Alzheimer’s Disease and Other
Dementia Related Disorders
Jason Schillerstrom, MD
schillerstr@uthscsa.edu
Learning Objectives

List the diagnostic criteria for Major Neurocognitive
Disorder.

Describe cognitive deficits across multiple domains

Describe the clinical, pathological, and
neuropsychological features associated with
Neurocognitive Disorder due to Alzheimer’s disease.

Distinguish between Neurocognitive Disorder due to
Alzheimer’s disease, cerebrovascular disease, Lewy
Body disease, and frontotemporal lobar degeneration.
Major Neurocognitive Disorder
1. Evidence of significant cognitive decline from a previous level of performance
in one or more cognitive domains based on:
◦ Concern of the individual, a knowledgeable informant, or the clinician that
there has been a significant decline in cognitive function; and
◦ A substantial impairment in cognitive performance, preferably
documented by standardized testing or, in its absence, another qualified
clinical assessment.
2. The cognitive deficits interfere with independence in everyday activities (i.e. at
a minimum, requiring assistance with complex instrumental activities of daily
living such as paying bills or managing medications).
3. The cognitive deficits do not occur exclusively in the context of a delirium.
4. The cognitive deficits are not better explained by another mental disorder.
Major Neurocognitive Disorder
Specify whether due to:

Alzheimer’s disease

frontotemporal lobar degeneration

Lewy body disease

vascular disease

traumatic brain injury

substance/medication use

HIV infection, prion disease

Parkinson’s disease

Huntington’s disease

another medical condition
Major Neurocognitive Disorder
Specify:
1. Without behavioral disturbances
2. With behavioral disturbances: if the cognitive
disturbance is accompanied by a clinically significant
behavioral disturbance such as psychosis, mood
disturbance, agitation, or apathy.
Specify:
1. Mild: difficulties limited to instrumental activities of
daily living
2. Moderate: difficulties with basic activities of daily
living
3. Severe: fully dependent
Key Points #1

The diagnosis of neurocognitive disorders
is based on clinical presentation.
◦ There are no “dementia labs”.
◦ There is no dementia imaging study.
◦ Laboratory and imaging are used to “rule out”
reversible causes.

There must be clinically significant
functional impairment.
Cognition – Complex Attention
Cognitive Domain
Complex Attention
Definition
Sustained
attention, divided
attention,
processing speed
Examples of Symptoms or
Observations
Major
-Difficulty in
environments with
multiple stimuli.
-Easily distracted.
Difficulty holding
new information.
-All thinking takes
longer than usual.
Minor
-Requires more
double checking
than previously.
-Thinking is easier
when not
distracted by radio,
TV, etc…
Cognition – Learning and Memory
Cognitive Domain
Learning and
Memory
Definition
Immediate
memory, recall
memory, remote
memory, implicit
learning
Examples of Symptoms or
Observations
Major
-Repeats self in
conversation.
-Asks same
questions again
and again.
-Cannot keep track
of a short list of
item.
Minor
-Increasingly relies
on lists.
-Needs occasional
reminders.
-Loses track of
whether bills have
been paid.
Cognition – Language
Cognitive Domain
Language
Definition
Expressive
language, word
finding, receptive
language
Examples of Symptoms or
Observations
Major
-Often uses
general terms such
as “that thing” and
“you know what I
mean”.
-Prefers pronouns.
-Echolalia.
-Mutism.
Minor
-Noticeable word
finding difficulty.
-Grammatical
errors.
Cognition – Perceptual Motor
Cognitive Domain
Perceptual Motor
Definition
Examples of Symptoms or
Observations
Visuoperception,
Major
-Difficulty with
visuospatial, praxis
using tools,
driving, navigating
in familiar
environments.
Minor
-May need to rely
more on others for
directions.
-May find self lost
when not
concentrating.
-Less precise in
parking.
Cognition – Social Cognition
Cognitive Domain
Social Cognition
Definition
Examples of Symptoms or
Observations
Recognition of
Major
-Clearly out of
emotions, theory of
acceptable range.
mind
-Insensitivity to
social standards in
conversation.
-Focuses
excessively on
topic despite
others disinterest.
Minor
-Less able to read
facial expressions.
-Decreased
empathy.
-Increased
extraversion or
introversion.
Cognition – Executive Function
Cognitive Domain
Definition
Executive Function Planning,
organizing,
decision making,
overriding habits,
mental flexibility
Examples of Symptoms or
Observations
Major
-Abandons
complex projects.
-Needs to focus on
one task at a time.
-Relies on others
to make decisions.
Minor
-Difficulty resuming
a task after an
interruption.
-Complains of
fatigue from the
effort of planning.
-Difficulty following
conversations of
multiple persons.
Key Point #2

There are multiple ways to be cognitively
impaired.

Executive function is the cognition that is
most strongly associated with self-care
abilities and decision making capacity.
Case Example #1: HPI

83yr female presents to clinic with her two
daughters.

Daughters are concerned:
◦ that their mother repeats her conversations
◦ cannot remember the names of her grandchildren
◦ became confused and disoriented when shopping at a
local mall.

The patient’s husband died one year ago and
daughters are surprised how much they have to
help their mother.
Past History

No past psychiatry history.

Only medical issue is hypertension
(treated with hydrochlorothiazide)

Retired teacher, 55yr marriage, 2 children

No clinically significant substance use
history.
Case #1: Neuropsychological Testing
Age: 83 years
GDS: 2/15
MIS: 6
MMSE: 18
CLOX1: 7
CLOX2: 7
EXIT25: 36
Alzheimer’s Disease

Insidious onset and gradual progression of
impairment in one or more cognitive
domains.

Subtypes include ‘early onset’ (65 years of
age or below) vs. ‘late onset’ (>65 years
of age).
Alzheimer’s Association Staging

Stage 1: No impairment
◦ The person does not experience any memory
problems.
◦ No evidence of symptoms of dementia.

Stage 2:Very mild cognitive decline
◦ The person may feel as if he or she is having
memory lapses — forgetting familiar words or
the location of everyday objects.
◦ But no symptoms of dementia can be detected
during a medical examination or by friends, family
or co-workers.
Alzheimer’s Association Staging

Stage 3: Mild Cognitive Decline
◦ Noticeable problems coming up with the right
word or name.
◦ Trouble remembering names of new people.
◦ Having noticeably greater difficulty performing
tasks in social or work settings.
◦ Forgetting material that one has just read.
◦ Losing or misplacing a valuable object.
◦ Increasing trouble with planning or organizing.
Alzheimer’ Association Staging

Stage 4: Moderate Cognitive Decline
◦ Forgetfulness of recent events.
◦ Greater difficulty performing complex tasks, such
as planning dinner for guests, paying bills or
managing finances.
◦ Forgetfulness about one's own personal history
(usually medical).
◦ Becoming moody or withdrawn, especially in
socially or mentally challenging situations.
Alzheimer’s Association Staging

Stage 5: Moderately severe cognitive decline
◦ Unable to recall their own address or telephone
number or the high school or college from which
they graduated.
◦ Become confused about where they are or what
day it is.
◦ Need help choosing proper clothing for the
season or the occasion.
◦ Still remember significant details about
themselves and their family.
◦ Still require no assistance with eating or using the
toilet.
Alzheimer’s Association Staging

Stage 6: Severe cognitive decline
◦ Lose awareness of recent experiences and
surroundings.
◦ Difficulty remembering the name of a spouse or
caregiver.
◦ Need help dressing properly and may, without
supervision, make mistakes such as putting
pajamas over daytime clothes or shoes on the
wrong feet.
◦ Need help handling details of toileting.
◦ Experience major personality and behavioral
changes, including suspiciousness and delusions.
Alzheimer’s Association Staging

Stage 7: Very severe cognitive impairment
◦ Lose the ability to respond to their environment
and to carry on a conversation.
◦ Need help with much of their daily personal care,
including eating or using the toilet.
◦ They may also lose the ability to smile, to sit
without support and to hold their heads up.
◦ Reflexes become abnormal.
◦ Muscles grow rigid.
◦ Swallowing impaired.
Well Elderly
AD Affects Both
ECF and Constructions
AD Pathology
http://www.umsl.edu/~homecare/brain1.PDD.jpg
AD Pathology
Tangle
Plaque
FDA Approved Medications

Acetylcholinesterase Inhibitors
◦
◦
◦
◦

donepezil (Aricept)
rivastigmine (Exelon)
galantamine (Razadyne)
tacrine (Cognex)
memantine (Namenda) – NMDA
antagonist
Summary of FDA Approved
Medications

All have demonstrated efficacy by the chosen
outcome measures.

However, the effect size is small.

Few patients actually show improvement.

Some outcome measures are less relevant.

Exercise.
Case Example #2: HPI

73yr man presents to clinic with his wife.

She expresses concern for her husband stating, “I
think he’s depressed. He just sits in his chair all
day doing nothing. I have to do everything.”

He no longer manages finances and he needs
assistance with his medications.

He denies feeling depressed and doesn’t
understand wife’s concerns.
Past History

Takes medication for diabetes, hypertension,
and elevated cholesterol.

Had heart catheterization for coronary
artery disease 5 years ago.

Retired produce salesman, married to
current wife 22 years, 3 adult children.

Smokes one pack per day. Drinks 6-12 beers
per week.
Case #2: Neuropsychological Testing
Age: 73 years
GDS: 2/15
MIS: 8
MMSE: 26
CLOX1: 4
CLOX2: 9
EXIT25: 30
Vascular Dementia

Evidence for decline is prominent in
complex attention and frontal-executive
function.

Memory is less impaired relative to loss of
executive function.

Focal neurological signs

Evidence of hypertension, valvular heart
disease, vascular disease, atrial fibrillation.
Vascular Dementia Affects the Executive
Control of Clock-drawing
Vascular Dementia
Vascular Dementia
Treatment

Must prevent future stroke / vascular
disease:
◦ Aspirin
◦ Anticoagulants
◦ Exercise

Off label treatments for apathy
◦ Antidepressants (sertraline)
◦ Stimulants (methylphenidate)
Case #3: HPI

93yr female is brought to clinic by her daughter (patient lives
with daughter).

Daughter reports significant cognitive and functional decline
over the past 1-2 years.

The patient reports occasionally seeing little men walking
across her mantle.

She was started on antipsychotic by PCP and had severe
dystonic reaction.

Daughter also reports that the patient talks and moves
excessively in her sleep.
Past History

Takes medications for heartburn, urinary
incontinence, constipation, hypertension, and
atrial fibrillation.

Reports frequent falls (3 in last year).

12th grade education, housewife, widowed
12 years.

No substance use history.
Case #3: Neuropsychological Testing
Age: 93 years
GDS: 1/15
MIS: 6
MMSE: 22
CLOX1: 5
CLOX2: 7
EXIT25: 24
Lewy Body Dementia

Core Features:
◦ Fluctuating cognition with pronounced
variations in attention or alertness.
◦ Recurrent visual hallucinations that are well
formed and detailed.
◦ Spontaneous features of parkinsonism, with
onset subsequent to the development of
cognitive decline.
Lewy Body Dementia

Suggestive Features
◦ Meets criteria for rapid eye movement (REM)
sleep behavior disorder.
◦ Severe neuroleptic (antipsychotic medication)
sensitivity.
Parkinsonism

Cognitive deficits are more closely
associated with rigidity and bradykinesia
as opposed to tremor.

Parkinsonism in DLB tends to be:
◦
◦
◦
◦
Less severe than that observed in PD
More symmetric compared to PD
Associated with more gait abnormalities
Less responsive to levodopa (Sinemet)
Visual Hallucinations

Fully formed, detailed, 3-dimensional
objects, people or animals

Occur in 59%-85% of autopsy confirmed
Lewy Body Dementia

Occur in early in the course of the
disease (relative to AD hallucinations)
Fluctuations

Mimics delirium: waxing and waning of cognition, behaviors,
and arousal.

10% - 80% with poor inter-rater reliability

Differentiating DLB from AD:
◦
◦
◦
◦

Daytime drowsiness
Daytime sleep of 2 hours or more
Staring into space for long periods
Times when the patient’s ideas are disorganized, unclear or illogical
3 out 4 has a positive predictive value of 83%
Other Features

REM Sleep Behavior Disorder: augmented
muscle activity and dream content; typically
precedes onset of dementia, hallucinations, and
Parkinsonism

Autonomic Instability

Perhaps a greater rate of decline

More responsive to acetylcholinesterase
inhibitors.
Lewy Bodies

Kondi Wong, Armed Forces Institute of Pathology
Case Example #4: HPI

APS called to investigate 60yr woman with self-neglect.

Squalor dwelling. No electricity, water, or sewer.

The client had a $2000 past due water bill and a ~$350 past
due electrical bill.

APS facilitated a voluntary placement in a supervised setting
where the client was allowed to take her dog. However, she
became upset with management and decided to leave.

Would like to renovate home. Plan is to have Channel 4
News do a fundraising story for her.
Case Example #4
#1
Case #4: Neuropsychological Testing
Age: 60 years
GDS: 1/15
MIS: 8
MMSE: 30
CLOX1: 6
CLOX2: 13
EXIT25: 26
Frontotemporal Dementia –
Behavioral Variant
1. Three or more of the following behavioral symptoms:
a. Behavioral disinhibition
b. Apathy or inertia
c. Loss of sympathy or empathy
d. Perseverative, stereotyped or compulsive
behavior
e. Hyperorality and dietary changes
2. Prominent decline in social cognition and/or executive
abilities
3. Relative sparing of learning and memory and perceptualmotor function.
Frontotemporal Dementia –
Language Variant

Prominent decline in language ability in
the form of speech production, word
finding, object naming, grammar, or word
comprehension.

Relative sparing of learning and memory
and perceptual-motor function.
Frontotemporal Dementia

Frontal and anterior temporal atrophy (typically
clearly detectable on CT or MRI scans), rarely
parietal atrophy

Frontotemporal hypometabolism

Pick bodies (silver staining/argentophilic)
intranuclear inclusions

Neuritic plaques/tangles not present
Frontotemporal Dementia
Frontotemporal Dementia
Frontotemporal Dementia
Off-Label Therapies for Agitation

Antidepressants

Benzodiazepines

Antipsychotics
◦ Black box warning
◦ Increased risk of falls, stroke, and death