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Transcript of Lewy Body Disease: The Undiscovered Country Donald R. Royall, MD Departments of Psychiatry,...
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Lewy Body Disease:Lewy Body Disease:The Undiscovered The Undiscovered
CountryCountryDonald R. Royall, MDDonald R. Royall, MD
Departments of Psychiatry, Medicine, Pharmacology, Departments of Psychiatry, Medicine, Pharmacology,
Family & Community MedicineFamily & Community Medicine
The University of Texas Health Science Center San AntonioThe University of Texas Health Science Center San Antonio
and the Audie L. Murphy VA GRECCand the Audie L. Murphy VA GRECC
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ObjectivesObjectives
The purpose of this presentation is to describe the The purpose of this presentation is to describe the propagation of Lewy Body pathology within the CNS and to propagation of Lewy Body pathology within the CNS and to illustrate how that has the potential to integrate a wide illustrate how that has the potential to integrate a wide variety of geriatric symptoms and syndromes into a variety of geriatric symptoms and syndromes into a common neurodegenrative model. Dr. Royall will use a common neurodegenrative model. Dr. Royall will use a case-vignette to illustrate the potential overlap between case-vignette to illustrate the potential overlap between Lewy Body disease (LBD) and so-called “vascular Lewy Body disease (LBD) and so-called “vascular dementia”. As a result of their participation, the audience dementia”. As a result of their participation, the audience will be able to discuss the potential utility of cardiac will be able to discuss the potential utility of cardiac imaging as a bio-marker for LBD. No pharmaceutical is is imaging as a bio-marker for LBD. No pharmaceutical is is indicated for the diagnosis or treatment of LBD. All indicated for the diagnosis or treatment of LBD. All discussed interventions are “off-label”. Dr. Royall reports discussed interventions are “off-label”. Dr. Royall reports no conflicts of interest. no conflicts of interest.
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Lewy Body DementiaLewy Body Dementia
• Most common “non-AD’ dementiaMost common “non-AD’ dementia• 21% of Clinically Diagnosed “AD” cases21% of Clinically Diagnosed “AD” cases• Has an early cholinergic deficitHas an early cholinergic deficit• Worse problem behaviorWorse problem behavior• ParkinsonismParkinsonism• FallsFalls• PsychosisPsychosis• Excess mortality Excess mortality
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Friederich Heinrich LewyFriederich Heinrich Lewy1885 - 19501885 - 1950
• 1913 – “eosinophilic inclusion bodies” 1913 – “eosinophilic inclusion bodies” in Parkinson’s disease in Parkinson’s disease
• 1919 – Tretiakoff: “1919 – Tretiakoff: “corps de corps de LewyLewy” ” in “locus niger” (substantia nigra) in “locus niger” (substantia nigra)
• 1962 – “Lewy Body Disease”1962 – “Lewy Body Disease”
• 1976 –1990s: Japan 1976 –1990s: Japan then UK & US reportsthen UK & US reports
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Lewy Body LesionsLewy Body Lesions
• Lewy Bodies contain Lewy Bodies contain abnormal abnormal neurofilaments that neurofilaments that contain tau and contain tau and ubiquitinubiquitin
medweb.bham.ac.uk
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What are the diagnostic What are the diagnostic symptoms?symptoms?
• Geriatric onsetGeriatric onset
• Cortical “Type 1” dementia presentationCortical “Type 1” dementia presentation
• Two of three:Two of three: Parkinsonism (gait, rigidity, “poker” face)Parkinsonism (gait, rigidity, “poker” face) Hallucinations (little people, animals, children)Hallucinations (little people, animals, children) ““Spells” (fluctuations, “good” day / ”bad”day, Spells” (fluctuations, “good” day / ”bad”day,
“sundowning”, nocturnal confusion)“sundowning”, nocturnal confusion)
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Clinicopathological SpectrumClinicopathological Spectrum ofof Lewy Body Dementia Lewy Body Dementia
Parkinson’sDisease
Alzheimer’sDisease
“Dementia with Lewy Bodies”
“pure” LB “variant” of AD
Dysexecutive“Type 2”Dementia
Amnestic“Type 1”Dementia
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What are the stages of LBD?What are the stages of LBD?
• AD variant much like Alzheimer’s but more AD variant much like Alzheimer’s but more fallsfalls, psychosis, agitation and a more , psychosis, agitation and a more aggressive courseaggressive course
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What are the stages of LBD?What are the stages of LBD?
• AD variant much like Alzheimer’s but more AD variant much like Alzheimer’s but more fallsfalls, psychosis, agitation and a more , psychosis, agitation and a more aggressive courseaggressive course• Cognitive features may reflect comorbid AD lesionsCognitive features may reflect comorbid AD lesions
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What are the stages of LBD?What are the stages of LBD?
• AD variant much like Alzheimer’s but more AD variant much like Alzheimer’s but more fallsfalls, psychosis, agitation and a more , psychosis, agitation and a more aggressive courseaggressive course• Cognitive features may reflect comorbid AD lesionsCognitive features may reflect comorbid AD lesions
• Pure LBD ??? Pure LBD ???
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Braak StagingBraak Staging
Six neuropathological Stages of Six neuropathological Stages of Alzheimer’s Disease (AD)Alzheimer’s Disease (AD)
Hierarchical progressionHierarchical progression Sequence “begins” in CNI (olfactory)Sequence “begins” in CNI (olfactory) Early hippocampal involvementEarly hippocampal involvement LimbicLimbic NeocortexNeocortex
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Dementia Develops Late in ADDementia Develops Late in AD
Royall et al., Exp Aging Res, 2002
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Dementia Develops Late in ADDementia Develops Late in AD
Royall et al., Exp Aging Res, 2002
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Dementia Develops Late in ADDementia Develops Late in AD
Royall et al., Exp Aging Res, 2002
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Dementia Develops Late in ADDementia Develops Late in AD
Royall et al., Exp Aging Res, 2002
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Braak Staging of LBDBraak Staging of LBD
Six neuropathological StagesSix neuropathological Stages Hierarchical progressionHierarchical progression Sequence “begins” in dorsal motor Sequence “begins” in dorsal motor
nucleus of CN X (DmX)nucleus of CN X (DmX) Early brainstem involvementEarly brainstem involvement
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Braak’s ProgressionBraak’s Progression
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Braak Staging Braak Staging Late neocortical involvementLate neocortical involvement
Occipital hypometabolismOccipital hypometabolism
Temporal lobe hypometabolismTemporal lobe hypometabolism
Orbitofrontal hypometabolismOrbitofrontal hypometabolism
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Braak Staging Braak Staging Late neocortical involvementLate neocortical involvement
Occipital hypometabolismOccipital hypometabolism visual hallucinations, parkinsonismvisual hallucinations, parkinsonism
Temporal lobe hypometabolismTemporal lobe hypometabolism
Orbitofrontal hypometabolismOrbitofrontal hypometabolism
Kobayashi et al., Kobayashi et al., Int. J. Geriatric Psychiatry,Int. J. Geriatric Psychiatry, 2009 2009
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Braak Staging Braak Staging Late neocortical involvementLate neocortical involvement
Occipital hypometabolismOccipital hypometabolism visual hallucinations, parkinsonismvisual hallucinations, parkinsonism
Temporal lobe hypometabolismTemporal lobe hypometabolism delusions /psychosisdelusions /psychosis
Orbitofrontal hypometabolismOrbitofrontal hypometabolism
Kobayashi et al., Kobayashi et al., Int. J. Geriatric Psychiatry,Int. J. Geriatric Psychiatry, 2009 2009
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Braak Staging Braak Staging Late neocortical involvementLate neocortical involvement
Occipital hypometabolismOccipital hypometabolism visual hallucinations, parkinsonismvisual hallucinations, parkinsonism
Temporal lobe hypometabolismTemporal lobe hypometabolism delusions /psychosisdelusions /psychosis
Orbitofrontal hypometabolismOrbitofrontal hypometabolism depression /anxietydepression /anxiety
Kobayashi et al., Kobayashi et al., Int. J. Geriatric Psychiatry,Int. J. Geriatric Psychiatry, 2009 2009
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Braak Staging Braak Staging Early brainstem involvementEarly brainstem involvement
substantia nigra - DAsubstantia nigra - DA n. basalis - AChn. basalis - ACh locus coerleus - NElocus coerleus - NE dorsal raphe - 5HTdorsal raphe - 5HT
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Braak Staging Braak Staging Early brainstem involvementEarly brainstem involvement
substantia nigra - DA substantia nigra - DA (parkinsonism)(parkinsonism) n. basalis - ACh n. basalis - ACh locus coerleus - NE locus coerleus - NE dorsal raphe - 5HT dorsal raphe - 5HT
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Braak Staging Braak Staging Early brainstem involvementEarly brainstem involvement
substantia nigra - DA substantia nigra - DA (parkinsonism)(parkinsonism) n. basalis - ACh n. basalis - ACh (cognitive fluctuations)(cognitive fluctuations) locus coerleus - NElocus coerleus - NE dorsal raphe - 5HTdorsal raphe - 5HT
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Braak Staging Braak Staging Early brainstem involvementEarly brainstem involvement
substantia nigra - DA substantia nigra - DA (parkinsonism)(parkinsonism) n. basalis - ACh n. basalis - ACh (cognitive fluctuations)(cognitive fluctuations) locus coerleus - NE locus coerleus - NE (agitation)(agitation) dorsal raphe - 5HTdorsal raphe - 5HT
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Braak Staging Braak Staging Early brainstem involvementEarly brainstem involvement
substantia nigra - DA substantia nigra - DA (parkinsonism)(parkinsonism) n. basalis - ACh n. basalis - ACh (cognitive fluctuations)(cognitive fluctuations) locus coerleus - NE locus coerleus - NE (agitation)(agitation) dorsal raphe - 5HT dorsal raphe - 5HT (depression /anxiety)(depression /anxiety)
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Central Autonomic CircuitCentral Autonomic Circuit
Orthostasis /fallsOrthostasis /falls Arrythmia (atrial fibrillation?)Arrythmia (atrial fibrillation?) SyncopeSyncope ConstipationConstipation Detrusor instability /“urge” incontinenceDetrusor instability /“urge” incontinence
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Extra-cranialExtra-cranial Origins? Origins?
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Extra-cranialExtra-cranial Origins? Origins?
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Extra-cranialExtra-cranial involvement involvement
Aurbach’s plexus (colon)Aurbach’s plexus (colon) Celiac ganglion (bladder)Celiac ganglion (bladder) GE junctionGE junction Pre-glanglionic cardiac sympathetic Pre-glanglionic cardiac sympathetic
dennervationdennervation
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Lewy bodies in extra-CNS organs Lewy bodies in extra-CNS organs a)a) SA node, b) esophagogastric junction, SA node, b) esophagogastric junction, c) adrenal medulla, d) celiac ganglion.c) adrenal medulla, d) celiac ganglion.Okada et al., Okada et al., Pathology International Pathology International 20042004
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Lewy bodies in the sinoatrial nodeLewy bodies in the sinoatrial nodeOkada et al., Okada et al., Pathology International Pathology International 20042004
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Lewy bodies in the sinoatrial nodeLewy bodies in the sinoatrial nodeOkada et al., Okada et al., Pathology International Pathology International 20042004
Associated with atrial fibrillation!Associated with atrial fibrillation!
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Extracranial Organs Extracranial Organs May be Affected FirstMay be Affected First
• Cardiac sympathetic denervation, Cardiac sympathetic denervation, diagnosable via cardiac scintigraphydiagnosable via cardiac scintigraphy• 123123I-metaiodobenzylguanidine (MIBG) is a I-metaiodobenzylguanidine (MIBG) is a
highly sensitive and specific diagnostic marker highly sensitive and specific diagnostic marker (Tateno et al., 2008)(Tateno et al., 2008)
• 6-[6-[1818F]fluorodopamine (FDA) impaired before F]fluorodopamine (FDA) impaired before the onset of parkinsonismthe onset of parkinsonism
•
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Cardiac Denervation by Cardiac Denervation by 6-[6-[1818F]fluorodopamine (FDA)F]fluorodopamine (FDA)
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123123I-metaiodobenzylguanidine I-metaiodobenzylguanidine (MIBG) cardiac scintigraphy (MIBG) cardiac scintigraphy
4 hr. H:M Ratio 1.02 1.554 hr. H:M Ratio 1.02 1.55
Gerson et al., 2002Gerson et al., 2002
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Escamilla-Sevilla, et al., 2009
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Meta-analysis of 2680 subjects Meta-analysis of 2680 subjects from 46 studiesfrom 46 studies
123123I-MIBG discriminates PD/LBD, RBD from I-MIBG discriminates PD/LBD, RBD from allall other conditions (c = 0.987)other conditions (c = 0.987)
R OC C urve
00.10.20.30.40.50.60.70.80.9
1
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
1-S pe cificity
Sen
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King, Mintz & Royall (in press)King, Mintz & Royall (in press)
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Late 2005 - 2006Late 2005 - 2006 79 yo HM79 yo HM PMHx: remote CHI (no LOC), AODM, HTN, Ao valve PMHx: remote CHI (no LOC), AODM, HTN, Ao valve
repair, CAD (CABG x 2), hyperlipidemia repair, CAD (CABG x 2), hyperlipidemia B12 = 545; folate = 434.2; TSH = 3.1B12 = 545; folate = 434.2; TSH = 3.1 ““Type 1” dementia Type 1” dementia
MMSE = MMSE = 19 /3019 /30 (recalls 3/3 w/ prompts; intact olfaction) (recalls 3/3 w/ prompts; intact olfaction) EXIT25 = EXIT25 = 24/50 24/50 (skilled nursing mean)(skilled nursing mean) CLOX1 = CLOX1 = 06/1506/15 CLOX2 = 12/15CLOX2 = 12/15 GDS = 01/15GDS = 01/15
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Mild Periventricular WMLMild Periventricular WML
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Late 2005 - 2006Late 2005 - 2006 ““vascular dementia”vascular dementia” sertraline trial > no improvementsertraline trial > no improvement venlafaxine trial > no improvementvenlafaxine trial > no improvement
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2007 - 20082007 - 2008 Feb. ‘07: Feb. ‘07: fall fall /hip contusion/hip contusion Nov. ’07: galantamine addedNov. ’07: galantamine added June ’08: galantamine 12 bidJune ’08: galantamine 12 bid
EXIT25 EXIT25 improvedimproved
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2007 - 20082007 - 2008 Feb. ‘07: Feb. ‘07: fall fall /hip contusion/hip contusion Nov. ’07: galantamine addedNov. ’07: galantamine added June ’08: galantamine 12 bidJune ’08: galantamine 12 bid
EXIT25 EXIT25 improvedimproved
July ’08: cellulitis /July ’08: cellulitis /deliriumdelirium spell spell
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2007 - 20082007 - 2008 Feb. ‘07: Feb. ‘07: fall fall /hip contusion/hip contusion Nov. ’07: galantamine addedNov. ’07: galantamine added June ’08: galantamine 12 bidJune ’08: galantamine 12 bid
EXIT25 EXIT25 improvedimproved
July ’08: cellulitis /July ’08: cellulitis /deliriumdelirium spell spell
Oct. ‘08: UTI /“confusional spells”Oct. ‘08: UTI /“confusional spells”
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2007 - 20082007 - 2008 Feb. ‘07: Feb. ‘07: fall fall /hip contusion/hip contusion Nov. ’07: galantamine addedNov. ’07: galantamine added June ’08: galantamine 12 bidJune ’08: galantamine 12 bid
EXIT25 EXIT25 improvedimproved
July ’08: cellulitis /July ’08: cellulitis /deliriumdelirium spell spell
Oct. ‘08: UTI /“confusional spells”Oct. ‘08: UTI /“confusional spells”
Nov. ‘08: Nov. ‘08: sees “cats”sees “cats” in clinic in clinic
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20092009 Jan. ’09: Jan. ’09: hypersomnolencehypersomnolence, , REM behavioral REM behavioral
disturbance disturbance, , parkinsonianparkinsonian gait; modafanil added gait; modafanil added
March ’09: March ’09: visual hallucinations; constipationvisual hallucinations; constipation
June ’09: galantamine 24mg bid, modafanil 200mg qdJune ’09: galantamine 24mg bid, modafanil 200mg qd Eating well, sleeping less, more talkative, no recent Eating well, sleeping less, more talkative, no recent hallucinations; positional tremor hallucinations; positional tremor
EXIT25 = 25; MMSE = 21EXIT25 = 25; MMSE = 21; ; CLOX1 = 10; CLOX1 = 10; CLOX2 =11CLOX2 =11, GDS = 2, GDS = 2
Aug. ‘09; Aug. ‘09; resting tremorresting tremor R >L R >L
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The “Vascular Dementia” The “Vascular Dementia” of Lewy Body Disease?of Lewy Body Disease?
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The “Vascular Dementia” The “Vascular Dementia” of Lewy Body Disease?of Lewy Body Disease?
Early cardiac involvementEarly cardiac involvement Atrial arrythmia, atrial fibrillationAtrial arrythmia, atrial fibrillation Syncope, orthostasis, falls & vasovagal Syncope, orthostasis, falls & vasovagal
“spells”“spells” ““Ischemic” WML, executive impairmentIschemic” WML, executive impairment ““Vascular Dementia”Vascular Dementia”
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The “Vascular Dementia” The “Vascular Dementia” of Lewy Body Disease?of Lewy Body Disease?
Early cardiac involvementEarly cardiac involvement Atrial arrythmia, atrial fibrillationAtrial arrythmia, atrial fibrillation Syncope, orthostasis, falls & vasovagal Syncope, orthostasis, falls & vasovagal
“spells”“spells” ““Ischemic” WML, executive impairmentIschemic” WML, executive impairment ““Vascular Dementia”Vascular Dementia”
Extra-cardiac involvementExtra-cardiac involvement Incontinence, constipation, sensitive Incontinence, constipation, sensitive
pharmacologypharmacology
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The “Vascular Dementia” The “Vascular Dementia” of Lewy Body Disease?of Lewy Body Disease?
Later brainstem involvementLater brainstem involvement REM behavioral disturbancesREM behavioral disturbances Cholinergic responsive cognitive fluctuationsCholinergic responsive cognitive fluctuations Psychiatric manifestationsPsychiatric manifestations Parkinsonism /visual hallucinationsParkinsonism /visual hallucinations Visuospatial deficitsVisuospatial deficits
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LBD symptoms emerge LBD symptoms emerge overover ICVD ICVD
spells suggest “TIA’s” spells suggest “TIA’s” Parkinsonism suggests “basal ganglia Parkinsonism suggests “basal ganglia
lesions”lesions”
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Royall et al. Royall et al. J Neuropsych Clin NeurosciJ Neuropsych Clin Neurosci, 2009, 2009
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Incident LBD among VCI Cases!Incident LBD among VCI Cases!
• 6 /35 (17.2%) have gone on to convert to clinical 6 /35 (17.2%) have gone on to convert to clinical LBD at a mean follow-up of 857 LBD at a mean follow-up of 857 408 days 408 days 2 /6 (33%) had MRI confirmed focal ischemic lesions 2 /6 (33%) had MRI confirmed focal ischemic lesions 5 /6 (88.3%) had white matter lesions5 /6 (88.3%) had white matter lesions
• An additional 10 (28.6%) are suspected of LBD, An additional 10 (28.6%) are suspected of LBD, but do not yet meet formal criteria but do not yet meet formal criteria
• 123123I-MIBG confirms cardiac sympathetic I-MIBG confirms cardiac sympathetic dennervationdennervation
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• The probable and possible LBD cases did not The probable and possible LBD cases did not differ at baseline from VCI subjects without LBD differ at baseline from VCI subjects without LBD symptoms on any clinical measure in our datasetsymptoms on any clinical measure in our dataset
• At the time of their conversion, 4 /6 At the time of their conversion, 4 /6 (66.7%) have parkinsonism, 6 /6 (100%) (66.7%) have parkinsonism, 6 /6 (100%) have REM sleep behavioral issues, 5 /6 have REM sleep behavioral issues, 5 /6 (83.3%) have visual hallucinations, and (83.3%) have visual hallucinations, and 4 /6 (66.7%) have confusional spells4 /6 (66.7%) have confusional spells
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Clinicians Sensitized?Clinicians Sensitized?
• We have considered the possibility that our clinicians We have considered the possibility that our clinicians have become sensitized to LBD symptoms over timehave become sensitized to LBD symptoms over time
• Time from first clinical evaluation to diagnosis of LBD Time from first clinical evaluation to diagnosis of LBD
(excluding possible cases) ranges from 469 to 1463 (excluding possible cases) ranges from 469 to 1463 days and is strongly days and is strongly positively positively correlated (r = 0.84) with correlated (r = 0.84) with the date of diagnosisthe date of diagnosis
• This argues FOR a linear delay between first evaluation This argues FOR a linear delay between first evaluation
and diagnosis, and AGAINST a bias towards shorter and diagnosis, and AGAINST a bias towards shorter delays to diagnosis as a function of the date of clinic delays to diagnosis as a function of the date of clinic enrollmentenrollment
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Hachinski Ischemic Scale (HIS) Hachinski Ischemic Scale (HIS) (Hachinski 1975):(Hachinski 1975):
““nightime confusion”nightime confusion” = REM disturbance?= REM disturbance?
““depression”depression” = raphe or L insula involvement?= raphe or L insula involvement?
““fluctuating course”fluctuating course” = cognitive spells?= cognitive spells?
““somatic complaints”somatic complaints” = extracranial involvement?= extracranial involvement?
These symptoms should load on the same factorThese symptoms should load on the same factor
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NINDS-ARIENS “VaD”NINDS-ARIENS “VaD”
1.C.II: “Clinical features consistent with the 1.C.II: “Clinical features consistent with the diagnosis of diagnosis of probableprobable vascular dementia vascular dementia include:include:
A. Early presence of a A. Early presence of a gait disturbancegait disturbance (small-step gait (small-step gait or marche à petis pas, … or parkinsonian gait.or marche à petis pas, … or parkinsonian gait.
B. History of unsteadiness and frequent unprovoked B. History of unsteadiness and frequent unprovoked fallsfalls..
C. Early C. Early urinary frequencyurinary frequency, urgency, and other urinary , urgency, and other urinary symptoms…symptoms…
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Honolulu-Asia Honolulu-Asia Aging Study (HAAS)Aging Study (HAAS)
Longitudinal study of heart disease and Longitudinal study of heart disease and stroke established in 1965 stroke established in 1965
8006 Japanese-American men8006 Japanese-American men Cognitive screening and autopsies since Cognitive screening and autopsies since
1991 1991 650 autopsies650 autopsies 350 w/ histology350 w/ histology
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Honolulu-Asia Honolulu-Asia Aging Study (HAAS)Aging Study (HAAS)
Lewy body counts in:Lewy body counts in: locus coerleus locus coerleuslocus coerleus locus coerleus substantia nigrasubstantia nigra L insulaL insula L temporal lobeL temporal lobe L frontal lobeL frontal lobe L occipital lobeL occipital lobe
240 w/ L and R insular histology240 w/ L and R insular histology
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Does Stroke Predict Lewy Body Does Stroke Predict Lewy Body Lesions Anywhere in the Brain?Lesions Anywhere in the Brain?
OORR CCII DDFF 22 pp ““SSttrrookkee”” 11..9966 11..1144 –– 33..3355 11 66..00 00..0022
AAggee 11..0077 11..0033 –– 11..1122 11 99..99 00..000022 ““DDeepprreessssiioonn””
((CCEESSDD >>99)) 11..6633 00..8855 –– 33..1100 11 22..22 00..1144
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Does Stroke Predict Lewy Body Does Stroke Predict Lewy Body Lesions Anywhere in the Brain?Lesions Anywhere in the Brain?
OORR CCII DDFF 22 pp ““SSttrrookkee”” 11..9966 11..1144 –– 33..3355 11 66..00 00..0022
AAggee 11..0077 11..0033 –– 11..1122 11 99..99 00..000022 ““DDeepprreessssiioonn””
((CCEESSDD >>99)) 11..6633 00..8855 –– 33..1100 11 22..22 00..1144
Adjudicated “stroke” does not. Adjudicated “stroke” does not.
Suggests “silent” lesions, microinfarcts and lacunes.Suggests “silent” lesions, microinfarcts and lacunes.
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In Which ROI is /are Lewy Body In Which ROI is /are Lewy Body Lesions Related to Stroke?Lesions Related to Stroke?
OORR CCII DDFF 22 pp LL IInnssuullaa 22..0077 11..0099 –– 33..9944 11 55..00 00..0033
AAggee 11..0077 11..0022 –– 11..1133 11 66..88 00..0011 ““DDeepprreessssiioonn””
((CCEESSDD >>99)) 22..4433 11..1100 –– 55..3388 11 44..88 00..0033
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In Which ROI is /are Lewy Body In Which ROI is /are Lewy Body Lesions Related to Stroke?Lesions Related to Stroke?
OORR CCII DDFF 22 pp LL IInnssuullaa 22..0077 11..0099 –– 33..9944 11 55..00 00..0033
AAggee 11..0077 11..0022 –– 11..1133 11 66..88 00..0011 ““DDeepprreessssiioonn””
((CCEESSDD >>99)) 22..4433 11..1100 –– 55..3388 11 44..88 00..0033
R insula, locus coerleus , substantia nigra, L frontal, L temporal, L parietal, R insula, locus coerleus , substantia nigra, L frontal, L temporal, L parietal, and L occipital do not. and L occipital do not.
Suggests autonomic mechanism.Suggests autonomic mechanism.
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In Which ROI is /are Lewy Body In Which ROI is /are Lewy Body Lesions Related to Stroke?Lesions Related to Stroke?
OORR CCII DDFF 22 pp LL IInnssuullaa 22..0077 11..0099 –– 33..9944 11 55..00 00..0033
AAggee 11..0077 11..0022 –– 11..1133 11 66..88 00..0011 ““DDeepprreessssiioonn””
((CCEESSDD >>99)) 22..4433 11..1100 –– 55..3388 11 44..88 00..0033
R insula, locus coerleus , substantia nigra, L frontal, L temporal, L parietal, R insula, locus coerleus , substantia nigra, L frontal, L temporal, L parietal, and L occipital do not. and L occipital do not.
Suggests autonomic mechanism.Suggests autonomic mechanism.
““Vascular Depression” may be LBD as well!Vascular Depression” may be LBD as well!
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Which Ischemic PathologiesWhich Ischemic Pathologiesare Related to L Insula Lesions?are Related to L Insula Lesions?
EEssttiimmaattee SSEE tt pp BBGG //tthhaall
mmiiccrrooiinnffaarrccttss 00..4444 00..2233 11..9922 00..005566
AAggee 00..0044 00..0022 22..2277 00..0022 ““DDeepprreessssiioonn””
((CCEESSDD >>99)) 00..2299 00..2288 11..0055 00..3300
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Which Ischemic PathologiesWhich Ischemic Pathologiesare Related to L Insula Lesions?are Related to L Insula Lesions?
EEssttiimmaattee SSEE tt pp BBGG //tthhaall
mmiiccrrooiinnffaarrccttss 00..4444 00..2233 11..9922 00..005566
AAggee 00..0044 00..0022 22..2277 00..0022 ““DDeepprreessssiioonn””
((CCEESSDD >>99)) 00..2299 00..2288 11..0055 00..3300
No associations with embolic and hemorrhagic lesions, neocortical No associations with embolic and hemorrhagic lesions, neocortical microvascular lesions, or total white matter microvascular lesions. microvascular lesions, or total white matter microvascular lesions.
Specific subcortical frontal circuit pathology suggests end-arteriolar Specific subcortical frontal circuit pathology suggests end-arteriolar hypoperfusion events.hypoperfusion events.
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Possible CNS ManifestationsPossible CNS Manifestations Syndrome of incontinence, gait disturbance, executive Syndrome of incontinence, gait disturbance, executive
impairment, and frontal WML?impairment, and frontal WML? Geriatric anxiety /depressionGeriatric anxiety /depression
Vascular Depression?Vascular Depression? Geriatric SuicidesGeriatric Suicides Geriatric PsychosesGeriatric Psychoses HoardingHoarding Sleep disorders Sleep disorders
REM disordersREM disorders• PTSD? PTSD?
Sleep apneaSleep apnea BruxismBruxism
NPH?NPH? Iatrogenic deliriumIatrogenic delirium
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Extra-cranial LBD Syndromes?Extra-cranial LBD Syndromes?
Syncopal fallsSyncopal falls Atrial fibrillationAtrial fibrillation Geriatric constipationGeriatric constipation Drug sensitivitiesDrug sensitivities Iatrogenic deliriumIatrogenic delirium Non-traumatic hip Non-traumatic hip
fracture fracture ““urge” incontinenceurge” incontinence TMJTMJ
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ConclusionsConclusions
Lewy Body Disease is the second most Lewy Body Disease is the second most common degenerative pathologycommon degenerative pathology
Lewy Body Syndrome is also common and Lewy Body Syndrome is also common and often misdiagnosedoften misdiagnosed
Still, Lewy Body Syndrome may follow Still, Lewy Body Syndrome may follow years of extracranial organ dysfunctionyears of extracranial organ dysfunction
and, Lewy Body Syndrome may be but one and, Lewy Body Syndrome may be but one CNS manifestation of Lewy Body Disease CNS manifestation of Lewy Body Disease
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ContactContact
For questions about this audio conference please For questions about this audio conference please contact Dr. Donald Royall at contact Dr. Donald Royall at [email protected]
For any questions about the monthly GRECC Audio For any questions about the monthly GRECC Audio Conference Series please contact Tim Foley at Conference Series please contact Tim Foley at [email protected] or call (734) [email protected] or call (734) 222-4328
To evaluate this conference for CE credit please obtain a To evaluate this conference for CE credit please obtain a „Satellite Registration‟ form and a „Faculty Evaluation‟ „Satellite Registration‟ form and a „Faculty Evaluation‟ form from the Satellite Coordinator at you facility. The form from the Satellite Coordinator at you facility. The forms must be mailed to EES within 2 weeks of the forms must be mailed to EES within 2 weeks of the broadcastbroadcast