts of the brain (Love, 2005; Yokota et al, 2007). Lewy-type pathology has been implicated in DLB, PDD, and PD.

Staging systems have been devised for the diagnosis of DLB:

* the Braak six-stage schema for PD-related pathology;

* the Consensus Guidelines for the Clinical and Pathologic Diagnosis of Dementia with Lewy Bodies developed by the Consortium on DLB; and

* a unified staging system proposed in 2009 by Beach et al. (2009; Braak, Ghebremedhin, Rub, Bratzke, & Del Tredici, 2004; McKeith, 2006).

These systems diagnose the severity of Lewy body disease based on where Lewy bodies proliferate and spread. In the Braak system, stages 1 and 2 in Lewy body pathology involve the medulla oblongata, the pontine tegmentum in the pons, the olfactory bulb, and the anterior olfactory nucleus adjacent to the bulb (Braak et al, 2004). Clinical symptoms appear and begin to worsen in stages 3 and 4, when Lewy bodies spread to the substantia nigra and nuclear gray areas in the midbrain and forebrain. Finally, in stages 5 and 6, Lewy bodies are found in the mature neorcortex, and the disease is at the end stage. On the other hand, the 1996 Consensus Guidelines authored by the Consortium on DLB identified distinct Lewy body disease patterns: brainstem-predominant, limbic/ transitional, and neocortical (McKeith, 2006). Beach et al. (2009) conducted a histopathological study of 417 brain necropsy samples from subjects with incidental DLB, PDD, PD, and AD with Lewy bodies who were enrolled in a patient registry and brain donation program; samples were stained for [alpha]-syn. Their discovery of distinct patterns of [alpha]-syn cluster and dispersion in different parts of the brain led them to propose a unified staging system for Lewy body disorders that accounts for regions not included in the Braak and Consortium staging systems: I-Olfactory Bulb Only, Ila-Brainstem Predominant, Ilb-Limbic Predominant, III-Brainstem and Limbic, and IV-Neocortical. These staging systems are indicated in Table 1.

Testing for DLB: Neuroimaging, Electroencephalography (EEG), and Biomarkers

Neuroimaging

Neuroimaging techniques have been used to differentiate between DLB, PDD, and AD. In functional magnetic resonance imaging (fMRI), blood oxygenation level-dependent signals are used to identify areas of the brain experiencing increased activation to a stimulus, whereas diffusion tensor imaging measures water diffusion in tissue to detect structural and functional changes (Manenti et al, 2007; Ogawa, Lee, Kay, & Tank, 1990). Positive emission tomography (PET) and single photon emission computed tomography (SPECT), on the other hand, require the intravenous administration of a radiotracer that binds to a specific neurochemical to allow detection of the degree of brain activity associated with that neurochemical (Koeppe, Gilman, Junck, Wernette, & Frey, 2008; Lee et al, 2010; Walker et al, 2007). Cardiac scintigraphy using [sup.123]I-metaidodobenzylguanidine ([sup.123]I-MIBG), a radioisotope form of guanethidine, has also been used to detect Lewy body disease. Guanethidine is a norepinephrine inhibitor used intravenously in some European countries for nerve blocks to relieve complex pain syndrome, but in its radioisotope form, [sup.123]I-MIBG is used in the United States as a radiotracer in cardiac scintigraphy to diagnose the presence of a pheochromocytoma (an adrenal gland tumor), as it allows the detection and functional assessment of postganglionic noradrenergic neurons (Joyce, Rizzi, Calo, Rowbotham, & Lambert, 2002; King, Mintz, & Royall, 2011; Maxwell, 1982). After several research teams in Europe and Japan reported consistent and significant correlations between Lewy body disorders and decreased [sup.123]I-MIBG uptake because of Lewy bodies and Lewy neurites found outside the brain tissue in autonomic ganglia, the Consortium on Dementia with Lewy Bodies supported the use of 123I-MIBG cardiac scintigraphy as a diagnostic tool for Lewy body disorders in 2005 (Hanyu et al, 2006; King et al, 2011). A quick comparison of fMRI, PET/SPECT, and [sup.123]I-MIBG cardiac scintigraphy is provided in Table 2.

Several antemortem neuroimaging studies have been able to differentiate DLB from other non-synucleinopathic dementia types. For example, medial-temporal lobe size is relatively preserved in DLB and PDD compared with AD (Johansen et al, 2010; Watson, Blamire, & O'Brien, 2009). Burton et al. (2009) found that MRI diagnosis of medial-temporal lobe atrophy, when matched to postmortem neuropathological data (Braak staging and quantitative analysis of amyloid-[beta] plaque, tau tangle and Lewy body load), resulted in 91% sensitivity and 94% specificity in distinguishing between DLB, AD, and vascular cognitive impairment. Vermuri et al. (2011) found an atrophy pattern involving the bilateral amygdalae, dorsal midbrain, and inferior temporal lobes in cases of DLB but not in AD or frontotemporal lobar dementia. Sabbatoli et al. (2008) found hippocampal atrophy in the CA1, CA2, and CA3 regions and the subiculum and presubiculum in patients with DLB, but not in patients with AD. Pievani, DeHaan, Wu, Seeley, and Frisoni (2011) found that DLB-related atrophy may also extend to the basal forebrain and hypothalamus.

Postmortem, no structural differences have been found between DLB and PDD in the brain; in both diagnoses, the substantia nigra and loci coerulei are poorly pigmented (Love, 2005). However, antemortem structural differences between DLB and PDD have been detected using fMRI and PET. fMRI data analyzed by Sanchez-Castaneda et al. showed that, in patients with DLB, performance on selective attention tasks was correlated with anterior cingulate and prefrontal volume, whereas visual memory correlated with right hippocampus and amygdala volume in participants with PDD. No correlation between gray matter volume and selective attention or visual memory was found (Sanchez-Castaneda et al, 2009). Lee et al. used diffusion tensor imaging, an fMRI technique, to compare white matter alterations between patients with DLB and PDD who completed tasks in visual recognition, semantic fluency, and ideomotor praxis. Patients with DLB performed much worse than PDD participants on all tasks, and white matter abnormalities in bilateral frontal, left temporal and parietal, bilateral insula, posterior cingular, and bilateral visual association areas in patients with DLB were more severe than those found in PDD patients (Lee et al, 2010). In a PET study comparing DLB, PD, and AD with elderly controls, Koeppe et al. observed blood-to-brain ligand transport and presynaptic binding of the radiotracer [sup.11]C-dihydrotetrabenazine ([[sup.11]C]DTBZ) in the striatum (the caudate nucleus and putamen) to evaluate cerebral blood flow, energy metabolism, and striatal dopaminergic innervation. Results revealed distinct patterns in [[sup.11]C]DTBZ binding between groups: greater binding asymmetry in the striatum was noted in patients with PD compared with those with DLB. Greater reduction in ligand transport was noted in DLB compared with AD, and the presence of [[sup.11]C]DTBZ in the striatum was significantly reduced in DLB and PD compared with AD and controls (Koeppe et al, 2008). Walker et al. (2007) found that, in patients with clinical and postmortem confirmation of DLB, AD, and controls, SPECT using fluoropropyl-carbomethoxy-iodophenyl-tropane (a radiotracer that binds to dopamine receptors) revealed significantly reduced posterior putamen binding in patients with DLB compared with patients with AD and controls.

Lastly, King et al. (2011) completed a metaanalysis of the use of [sup.123]I-MIBG cardiac scintigraphy for the diagnosis of DLB; 46 studies and 2,680 participants were included. They discovered that the test yielded 94% specificity and 91% sensitivity between three subgroups:

* those with PD, DLB, and rapid eye movement (REM) sleep behavior disorder;

* those with AD, frontotemporal dementia, multiple system atrophy, progressive supranuclear palsy, and VAD; and

* asymptomatic controls.

These findings indicate that, to date, [sup.123]I-MIBG cardiac scintigraphy is the most specific and sensitive test for DLB. However, in the United States, the FDA has approved the use of [sup.123]I-MIBG cardiac scintigraphy only for the diagnosis of pheochromocytoma. Using the test to support a DLB diagnosis is not reimbursed by Medicare/Medicaid or a private insurance (King et al, 2011).

EEG

Core features of DLB include fluctuating cognition and REM sleep disorder. Although rarely used in DLB diagnosis, EEG has the ability to capture DLB-related historical transient neurological changes that imaging techniques cannot (Bonanni et al, 2008; Mollenhaueretal, 2010; Reilly et al, 2010; Robillard, 2007). In their study of patients with DLB, PDD, and AD and, at the same time, mild cognitive impairment, Bonanni et al. reported EEG abnormalities that varied between DLB, PDD, and AD. Dominant (i.e., the hemisphere of the brain attenuated by left- or right-handedness) frequency range and variability differed significantly between participants with early-stage DLB and AD. In addition, 46% of participants with PDD exhibited abnormalities similar to those with DLB. Also, stable and distinct frequency alpha band patterns indicating steady inhibitory activity were found in those with AD, whereas the irregular band patterns found in DLB and PDD patients corresponded with the presence and/or severity of cognitive fluctuations.

Biomarkers

[alpha]-Syn

As mentioned, [alpha]-syn is the primary component of Lewy body structure. Its transformation from soluble to insoluble form and subsequent alterations in its clearance is hypothesized as the trigger for neuropathogenesis in Lewy body disorders (Crews et al, 2010; Ohrfelt et al, 2009). Decreased cerebrospinal fluid (CSF) levels of soluble [alpha]-syn are expected in DLB, because Lewy bodies and Lewy neurites aggregate at specific areas of the brain tissue and at the synapses. However, recommendations for its use as a sole biomarker for DLB remain mixed, given contradictory findings from several studies that compared [alpha]-syn levels in CSF across dementia types (SchulzSchaeffer, 2010). Ohrfelt et al. reported significantly higher CSF levels of [alpha]-syn in patients with DLB and PD compared with patients with AD; no difference in [alpha]-syn levels was found between patients with DLB and PD. On the other hand, Noguchi-Shinohara et al. (2009) and Reesink et al. (2010) found no significant difference in CSF [alpha]-syn levels between DLB and AD groups, although Noguchi-Shinohara et al. noted that [alpha]-syn levels appeared to be associated with illness duration in DLB but not in AD, whereas Reesink et al. (2010) observed that lower [alpha]-syn levels corresponded with lower Mini Mental State Examination (MMSE) scores in patients with DLB only. Ballard et al. (2010) compared CSF [alpha]-syn levels of patients with DLB with age-matched controls and found that, even in cases of mild dementia, levels in patients with DLB were significantly lower than controls. Kasuga et al. compared CSF levels of [alpha]-syn, amyloid-[beta], and tau (the protein that comprises the "tangles" found in AD) between patients diagnosed with unclassified dementia, AD, DLB/PDD, VAD, and dementia related to frontotemporal lobar degeneration, progressive supranuclear palsy, and normal pressure hydrocephalus. They found that DLB was associated with significantly lower [alpha]-syn levels compared with all other dementia types; in addition, in DLB, [alpha]-syn levels correlated with amyloid-[beta] levels (Kasuga et al, 2010). Schulz-Schaeffer suggested that synaptic dysfunction may be the cause of neurodegeneration in Lewy body disorders, based on recent reports that more than 90% of [alpha]-syn aggregates in DLB are deposited in the presynapses. King et al. (2011) and Schulz-Schaeffer hypothesize that this may be the cause of neurotransmitter deficiency at synaptic terminals and resulting symptoms (i.e., tremors, bradykinesia, postural instability, attention deficit, and fluctuating cognition) found in patients with Lewy body disorders. It also indicates that Lewy body pathology is not confined to intracranial tissue. Future improvements in biomarker research may help better define how exactly [alpha]-syn results in Lewy body pathology, but nevertheless, [alpha]-syn is considered a characteristic biomarker for DLB.

Amyloid Beta (A[beta])

Many patients with synucleinopathies (diseases associated with [alpha]-syn, such as PD, DLB, and multiple system atrophy) also have Alzheimer-type pathology, and concurrent diagnosis of DLB and PDD with AD is possible (Crews et al, 2010; Love, 2005; Ohrfelt et al, 2009; Tsuboi et al, 2007; Yokota et al, 2007). According to Maetzler et al, studies estimate that 15%--20% of patients diagnosed with AD based on their cortical A[beta] burden also have enough cortical and subcortical Lewy body load for concomitant Lewy body disease. Conversely, about 25% of patients with Lewy body disease have sufficient cortical A[beta] load for an AD diagnosis (Hulettee, 1995; Ranginawala, Hynan, Weiner, & White, 2008). One of the tools used to evaluate A[beta] load is PET with [11C]PIB, a radiotracer that binds to A[beta] in brain cortical and striatal tissue because PIB binding in the presence of AD has been established (Edison et al, 2007; Maetzler et al, 2009). Edison et al. investigated A[beta] load using this technique in subjects with DLB, PDD, and PD and age-matched controls; significant increases in [11C]PIB uptake in cortical, cingulate, and striatal areas and significant amyloid loads were found only in the DLB group. Maetzler et al. also tested [11C]PIB uptake in subjects with DLB, PDD, and PD and controls; the four subjects with DLB and four subjects with PDD with positive PIB cortical uptake scored lower on the MMSE compared with those who were PIB-negative. This mirrors postmortem findings of increased cortical A[beta] burden in patients with DLB who had low MMSE scores (Braak et al, 2004).

A[beta] occurs in several forms; the cortical and subcortical plaques deposited in brains with AD, DLB, and PDD are composed mainly of the A[beta]1-42 type ("42" refers to the number of its amino acid chains; Bibl et al, 2006; Johansen et al, 2010). Aside from detecting significant A[beta] loads in those already diagnosed with DLB or PDD, the use of CSF-derived A[beta]42 in discriminating between DLB and PDD yielded poor results. Bibl et al. discovered an oxidized form of A[beta]1-40 (which they named A[beta]1-40*) and found elevated levels in patients with DLB, yielding 81% sensitivity and 71% specificity for DLB, compared with AD or PDD. Despite the much improved sensitivity and specificity that A[beta]1-40 * might offer, A[beta] is not recommended as a sole biomarker for AD or DLB diagnosis. Other biomarkers and clinical criteria should be considered when diagnosing and discriminating between dementia types.

Clinical Diagnostic Criteria for DLB

Key, Suggestive, and Supportive Characteristics

As mentioned, DLB is the diagnosis assigned when dementia onset occurs less than 1 year after Parkinsonian symptoms appear. In PDD, dementia onset occurs several years after PD is diagnosed (Love, 2005; Metzler-Baddeley, 2007; Mollenhauer et al, 2010; Robillard, 2007; Tsuboi et al, 2007). Clinical characteristics of DLB are categorized as follows (Table 3):

* Key or central characteristics: Characteristics that must be present for a positive diagnosis.

* Suggestive characteristics: Associated characteristics that may also be used to support the diagnosis.

* Supportive characteristics: Characteristics not specifically diagnostic for the disease but support the diagnosis if concurrent with key characteristics (Mollenhauer et al, 2010).

According to the clinical diagnostic criteria outlined by the Consortium on Dementia with Lewy Bodies, DLB is diagnosed if dementia is present with two of three key characteristics:

* fluctuating cognition (changes in alertness and/or attention may cycle in the span of minutes up to weeks);

* recurrent, detailed visual hallucinations; and

* spontaneous Parkinsonism (bradykinesia or rigidity; McKeith, 2006; Metzler-Baddeley, 2007; Mollenhauer et al, 2010; Reilly et al, 2010; Robillard, 2007; Tiraboschi et al, 2006).

In addition, the following characteristics are considered highly suggestive of DLB:

* REM sleep behavior disorder (RBD);

* severe neuroleptic sensitivity; and

* significantly reduced dopamine uptake in the basal ganglia (McKeith, 2006; Metzler-Baddeley, 2007; Mollenhauer etal, 2010; Reilly etal, 2010; Robillard, 2007).

Finally, autonomic dysfunction--manifested by frequent falls, episodes of syncope, orthostatic hypotension, or urinary incontinence--is considered a supportive characteristic and may be one of the earliest indicators of DLB (Allan et al, 2007; King et al, 2011; Mollenhauer et al, 2010; Reilly et al, 2010). These criteria are summarized in Table 4.

Findings of Interest

A summary of findings from selected studies of DLB characteristics is discussed here and provided in Table 5.

Fluctuation in Cognition

Fluctuation in cognition and global performance is a key characteristic of DLB and is the result of attentional dysfunction (Bradshaw, Saling, Anderson, Hopwood, & Brodtmann, 2006; Edison et al, 2007; Mollenhauser et al, 2010; Reilly et al, 2010; Robillard, 2007; Schulz-Schaeffer, 2010). Bradshaw et al. tested patients with features of probable (i.e., dementia is present with one key or suggestive characteristic) DLB, probable AD, and healthy age-matched controls on a series of reaction time tasks that progressed in difficulty. They found that the group diagnosed with probable DLB showed greater attentional impairment and fluctuation compared with the other groups. They also noted that attentional impairment in patients with DLB was greatest during tasks that required more visuospatial recognition and executive control. This appears to confirm Schulz-Schaeffer's hypothesis that synaptic Lewy body aggregation contributes to the attentional deficit noted in DLB. Perriol et al. (2005) compared levels of prepulse inhibition (the ability to filter incoming sensory or cognitive information) by measuring the amplitude and duration of the startle reflex induced by sound pulses at different volumes. EEG and electrooculogram data from patients with DLB revealed significantly worse inhibitory disturbance than in patients with PDD and AD.

Visuospatial Impairment and Visual Hallucinations

Visuospatial ability, or the ability to recognize and manipulate patterns in space, is impaired in DLB (Mollenhauer et al, 2010; Mondon et al, 2007; Reilly et al, 2010; Robillard, 2007; Sauer et al, 2006; Tiraboschi et al, 2006;). Sauer et al. reported that task performance differences on visual stimuli tests between participants with DLB and AD reflected trends in neuron counts within the superior temporal sulcus, the brain region associated with gazing and motion. Previous studies reported that brains of patients with AD had fewer neurons in this region than those with DLB. Although Mondon et al. found no difference in global cognitive performance between patients with DLB and PDD on memory and executive function, they observed that patients with DLB performed significantly worse than patients with PDD on visual object recognition and storage capacity. Tiraboschi et al. found that, in 23 cases of DLB and 94 cases of AD confirmed by autopsy, antemortem assessment data revealed that visuospatial impairment was the most sensitive (74%) variable and visual hallucination was the most specific (99%) variable for DLB. They concluded that visual hallucinations were the best positive predictor of DLB at autopsy, at 83%; lack of visuospatial impairment was the best negative predictor, at 90%.

Motor Decline

The presence of Lewy body clumps at presynaptic terminals has been hypothesized as the cause of tremors, bradykinesia, postural instability, and cognitive decline found in patients with Lewy body disorders (Schulz-Schaeffer, 2010). Bum, Rowan, Allan, O'Brien, and McKeith (2006) conducted a 2-year study of cognitive and motor decline in a cohort of patients with DLB, PDD, and PD and age-matched controls and found that motor deficit subtypes were correlated with dementia type. They found that most patients with DLB and PDD had postural instability gait difficulty (PIGD), and tremor dominant and PIGD types were evenly distributed in the PD group. Furthermore, they found that PIGD was significantly associated with increased cognitive decline. Data from 22 Alzheimer Disease Centers across the United States showed that increased risk of decline in four daily, functional activities (performing basic kitchen tasks, playing games or participating in hobbies, paying attention, or understanding) for those with DLB, at 1.5-2 times the risk of decline associated with an AD diagnosis (Gill, Koepsell, Hubbard, & Kukull, 2011).

RBD

RBD, characterized by movement related to dream enactment, is significantly correlated with and is considered predictive of DLB and other [alpha]-syn-related disorders. In their study of 234 patients diagnosed with DLB, AD, frontotemporal lobar dementia, or corticobasal syndrome, Ferman et al. (2011) found that REM sleep disorder was six times more likely to predict DLB at autopsy in patients who met DLB diagnostic criteria (i.e., had the three key/central characteristics) antemortem. The association between RBD and DLB has been shown consistently for over a decade (Boeve, Silber, Fernan, Lucas, & Parisi, 2001; Matsumara, Ichino, Kudou, Tachibana, & Imamura; 2009; Metzler-Baddeley, 2007; Turner, 2002).

Autonomic Dysfunction

Allan et al. (2007) compared autonomic function between AD, VAD, DLB, and PDD; they assessed participants' cardiovascular autonomic function using Ewing's battery of clinical autonomic tests, parasympathetic tests, sympathetic tests, measurement of heart rate variability, and orthostatic hypotension. Participants were rated using Ewing's classification of autonomic failure (normal, early, definite, severe, and atypical). Results from 38 controls, 39 patients with AD, 30 patients with VAD, 30 patients with DLB, and 40 patients with PDD showed that those with dementia had higher prevalence of orthostatic hypotension and autonomic neuropathy compared with controls. Those with DLB and PDD had significantly worse dysfunction than those with AD or VAD and controls. Those with VAD showed limited impairment in Valsalva ratio and orthostasis tests, whereas the only impairment found in patients with AD was on the orthostasis test. Patients with PDD showed worse impairment in both parasympathetic and sympathetic function tests compared with controls and patients with AD. By contrast, impairments in all parasympathetic tests (deep breathing and respiratory sinus arrhythmia, orthostasis, Valsalva ratio) and in the orthostasis test for sympathetic function (change in blood pressure) were found in patients with DLB.

Olfactory Impairment

According to Beach et al. (2009), olfactory bulb, medulla, pons, and amygdala function is most altered in those with incidental DLB and AD with DLB, but the olfactory bulb is most affected in AD with DLB and may be considered another method for discriminating between dementia subtypes. In a study comparing presence and/or degree of anosomia (inability to smell) between mild AD, mild DLB, and mild cognitive impairment groups, Williams et al. (2009) reported that patients with mild DLB performed worse than all other groups on a 16-item olfactory identification and threshold test, reporting 81% sensitivity for distinguishing mild DLB from mild AD.

Sensitivity to Cholinesterase Inhibitors and Antipsychotics

Patients with DLB are frequently diagnosed with cardiovascular autonomic dysfunction and are more susceptible to the side effects of cholinesterase inhibitors, which can increase tremor and exert effects on the sinoatrial (SA) and atrioventricular nodes and result in atrioventricular block or bradycardia; given this, cholinesterase inhibitors should be used with caution (Ballard et al, 2006; Weintraub & Hurtig, 2007). Although there are no FDA-approved medications for the treatment of DLB, reports from clinical trials and off-label use of the cholinesterase inhibitors galantamine and rivastigmine, the NMDA receptor antagonist memantine, and levodopa indicate that these medications contribute to improvements in alertness, attentional task performance, and motor function and decreases in fluctuating cognition, visual hallucinations, and sleep disturbances (Aarsland et al, 2009; Ballard et al, 2006; Edwards et al, 2007; Molloy et al, 2006; Weintraub & Hurtig, 2007). Atypical antipsychotics such as quetiapine and clozapine are not recommended for patients with DLB because of their severe neuroleptic sensitivity, which is typically manifested by worsening confusion, sedation, extrapyramidal symptoms, and decreased mobility that can range from rigidity to postural instability in this patient population (Weintraub & Hurtig, 2007). As a result, drug studies on patients with DLB have been limited to cholinesterase inhibitors, which appear to be a more effective alternative for treating psychosis.

Nursing Interventions for Consideration Patient Safety

Autonomic Dysfunction

Although all patients with dementia should be considered at risk for falls because of disorientation related to cognitive decline, addressing the safety risk related to the prevalence of autonomic dysfunction in patients with DLB is a top priority. Symptoms of autonomic dysfunction include increased variability in heart rate and blood pressure, bowel and/or bladder incontinence, and loss of proprioception (sense of one's body position and orientation relative to the environment; Allan et al, 2007; King et al, 2011; Mollenhauer et al, 2010; Reilly et al, 2010). These changes often result in loss of balance, unsteady gait, generalized weakness, and disorientation. In many cases, elderly patients with dementia already have impaired mobility resulting from other comorbidities (Roman, 2009). Nurses should be aware of existing and new sensory or motor deficits and ensure that assistive devices (such as mobility aids, bed alarms, call lights) are available as needed; placing these patients in rooms closer to the nurses' station allows easier visualization and access to the patient (Roman, 2009). If these episodes occur frequently and the patient needs stricter monitoring, the nurse should request one-to-one monitoring.

Fluctuating Cognition and Sleep Disturbances

Fluctuating cognition in DLB may or may not reflect sundowning, or disorientation related to periods of transition between night and day, and is not delirium, which is characterized by acute changes in level of consciousness, disordered thinking, and increased inattention (Gallagher & Long, 2011). Nevertheless, all three cognitive states may be present in the patient with DLB, especially if AD is also present (Hulette et al, 1995; Ranginwala et al, 2008). In addition, sleep disturbances in DLB result from disrupted REM sleep, so nurses need to ensure good sleep hygiene, frequent rounding, and use of bed alarms for this patient population. Physical restraints during episodes of agitation should be a last resort because they can exacerbate the patient with DLB's loss of proprioception. Finally, as mentioned, nurses should remember that cholinesterase inhibitors are the only medications recommended for addressing agitation in patients with DLB (Weintraub & Hurtig, 2007).

Patient/Caregiver Education

Nurses should remind patients with DLB and their caregivers that biomarker testing for dementia diagnosis remains suggestive but not definitive. Biomarkers may be present in asymptomatic individuals, and postmortem analysis verified by antemortem biobehavioral data is still considered the most definitive method of diagnosis (Johansen et al, 2010; Love, 2005). Of note is that definitive diagnosis and continued progress in research on dementia relies on access to brain tissue samples and brain bank donations for postmortem analysis of dementia-related neuropathology (Love, 2007). In some nationalized healthcare systems, such as the United Kingdom, national patient registries and postmortem organ donation banks are well advertised, which can mean easier access to centralized repositories for patient data and biological samples. Similar national or regional programs can also be found across the United States; an example is the Arizona-based Sun Health Research Institute, which features a participant database and a Brain Donation Program (Beach et al, 2009; Love, 2007). Nurses should be aware of two important considerations related to patient participation in these programs. First, the consent for brain necropsy must be obtained antemortem as early as possible because the process is time dependent and complex (Love, 2007). In addition, the patient and/or caregivers may limit the use and access to the donated sample based on cultural and spiritual beliefs; donating for necropsy may have different meanings for the patient and/or caregiver compared with donation for organ and tissue harvesting. Nurses who provide up-to-date patient, caregiver, and even healthcare provider education about registry programs and donation banks for dementia-related disorders are well poised to act as patient and caregiver advocates while also supporting the research mission to improve interventions and quality of life.

Summary

As described in this article, the neuropathology and clinicopathology of DLB is indeed complex, and the knowledge base for all dementia types is ever evolving. Nursing's distinct focus on identifying, managing, and improving the person's biopsychosocial response to health and environment means that nurses have the unique opportunity and responsibility, as patient advocates and lifelong learners, to inform this knowledge base in ways that regard pathology as only one of many components in the dementia experience. McKeith (2006) notes that one of the most difficult obstacles for caregivers of DLB is that they are often more educated about DLB than the healthcare professionals who may care for their family members, and yet, they may still require further education about the disease process and/or its long-term implications for their family members' care. In addition, patients with DLB and other dementias are often rendered incapable of participating in their care. Not only are nurses ideally positioned to educate patients, caregivers, and other healthcare professionals about DLB, they are also obliged to address these needs by developing patient-centered interventions that incorporate the best scientific evidence available about DLB and maximize the patient's contribution to their care plan. An important first step that nurses can take is to increase awareness of DLB, which highlights how different dementia types are characterized by distinct pathology and symptoms. Such awareness is nothing short of an imperative for providing holistic nursing care.

References

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Questions or comments about this article may be directed to Gretchel Ajon Gealogo, MSN RN-BC CMSRN MHR, at gealogo@livemail.uthscsa.edu. She is a PhD Candidate at the School of Nursing, University of Texas Health Science Center San Antonio.

The author declares no conflicts of interest.

DOI: 10.1097/JNN.0b013e3182a3e2b
TABLE 1. Staging Systems for Dementia With Lewy Bodies

                                      Consensus Guidelines for the
Braak Six-Stage Schema for             Clinical and Pathological
Parkinson-Disease-Related                Diagnosis of Dementia
Pathology                                   With Lewy Bodies

Stage   Brain region affected        Stage   Brain region affected

1       Medulla oblongata,               Brainstem predominant
        pontine tegmentum,

2       olfactory bulb, anterior
        olfactory nucleus

3       Substantia nigra,                 Limbic transitional

4       nuclear gray areas in
        midbrain and forebrain

5       Mature neocortex                       Neocortex

6

Braak Six-Stage Schema for             Staging System for Lewy Body
Parkinson-Disease-Related                 Disorders Proposed by
Pathology                                  Beach et al. (2009)

Stage   Brain region affected      Stage   Brain region affected

1       Medulla oblongata,          IIa    Brainstem        III
        pontine tegmentum,                 predominant   Brainstem
                                                         and limbic

2       olfactory bulb, anterior     I     Olfactory
        olfactory nucleus                  bulb only

3       Substantia nigra,           IIb    Limbic

4       nuclear gray areas in              predominant
        midbrain and forebrain

5       Mature neocortex            IV            Neocortical

6

Note. Braak et al., 2004; McKeith, 2006.

TABLE 2. Imaging Techniques Used in DLB Diagnosis

Magnetic Resonance
Imaging (MRI)                                   Positron Emission
Functional MRI          Diffusion Tensor        Tomography
                        Imaging

Blood oxygenation       Water diffusion in      A radiotracer
level-dependent         brain tissue is         (administered
signals are used to     measured to detect      intravenously) binds
identify areas of the   structural and          to a specific
brain experiencing      functional changes.     neurochemical to
increased activation                            detect levels of
to a stimulus.                                  brain activity
                                                associated with the
                                                targeted
                                                neurochemical.

Magnetic Resonance
Imaging (MRI)           Single Photon Emission
Functional MRI          Computed Tomography        [sup.123]I-MIBG
                                                 Cardiac Scintigraphy

Blood oxygenation                                Typically used to
level-dependent                                  diagnose presence of
signals are used to                              pheochromocytoma
identify areas of the                            (adrenal gland tumor)
brain experiencing                               by allowing location
increased activation                             and functional
to a stimulus.                                   assessment of
                                                 postganglionic
                                                 nonadrenergic
                                                 neurons. Lewy body
                                                 disorders are
                                                 significantly
                                                 associated with
                                                 decreased [sup.123]
                                                 I-MIBG uptake.

Note. Hanyu et al., 2006; King el al., 2011: Koeppe el al., 2008;
Manenti et al., 2007; Ogawa el al., 1990; Walker et al., 2007.
I-MIBG = l-metaidodobenzylguanidine; DLB = dementia with Lewy bodies.

TABLE 3. Clinical Diagnostic Criteria for DLB

                                                      Supportive
                                                 Characteristics: Not
Key/Central                  Suggestive              Specifically
Characteristics: Must     Characteristics:        Diagnostic for DLB
Be Present for a             Associated            but Support the
Positive Diagnosis      Characteristics That         Diagnosis if
                         May Also Be Used to     Concurrent With Key
                          Support Diagnosis        Characteristics

Fluctuating cognition   Rapid eye movement      Frequent = indicators
(may cycle in span of   sleep disturbances      falls      of
minutes to weeks)                                          autonomic
                                                           dysfunction
Recurrent and           Severe neuroleptic      Syncope
detailed visual         sensitivity
hallucinations

Spontaneous             Significantly reduced   Orthostatic
Parkinsonism            dopamine uptake in      hypotension
(bradykinesia or        the basal ganglia       Urinary
rigidity)                                       incontinence

Note. McKeith, 2006; Metzler-Baddeley, 2007; Reilly et al., 2010;
Robillard, 2007; Mollenhauer et al., 2010; Tiraboschi et al., 2006;
Allan et al., 2007; King et al., 2011. DLB = dementia with Lewy bodies.

TABLE 4. Summary of Findings From Selected DLB Biomarker Studies

Biomarker                    Authors/Study         Dementia Subtype
                                                        Groups

CSF [alpha]-syn levels    Ohrfelt et al.         DLB, PD, AD
                                         -2009

                          Noguchi-Shinohara      DLB, AD
                          et al. (2009)

                          Reesink et al.         DLB, AD
                          (2010)

                          Ballard et al.         DLB, age-matched
                          (2010)                 controls

CSF levels of             Kasuga et al.          Unclassified
[alpha]-syn,              (2010)                 dementia, AD, DLB/
amyloid-[beta],                                  PDD, vascular
and tau                                          dementia, dementia
                                                 related to
                                                 frontotemporal lobar
                                                 degeneration,
                                                 progressive
                                                 supranuclear palsy,
                                                 and normal pressure
                                                 hydrocephalus

A[beta] in cortical       Edison et al.          DLB, PDD, PD, and
and                       (2008)                 age-matched controls

striatal tissue           Maetzler et al.        DLB, PDD, PD, and
                          (2009)                 controls

                          Braak et al. (2004)    DLB

CSF A[beta]1-40*          Bibl et al. (2006)     DLB, PDD, AD
levels

Biomarker                                   Results

CSF [alpha]-syn levels    Significantly higher levels in DLB and PD
                          compared with AD; no difference between DLB
                          and PD

                          [alpha]-syn levels appeared to be
                          associated with illness duration in DLB but
                          not in AD

                          Lower [alpha]-syn levels corresponded with
                          lower MMSE scores in DLB patients

                          Levels in patients with DLB were
                          significantly lower than controls

CSF levels of             DLB associated with significantly lower
[alpha]-syn,              [alpha]-syn levels compared with all other
amyloid-[beta],           dementia types; a-syn levels correlated
and tau                   with amyloid-[beta] levels in DLB

A[beta] in cortical       Significant A[beta] loads only in the DLB
and                       group

striatal tissue           Lower MMSE scores in DLB and PDD with
                          increased cortical A[beta] burden

                          Lower MMSE scores in DLB and PDD with
                          increased cortical A[beta] burden

CSF A[beta]1-40*          Elevated levels in DLB compared with PDD
levels                    and AD

Note. DLB = dementia with Lewy bodies; [alpha]-syn = alpha-synuclein;
PD = Parkinson disease; AD = Alzheimer disease; PDD = Parkinson
disease with dementia; MMSE = Mini Mental State
Examination; CSF = cerebrospinal fluid; A[beta] = amyloid beta.

TABLE 5. Summary of Findings From Selected Studies of DLB
Characteristics

DLB Characteristics           Authors             Dementia Subtype
                                                        Groups

Fluctuation            Bradshaw et al.          DLB, probable AD,
in cognition           (2006)                   healthy age-matched
                                                controls

                       Perriol et al. (2005)    DLB, PDD, AD

Visuospatial           Sauer et al. (2006)      DLB, AD
impairment

                       Mondon et al. (2007)     DLB, PDD

Visuospatial           Tiraboschi et al.        DLB, AD
impairment,            (2006)
visual
hallucinations

Motor decline          Burn et al. (2006)       DLB, PDD, PD,
                                                age-matched controls

                       Gill et al. (2011)       DLB, AD

REM sleep              Fernan et al. (2011),    DLB, non-
behavior               Boeve et al. (2001),     synucleopathies
disorder               Turner (2002),
(RBD)                  Metzler-Baddeley
                       (2007), Matsumara
                       et al. (2009)

Autonomic              Allan et al. (2007)      Controls, AD, VAD,
dysfunction                                     DLB, PDD

Olfactory              Williams et al. (2009)   DLB, AD, mild
impairment                                      cognitive impairment

Sensitivity to         Ballard et al. (2006)    DLB
cholinesterase
inhibitors

Sensitivity to         Weintraub & Hurtig       DLB
antipsychotics         (2007)

DLB Characteristics                        Results

Fluctuation            DLB showed greater attentional impairment and
in cognition           fluctuation compared with the other groups;
                       attentional impairment in patients with DLB was
                       greatest during tasks requiring increased
                       visuospatial recognition and executive control.

                       Significantly worse inhibitory disturbance in
                       DLB than in PDD and AD.

Visuospatial           Worse task performance on visual stimuli tests
impairment             in DLB than AD.

                       No difference in global cognitive performance
                       between patients with DLB and PDD on memory and
                       executive function; significantly worse visual
                       object recognition and storage capacity in DLB
                       than PDD.

Visuospatial           Visuospatial impairment was the most sensitive,
impairment,            and visual hallucinations were the most
visual                 specific variables for DLB; visual
hallucinations         hallucinations were the best positive predictor
                       of DLB at autopsy, whereas lack of visuospatial
                       impairment was the best negative predictor.

Motor decline          Most patients with DLB and PDD had postural
                       instability gait difficulty (PIGD); tremor
                       dominant and PIGD types evenly distributed in
                       PD group; PIGD significantly associated with
                       increased cognitive decline.

                       DLB risk of decline in performing basic kitchen
                       tasks, playing games, participating in hobbies,
                       paying attention, or understanding at 1.5 to 2
                       times risk of decline in AD.

REM sleep              RBD significantly correlated with or predictive
behavior               of DLB and other a-syn-related disorders.
disorder
(RBD)

Autonomic              Higher prevalence of orthostatic hypotension
dysfunction            and autonomic neuropathy in dementia compared
                       with controls; DLB and PDD had significantly
                       worse dysfunction than those with AD or VAD and
                       controls; impairments in all parasympathetic
                       tests (deep breathing and respiratory sinus
                       arrhythmia, orthostasis, Valsalva ratio) and in
                       the orthostasis test for sympathetic function
                       (change in blood pressure) were found in DLB
                       only.

Olfactory              DLB performed worse than all other groups in
impairment             olfactory identification and threshold test;
                       test had 81% sensitivity for distinguishing DLB
                       from AD.

Sensitivity to         Increased risk for tremor, AV block,
cholinesterase         bradycardia with use of this drug class.
inhibitors

Sensitivity to         Increased risk for confusion, sedation,
antipsychotics         extrapyramidal symptoms, and decreased
                       mobility.

Note. DLB = dementia with Lewy bodies; [alpha]-syn = alpha-synuclein;
PD = Parkinson disease; AD = Alzheimer disease; PDD = Parkinson
disease with dementia.
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Author:Gealogo, Gretchel Ajon
Publication:Journal of Neuroscience Nursing
Article Type:Report
Date:Dec 1, 2013
Words:9062
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