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The Clinical Features and Rehabilitation

Challenges of Alzheimer’s and Non

Alzheimer's Degenerative Dementias -

NADD: An Educational Program for

Rehabilitation Professionals

Dina I. Drubach, DSc.PT

Learners ObjectivesSession I & II

• Describe the pathophysiology, and clinical features of

patients with Alzheimer’s Disease- AD.

• Describe the pathophysiology, and clinical features of

patients with Non- Alzheimer’s degenerative dementia –

NADD

• Identify the rehabilitation needs of patients with

Alzheimer’s Disease and Non- Alzheimer’s Disease

• Identify and gain familiarity with scales that measure

various important aspects of Alzheimer’s Dementia

Art of Listening to the story One view- What do you see?

Let’s Examine what we see in our

own reflection and start with

“Self”

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Program Outline

Two sessions

• Session I

– Background and Definition

– History

– Neuropathological Findings

– Imaging

Program Outline

• Session II

– Explain specific signs and symptoms

– Incidence and prevalence

– Review International Classification of

Functioning and Disability (ICF model)

– Rehabilitation pearls

Definition of Non Alzheimer’s

Degenerative Dementia

• A group of disorders which share some

common clinical and pathophysiological

features with Alzheimer’s Disease and yet

have unique features of their own.

International Classification of Functioning

Disability and Health (ICF), = One Approach

• Provides a systematic model to assist in approach for a treatment plan towards disablement

• This approach also gives the patient and caregiver a model that assists in decisions towards a proactive future

• Important for patient and families to come to a decision they are content with, early in the illness

• There is no “right” or “wrong” decision, just one that they can made together-early

http://whqlibdoc.who.int/publications/2005/9241592672.pdf

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BODY FUNCTION &

StructureACTIVITY PARTICIPATION

DISEASE

Page 1

The ICF Model(WHO 2002)

3 LEVELS OF HUMAN

FUNCTION

EXAMPLESEXAMPLES

SEADL SCALEBERG BALANCE SCALE

GAIT SPEED

EXAMPLESEXAMPLES

PDQ-39SF-36

UPDRS

EXAMPLESEXAMPLES

6 MINUTE WALK TESTCLOCK DRAWING TESTHAMSTRING LENGTH

WHO 2002

“What to measure?”

International Classification of Functioning Disability and

Health

BODY FUNCTION AND STRUCTURE: Examples: Visual

perceptual, ROM, Strength, Sensation, Postural

control

ACTIVITY: Examples: ADLs-i.e. Schwab & England

ADL, Gait, Balance “task”

PARTICIPATION: Examples: Global health measures,

Quality of life,“Impact”measures,

Neuropsychiatric Inventory

ENVIRONMENTAL FACTORS

History

• Alzheimer’s Disease (AD)-initially described 1906. Degenerative etiology with gradual progression

• Lewy body dementia (LBD) – initially characterized in 1900’s F. Lewy first described changes in neurons seen under a microscope in patients who had Parkinson’s disease

• Progressive supranuclear palsy (PSP) – initially characterized in the 1960s

• Corticobasal degeneration CBD – initially characterized in the late 1960’s

Aminoff, M. J., Boller, F., & Swaab, D. F. (2008)

Syndrome vs. Disease

• Syndrome: a constellation of clinical

features-signs and symptoms

• Disease: a group of pathological findings

• There is less than perfect correlation

between specific syndromes and specific

neuropathological entities

Drubach, DA 2009

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Clinical Diagnosis of DementiaCore features

• Previously normal cognition

• Memory impairment

• Cognitive problem of sufficient

significance to interfere with

usual social

life/relationships/work

• Normal

sensorium/alertness/conscious

ness

• Absence of major depression

impairing cognition

• Presumed to be due to

“organic” CNS lesion/disease

Plus at least one of the

following:• Impaired abstract thinking

• Impaired judgment

• Personality change

• Aphasia/apraxia/agnosia/spatia

l disorientation

Diagnostic and Statistical Manual for Mental Disorders. 3rd. Ed. Revised. APA 1987

Dementia Syndromes

• Alzheimer’s Disease (AD)

• Lewy body dementias (LBD)

• Frontotemporal lobar degeneration (FTLD)

• Progressive supranuclear palsy (PSP)

• Corticobasal ganglionic degeneration (CBGD or

CBD)

Cognitive Domains

• Orientation, attention, concentration

• Learning and memory

• Executive functions

• Visual perceptual/visuospatial

• Language

• Praxis

• Behavior

Cummings, J. L., & DF., B. (1992)

Functions affected in dementias

• Learning: ability to acquire new information

• Memory: ability to recall and utilize learned

information

• Language: ability to interpret and deliver a

message (verbal and non-verbal)

• Executive Functions: ability to initiate

behavior and respond appropriately to an

internal or external stimulus

Wells, C. (1977)

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Functions affected in dementias

continued

• Visual: constructional and spatial abilities:

ability to localize a point in space in relation

to another

• Perception: ability to acquire, internalize,

and interpret information by the conscious

mind

• Praxis: Translating an idea into action

Wells, C. (1977)

Lewy Body Disease

Progressive Supranuclear Palsy

Cortico Basal Deg.

Alzheimer’s Disease

FTD-Language

FTD-Behavior

Memory

Behavior

LanguagePraxis

Falls

Parkinsonism

Drubach, DA 2010

Corticobasal Degeneration-

CBD

Progressive Supranuclear

Palsy PSP

Lewy Body

DementiaDLB

Frontotemporal Dementia FTD

Frontotemporal Degeneration

language variant FTD lv

Dementia + + ++++ ++++

Motor control ++++ ++ +

EPS ++++ +++ ++++

Psychosis ++++

Language + ++ ++++Behavior ++ +++++

Drubach, DA and Drubach, DI 2010

Pathophysiology

• Teasing apart the clinical presentation of

AD & NADD is complex

• Symptoms may overlap across syndromes

• Key is determining the prominence, as

opposed to the presence, of a symptom at

a given stage in the disease

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Definition of Degenerative

• Caused by progressive death of brain cells

• Intracellular deposition of abnormal

proteins (proteinopathies)

• Selective anatomical vulnerability

Dickson, Dennis Int J Clin Exp Pathol 2010; 23www.ijcep.com/IJCEP908006 2010

Normal neuron Abnormal neuron

Ubiquitin+

TDP-43+

degradedproteins

wasteproteins

clumpedproteins

wasteproteins

PathophysiologyCorticobasal degeneration, Frontotemporal

degeneration and Progressive Supranuclear Palsy

PathophysiologyCorticobasal degeneration, Frontotemporal

degeneration and Progressive Supranuclear Palsy

Boeve, BF 2009

Progressive Supranuclear Palsy

Corticobasal Degeneration

Lewy Body Dementia

Frontotemporal Degeneration

Frontotemporal Degeneration language variant

Tau ++++ +++ +++ ++

α-synuclein

+++

Ubiquitin +Aβ amyloid +

Tdp43 +

Drubach & Drubach, 2010

Pathophysiology:

Tauopathy

• Proteins that stabilizes

microtubules

• Abundant in neurons in

CNS, and less common

else where

• When tau proteins are

defective and no longer

stabilize microtubules

properly, they can result

in cellular death

• Neurofibrillary tangle-NFT

Microscopy image of a neurofibrillary tangle, confirmed by hyperphosphorylated tau protein http://en.wikipedia.org/wiki/Neurofibrillary_tangle

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MRI and microscopic view of AD &

NAD pathology

http://www.mayoclinic.org/medicalprofs/non-alzheimers-dementias.html

Imaging

• Structural

– Magnetic Resonance Imaging (MRI)

– Computed Tomography (CT)

• Functional

– Positron Emission Tomography (PET)

– Single Photon Emission Tomography (SPECT)

– Functional MRI (fMRI)

Structural Imaging

• MRI

–Gold Standard

–Superb Resolution

–Expensive

–Contraindicated in pts with

metal devices (Pacemakers)

–Magnetic fields ?

• CT

–Lesser resolution than MRI

–No contraindication in patients

with metal devices

–Cheaper

MRI

Functional Imaging• PET

– The gold standard

– Can use different tracers

– Expensive

– Covered by medicare in certain circumstances

– Radioactivity

• SPECT

• Functional MRI

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Session II

Specific signs and symptoms

Alzheimer’s Disease (AD)

Dementia with Lewy Body (DLB)

Progressive Supranuclear Palsy (PSP)

Corticobasal Degeneration (CBD)

Learners Objectives

• Recognize signs, symptoms and progression of each of the disorders

• Distinguish between difficulties with activities and participation through the use of International Classification of Functioning, Disability and Health (ICF) model

• Appreciate alternative strategies for approaching fall prevention, and managing behaviors

Session II

Test your knowledge?

• What is the difference between syndrome and

disease?

DementiaDementia

10%

AD vascular dementiaAD vascular dementiaAlzheimer’s disease (AD)Alzheimer’s disease (AD)

53%

8%

VasculardementiaVasculardementia

8%Fronto-

temporal dementia

Fronto-temporal dementia

6%OtherOther

5%

DLBDLB10%

AD + dementia with Lewy bodies (DLB)AD + dementia with Lewy bodies (DLB)

Petersen 2013

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Alzheimer’s Disease

ALZHEIMER’S DISEASE

• Degenerative etiology

• Gradual progression

• Basic neurological exam normal

early

• Clinical-pathology correlation 80-

90%

Petersen 2013

CP926864- 31Petersen 2013

New Diagnostic Criteria for the

Alzheimer’s Disease Spectrum

Petersen 2013

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New Criteria for the AD Spectrum

• 3 clinical phases

– Dementia

– Mild cognitive impairment

– Pre-clinical

• Separate clinical and pathophysiology

• Use of biomarkers to link clinical syndrome

to pathophsiology

Petersen 2013

New Criteria for the AD Spectrum

• 3 clinical phases

– Dementia

– Mild cognitive impairment

– Pre-clinical

• Separate clinical and pathophysiology

• Use of biomarkers to link clinical syndrome

to pathophsiology

Petersen 2013

Alzheimer’s Disease Spectrum

MCI Due to AD

Preclinical AD

Dementia Due to AD

CP926864- 35Petersen 2013

Clinical Pathophysiology of AD

• Characterize the disease along the clinical

spectrum

• Characterize the disease along the

pathophysiological spectrum

Petersen 2013

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Biomarkers for AD

• Early biomarkers

– Amyloid deposition

– PET imaging

– CSF amyloid

• Later biomarkers

– Neurodegeneration

– Structural MRI

– FDG PET

– CSF tau

Petersen 2013

Neuroimaging in AD

Neuroimaging in AD

• Structural MRI

• Functional imaging

– FDG PET

• Molecular imaging

– Amyloid PET imaging

Structural Imaging in AD

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Structural MRI: Atrophy and AD Stage

Control, 70 F MCI, 72 F AD, 74, F

Petersen 2013

Hippocampus & ERC volume Measurement - tracing

Functional Imaging in AD

2/4/2008 FDG ScanParietal temporal hypometabolism (Global FDG AD score of 1.14 is abnormal) Petersen 2013

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Molecular Neuroimaging

02-155-940 02-310-847 06-209-892

32.5

21.5

10.5

0

Low

Low

Hig

hH

igh

CNCN aMCIaMCI ADAD

00-863-895 01-873-114

CNCN aMCIaMCI

PIB Examples – Full Spectrum

3001475-2

PiB Imaging

Percent Positive

Normals: 30%

MCI: 60%

AD: 90%

Status of Amyloid Imaging

• C11 Pittsburgh Compound B (GE)

• F18 Florbetapir (Avid/Lilly)

• F18 Flutemetamol (GE)

• F18 Florbetaben (Bayer)

• F18 AZD4694 (Navidea)

Petersen 2013

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AD TREATMENTS

CHOLINESTERASE DRUGS

DONEPEZIL (ARICEPT)

RIVASTIGMINE (EXELON)

GALANTAMINE (RAZADYNE)

NMDA ANTAGONIST

MEMANTINE (NAMENDA)

CLINICAL DEMENTIARATING (CDR): 0 0.5 1 2 3

National Alzheimer’s Coordinating Center , Washington Univ. 2011

NON ALZHEIMER’S DEGENERATIVE

DEMENTIAS

Non Alzheimer’s Degenerative

Dementias- NADD

• Dementia with Lewy Body (DLB)

• Progressive Supranuclear Palsy (PSP)

• Corticobasal Degeneration (CBD)

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Dementia with Lewy bodies (DLB)• Second most common cause of dementia

age >65

• Combines features of Idiopathic Parkinson’s Disease (IPD) & Alzheimer’s Disease (AD)

– Motor, cognitive, psychiatric, autonomic, sleep

– Pathological findings: except for localization, pathology cannot be differentiated from IPD

• Most complex degenerative disease to treat

Incidence and Prevalence

• Now considered the primary cause of

dementia in 12-25% of patients (2nd behind

Alzheimer’s disease)

• Probably over 1 million Americans affected

• Major public health issue

Incidence and Prevalence

Lewy Body Dementia Association

• approximately 20% of all dementia cases

are LBD

• more than 800,000 people in the United

States

• there are no other clear numbers of

prevalence due to complexity of diagnosis

Dementia with Lewy Bodies: Consortium Diagnostic Criteria

• Dementia +

Core Criteria - need 2 for Probable DLB

• Fluctuating cognition, attention, alertness

• Recurrent visual hallucinations

• Spontaneous extrapyramidal signs

(Cog wheeling, rigidity, bradykinesia)

( McKeith, 2005)

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Dementia with Lewy Bodies: Consortium Diagnostic Criteria

Suggestive Features

• Severe neuroleptic sensitivity

• REM Sleep Behavior Disorder

• Low dopamine transporter uptake with PET

( McKeith, 2005)

Dementia with Lewy Bodies:

Consortium Diagnostic Criteria

Supportive Criteria

• Repeated falls

• Transient unexplained loss of consciousness

• Severe autonomic dysfunction (orthostatic

hypotension)

• Auditory hallucinations

• Systematized delusions

• Depression

( McKeith, 2005)

Disordered arousal in DLB

• Excessive daytime sleepiness

• Fluctuations in alertness

– Wide variations in cognition and function

because of different levels of arousal

• Prominent visual Hallucinations

– ? The intrusion of a sleep phenomenon

(dreaming) during wakefulness

• REM sleep behavior disorder

Boeve, BF et al. (2007)

REM Sleep Behavior Disorder

• A parasomnia featuring:

– Violent dreaming, often described as being chased or attacked by people or animals

– Leads to violent physical activities during sleep

• Thrashing about in sleep

• Falling out of bed

• Striking bed partner

• Physical injuries

• A powerful predictor of subsequent DLB (or multiple system atrophy) up to 10 years later

Boeve, B. F. et. al 2004

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Pathology of DLB

• Usually a mixture of AD pathology and

synuclein pathology

• α-Synuclein = the key protein in

intranuclear inclusions � Lewy Bodies

• Lewy Bodies located in:

– Brainstem locus ceruleus

– Substantia nigra

– Amygdala

– Cingulate cortex, neocortex

Boeve, B. F. et al 2007

Synucleinopathies

Lewy Body Disease (LBD)

Dickson, D. 2010; 3(1): 1–23

MRI Findings

• Relative preservation of hippocampal and

medial temporal volume

• No specific findings

• Useful to consider other etiologies

Josephs, K. A. et. al 2010

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Normal

Dementia with Lewy Bodies

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International Classification of Functioning

Disability and Health (ICF), = One Approach

• Provides a systematic model to assist in approach for a treatment plan towards disablement

• This approach also gives the patient and caregiver a model that assists in decisions towards a proactive future

• Important for patient and families to come to a decision they are content with, early in the illness

• There is no “right” or “wrong” decision, just one that they can make together-early

http://whqlibdoc.who.int/publications/2005/9241592672.pdf

“What to measure?”

Using the ICF- DLB

• BODY FUNCTION AND STRUCTURE: Examples:

Visual perceptual, ROM, Strength, Sensation,

Postural control

• ACTIVITY: Examples: ADLs-i.e... SEADL, Gait,

Balance “task”

• PARTICIPATION: Examples: Global health

measures, Quality of life,“Impact”measures, NPI

75

WHO 2002

Measuring Quality of Health-

Therapists have a role in decreasing severity and

frequency to ER and cost of care

• 6. Querying about falls– All visits for patients with a diagnosis of Parkinson disease where

patients (or caregivers, as appropriate) were queried about falls

• 7. Parkinson’s disease rehabilitative therapy options– All patients with a diagnosis of Parkinson’s disease (or caregivers,

as appropriate) who had rehabilitative therapy options (e.g., physical, occupational, or speech therapy) discussed at least annually

• 8. Parkinson’s disease–related safety issues counseling– All patients with a diagnosis of Parkinson’s disease (or caregivers,

as appropriate) who were counseled about context-specific safety issues appropriate to the patient’s stage of disease (e.g., injury prevention, medication management, or driving) at least annually

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Clinical Global Impression of

Severity and Change

CGI-S / CGI-CCGI-C Interviews

Schwab and England Activities of

Daily Living (SEADL) Rehabilitation Pearls

• #1 unpredictable – multiple fluctuations – daily, minute to

minute

• Fall prevention and management- reduce risk and

minimize severity of falls- “make the floor your friend”

• Educate family on visual perceptual difficulties

• Engage in social functions to promote increased overall

activity to decrease negative consequence of isolation

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“That was me then, this is me

now.”

Jackie Bakke, PSP research participant

Progressive Supranuclear Palsy (PSP)

Core Features

• Progressive problems with balance and

walking

• Slow movement, falling, body stiffness

• Restricted eye movements

PSP

FTD

CBD

Apraxia

Dystonia

Language

Behavior

Executive

Eye Movement,

falls

Parkinsonism

PSP-CBD-FTD Spectrum Syndrome Incidence and Prevalence

• Approximately 20,000 Americans - or one in

every 100,000 people over the age of 60

• Patients are usually middle-aged or elderly

• Men are affected more often than women

http://www.ninds.nih.gov/disorders/psp/detail_psp.htm

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PSP: Clinical Features

• Motor Dysfunction (Symmetric)

– Akinesia

– Frontalis hyperactivity

– Postural instability with early falling

– Vertical supranuclear gaze paresis - amplitude

& velocity

• bilateral anti-saccadic dysfunction

– Axial > appendicular rigidity

– Retrocollis

– Symptomatic myoclonus- basal gangliaLitvan et al. 1996

PSP: Clinical features

• Cognitive Impairment

– Executive dysfunction

– Bradyphrenia

– Non-fluent aphasia (apraxia of speech)

– Absence of episodic memory loss or severe

dementia

• Not well studied

PSP: Clinical Features

• Neuropsychiatric features

– Apathy

– Disinhibited behavior

– Depression

– Anxiety

– Psychosis

Progressive Supranuclear PalsyClinical Features

•Symmetric rigidity and bradykinesia

• axial > appendicular

• levodopa unresponsive

•Postural/gait instability

• frequent falls

• Extraocular movement dysfunction

• saccadic pursuits

• delayed, slowed saccades

• supranuclear gaze palsy,

particularly downgaze

• apathy, bradyphrenia

•Symmetric rigidity and bradykinesia

• axial > appendicular

• levodopa unresponsive

•Postural/gait instability

• frequent falls

• Extraocular movement dysfunction

• saccadic pursuits

• delayed, slowed saccades

• supranuclear gaze palsy,

particularly downgaze

• apathy, bradyphrenia

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PSP MRI

61 y.o. PSP

• Midbrain

atrophy-

“hummingbird

sign” clinical

features of extra

ocular

abnormality in

eye movements

• Including mid

brain atrophy

PSP-FTD-CBD Spectrum 57 years old female

PSP Gait

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International Classification of Functioning,

Disability and Health (ICF)= One Approach

• Provides a systematic model to assist in approach for a treatment plan towards disablement

• This approach also enables the patient and caregiver a model that assists in decisions towards a proactive future

• Important for patient and families to come to a decision they are content with, early in the illness

• There is no “right” or “wrong” decision, just one that they can make together-early

“What to measure?”

Using the ICF-PSP

• BODY FUNCTION AND STRUCTURE: Examples:

Visual perceptual, ROM, Strength, Sensation,

Postural instability

• ACTIVITY: Examples: ADLs, Gait, Balance “task”

• PARTICIPATION: Examples: Global health

measures, Quality of life,“Impact”measures,

NPI

LBD, PSP, CBD, and AD

Management

LBD, PSP, CBD, and AD

Management• Approach – ask patients and caregivers to list and then rank which symptoms/problems are most bothersome, which allows the clinicians to tailor the management plan

•Problem list:

• Cognitive

• Neuropsychiatric

• Motor

• Speech/swallowing

• Sleep

• Approach – ask patients and caregivers to list and then rank which symptoms/problems are most bothersome, which allows the clinicians to tailor the management plan

•Problem list:

• Cognitive

• Neuropsychiatric

• Motor

• Speech/swallowing

• Sleep

Boeve 2002

PSP, CBD, FTD, and LBD

Pharmacological Management

PSP, CBD, FTD, and LBD

Pharmacological Management• There are no FTD-approved medications specifically developed to impact LBD, CBD, FTD,

•Few well-designed studies show that any medication improves symptoms in any of these disorders

•Considerable debate among clinicians if any medications are worth using in patients with any of these disorders

•Almost all medications to be discussed are expensive and are associated with mild to severe side-effects

• There are no FTD-approved medications specifically developed to impact LBD, CBD, FTD,

•Few well-designed studies show that any medication improves symptoms in any of these disorders

•Considerable debate among clinicians if any medications are worth using in patients with any of these disorders

•Almost all medications to be discussed are expensive and are associated with mild to severe side-effects

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Rehabilitation Pearls-What a Therapist needs to

know:

• #1 Fall prevention and management- minimize risk and severity- “Fall Rehearsal”

• Decrease visual gaze-up and down- scanning for barriers, lighting can make a big difference

• wear sunglasses due to sensitivity to light

• Listen to both the patient and the caregiver

Rehabilitation Pearls-What a Therapist needs to

know:

• Assistive devise-maintain mobility to

decrease risk of pulmonary embolism,

urosepsis

• Review of postural drainage

• Reduce risk of respiratory complications-

aspiration, pneumonia

Corticobasal Syndrome (CBS)

CBS - Clinical diagnosis

• Corticobasal degeneration (CBD) is a pathological diagnosis

• Predicting CBD from CBS is average/poor

• Pathological etiology of CBS include:

– CBD, PSP

– Pick’s disease, Alzheimer’s disease

– Neurofilament inclusion body disease (NIBD)

– Frontotemporal lobar degeneration with ubiquitin only immunoreactive changes

– FTDP-17

– CJD

Boeve,BF et al. 2003

Corticobasal DegenerationEpidemiology

• Bower et al (1997) - no CBD cases in study of

parkinsonism in Olmsted County

• Autopsy records of the Mayo Clinic from 1970-2001

– 2 residents of Olmsted County, Minnesota, and

had CBD pathology

– 1 with the CBS, 1 with “Alzheimer’s disease”

• Bower et al (1997) - no CBD cases in study of

parkinsonism in Olmsted County

• Autopsy records of the Mayo Clinic from 1970-2001

– 2 residents of Olmsted County, Minnesota, and

had CBD pathology

– 1 with the CBS, 1 with “Alzheimer’s disease”

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Corticobasal DegenerationEpidemiology

• In the Mayo Alzheimer’s Disease Research Center

– We are typically following 10-15 patients with the CBS who reside in Minnesota

– Minimum prevalence estimate 10-15/5,000,000 =

– 2-3 per million

– Prevalence of CJD ~ 1 per million

• The unfortunate reality of current funding in CBS/CBD is that since Alzheimer’s disease and Parkinson’s disease are so much more common, and CJD is much more “famous” despite its rarity

• In the Mayo Alzheimer’s Disease Research Center

– We are typically following 10-15 patients with the CBS who reside in Minnesota

– Minimum prevalence estimate 10-15/5,000,000 =

– 2-3 per million

– Prevalence of CJD ~ 1 per million

• The unfortunate reality of current funding in CBS/CBD is that since Alzheimer’s disease and Parkinson’s disease are so much more common, and CJD is much more “famous” despite its rarity

Boeve, BF et al. 2003

Topographic distribution of degeneration:

• Asymmetric parietofrontal cortex

A B C

A

B

C

Corticobasal Syndrome

Manifestations

• Disorders of Motor Control

• Extrapyramidal Signs

• Language Disorders

• Cortical Sensory Abnormalities

• Neuropsychiatric Manifestations

Boeve, B. F. (2005)

Disorders of Motor Control

• Apraxia

• Alien limb phenomenon

• Levitation

• Mirror Movements

• Dysphagia

Boeve et al, 2003

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Extrapyramidal Signs

• Tremor

• Rigidity

• Dystonia

• Supranuclear Gaze Palsy

• Myoclonus

Boeve et al, 2003

Language Disorders

• Dysarthria

• Aphasia

• Apraxia of Speech

• Yes-No Reversals

Boeve et al, 2003

Cortical Sensory Abnormalities

• Dysgraphestesia

• Astereognosis

• Tactile Defensiveness (Dysesthesias specifically brought on by human touch)

Neuropsychiatric and Cognitive

Neuropsychiatric:

• Depression

• Emotional Lability

• Personality Changes

• Frontal Release Signs

Cognitive:

• Memory

• Visuospatial

• Attentional

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Asymmetric cortical atrophy, especially frontoparietal, with the more prominent atrophy existing opposite the side most severely affected clinically

Asymmetric cortical atrophy, especially frontoparietal, with the more prominent atrophy existing opposite the side most severely affected clinically

Corticobasal Syndrome Radiologic Findings

Corticobasal Syndrome Radiologic Findings

Corticobasal SyndromeRadiologic Findings - PET

Corticobasal SyndromeRadiologic Findings - PET

Oct 2005 Dec 2002

Underlying pathologies:• Corticobasal degeneration

• Alzheimer’s disease

• Pick’s disease

• Progressive supranuclear palsy

• FTLD-U

• Neurofilament inclusion body disease

• Nonspecific degenerative changes

• Creutzfeldt-Jakob diseaseReference: Boeve BF, Maraganore DM, Parisi JE, Ahlskog JE, Graff-Radford N, Caselli RJ, Dickson DW, Kokmen E, Petersen RC. Pathologic heterogeneity in clinically diagnosed corticobasal degeneration. Neurology 1999;53:795-800

Corticobasal Syndrome

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Corticobasal DegenerationNeuropathologic Findings

Corticobasal DegenerationNeuropathologic Findings

Ballooned neuronCoiled body Neuronal threads

Astrocytic plaque

Tau stain Tau stain Neurofilament stain

Courtesy Dr. Dennis Dickson

Corticobasal DegenerationNeuropathologic Findings

Corticobasal DegenerationNeuropathologic Findings

Courtesy Joseph Parisi

Oligodendroglial coiled body

tau immunostain

“What to measure?”

Using the ICF-PSP

• BODY FUNCTION AND STRUCTURE: Examples:

Visual perceptual, ROM, Apraxia, Sensation,

Postural instability

• ACTIVITY: Examples: ADLs, Gait, Balance “task”

• PARTICIPATION: Examples: Global health

measures, Quality of life,“Impact”measures,

NPI

Apraxia

• Definition: the loss of the ability to make familiar, purposeful movements, manifested as difficulty using familiar objects or doing familiar things. Examples include using utensils, combing one’s hair, and dressing

• Classification

• Measuring tools

• Neurophysiology

• Management

Leiguarda et al, 2003

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Rehabilitation Pearls

• Meaningful exercise programs- targeted to

key areas

• Motor apraxia- gait training

• Assistive devise and possible w/c

assessment

• Fall prevention and management

CBD LBD PSP FTD FTDbv

Frontal + + +++ ++++

Parietal ++ +

Temporal ++ ++

Occipital +++ +

Brainstem +++

What does the future hold?

• Goal is to have therapies that delay the onset and

even reverse the symptoms of neurodegenerative

diseases

• Therapies will be personalized on the basis of

genetic and biochemical studies

• Biomarkers such as imaging and blood proteomics

and/or metabolomics will be used as screening

tools and predictors of subsequent disease

Young AB. J Neurosci. 2009 Oct 14; 29(41):12722-8.

AcknowledgmentsMayo Clinic Behavioral NeurologyDaniel Drubach, MDBrad Boeve, MDKeith Josephs, MDDavid Knopman, MDRonald Petersen, PhD, MDMayo Clinic Laboratory Medicine and PathologyJoseph Parisi, MDDennis Dickson, MD

Mayo Clinic Physical Medicine and RehabilitationHeidi Dunfee, PT, DScPTJulie Tilley, PT, DPT, MSEd,Brad King, PT, DScPT

Mayo School of Health SciencesDesiree J. Lanzino, PT, PhD

Department of Physical Therapy and Rehabilitation ScienceUniversity of Maryland, School of Medicine

Leslie B. Glickman, PT, PhDMonica Grant, PT, DScPTGad Alon P.T, Ph.D. Michael Harris-Love, PT, DscPTFrances E. Huber, EdD, PT, OCS Jeff Hawk, MPT, MDE Terry Heron

4/8/2013

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Questions?