Transcript CLINICAL PROTOCOL FOR OM MANAGEMENT

Geriatric Medicine
Jenny Basran MD, FRCPC
Associate Professor & Head, Division of Geriatric Medicine
University of Saskatchewan
Meet Mrs. B
• 81 year old woman presents to ER with chest pain, not
responsive to NTG, ST changes with trop leak. Past history
angina.
• Goes to cath lab  PTCA, but no stent required
• Paged to see Mrs. B on ward because she is confused and does
not want to take her medications.
What are you thinking about as you go up to see her?
WHAT IS COGNITIVE
IMPAIRMENT?
• Change in how you think
• Change from baseline
• Often the body’s only way of telling you there is
something wrong
• Rather than classical signs and symptoms
What should be your first
question?
FIRST QUESTION –
ACUTE VS CHRONIC?
Cognitive
Impairment
Acute
Subacute /
chronic
How can you tell?
• Patient usually can’t tell you
• Ask the family and other caregivers – nursing home,
GP, home care, etc
• If you don’t know, must assume acute
• Treatable
• Can be life threatening
Past history & Meds
• Type 2 diabetes X 10 years
•
•
•
HgbA1c 6%, chemstrips checked OD (4-8)
Metformin 500 mg bid (Cr Cl 65 ml/min)
No proteinuria, neuropathy; yearly optho
• Hypertension X 20 years
•
•
BP 130/70 lying & 120/60 standing; no SXS
Diovan (Valsartan) / HCTZ 160/12.5 mg OD
• Hyperlipidemia X 8 years – lipitor 20 mg OD
• Osteoporosis – vertebral fracture 1 year ago
•
•
fosavance 70 mg OD, Calcium 500 mg BID
eats dairy regularly
• Macular degeneration – 5 years, vitalux
Past Medical History
& Meds
• Urinary incontinence X 1 year
• Urge with nocturia once/ night, on detrol
• Previous CAD – LV OK; ASA 81 mg OD  plavix
added
• Insomnia – clonazepam prn (almost daily)
• OA knees / hands – occas tylenol prn
• OTCs – gingko OD, Vitamin E 400 IU
• Previously on HRT for menopause
Social History &
Fxnal History
• Lives alone in bungalow. Widowed 5 years ago
• 2 children – both live in Alberta, but regular contact by
phone
• Lifetime nonsmoker and glass of wine at night with
supper.
• Functionally
• Occasional falls – vague re: situation
• Independent with ADLs & IADLs
• Uses hearing ai
• Family History – mom – 90’s – memory probs
What do you need
now?
• Labs – CBC, e’lytes, BUN, CR
• Extended labs – Ca, Mg, PO4, albumin
• Drug levels if appropriate – ie: digoxin, lithium, etc
• Drug tox screen if worried about overdose or errors
• Liver panel
• TSH, B12, glucose
• ECG – need baseline anyway, but could be cardia
• CXR – especially if clinically warrants
• U/A – will be positive often, so can’t stop here
• Others – as warrants
Mrs. B
• Her vitals are stable but she is clearly disoriented and
starting to get agitated. She is easily distracted.
• Her daughter is concerned because her mother is not
usually like this.
• The nurses are concerned because she seems to be getting
worse, although notes periods when she seems OK
• You review her meds – only prn BZDP & tylenol not
ordered on admission
• Lab work normal, U/A suggests UTI (pt has foley)
• ? Diagnosis
Cognitive
Impairment
Acute
Delirium
Subacute /
chronic
Key Features of Delirium
1.
Acute onset and fluctuating course
•
•
Usually develops over hours to days or may be abrupt
Unpredictable fluctuations (within interview or over day)
with periods of lucidity
•
2.
Inattention
•
3.
Easily distractable
Confusion Assessment
Method (CAM)
= 1 + 2 + (3 or 4)
Disorganized thinking
•
4.
Often worse at night
Illogical, bizarre; delusion of persecution common
Altered level of consciousness
Mrs. B
• What predisposing and precipitating factors for
delirium are present?
• Predisposing – older age, polypharmacy, sensory
impairment
• Precipitating – cardiac disease, foley, UTI, BZDP
suddenly stopped, OA pain (not getting tylenol)
What is your Plan?
• Plan
• rule out other causes of delirium, especially cardiac
• restart low dose BZDP – was taking daily at home
• scheduled tylenol – while awake
• Prevention – non pharmacological interventions
• hearing aid, glasses
• mobilizing, eating, limited daytime naps
• family to sit with her at bedtime – back rub, music
Mrs. B
• What if the Mrs. B had been really agitated and pulling
out her IV along with refusing to take her meds?
• Is the approach any different?
HalDOL Bridge
(ONLY
IF
PATIENT
HARMING THEMSELVES OR OTHERS)
 Severe delirium: 0.5-1.0 mg IM or po (IV short acting) –
NOTE DOSE
 Repeat dose Q30 – 60 minutes until calm achieved
 Max dose 3-5 mg / 24 hours
 Maintenance = 50% loading dose in divided doses (ie:
TID) over the next 24 hour. Taper asap over next few
days
 Ie: 3 mg given to calm  give 1.5 mg next day in divided
doses (0.5 mg TID)  then 0.5 BID  then 0.5 OD  then
discontinue
 Bridge to keep them safe while the treatment takes effect
 If gets worse  you missed something, keep looking
Haldol
• Never PRN
• Never give to patient with parkinsonism
• Monitor
• Daily ECG – prolonged QTc
• Tardive dyskinesis – increased stiffness first sign
Why is it important
to treat delirium?
• Mortality & morbidity the same as:
• Having a MI in hospital
• Being septic in hospital
• Often missed because can be:
• Hyperactive – hallucinations, agitation, paranoid
• Hypoactive – sleeps all the time, wont eat, wont move
• Combination of both - fluctations
Mrs. B –
8 weeks after discharge
• 81 year old woman presents to ER with chest pain, not
responsive to NTG, ST changes with trop leak. Past history
angina.
• Goes to cath lab  PTCA, but no stent required
• Course in hospital – delirium  UTI treated & BZDP
restarted, scheduled tylenol. Cardiac status stable  back to
cognitive baseline on discharge. Discharged on same meds plus
plavix and higher dose of lipitor (80 mg OD)
• Sees you 8 weeks after discharge with her daughter. Daughter
is visiting but going back to Alberta in 2 weeks and is
concerned about her mother’s memory & her ability to
manage.
Cognitive
Impairment
Acute
Delirium
Subacute /
chronic
Reversible
Irreversible
History
– Most important
• Must discuss with family / caregiver. Patient often has limited insight.
• Time course & functional impairments
• Ask for specific examples •
What are they forgetting?
•
•
•
•
•
Names of close friends or family?
Appointments, medications (irregular refill periods)
Repeatedly asking same question
Visual hallucinations? Unexplained falls?
Personality changes? Unusual behavior?
• Safety issues
•
•
•
•
Do they ever leave the stove on or water running?
Do they eat healthy and regularly?
Have they had any problems driving or getting lost in familiar areas
Have they become aggressive?
• Legal issues – do they have POA, will and living will in place?
History: 10 WARNING
SIGNS
1.
•
2.
•
3.
4.
•
•
5.
Memory loss that affects day to
day function
6.
Difficulty performing familiar
tasks
7.
Problems with language
Forgetting simple words,
substituting words
Disorientation of time and place
Lost on own street, unable to get
home
Poor or decreased judgment
•
•
Short term more than long term
Preparing meals, forget you ate
it
Dress inappropiate for weather
Problems with abstract thinking
Balance checkbook, not
understanding what a birthday is
Misplacing things
•
8.
Put in inappropriate place
Change in mood or behavior
•
9.
Mood swings for no reason
Changes in personality
•
•
Confused, suspicious, withdrawn
Apathy, acting inappropriately
10. Loss of initiative
•
Needs prompting to become
involved
Alzheimer Society of Canada
Physical Exam
• May be completely normal
• Focal neurological signs
•
•
•
•
Up-going plantar  stroke
Peripheral neuropathy  rule out B12 deficiency
Slow reflexes  hypothyroidism
Primitive reflexes  frontal or advanced cerebral atrophy
• Cognitive Testing
• Mini – Cog - part of normal neuro exam
• 3 word registration, clock & 3 word recall
• MMSE and Clock Drawing Test – if abnormal Mini-Cog
• MOCA can be used for mild cognitive impairment
• The score does NOT make diagnosis
• Adjust for age, education
• How much of a struggle is it for them to complete?
InvestigationsCanadian Guidelines
• Labs – RULE OUT reversible causes
• CBC, electrolytes, TSH, B12, serum Calcium, serum
glucose
• If warranted: liver function (ETOHic), CXR – lung Ca
• Indications for Neuroimaging
• Structural Imaging – CT / MRI – reasonable per
Clarfield Criteria
• Functional Imaging – PET / SPECT in the differential
diagnosis of dementia, particularly those with
questionable early stage dementia or those with
frontotemporal dementia
• fMRI and MRS scanning are not recommended, but
promising
Clarfield criteria
for CT:
• age < 70
• new onset dementia , < 1 year
• atypical presentation
• rapid unexplained deterioration
• unexplained focal signs, symptoms
• head injury
• incontinence, gait ataxia
• need for reassurance of patient, family
1.Clarfield, CMAJ, (1991), vol.144(7), 851-853
2.Patterson et al., (1999) CMAJ, vol.160,(Supp.12),S1-15
Atrophy in Alzheimer’s
disease
Atrophy of the brain in AD: Medial temporal lobes
are affected first and most severely
Figure from: 8. http://pathology.ouhsc.edu/DeptLabs/diagnostic_center_for_alzheimer.htm
Mrs. B - Clinic Visit
• Patient not really concerned about her memory
and thinks she is OK
• Daughter
• Progressive memory last year – repeats herself, trouble names
and birthdays.
• Low mood, mother up at night – easily confused
• Eats mostly frozen dinners, but rotting food in fridge.
• Eats lots of blueberries
• Not sure taking her meds correctly and found a few overdue
bills around the house.
• Concerned about her driving. Was driving to Market Mall but
not recently.
Clinic Visit
• Vitals stable, BP 130/70, HR 80
• Physical exam - unremarkable
• MMSE 22/30 (-2 orientation, -3 recall, -1 WORLD, -2
language)
• Clock – hands placed wrong, slight spacing errors
• FAQ = 26
• Geriatric Depression Scale – 3/15
What is the differential
diagnosis?
• Delirium – in hospital, but
daughter agrees back to
baseline
• Depression – possible –
widowed, post-MI, but GDS
3/15 and patient denies
Cognitive
Impairment
Delirium
• Dementia – progressive loss
memory and function
• reversible loss of cognition
• Mild cognitive impairment
or true dementia
Subacute /
chronic
Acute
Reversible
Depression,
Structural,
Metabolic, etc
Irreversible
Mild Cognitive
Impairment
Dementia
DEPRESSION vs DEMENTIA
The symptoms of depression and dementia often overlap;
patients with primary depression:
• Demonstrate  motivation during cognitive testing
•
“I don’t know” – ie: results in loss of points on MMSE
• Tell us that memory problems are a lot worse than we find
on testing.
• Language and motor skills remain normal
If you suspect depression  need to treat first before
diagnosis of dementia can be made
What is the differential
diagnosis?
• Delirium – in hospital, but
daughter agrees back to
baseline
• Depression – possible –
widowed, post-MI, but GDS
3/15 and patient denies
Cognitive
Impairment
Delirium
• Dementia – progressive loss
memory and function
• reversible loss of cognition
• Mild cognitive impairment
or true dementia
Subacute /
chronic
Acute
Reversible
Depression,
Structural,
Metabolic, etc
Irreversible
Mild Cognitive
Impairment
Dementia
IS IT reversible?
• Medication side
effects
• Depression
• Vitamin B12
deficiency
• Chronic alcoholism
• High calcium levels
• Neurological disorders –
normal pressure
hydrocephalus
• Certain tumors or
infections of the brain
• Metabolic imbalances,
including thyroid, kidney
or liver disorders
What medications could be
affecting her cognition?
• Detrol – anticholinergic
• Clonazepam – BZDP  sedating
• Added risk of falls
• ? Wine – need to confirm the amount
• ? Metformin – ? hypoglycemia, falls
• ? Diovan (Valsartan) – low blood pressure, orthostatic
hypotension
Is IT Dementia?
• A decline from a previous level of cognitive function
• memory
• language (naming)
• Executive abilities – planning, abstract thinking, organization,
conceptual shift
• construction/visuospatial function
• Personality change
• Insidious and progressive
• KEY QUESTION:
• Impairment is sufficient to interfere with function and Activities of
Daily Living.
Mild Cognitive
Impairment
• Memory complaints
• Memory impaired for age ( generally 1.5 SD)
• General cognitive function: normal for age
• Normal activities of daily living
• Not meeting dementia criteria = Function Not Affected
Petersen RC et al Arch Neurol 56(3)303-308 1999
Common Risk Factors for
Developing MCI
• Elevated systolic BP
• Hypertension
• Elevated cholesterol in mid-life
• Low level of education
• African-American descent
• Cerebral infarcts evident on MRI
• Depression
• Mechanisms may be vascular atherosclerotic mechanisms, or
directly through hastening the pathophysiology of AD.
1 Launer
LJ et al. JAMA, 1995; 2 Carmelli D et al. Neurology, 1998;
M et al. Neurology, 2001; 4 Lopez OL et al. Arch Neurol, 2003.
3 Kivipelto
MILD COGNITIVE IMPAIRMENT
•
Areas of brain begin to shrink
•
Cognitive problem (usually
memory) but does not interfere
with activities
•
•
•
Memory storage & retrieval
problem
Executive function
apathy
•
Treatment – monitor patient
and vascular risk factors
•
10-25% progress to dementia
per year (vs 1-2% non-MCI)
Course of Aging, MCI
and AD
Cognitive Decline
Brain Aging
Brain
Aging
“Brain
”AD
MCI
Mild
Moderate
Clinical
AD
Moderately
Severe
Severe
Time (Years)
(Ferris, 4/03)
DEMENTIA IN CANADA
• 8% of all individuals > 65 years old
Age Range
All
Community
Long Term
Care
65-75
2.4 %
1%
42 %
75-85
11 %
7%
53 %
85+
34 %
17 %
66 %
• Incidence / Prevalence  with age
• 1 in 10 over the age of 75
• 1 in 3 over the age of 85
• Annual cost = 3.9 billion dollars
• AD = 747/1125 (66%) of dementia cases (CSHA)
• 95% sporadic
Canadian Study of Health & Aging. CMAJ 1994:150:899-913
Projected Prevalence
of AD
300,000 Alzheimer’s Cases Today > 750,000 Projected Within a
850
Generation
750
750
650
000’s
550
500
450
350
300
250
150
0
2000
2011
2031
Canadian Study of Health & Aging Working Group. CMAJ 1994; 150:899-913
The 5/50 plan:
Delaying the onset of AD by 5 years
would be associated with a reduction
in AD prevalence of 50%
A modest delay, such as 1 year, would
reduce AD/dementia prevalence by 5%.
Brookmeyer, Gray & Kawas, Am J Publ Health 88 (9), 1337-1342 1998 .
Benefits of Early
Intervention
• Drug therapy – slows down progression of dementia
• Not appropriate to expect an improvement
• Improve family / caregiver stress
• Plan for change before need becomes urgent
• Education – anticipate change and have some ways to cope
• Allows time to prepare for taking over roles of dementia patient
• Enhance patient’s sense of control
• If early, can participate in management decisions
• Future planning – POA, will, living will, end of life care
• Promote safety – medications, wandering, driving, falls
DIFFERENT TYPES OF DEMENTIA
Other dementias
Frontal lobe dementia
Creutzfeldt-Jakob disease
Corticobasal degeneration
Progressive supranuclear palsy
Many others
Vascular dementias
Multi-infarct dementia
Binswanger’s disease
Dementia with Lewy bodies
Parkinson’s disease
Diffuse Lewy body disease
Lewy body variant of AD
Vascular dementias
and AD
AD and dementia
with Lewy bodies
AD
5% 10%
65%
CSHA - CMAJ 1994; Small et al, 1997; APA, 1997; Morris, 1994.
5%
7% 8%
• Alzheimer’s Disease (AD)
4 major types
of dementia
• Includes Mixed-AD
• Vascular Dementia (VaD)
• Includes large & small vessel
disease
• Frontotemporal Dementia
(FTD)
• Includes Pick’s disease,
progressive nonfluent aphasia,
& semantic dementia
• Dementia with Lewy Body
(DLB)
• Includes Parkinson’s disease
dementia
~105 years
ago…
• 51 yo German woman admitted Nov 25, 1901 to
psychiatry under Dr. Alois Alzheimer
• Hx – cog impairment (memory, language,
orientation) & behavioral probs (paranoia,
agitation)
Auguste D
Lancet,
1997;349:1546-49
• Progressive decline  died Apr 6, 1906 
neuropathology showed plaques & tangles
• Dr. Alzheimer reported case 1907
DSM Criteria for AD
• 1. Insidious Onset with progressive decline
• 2. Memory Impairment and at least one of the
following:
•
•
•
•
Aphasia (language)
Apraxia (unable to carry out directed movement)
Agnosia (unable to recognize specific items in environment)
Disturbance in executive functioning
• 3. Interferes with daily function
• 4. Does not occur exclusively during delirium and not
due to other neurological, psychiatric, toxic, metabolic
or systematic diseases
Genetic Causes & Risk
Factors
• Genetics:
• 90-95% Alzheimer cases due to genetic risk factors or
idiopathic origins
• APOE 4 allele (esp if two copies)
• 5-10% autosomal dominant AD
• Mutations of APP, PS1, PS2
• <1% trisomy 21
• Risk Factors
• Age, education, head trauma, female, education, fhx
• Vascular RF, depression, psychosocial
Neuropathologic Changes
Characteristic of AD
Normal
AD
AP
AP=amyloid plaques; NFT=neurofibrillary tangles
Courtesy of George Grossberg M.D.; St. Louis University.
NFT
Patient HM
Henry Gustov Molaison
(1926-2008)
ALZHEIMER’S DISEASE
• Onset: gradual
• Cognitive symptoms: primarily memory, aphasia
• Motor symptoms: rare early, apraxia later
• Primitive reflexes
• Progression: gradual, over 8–10 yr on average
• Behavior: apathy common
• Lab tests: normal
• Most common dementia (~60%)
Alzheimer’s Disease Progresses
Through Distinct Stages
Dementia/Alzheimer’s
Mild
Stage
Moderate
Severe
Symptoms
• Memory loss
• Language
problems
• Mood swings
• Personality
changes
• Diminished
judgment
• Behavioural, personality
changes
• Gait, incontinence,
motor disturbances
• Unable to learn/recall new
information
• Bedridden
• Long-term memory affected
• Wandering, agitation,
aggression, confusion
• Require assistance w/ADL
• Unable to perform ADL
• Placement in LTC needed
William Utermohlen
Self portrait 1967
Diagnosed with AD
1995
1996
1997
www.williamutermohlen.org
1997
1998
1999
2000
LTC 2004, Died 2007
How to proceed with Mrs. B –
non pharmacological
• Meals on wheels
• Bubble pack medications
• Recommend lifeline
• Home care – monitor med mgmt, check weights,
chemstrips, and vitals
• Daughter – change bill payment to automatic, discuss
POA, will
• Encourage to resume Market Mall social & physical
activity, continue puzzles
• Assess driving –Trails B, letter to SGI for driving test
• Caution with wine at night – limit one per day?
Pharmacological
Interventions?
• d/c ditropan
• estrogen cream and refer to pelvic floor program
• d/c gingko – no benefit
• increased risk of bleed with plavix and ASA
• d/c Vitamin E – no benefit, possible harm
• Start long process of weaning off clonazepam
• Decrease metformin to 250 mg BID  avoid
hypoglycemia, goal HgbA1c 8%
• Monitor blood pressure to avoid orthostatic drops
Would you start a
cholinesterase inhibitor?
• No
• Do blood work to rule out reversible causes of
dementia – Ca, B12, TSH
• Just stopped a lot of meds and need to assess the
patient after these changes before starting something
new
2 months later
• Tolerated the changes. Feels better overall.
•
MMSE 25 (from 22), losses: - 2 orientation, -2 recall, -1 3 stage
command . Clock unchanged.
•
FAQ 22 (from 26), GDS 3/15
• Clonazepam now every other night, but still having trouble
sleeping.
• Blood work normal. Chemstrips 7-10. Blood pressure good.
• Daughter sent note – still some memory problems. Will go out if
encouraged.
• Home care – patient eating more, more upbeat
Now do you want to start
cholinesterase inhibitor?
• Does she have dementia? What kind?
• What is available?
• What baseline work-up?
• How do you monitor?
Mild AD
• ↑ # plaques
& tangles
damage
areas of the
brain
• Stage
where
people seek
help
MANAGEMENT – MILD AD
• Future planning – will, EPOA, PD
• Safety issues – meds, finances, driving, behavior
• Education / Support – Alzheimer Society
• Caregiver
• ongoing assessment of vitality & caregiver stress
through all stages of AD
• Discuss treatment options
• Medications do not reverse loss, but can slow down
progression and improve apathy for some
PHARMACOLOGICAL THERAPY IN
DEMENTIA
• Current medications only treat symptoms
• Treatment goals:
• Temporarily stabilize cognitive & functional decline 
delay institutionalization
• Improve memory & other cognitive functions
• Maintain or improve self-care abilities
• Improve behavioral abnormalities
• Improve mood & quality of life – both for patient &
caregiver
OPTIONS
• Cholinesterase Inhibitors
• mild to moderate AD
• Donepezil, rivastigmine, galantamine
• Contraindications – bradycardia or AV block, active peptic
ulcer, epilepsy (lowers seizure threshold), ? Asthma
• Side effects – GI, nightmares, bradycardia, worsens UI &
agitation
• NMDA antagonist – memantine
• Moderate to severe AD
• Can be used alone or in combination with cholinesterase
inhibitor
• Cognitive response rates:
• Improve - 25%
• Stabilize - 50%
• No benefit - 25%
How do you
know if ChEI is
working?
• Cognition, function,
behavior, global
function, caregiver
burden
• Effects are modest
• Stabilization is a good
result……
• Improvement is a bonus
• Even “responders” will
eventually decline but
still ahead of the not
treated
Now do you want to start
cholinesterase inhibitor?
• Does she have dementia? What kind?
• Mixed Dementia
• What is available? Which one are you going to choose?
• Aricept – once a day
•
•
2.5 mg in am X 1 week, then 5 mg OD X 6-8 weeks
If tolerates  can increase to 10 mg OD in am
• What baseline work-up? ECG
• How do you monitor?
• Family to monitor symptoms – more engaged
• May worsen urinary incontinence
• Watch GI side effects
One year later
• On Aricept 10 mg OD, tolerating well
• Urinary incontinence – improved with rehab &
estrogen; recently increasing and using pads but not
limiting activity
• MMSE = 23 (prev 24)  benefit? Yes
• FAQ= 20, home care continues
• Will slowly progress and Mrs. B will have decreased
function. Need to assess her caregiver (s) as well for
burnout and stress.
SEVERE IMPAIRMENT
• Plaques & tangles widespread
throughout brain  further
shrinkage
• Nearly unintelligible verbal
output
• Remote memory gone
• Unable to copy or write
• No longer grooming or dressing
• Weight loss, seizures, skin
infections, difficulty swallowing
• Most people with AD die of
other illnesses – usually
aspiration pneumonia
MANAGEMENT - LATE STAGE AD
• Consider discontinuing pharmacotherapy
• Try off for a few weeks then reassess
• End of life care
• Comfort measures
• Family bereavement / grief
• May occur earlier with LTC placement – separation
from spouse / family
VASCULAR DEMENTIA
• Onset: may be sudden/stepwise
• Cognitive symptoms: depend on anatomy of ischemia
• Motor symptoms: correlates with ischemia
• Progression: stepwise with further ischemia
• Lab tests: normal
• Evidence of cerebrovascular disease – history, physical
exam or imaging
• 10-20% of dementia patients
Cardiovascular Disease and
End-Organ Damage
Risk factors
Diabetes
Smoking
Obesity
Hypertension
Hypercholesterolemia
CAD,
Heart attack,
Heart failure
Cardiovascular disease
Atherosclerosis
Stroke,
Transient Ischemic
Attack (TIA)
Adapted from Nyenhuis DL et al. J Am Geriatr Soc, 1998
VaD: A Heterogeneous
Disorder
Cardiovascular Risk Factors
Hypertension Diabetes Genetics Hypercholesterolemia Heart Disease
Ischemic Damage to Cerebral Vasculature
Multiple Distinct Pathologies
Large Vessel Infarcts
• Strategic Single Infarcts
• Multi-infarct Dementia
Small Vessel Infarcts Hemorrhage
• Multiple Lacunae
• Binswanger’s Disease
• CADASIL
• Chronic SDH
• SAH
• ICH
Hypoperfusion
• Global (e.g., cardiac
arrest)
• Hypotension
Final Common
Pathway
Damage to critical
cortical and subcortical
structures
 Cholinergic
transmission
VaD
Damage/interruption of
subcortical circuits and
projections
Erkinjuntti T. CNS Drugs, 1999
Brain Imaging of VaD
3 Types of VaD
Multiple large
vessel infarcts
Bilateral strategic
thalamic infarcts
Binswanger’s
disease
Source: Stephen Salloway, MD
Overlap Between Alzheimer’s
Disease (AD) and VaD
Cholinergic deficit
AD
Probable Possible Mixed Possible Probable
Amyloid plaques
Genetic factors
Neurofibrillary tangles
Mixed
AD/CVD
VaD
Stroke/TIA
Hypertension
Diabetes
Hypercholesterolemia
Heart disease
Kalaria RN, Ballard C. Alzheimer Dis Assoc Disord, 1999
MIXED DEMENTIA
• Alzheimer Disease + Vascular dementia
• Becoming more common as more research into this
area
• Treatment
• Cholinesterase inhibitors
• Manage vascular risk factors – high blood pressure,
cholesterol, activity, weight, DM, smoking
DEMENTIA with LEWY
BODY
• Onset: gradual
• Cognitive symptoms: memory, visuospatial, hallucinations,
fluctuations
• Motor symptoms: parkinsonism
• Progression: gradual, but usually faster than AD
• Lab tests: normal
Diagnostic Criteria - DLB
• Dementia + features (2-3/3)
• Spontaneous parkinsonism
• Visual hallucinations (well formed/ detailed)
• Fluctuating course (attention / alertness)
• Supportive features
•
•
•
•
Falls & syncope (unexplained)
Severe autonomic dysfunction (OH, UI)
Neuroleptic sensitivity
REM sleep behavior disorder
FRONTO-TEMPORAL
DEMENTIA
• Onset: gradual, usually age <60
• Cognitive symptoms: executive: disinhibition,
apathy, behavior changes
• Motor symptoms: none; may be associated with
ALS in rare cases
• Progression: gradual but faster than AD
• Lab tests: normal
• Tx: nothing for cognitive / functional impairment
• behavioral challenges – SSRIs, neuroleptics
Phineas Gage
Phineas Gage was a railroad worker in the 19th century living in Cavendish,
Vermont. One of his jobs was to set off explosive charges in large rock in
order to break them into smaller pieces. On one of these instances, the
detonation occurred prior to his expectations, resulting in a 42 inch long, 1.2
inch wide, metal rod to be blown right up through his skull and out the top.
The rod entered his skull below his left cheek bone and exited after passing
through the anterior frontal lobe of his brain.
Frontal
Remarkably, Gage never lost consciousness, or quickly regained it (there is
still some debate), suffered little to no pain, and was awake and alert when he
reached a doctor approximately 45 minutes later. He had a normal pulse and
normal vision, and following a short period of rest, returned to work several
days later. However, he was not unaffected by this accident.
http://www.sruweb.com/~walsh/gage5.jpg
Learn more about Phineas Gage:
http://en.wikipedia.org/wiki/Phineas_Gage
Frontal
Frontotemporal
Dementia
• Core diagnostic features:
•
•
•
•
Early decline in social interpersonal conduct
Early impairment in regulation of personal conduct
Early emotional blunting
Early loss of insight
• Supportive diagnostic features:
•
•
•
•
•
•
Decline in personal hygiene & grooming
Mental rigidity & inflexibility
Distractability & impersistence
Hyperorality & dietary changes
Perseverative behavior
Utilization behavior
FTD – Cognitive Features
• Personality changes
• Executive dysfunction
• Language problems – nonfluent or fluent
•
•
•
•
Economy of output
Concreteness of thought
Echolalia
Perseveration
• Memory & visuospatial skills relatively preserved
Other diagnoses associated
with dementia
• Normal pressure hydrocephalus (NPH)
• Gait difficulties, frontal deficits, urinary incontinence
• Creutzfeldt-Jakob Disease (CJD)
• Myoclonus, pyramidal signs, EEG findings, rapid
progression
• AIDS dementia
• Impaired concentration, slow thinking, apathy
• Motor abnormalities – gait unsteadiness, motor slowing
DIFFERENT TYPES OF DEMENTIA
Other dementias
Frontal lobe dementia
Creutzfeldt-Jakob disease
Corticobasal degeneration
Progressive supranuclear palsy
Many others
Vascular dementias
Multi-infarct dementia
Binswanger’s disease
Dementia with Lewy bodies
Parkinson’s disease
Diffuse Lewy body disease
Lewy body variant of AD
Vascular dementias
and AD
AD and dementia
with Lewy bodies
AD
5% 10%
65%
CSHA - CMAJ 1994; Small et al, 1997; APA, 1997; Morris, 1994.
5%
7% 8%
Take Home Messages
• Don’t miss diagnosis of delirium – it is an acute change –
with significant morbidity and mortality consequences if
not managed appropriately
• Haldol is bridge to keep patient safe if needed
• Make sure you rule out reversible causes of cognitive
change, whether acute or subacute
• Dementia is a diagnosis made over time, but the earlier the
better.
• Key to diagnosis is the history – especially from the caregiver.
• Function needs to be affected for diagnosis of dementia.
Cognitive
Impairment
Subacute /
chronic
Acute
Delirium
Reversible
Depression,
Structural,
Metabolic, etc
Irreversible
Mild
Cognitive
Impairment
Dementia
Growing Old is not
for Sissies