Dementia - UNC School of Medicine

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Transcript Dementia - UNC School of Medicine

Cognitive Impairment
and Dementia
Debra Bynum, MD
Associate Professor of Medicine
Division of Geriatric Medicine
University of North Carolina
• What is Mild Cognitive Impairment? What is Dementia?
• Dementia, Delirium and Depression
• What are the different types of Dementia?
• Risk Factors and Prevention
• Treatment
• Future Directions
• Key points
What is Dementia
• I know it when I see it…..?????
DSM IV Definition
• Memory impairment associated with(at least 1):
Aphasia (disturbance in language)
apraxia (impaired motor ability)
agnosia (inability to identify objects)
disturbance in executive functioning (ie, planning, organizing,
sequencing, and abstracting)
• Impact social, functional, or occupational activities
• Decline from a previous level of functioning
• Does not occur solely in the setting of delirium
DSM 5 Definition…
• Two Biggest Changes
• Terminology: Minor and major neurocognitive disorder
rather than Dementia
• Does NOT rely on presence of memory impairment
Domains of neurocognitive
• Memory
• Orientation
• Language
• Perceptual
Minor neurocognitive disorder
• Evidence of modest cognitive decline (change from baseline) in
at least one domain
• And a decline in neurocognitive performance testing (1-2
Standard Deviations below norm)
• Cognitive deficits do not interfere with independence (IADLs
or complex activities), but require greater effort or
compensatory changes or accommodation to maintain
• Cannot occur exclusively during episode of delirium
• Not attributable to another disorder such as schizophrenia or
major depression
Major neurocognitive disorder
• Substantial cognitive decline (change) in one or more
domain based on concerns of individual, informant, or
• Decline in neurocognitive performance on testing (2 or
more Standard Deviations below norm….)
• Interfere with independence
• Do not occur exclusively in presence of delirium
• Not attributable to another disorder (schizophrenia,
Assessment Tools
• Mini Mental Status Exam, 3 item recall
• Clock drawing
• Trails B
• Must have memory changes with other changes
(aphasia, apraxia, executive function, etc)
• MMSE: can be influenced by primary language
and educational level!!
• Commonly used
• Limitations:
Educational level
Hearing and sight
Does not work as well for people at either end of the
“spectrum” -- previously highly functional/well
educated or poorly educated/learning problems
• Able to more sensitively detect MCI
• Problem: Includes parts of many other tests we
commonly used
• Memory disorders clinic
• Lots of information
• Often more time consuming
• My preferred tool for general use
• 3 item recall plus clock draw
• I like to do clock draw on all patients
Trails B
• Good for executive functioning
• The only test that has any predictive value for
driving ability
Verbal Fluency
• Phonetics: F words – frontotemporal dementia
• Categories (animals, vegetables): Alzheimer’s
Key Points….
• The score on any assessment or screening
instrument (such as the Mini Mental Status Exam)
is not a component of the definition of dementia
• You can have a low MMSE and NOT have
dementia, You can have a nearly normal MMSE
and HAVE dementia
• Memory changes MUST impact everyday activities
and functional status
Mild Cognitive Impairment
• Memory changes without the significant impact on
daily activities, do not meet criteria for dementia but
do not have normal cognitive functioning
• Very mixed group of people who have this label
• On average, risk of progression from MCI to
dementia 10% per year
More terms
• Dementia
• Delirium
• Depression
• Acute state of confusion
• Characteristics:
Change in consciousness (more agitated or less alert)
Inattention, inability to focus
Waxes and wanes
• Acute change from baseline
• Sign of underlying problem
Infection (even urinary tract infection, pneumonia)
Recent surgery or procedure
Sleep deprivation
• Frequently seen in hospital, change of environment,
acute illness (30-40% of hospitalized elders may develop
delirium– often missed)
• Can be seen in patients with dementia
• Can be seen in patients without dementia
• Does not diagnose with dementia
• Is associated with increased risk of developing
• Depression in older people can be associated with
memory problems and apathy, both symptoms that
are also seen in dementia (previously referred to as
• Depression in later life is associated with an
increased risk of developing cognitive impairment
and dementia
Common Types of Dementia
• Alzheimer Disease
• Vascular Dementia
• Overlap (AD/Vascular) dementia
• Fronto-temporal dementia
• Dementia with Lewy Body
• Dementia due to Parkinson’s Disease
• Parkinson “Plus” syndromes with dementia
• Alcohol related dementia
• Infections: HIV, neurosyphilis, prion disease (mad cow)
Alzheimer Disease
• Gradual short term memory loss
• Personality changes
• Visuospatial problems: difficulty with clock drawing,
getting lost in previously familiar settings
• Apraxia : motor problems, affect ability to dress and
• Medial temporal lobe atrophy on MRI
• Early disease: AD pattern of inheritance
• Difficulty with naming categories (animals, vegetables)
Vascular Dementia
• Classic: Step wise decline
• May have associated vascular dementia, vascular
• May have less visuospatial dysfunction (can copy
clock face, but cannot remember how to draw it )
• Reality: Most cases of dementia in older patients
are mixed AD and Vascular (largest risk factor for
both is age)
• Observations that vascular risk factors increase
risk for AD as well as vascular dementia
• Studies that demonstrate cholinesterase inhibitors
work just as well (or poorly) in patients with
vascular dementia and AD
Frontotemporal Dementia
• Behavioral symptoms (disinhibition)
• Executive function problems
• Language dysfunction (difficulty naming words that
begin with certain letter….)
• Frontal release signs
• Can occur in patients with motor neuron diseases
• Can have earlier onset and more often familial than AD
Dementia with Lewy Body
• 15-25% cases of dementia in patients >65
• Early visual (vivid) hallucinations
• Prior sleep disorders (may precede dementia by years)
• Parkinsonian features (not overt tremor, but some
stiffness, cogwheeling)
• More rapid decline
• Decline with antipsychotics (especially typical agents)
• Fluctuating course (can resemble delirium with good
days and bad days)
DSM 5 criteria
Core diagnostic features of Lewy body dementia include the following:
• fluctuating cognition with pronounced variations in attention and alertness;
• recurrent visual hallucinations that are typically well formed and detailed; and
• spontaneous features of Parkinsonism with onset at least one year later than the
cognitive impairment.
Suggestive diagnostic features of Lewy body dementia include the following:
• rapid eye movement sleep behavior disorder;
• severe neuroleptic sensitivity; and
• low dopamine transporter uptake in basal ganglia demonstrated by SPECT or PET
Dementia with Parkinson’s
• 30% of patients with PD will develop cognitive
decline and dementia
• Typically dementia comes MUCH later in the
course of PD
• Can have vascular etiology to PD and dementia
(may be more acute decline and more resistant to
treatment, less response to sinemet and other
Parkinson Plus Syndromes
• Multiple Systems Atrophy/Shy Drager syndrome
Some parkinsonian features (stiffness, gait instability)
Usually not much of a tremor if any
Can be more quickly progressive
Associated with significant orthostasis (drop in blood
pressure with standing) and other neurological
problems (urinary retention causing a bladder that does
not work, erectile dysfunction, constipation)
Alcohol related dementia
• Can also have gait/balance problems due to long
term effects on cerebellum
• Memory loss can be associated with elaborate stories
and confabulation (Korsakoff ’s syndrome)
• We often underestimate…
• Neurosyphilis
• Prion disease (mad cow)
• Remembering to think about and screen for STD in
older people
Risk Factors for cognitive
Diabetes, hyperlipidemia, smoking
ETOH abuse
Prior Severe Head trauma
Genetic Factors
• ApoE gene (variable association, less association with decline in older age)
• Down syndrome
Risk Factors/Associations
• Late life depression
• Delirium
• No clear evidence to support preventing cognitive
decline with Vitamin E, Gingko Biloba, leisure
activities, fish oil, estrogen, NSAIDS…..
• Observational studies looking at lifestyle changes,
mental activity (crosswords, puzzles), etc all
challenging because of potential selection bias
• “Vitamin E is a drug looking for a disease….”
• Dr. Zell Hoole
• Most evidence suggestive of preventing future cognitive
decline by preventing vascular disease (preventing or
treating HTN, hyperlipidemia, obesity, smoking
• Biggest impact likely by targeting vascular risk factors
in midlife
• Tightest link between treating HTN and decreasing
development of dementia
• Prevention of both vascular and Alzheimer type
• Take home point: exercise, lowering vascular risk
factors, basically taking care of yourself in early/mid
life decrease your risk for dementia
• Educational level reported to be protective, but likely
more that this serves as a “cushion”
• Genetics and factors that we still do not understand
• Unfortunately, there is NO current treatment that
makes dementia better or reverses cognitive
• Medications that are commonly marketed overall
slow the progression of the decline in cognitive
function -- patients still get worse over time, but the
medications seem to slow the rate
• Overall the effect on slowing the decline is very very
Treatment options
• Cholinesterase Inhibitors
• Donepezil (aricept), galantamine, rivastigmine
• All are similar in effect
• All show a small effect to slow the decline of
progression and give people a few additional months
before the need for nursing home placement
Cholinesterase Inhibitors
• Side effects:
• Nightmares and sleep problems
• Urinary incontinence (the opposite effect of ditropan
– givs some people urge urinary symptoms)
• Slow heart rate/bradycardia
• Nausea, decreased appetite, weight loss
Cholinesterase Inhibitors
• Work just as well (or not as well, depending on your
view) in vascular disease as in Alzheimer’s disease
(probably because most people actually have mixed
pattern of dementia)
• Approved for use in moderate to severe dementia
• Some evidence to support use in severe dementia,
although benefits seem to trail off
• No evidence to support use in Mild Cognitive
• NMDA receptor antagonist
• Small clinical benefit in patients with moderate to severe AD
(studies limited)
• Marginal benefit in patients with mild to moderate AD
• Marginal benefit in patients with mild to moderate vascular
• Patients taking memantine were slightly less likely to
develop agitation/behavioral symptoms
• Well tolerated with no significant side effects, but costly
?Combination cholinesterase
inhibitors and memantine
• Study in NEJM 2012:
• Patients with moderate to severe dementia
• Previously on donepezil/aricept at least 3 months
• 4 arms: all placebo, aricept only, both aricept and
memantine, only memantine
Study results
• Patients in all groups declined over the year
• Patients in donepezil only group declined less than
other groups
• Patients in memantine group also declined less than
combination or placebo group, but less effect than
• Less benefit seen in patients with more severe dementia
(basically no change in those patients)
Take home from NEJM study
• Patients taking donepezil, probably ok to continue
• NO benefit to having patients on both drugs
• Could consider change to memantine if not
tolerating donepezil due to side effects
Treatment: other drugs
• Stopping medications that may be making confusion
worse (benadryl, ambien, benzodiazepines)
• ?statins: Data unclear (some data suggesting statin
use prevents future decline of cognitive functioning,
some case reports of increased confusion on statins
in patients with dementia)
Treating behavioral symptoms
with dementia
• Agitation, sundowning, aggressive behaviors can
occur with dementia
• Reflex to treat with psychoactive drugs
(antipsychotics such as risperidone/haldol):
associated with slight increase risk of mortality and
never proven to be of benefit: bottom line, weigh
risks and benefits in individual patient
Treating depression in patients
with dementia
• Difficult to assess and data unclear
• Some patients seem to benefit, others do not, weigh
risks of antidepressants (side effects, decrease blood
pressure when standing, falls, fractures increased
with most agents)
• Dementia: hard to differentiate apathy of dementia
from apathy with depression
• Bottom line: consider trial, but also consider
discontinuing, weighing risk of side effects closely
Future directions
• More specific diagnosis with use of imaging, PET
scans, CSF and blood work
• Working within the new criteria of the DSM 5
• Treatment options other than cholinesterase
• Mild cognitive impairment, Dementia, delirium, and
depression: separate definitions, all tied together
• Many different types of dementia, but most commonly
people have combination of vascular and alzheimer
• Risk factors/prevention: primarily CV health!
• Treatment: still disappointing overall
• Future directions: more specific and earlier diagnoses,