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Dementia Associated with Lewy Body and Parkinson’s Disease. Karen Mullins, D.O. University of Tennessee Knoxville Neurology Clinic. Lecture Objectives. Describe clinical presentations of Lewy Body and Parkinson’s Associated Dementia(PAD) - PowerPoint PPT Presentation
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Dementia Associated with Lewy Body and Parkinson’s Disease
Karen Mullins, D.O.University of Tennessee
Knoxville Neurology Clinic
Lecture ObjectivesDescribe clinical presentations of Lewy Body
and Parkinson’s Associated Dementia(PAD)Describe pathophysiological mechanisms
associated with Lewy Body Dementia (LBDD) and PAD
Review both pharmacologic and nonpharmacologic treatments for LBDD and PAD
Clinical Presentation Of LBDFluctuations in cognitive functionVarying levels of alertness and attentionExcessive daytime drowsiness or daytime
sleep >2 hoursEpisodes of staring off into spaceEpisodes of disorganized speech
Clinical Presentation Of LBDVisual hallucinationsDelusionsREM sleep behavior disorderImpaired excecutive function, visuospatial
function (Stroop, digit span backwards)
Clinical Presentation of LBDParkinsonism
Appears early in course of diseaseMay not be enough to meet full criteria for PDLess frequent rest tremorMay see myoclonusOrthostatic hypotension
Clinical Presentation LBDCapgras syndrome: delusion that people in
the environment are not themselves but actually doubles
Also see passive personality traits- decreased emotional responsivity, lack of interest in hobbies, increasing apathy , purposeless hyperactivity
Kurtz AL et al., Curr Treat Opt Neuro, 2011;13:242-254.
Diagnostic CriteriaDementia with Lewy Bodies (DLB)Consensus diagnostic criteria for DLB were first
established in 1996Dementia accompanied by ≥ 1 of three core symptoms
Fluctuating cognition, visual hallucinations, and motor parkinsonism
Criteria were expanded in 2005 Neuroleptic sensitivity and RBD Specific imaging findings on dopamine SPECT imaging
or MIBG cardiac scintigraphy Dementia with progressive cognitive deficits that
result in social and occupational dysfunction must be present for either probable or possible DLB
PD DementiaTypically dementia occurs later in diseaseMust meet criteria for PD first
TremorRigidityAkinesia/bradykinesiaPostural instability
Manifestations at PD OnsetTremor at restBradykinesiaRigidityMicrographiaHypophoniaMasked faceStooped, shuffling gaitSlowing of activities of daily livingDecreased arm swing when walking
Barbosa et al. Psychiatr Clin North Am. 1997;20:769-90. Playfer. Postgrad Med. 1997;73:257-64.
Kehagia AA et al., Lancet Neurol, 2010;9:1200-1213.
Early Deficits in PDFronto-striatal Syndrome
Cognitive flexibility
Planning
Working memory
Learning
Prodrome to dementia?
Kehagia AA et al., Lancet Neurol, 2010;9:1200-1213.
Mild Cognitive Impairment in PD20% - 57% of patients are affected in 3-5 years of PD
diagnosis
PD as a fronto-striatal syndromeDeficits clear when patients need to act based on
internal rather than external cues
DA DependentFlexibility, switching between known tasks, working
memory
DA IndependentMental rotation, verbal memory
Kehagia AA et al., Lancet Neurol, 2010;9:1200-1213.
PD DementiaDiagnostic CriteriaPDD associated with mortalityLongitudinal estimates of its cumulative
prevalence are 75% to 90%PD patients are three to five times more
likely to develop dementia compared with healthy individuals
Closely related to dementia with Lewy bodiesBoth are distinguishable from ADLewy bodies, plaques, and vascular changes
are present in bothDifferent temporal profiles
Diagnostic Criteria for PDDDiagnosis of PD by the Queen Square brain bank
criteriaPD precedes dementia onsetMMSE score of <26Severe cognitive dysfunction that interferes with daily
livingImpairment on at least tow
Three-word recall (MMSE) Overlapping pentagons (MMSE) Months reverse or sevens backward (MMSE) Lexical fluency Clock drawing
Absence of major depression, delirium, or other abnormalities that obscure diagnosis
Neuropsychological Deficits in PDDExecutive
Wisconsin card sorting test; Stroop performance; Odd-Man-Out, verbal fluency
Working Memory Digit and spatial span
Memory Free and cued recall, auditory verbal learning
Visuospatial Abilities Clock drawing, Benton line orientation, face
recognition, fragmented letters
Key Points : LBDD vs PADLBDD presents with dementia early on in the
diseaseLBDD are more likely to have hallucinations,
delusions early on in disease courseLBDD have fewer Parkinsonian symptomsPAD must meet criteria for PD, dementia
occurs later in disease course
Pathophysiology LBDDLewy Bodies- eosinophilic inclusion bodiesPresent in brainstem and cerebral cortexSee changes in basal ganglia>>reduction in
# of cholinergic projections to thalamic reticular nucleus>> reduction in cholinergic neurotransmission
Specific to LBD: correlation between hallucinations, staring spells and decreased cholinergic function
Pathophysiology LBDDNagahama et al found SPECT scan studies of
145 DLB patients revealed:Visual hallucinations- hypoperfusion of
parietal-occipital association corticesMisidentifications- hypoperfusion of the limbic-
paralimbic structuresDelusions- hypoperfusion of the frontal cortices
Pathophysiology of PADSee loss of pedunculopontine cholinergic
neurons>>loss of dopamine, norepinephrine or acetylcholine neurotransmitters
May see inability of ACH transporting ions to bind to receptors
Als0 see presence of abnormal tau genes
Silbert LC et al., Brain Path, 2010;20:646-653.
Imaging in PD DementiaAmyloid ImagingCortical amyloid deposition is significantly
increased in DLB Amyloid burden in PDD and PD-ND similar
PDD subjects shown to have significantly decreased PiB binding compared to AD or DLB with similar dementia severity
Occipital cortex Severely compromised in DLB, PDD and PD-ND Relative sparing in AD
Kurtz AL et al., Curr Treat Opt Neuro, 2011;13:242-254.
Clinicopathologic Spectrum of Dementia
Kurtz AL et al., Curr Treat Opt Neuro, 2011;13:242-254.
Cognitive Impairment in PDCholinesterase InhibitorsStudied in DLB and PDD
Provide benefit in treating cognitive and neuropsychiatric symptoms
Types:Rivastigmine approved in 2006Donepezil Galantamine
Kehagia AA et al., Lancet Neurol, 2010;9:1200-1213.
Cognitive Impairment in PDTreatment Strategies
RivastigmineDual acetylcholinesterase and
butyrylcholinesterase inhibitionImproved apathy, anxiety, delusions
nad hallucinations in DLB patientsImproved ADL in PDD relative to
baselineOnly stabilize AD patients
Kehagia AA et al., Lancet Neurol, 2010;9:1200-1213.
Cognitive Impairment in PDTreatment Strategies
DonepezilAcetylcholinesterase inhibitionTested in smaller studiesImprove cognition as measured by MMSEDid not exacerbate parkinsonism
Kehagia AA et al., Lancet Neurol, 2010;9:1200-1213.
Cognitive Impairment in PDTreatment Strategies
MemantineOriginally tested as a PD
treatmentGlutamatergic compoundNon-competitive antagonist of
nicotinic acetylcholine receptors
2009 test in PDD and DLB Improved MMSE and global
change score Ameliorated cognition in PDD
May have differential therapeutic responsivity
Burn DJ et al., Brain Path, 2010;20:672-678.
Mild Cognitive Impairment in PDAtomoxetine
Norepinephrine reuptake inhibitor
Recent open-label studyImprovements in clinicians global impression
of change and executive functionAEs included gastrointestinal disturbanceOne patient exhibited hypermania
Further studies are needed
Burn DJ et al., Brain Path, 2010;20:672-678.
Mild Cognitive Impairment in PDSafinamide
Dopaminergic and glutamatergic properties
Undergoing evaluation in early and late PD
Preliminary study suggest some benefit on executive dysfunction in early PD
Kurtz AL et al., Curr Treat Opt Neuro, 2011;13:242-254.
Cognitive Impairment in PDTreatment
Treatment Options LBDDAcetylcholinesterase InhibitorsAtypical neurolepticsAntidepressantsDopaminergic agents
AgonistsCarbidopa/levodopa
Treatment Options LBDDBenzodiazepinesAntiepilepticsGingko baloboa
Nonpharmacologic Options LBDD/PADNo approved surgery (DBS)Keep routineDoor alarms/chimesGeropsychiatric evaluation/home health
Nonpharmacologic Treatment PAD/LBDD
Exercise??Music therapyYoga/tai chiCognitive exercisesAdequate nutrition
Disease Course PADMore predictable than DLBD as dementia
occurs later in disease courseIf cognitive issues are due to medication side
effects then often controllable or even reversibleAdjust PD medsExclude underlying infectionTreat with atypical antipsychotic
Kehagia AA et al., Lancet Neurol, 2010;9:1200-1213.
PD DementiaVisual HallucinationsPredict rapid cognitive deterioration and
dementia onsetAssociated with cortical Lewy bodies Temporal regionsHippocampal atrophy associated with verbal
learning deficits in PDD patients having hallucinations
Patients with visual hallucinations also have frontal hypermetabolism and orbitofrontal atrophy that correlates with visual memory deficits
Disease Course in LBDDDisease symptoms fluctuateHarder to controlMore sensitive to medicationsAs dementia occurs earlier on in illness, pts
often require assistive care earlier
Caregiver SupportLocal support groupsWebsites:
wemove.org pda.orglbda.orgclincialtrials.gov
Home physical therapy, nursing etc.Strong social support group
Kurtz AL et al., Curr Treat Opt Neuro, 2011;13:242-254.
Defining Characteristics
Take Home PointsBoth LBDD and PAD patients should be on an
acetylcholinesterase inhibitor early on- TREAT EARLY!
Providing the caregiver with support is essential
Further research is needed to identify biomarkers to distinguish PAD from DLBD
Earlier diagnosis of PD may delay onset of PAD
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