LEWY BODY DEMENTIA/ PARKINSONS DISEASE DEMENTIA.

Insights Into a Common Spectrum Disorder. Dr. Albert Chen Clinical Gerontologist June 29th 2012.

"From the brain and the brain alone arise our pleasures, joys, laughter and jests, as well as our sorrows, pains and griefs" Hippocrates By their benevolant labours its real nature may be ascertained, and appropriate modes of relief, or even of cure, pointed out. James Parkinson 1817.

CONTENTS
Why

discuss dementia now? Whats behind brain degeneration with aging? History & Epidemiology of LBD Clinico-Pathological insight into LBD Differential Diagnosis & Treatment Current & Future Challenges What did we just talk about?

THATS WHY WE NEED TO DISCUSS DEMENTIA!

Aetiology of Primary Degenerative Dementia.

Alzheimers disease (AD) Frontotemporal lobar degeneration Behavioural, frontotemporal dementia Progressive, non fluent aphasia Semantic dementia Dementia with Lewy bodies (DLB) Prion diseases Parkinsons disease dementia (PDD) Corticobasal degeneration syndrome / Progressive supranuclear palsy (PSP) Huntingtons disease (HD) Motor neuron disease (ALS), Multiple Systemic Atrophy
9

PESTICIDES & INSECTICIDES

ALCOHOL & TOBACCO

INCREASED IONIZING RADIATION O2 -

OH.

INCREASED RADIOACTIVITY EXPOSURE

OBESITY

FREE RADICAL PROLIFERATIO N

O2 DIABETE S
Chen A.W. (2008)

METABOLI C SYNDROM E

PROCESSE D FOOD

FOOD PREPARATION METHODS

LEWY BODY DEMENTIA (PDD/DLB) (~15-20%)

Frontotemporal Degeneration Subcortical Disease

ALZHEIMERS DISEASE (~65%)

CVD & STROKE

Small Vessel Disease CADASIL

OTHER non-CNS DISEASES

DEMENTIA

???

Unknow n Factors

Frequency of Various Dementias

Dementia Type

Various

Rabins

Barker et al.

AD LBD Vascular Dementia FTD Mixed

60-70 % 2030% 15-30% 13.321.9%

66% 8-15% 1520% 5%

42% 8% 3% 4% 42%

LEWY BODY DEMENTIA/ PARKINSON DISEASE DEMENTIA.

A SPECTUM DISORDER
COMPREHENSIVE OVERVIEW

Dr Friedrich Heinrich Lewy (1885-1950)

Konstantin Nikolaevitch Tretiakoff

(December 26, 1892 1958)

Recent History of LBD Late identification due to difficulty visualizing

Lewy bodies in cortex. AD with rigidity and rapid progression, or with plaques but no tangles. LBD first reported by Kosaka et. al. 1978 Type I (LB in midbrain, eg. Parkinsons disease) Type II (transitional form) Type III (LBs in cortex, eg. LBD)

DEMENTIA WITH LEWY BODIES.

IAN McKEITH
Every

7 s a new case of dementia worldwide. Pathological studies suggest that 15-20% are due to DLB, a condition unrecognised 15 yrs ago. The functional impairments and cost of managing DLB is twice that of AD. Correct management can bring significant benefits. DLB is part of a spectrum of disease, including Parkinsons and Autonomic Failure. To beat it we must talk more with colleagues, cutting across specialities boundaries

LEWY BODY DEMENTIA IS NOT A RARE DISEASE

It accounts for up to 20% of dementia cases in the U.S. thats up to 1.3 million cases in the U.S. alone, with only 30%-50%

Round, eosinophilic cytoplasmic inclusion bodies with pale halo. irregular shape, halo less prominent in cortical LBs, difficult to visualize. Easier to visualize with newer immunofluourescent stains. Composed of abnormal neurofilaments (mostly polymerized alpha-synuclein and ubiquitin).

Lewy Bodies

Whats in a Name?
Lewy

Body disease (LBd) Diffuse Lewy Body disease (DLBd) Lewy Body Dementia (LBD) Dementia with Lewy bodies (DLB) Alzheimers disease, Lewy body variant (ADLBv)
Dementia, Lewy body type

Senile

Parkinsons

Disease Dementia

(PDD)

LEWY BODY DISEASE SPECTRUM

SUBCLINICAL PHENOTYPE
Sub. Nigra
CORTEX

PARKINSON S DISEASE

PAF

LEWY BODY DEMENTIA

Progression
Chen A.W 2012

Lets get the classificati on right!

LEWY BODY DEMENTIA

PARKINSONS DISEASE DEMENTIA

(PDD)

DEMENTIA WITH LEWY BODIES

(DLB)

Lewy Body Disease Presenting Features.

Dementia

alone Parkinsonism alone Parkinsonism with dementia Psychiatric disorder, absent dementia Orthostatic hypotension Altered consciousness... transient Falls Primary autonomic failure
Age:

50 -83 yrs. M>F ~ 10% decline per annum (McKeith et al. 1992., Byrnes et al 1989.)

Dementia With Lewy Bodies (DLB)

FLUCTUATING COGNITION

PARKINSONISM

Heyman A et al. Neurology. 1999;52:1839-1844. Ballard CG et al. Dement Geriatr Cogn Disord. 1999;10:104-108. Barber R et al. Neurology. 1999;52:1153-1158.
Chen A.W 2008

VISUAL HALLUCINATIONS

DEMENTIA

LBD

Dementia With Lewy Bodies (DLB)

RBD
Autonomic Dysfunctio n

FLUCTUATING COGNITION

PARKINSONISM

Heyman A et al. Neurology. 1999;52:1839-1844. Ballard CG et al. Dement Geriatr Cogn Disord. 1999;10:104-108. Barber R et al. Neurology. 1999;52:1153-1158.

VISUAL HALLUCINATIONS

DEMENTIA
depress ive

LBD

Visuospatia l Deficit
NEUROLEPTIC SENSITIVITY

DEMENTIA
de..... mentia
An

acquired deterioration of global cognitive functions in previously unimpaired persons... Severe enough to impair their normal functioning.

Two Types of Dementia

POSTROLANDIC
Memory
FRONTAL/SUBCORTICAL

deficits

Aphasia Apraxia Agnosia Personality preserved MMSE valid

Memory deficits Loss of goal-oriented behavior, behavioral plasticity. Personality Changes - Disinhibition - Abulia Incontinence MMSE useless

 Similar

to Alzheimers disease in presentation.

LBD is a Post-Rolandic Dementia

Neuropsychological testing similar to AD (may

be a bit more executive and visiospatial deficit)

SPECT, PET findings like AD (parieto-temporal

hypo-metabolism)

Similar, or slightly earlier, age of onset, but more rapid progression (mean survival 5-8 years).

Subcortical Dementias
Parkinson's

disease (PD); Huntington's disease (HD); multiple system atrophy; idiopathic basal ganglia calcification; multi-infarct dementia; and, AIDS dementia complex

DEMENTIA SYNDROMES
Memory Judgment Attention Executive functions. Visuospatial Language Depression Psychosis Hallucination Apathy Agitation anxiety

Cognitive

Apraxia ADL IADL

Behaviour al

Chen A.W 2010

NeuroPs ychiatric

Functional

Wandering Pacing Repititive

Alzheimers disease Outreach Programme (Jamaica)

Alzheimer Warning Signs Top Ten

1. Recent memory loss affecting job 2. Difficulty performing familiar tasks 3. Problems with language 4. Disorientation to time or place 5. Poor or decreased judgment 6. Problems with abstract thinking 7. Misplacing things 8. Changes in mood or behavior 9. Changes in personality 10. Loss of initiative

Lewy Body Dementia

Dementia

similar to that of Alzheimers.

Significantly

greater fluctuation in condition from day to day, compared to AD. 81% have periods of marked unexplained confusion, mimicking delirium.

Twice

as common in men. (1.6-2:1)

Generally non-familial, but a few autosomal dominant cases reported

Acta Neuropathol.1998 Aug;96(2):207-10.

Autosomal dominant diffuse Lewy body disease.

Wakabayashi K,Hayashi S,Ishikawa A,Hayashi T,Okuizumi K,Tanaka H,Tsuji S,Takahashi H. Source: Brain Disease Research Center, Brain Research Institute, Niiata University, Japan. koichi@bri.niigata-u.ac.jp

Abstract: We describe a Japanese family with parkinsonism and later-

onset dementia. The proband developed parkinsonism at the age of 61 years, followed by dementia starting when she was 67. Her uncle, who was also her husband, died at the age of 78 years after 7- and 5-year histories of parkinsonism and dementia, respectively. Pathological examination of these two patients showed marked neuronal loss with Lewy bodies (LBs) in the brain stem pigmented nuclei and numerous cortical LBs and ubiquitin-positive hippocampal CA2/3 neurites were observed. The proband also had many amyloid plaques. Their two sons developed similar parkinsonism at the ages of 39 and 28 years and also suffered later-on-set dementia. These findings strongly suggest that this family has autosomal dominant diffuse LB disease

Journal of Neuropathology & Experimental Neurology: January 2009 - Volume 68 - Issue 1 - pp 73-82 Early-Onset Familial Lewy Body Dementia With Extensive Tauopathy: A Clinical, Genetic, and Neuropathological Study.
Clarimn, Jordi PhD; Molina-Porcel, Laura MD; Gmez-Isla, Teresa MD, PhD; Blesa, Rafael MD, PhD; Guardia-Laguarta, Cristina BSc; GonzlezNeira, Anna PhD; Estorch, Montserrat MD, PhD; Ma Grau, Josep MD, PhD; Barraquer, Llus MD, PhD; Roig, Carles MD, PhD; Ferrer, Isidre MD, PhD; Lle, Alberto MD, PhD

Abstract: We describe a Spanish family in which 3 of 4 siblings had dementia with Lewy bodies, 2 of them starting at age 26 years and the other at 29 years. The father has recently been diagnosed with Lewy body disease, with onset at 77 years. Neuropathological examination of the brain of the index patient disclosed unusual features characterized by diffuse Lewy body disease and generalized neurofibrillary tangle pathology but with no amyloid deposits in any region. Moreover,

Cognitive Symptoms Common to AD and LBD.

Behavioral

changes Decreased judgment Confusion and temporal/spatial disorientation Difficulty following directions Decreased ability to communicate

DLB COURSE
The

course of DLB is progressive, with cognitive test scores declining about 10% per annum, similar to AD. Cognitive fluctuations may contribute to large variability in repeated test scores, eg, by five Mini-Mental State Examination (MMSE) points difference over the course of a few days or weeks, making it difficult to be sure of the severity of cognitive impairment by single examination.

Neurotransmitter Changes in LBD.

AcetylCholine

90-95%

Dopamine

30-50%

No Serotonergic deficit.
Ach NE Glu 5HT
Chen A.W 2008

Dementia patients with LBP may respond more favorably to treatment with cholinesterase inhibitors but are more likely
to develop hypersensitivity reactions to antipsychotic medications.

Liberini P, Valerio A, Memo F, Spano P. Lewy-body dementia and responsiveness to cholinesterase inhibitors: a paradigm for heterogeneity of Alzheimers disease? Trends Pharmacol Sci 1996; 1996:155-160. Ballard C, Grace J, McKeith I, Holmes C. Neuroleptic sensitivity in dementia with Lewy bodies and

CLINICAL COMPARISON

LBD vs. DAT

James E. Gavin et. al. 2008. Current Issues in Lewy Body Dementia

LBD Places High toll on Families

A

cross-sectional study evaluated 84 patients with DLB or AD in a secondary care setting. Bristol Activities of Daily Living Scale (BADLS) to assess functional impairments, Unified Parkinsons Disease Rating Scale (UPDRS) to assess motor impairments, Neuropsychiatric Inventory (NPI) and Mini-Mental Status Examination (MMSE) to assess cognitive function.

Results
The

study concluded that patients with LBD were more functionally impaired than patients with AD with similar cognitive scores. LBD patients also had more motor difficulties than AD patients. Total score on motor difficulties was highly correlated to functional impairment in areas of dressing, hygiene, teeth cleaning, bath/shower, toilet, transfers and mobility.

Results II

AD

patients were not shown to be significantly more impaired than LBD patients in any of the functional areas studied.

LBD vs AD

DLB were 2 times more likely to die at comparable ages compared with people with AD. The average survival time for DLB was 78 years of age and for AD was 85 years of age. Men were 1.5 times more likely to die sooner than women.

Survival From Diagnosis

Individuals

with DLB had an average survival of 7 years. AD individuals lived 8.5 years.

Comparative Level of Care

LBD

patients used more than double the amount of resources compared to AD patients. Specifically, DLB patients used greater resources in accommodations. Required more outpatient care, informal care, community services and pharmacological therapy.

Apathy: LBD vs. AD

Apathy,

along with other neuropsychiatric features, was measured and found to be higher in DLB patients than AD patients.

Cost

of care for DLB patients with apathy was almost three times as high as in AD patients with apathy.

FLUCTUATING COGNITION
LEWY BODY DEMENTIA

What Fluctuates? Alertness

Attention Memory Thinking Executive Functions Communicative Skills Apraxia, Agnosia

 Clinician

Assessment of Fluctuation Scale One Day Fluctuation Assessment Scale.

Frequency and Severity of occurrence are the main aspects of FC that differentiate DLB from AD and other dementias. the marked amplitude between best and worst performance

Does the patient ever have spontaneous impaired alertness and concentration,that is, appear drowsy but awake, look dazed, not be aware of what is going on around? Has the level of confusion experienced by the patient tended to vary a lot recently from day to day or week to week? Has the patient had a period (or periods) today when he or she seemed to be confused and muddled and then a period (or periods) when he or she seemed to be

FC unrelated to situational demands. Confabulatory or fleeting delusional quality. short lived alterations in cognitive and functional abilities. lapse in the stream of awareness or attention

Fluctuating Cognition LBD DAT

Cant focus properly. Blank staring during which the patient appeared to disengage from the ongoing flow of activity or conversation

Situational confusion Persisting or enduring quality to FC Actions or thoughts are deflected onto another task or question as a result of memory failure Repetitiveness in
conversation Forgetfulness

PARKINSONISM
LEWY BODY DEMENTIA

Motor Symptoms Common to PD & LBD

Muscle stiffness Difficulties with balance Shuffling gait Stooped posture PD 100% LBD > Slow movements 70% Restless leg syndrome Tremors
EPS PREVALENCE

Parkinsonian Features
Relatively

mild, onset usually at time of dementia

(+ or 1 year).

Mostly gait changes and rigidity, tremor is rare

- postural instability worse than PD (Burn et al. 2006)

Response to L-dopa not very robust

-Slightly better response in younger patients -usually doesn't worsen hallucination

Rule out recent, up to 3 months, neuroleptic exposure.

VISUAL HALLUCINATION
LEWY BODY DEMENTIA

Psychotic Symptoms
May

be first symptom Present in 75 to 80% of cases of LBD Usually visual hallucination (phantom boarder, at times years before dementia) More prominent, appears earlier than in AD Hallucinations usually not distressing

PVH in LBD
Usually

of people or animals but may be inanimate objects such as statues or pieces of furniture. Occurs in most (> 60%) LBD cases. Usually without emotional content. Usually vivid, colourful... Detailed... Related or unrelated auditory hallucinations may co-exist.

Visual hallucinations in DLB are associated with greater deficits in cortical acetylcholine and predict better response to cholinesterase inhibitors.
Perry

EK, McKeith I, Thompson P, et al. Topography, extent, and clinical relevance of neurochemical deficits in dementia of Lewy body type, Parkinson's disease and Alzheimer's disease. Ann N Y Acad Sci. 1991;640:197-202. McKeith IG WK, Perry E, Ferrara, R. Hallucinations predict attentional improvements with rivastigmine in dementia with Lewy bodies. Dement Geriatr Cogn Disord. 2004;18:94-100.

TREATMENT DILEMMA
EPS
PSYCHOSIS

TREAT HALLUCIANTIONS.......
EPS

HALLUCINATIONS & PSYCHOSIS

Chen A.W.

TREAT ESP.............
HALLUCINATIONS & PSYCHOSIS

EPS

Chen A.W.

Management of Psychotic Symptoms.

Caregiver

education, benign neglect

Increased socialization, lighting Avoid anticholinergics Minimize/optimize antiparkinsonians

Atypicals at times. -avoid risperidone and aripripazole

NEUROLEPTIC SENSITIVITY
LEWY BODY DEMENTIA

Neuroleptics and LBD Most patients have severe reaction to

typical (and atypical) neuroleptics, including
severe akinesia, dystonia and NMS-like symptoms. > 50% affected

Greater sensitivity than in PD. Prolongs hospitalization in 81%, reduces lifespan in 50% (McKeith et al 1992) Doubles rate of cognitive decline (McShane et
al. 1997)

A severe , unexpected reaction to low dose antipsychotic strongly suggests LBD

Neuroleptics et. al.

Dopamine

Blockers Not restricted to anti-psychotics. Anti-emetics Chlorpromazine Prochlorperazine. Promethazine.

Neuroleptic sensitivity in Parkinson's disease and parkinsonian dementias. . Background:

Method:

Aarsland et at. J Clin Psychiatry 2005 May;66(5):633-7 Severe sensitivity to neuroleptic agents is a major clinical problem in dementia with Lewy bodies (DLB), but has not been determined in Parkinson's disease (PD) and PD with dementia (PDD).
Severe neuroleptic sensitivity reactions (NSRs) were evaluated according to an operationalized definition blind to clinical and neuropathologic diagnoses in prospectively studied patients exposed to neuroleptics from 2 centers. The study was conducted from June 1995 to May 2003.

Results: Ninety-four patients were included (15 with DLB, 36 with PDD, 26 with
PD, 17 with Alzheimer's disease, all diagnosed with various operational criteria). Severe NSR only occurred in patients with Lewy body disease: DLB (8 [53%]), PDD (14 [39%]), and PD (7 [27%]), but did not occur in Alzheimer's disease (p = . 006). Severe NSR was not associated with other clinical or demographic features. In DLB, severe NSR was not associated with neuropathologic indices (Consortium to Establish a Registry for Alzheimer's Disease staging, Braak staging, or cortical distribution of Lewy bodies).

Possible Signs of NSR

Excessive

initial sedation Sudden onset of rigidity Postural instability, Falls. Rapid general deterioration, Increased confusion, Immobility, rigidity, Fixed flexion posture, Decreased food intake

NEUROLEPTIC MALIGNANT SYNDROME

FALTER

F Fever A Autonomic instability L Leukocytosis T Tremor E Elevated enzymes (elevated CPK) R Rigidity of muscles

Altered consciousness Tachypnoea Elevated arterial pressure

 Discontinue

all antipsychotics. Supportive measures: circulatory and ventilatory support as needed. Cooling blankets and antipyretics can be used to control temperature. Aggressive fluid resuscitation and alkalization of urine can help prevent acute renal failure and enhance excretion of muscle breakdown products. Benzodiazepines and physical restraints may be useful.
The value of other interventions, such as dantrolene, amantadine, bromocriptine, and electroconvulsive therapy, is uncertain

Treatment & Management

Current Clinical Experience Olanzapine appears to be poorly tolerated.

Risperidone has been associated with high risk of neuroleptic malignant syndrome. Clozapine use remains controversial because of its potent anticholinergic action and risk of agranulocytosis. Established efficacy in PDD/LDB Quetiapine has been shown to reduce psychiatric manifestations of DLB without causing neuroleptic sensitivity or increasing EPS.
Hence, quetiapine is an attractive candidate for the treatment of psychoses in DLB and other dementias.

AUTONOMIC DYSFUNCTION
LEWY BODY DEMENTIA

Autonomic Dysfunction
62% of patients with DLB experience significant autonomic failure, and dysautonomia is observed in up to 80% of patients with PD
Approximately

Autonomic Dysfunction:
Blood

pressure fluctuations (e.g. postural/orthostatic hypotension). Heart rate variability (HRV), Constipation, Sialorrhea , Sleep disturbances Urinary problems, Hyperhidrosis, decreased sweating/heat intolerance. Syncope (fainting), Temperature dysregulation. Dry eyes/mouth, and difficulty swallowingwhich may lead to aspiration pneumonia. Sexual disturbances/impotence,

OH
Primary Autonomic Failure/dysf unction of CVS in LBD Supine or nocturnal hypertensi on Postprandi al hypotensio n, (PPH) Carotid 60% Sinus Syndrome 40%

QTc
Chen A.W.

Bradyarrhythm ias

Potential inducers of OH in LBD Antiparkinsonian medications,

Diuretics, alpha-blockers, Oral nitrates, Tricyclic antidepressants, beta-blockers, alpha-1 adrenergic receptor antagonists, Calcium channel blockers, monoamine oxidase inhibitors, ethyl alcohol abuse.

Autonomic dysfunctions in dementia with Lewy bodies.

Horimoto et. al. J Neurol.2003 May;250(5):530-3
29

DLB were retrospectively examined for autonomic symptoms. Twenty-eight cases showed some kind of autonomic dysfunction. (96.5%) Urinary incontinence (97 %) , urinary retention 28% Constipation (83 %) . Episodic hypotension 28% There were 18 cases (62 %) with severe autonomic failure. LBD of all pathological subtypes exhibits some kind and level of autonomic symptoms .

Treating OH
Compression

stockings Frequent, small meals, High-salt diet, Increased fluid intake Fludrocortisone, Midodrine, Ephedrine. SSRIs

REM SLEEP BEHAVIOR DISORDER (RBD)

LEWY BODY DEMENTIA

Anatomy of Sleep
N-REM SLEEP
Stage 11 Stage II Stage III Stage IV
Dreaming Irregular Breathing Muscular Atonia Elevated Blood Pressure Rapid Movement of Eyes

REM SLEEP
Che n A. W (2012)

REM-Sleep Behavior Disorder (RBD).

(Parasomnia)

Characterized

by loss of muscle atonia during dreaming, producing acting out of dream (e.g., punching, kicking, rolling off bed, yelling, screaming) RBD is characterized by the acting out of dreams that are vivid, intense, and violent. Highly sensitive & specific for synucleopaties (PD, DLB, MSA.) An acute form may occur during withdrawal from alcohol or sedative-hypnotic drugs.
Very responsive to low dose clonazepam.

Clinical Correlates of RBD

DEPRESSIVE PHENOTYPE
LEWY BODY DEMENTIA

Depressive Symptoms Increased irritability,

Poor concentration, lack of attention during interactions, Sadness or a negative mood, Poor appetite or sleep, or the opposite over-eating and sleeping too much Withdrawal from normal activities General apathy

NEUROIMAGING
LEWY BODY DEMENTIA

Imaging Alzheimer Comparis s on

CT/MRI Deep WM lesions on MRI Generalized atrophy. > MTL Moderate increase relative to normal

LBD
Generalized atrophy. Sparing MTL Moderate increase relative to normal

Peri-venricular WM on Comparable to normal Comparable to normal MRI SPEC (blood flow) SPEC (dopamine transporter) Global reduction. > posterior P-T, MTL ~ Normal for age Global reduction. > occipital. MTL normal Reduced in putamen, similar to PD

Functional imaging (PET) in other dementias: Dementia with Lewy Bodies

18FGlucose

18F-Dopa

Normal control
PET image provided by, and used with the kind permission of, Dr Pablo Martnez-Lage
90

DLB

SPECT control vs. LBD

control

LBD

D2 receptors in striatum - DLB neuroleptic

tolerant

D2 receptors in striatum - neuroleptic sensitive

Guidelines for Diagnosis of DLB

(McKeith et al., Neurology 1996;47:1113-1124)

Mandatory:

Dementia

Core features:1. cognitive & behavioral fluctuations, 2. Parkinsonism, 3. visual hallucination, also 4.REM-sleep behavior disorders.

Supporting features: 1.syncope (often due to orthostatic hypotension), 2.repeated falls, 3.transient loss of consciousness, 4.paranoid delusions, 5.neuroleptic sensitivity, 6.non-visual hallucinations.

Patient Name: Address:

Age: Date: ..

Please answer the following questions, yes or no!

1. Is there evidence of Cognitive Impairment?

YES / NO

2. Is there shuffled gait or rigidity? YES / NO 4 3. Is there evidence/history of vivid visual hallucinations? YES / NO 4 4. Is there fluctuation of cognition or attention? YES / NO 5. Is there a history of sensitivity to neuroleptics? YES / NO 6. Is there complains of sleeping disorder, acting out dreams? YES / NO 7. Is there a history of frequent falls or black-outs? YES / NO 8. Is memory relatively intact? YES / NO 9. Is there hypotension, constipation or excessive sweating? YES / NO 10. Is there an evident tremor? YES / NO 2 11. Did motor signs and cognitive impairment occur within 18 months of each other? YES / NO 12. Are there false ideas about other persons or situations? YES / NO 2 TOTAL SCORE: /34 Interpretation: 20 or more Lewy Body Dementia

4 4 2 2 2 2 2

Hypothetical Treatment Model LBD.

Neuro-Chemical Deficit/ Syndrome ACETYLCHOLINE DEFICIT PARKINSONISM NO SEROTONIN DEFICIT Yet Depressed Affect REM SLEEP BEHAVIOR DISORDER PSYCHOSIS/HALLUCINATION GLUTAMATE Autonomic Dysfunction Mechanism of interaction
DELAY BRAKEDOWN OF ACETYLCHOLINE IN SYNAPTIC CLEFT BY INHIBITING ACETYLAND BUTYL CHOLINESTERASE

Proposed Treatment
DONEPEZIL RIVASTIGMINE GALANTAMINE HCL

INCREASE DOPAMINE LEVEL INHIBIT REUPTAKE OF 5HT ?? SYNUCLEOPATHIES BENIGN NEGLECT CAREGIVER TRAINING
NMDA- RECEPTOR INHIBITION

Sinemet ?? ?? Benign neglect, PT SSRIS NOT NEEDED?? AChEI may help MELATONIN CLONAZEPAM SEROQUEL MEMANTINE HCL Salt & fluid intake, SSRI, Elevate bed head, laxatives

OH, PPH, Constipation, CSS

WISH LIST
Better

understanding of free radical brain interaction. Develop new drugs to prevent FR brain damage. New drugs to chelate cross-linked protein aggregate from brain. Cross the new BBB frontier. nitromemantines Improved awareness of LBD & other dementias. Increased willingness of PCP to diagnose early, and treat persons with dementia. Better tolerated, safer, more effective drugs to treat the various neurotransmitter deficits. Combination drugs to address multiple deficits.

shoulders of giants, so that we can see more than they, and things at a greater distance, not by virtue of any sharpness of sight on our part, or any physical distinction, but because we are carried high and raised up by John ofsize. Salisbury, their giant "

THANK YOU!

A woman in her early 50s was admitted to a hospital because of increasingly odd behavior. Her family reported that she had been showing memory problems and strong feelings of jealousy. She also had become disoriented at home and was hiding objects. During a doctor's examination, the woman was unable to remember her husband's name, the year, or how long she had been at the hospital. She could read but did not seem to understand what she read, and she stressed the words in an unusual way.

You have dementia, none of the drugs work so theres is little to do, so get your finances in order and plan for a painful next few years when you won't recognize your family, will Frustrate need to live in a d doctor

FREE RADICAL THEORY OF AGEING.

Organisms

age because cells accumulate free radical damage over time. A free radical is any atom or molecule that has a single unpaired electron in an outer shell. Cross linkage between proteins. Free radicals: superoxide ( O2- ), H2O2, OH. Antioxidants: Vit. A, Vi. C, Vit. E, SOD

Queries
What

governs the type of precipitate formed by free radical induced protein aggregation? How do we reduce CNS free radical proliferation? How do we remove free radicals and crosslinked protein aggregates from the brain?

LBD Prevalence

LBD accounts for 15-20% of dementia cases in hospital autopsy series.

UK community-based dementia case register studies confirms.

Dementia with Lewy bodies

Ian McKeith,MD, FMedSci

A recent community study of 85+ year olds found 5.0% to meet clinical diagnostic criteria for DLB, representing 22% of all demented Cases.

Rahkonen T, Eloniemi-Sulkava U, Rissanen S, Vatanen A, Viramo P, Sulkava R. Dementia with Lewy bodies according to the consensus criteria in a general population aged 75 years or older. J Neurol Neurosurg Psychiatry. 2003;74:720-724.

Prevalence of LBD
to 30% of all dementias at autopsy. Possibly more common than vascular dementia. Most common incorrect diagnosis in brain bank programs.

Neuropathology In DLB A. Substantial nigra hematoxylin-eosin stain, arrows -- Lewy bodies. C. Cerebral cortex hematoxylin-eosin stain, arrows -- Cortical Lewy body. E. Basal forebrain synuclein stain, arrow -- Lewy body, arrowhead -- Lewy neurite G. Cerebral cortex synuclein stain, arrow -- Cortical Lewy body, arrowhead -- Lewy neurite

Dementia with Lewy Bodies