Cognitive and
Neuropsychiatric Effects
of Stroke
Thomas Sugalski, Ph.D.
Psychology Associates of Bethlehem
March 7, 2015
De Sales University
Vascular Cognitive Impairment
- Introduction Heterogeneous group of cognitive disorders
Share vascular cause
No “typical” patient
Symptoms range from mild to severely disabling
Executive dysfunction or classical AD phenotype
Presentation depends
Location, extent of cerebrovascular disease
Severity of co-existing neurogenerative
pathology
History of Terminology
Understanding of how syndrome has evolved
“Senile dementia”, “hardening of arteries”
Multi-infarct dementia
Used interchangeably with Vascular Dementia VaD
VaD superseded by VCI
Recognize dementias with mixed neurodegenerative (AD) and
vascular features
Step away from “Alzheimerization of dementia”
• Recognizing that memory impairment may not be one of
cognitive domains affected
• Vascular Cognitive Impairment, No Dementia - VCIND
Clinical Subtypes of Vascular Cognitive
Impairment
Subtype
Description
Vascular Dementia
(VaD)
Disorders in the original VaD construct
(post-stroke dementia, multi-infarct
dementia, subcortical dementia syndromes)
Mixed dementia
(Alzheimer
disease/VaD)
Cognitive impairment associated with a
mixed vascular and neurodegenerative cause
(most often AD)
Vascular cognitive
impairment, no
dementia (VCIND)
Cognitive impairment of presumed vascular
cause whose symptoms are not associated
with significant functional impairment
Epidemiology
Cognitive impairment with vascular etiology common
1/3rd those with dementia show vascular pathology at
autopsy
2nd most common form of impairment after AD
Prevalence - 1.5% over age 70 to 39% over 65
Incidence -VaD ranges from 6 to 12 cases/1000 over age 70
VCI affect increasing number of patients
Population aging
Increasing prevalence cardiovascular disease
Conceptual Neuropathological
Subtypes of VCI
Large Vessel Disease
Small Vessel Disease
Non-infarct Ischemic Changes
Conceptual Neuropathological Subtypes
Large Vessel Disease
Post-stroke dementia clinical archetype for VCI
caused by large vessel disease
Prevalence dementia after stroke 14-32%
3 months 20%
5 years 33%
Post stroke dementia has shown inconsistent
relationship:
Smoking
DM
HTN
Hyperlipidemia
?
Number of risk factors
More robust predictor
Neuropathological Subtypes
Large Vessel Disease
Dementia can occur
Single strategic infarct  Multiple strokes/varying size and
locations
• Angular gyrus  Caudate
 Basal Ganglia
• Hippocampus  Globis Pallidus  Basal Forebrain
• Thalamus
Post-stroke dementia more common
Older age
Low educational attainment
Pre-existing cognitive impairment
Neuropathological Subtypes
Small Vessel Disease – Most common cause VCI
Leukoaraiosis
Subcortical infarcts
Neuropathological Subtypes
Leukoaraiosis (Small Vessel Disease)
Describes diffuse, punctate, or confluent white matter
abnormalities
MRI (hyperintensity of white matter), CT (hypodense)
Occurs with infarcts, leukodystrophies, metastases,
inflammatory condition
Detected in most older adults
No distinct cognitive profile
White matter changes associated with
• Increased risk of stroke
• Dementia
Neuropathological Subtypes
Leukoaraiosis (continued)
Small amounts of white matter abnormalities
• Memory/language impairment some patients
Large amounts
• Cognitive impairment
• Motor deficits
• Personality change
• Urinary incontinence
• Gait disturbance
In deep white matter
• Executive impairment
• Slowed processing speed
• Working memory
• Visuo-spatial abnormalities
Neuropathological Subtypes
Sub-cortical Ischemic Vascular Disease (SIVD)
Occurs through…
 Small vessel infarct
 Ischemia
 Incomplete ischemia
Within…
• Cerebral white matter
• Basal Ganglia
• Brainstem
• Prefrontal subcortical circuit
 Thalamo-cortical circuit
Neuropathological Subtypes
Pattern lesions associated with clinical syndrome
Pre-frontal subcortical circuit (pre-frontal cortex, caudate,
pallidum, and thalamus) or Thalamo-cortical circuit
“subcortical syndrome”  “dysexecutive” syndrome
• Deficits in ability to plan, organize, initiate, and shift
between tasks
Three distinct frontal lobe syndromes
Dorsolateral (executive functions and impaired recall)
Orbitofrontal (behavior, emotional changes)
Anterior cingulate (ebulia, akinetic mutism)
Neuropathological Subtypes
Non-infarct Pathology in VCI
Not all lesions are infarcts
Neuropathological abnormalities
• Amyloid proteins aggregating in vessel walls and
cortical arteries, aterioles, capillaries, veins
Cognitive profiles similar to SIVD
When to Look for VCI?
Becoming more common in aging population
Cognitive screening
Over age 65
Vascular risk factors
• HTN
• DM
• Hyperlipidemia
• Evidence white matter disease
Common Neuropsychological Symptoms
Executive Dysfunction
Central functions that control other abilities
• Plan
• Organize
• Decision making
Problems most detectable in non-routine situations
Classes of executive disorders
• Behavioral
• Cognitive
Common Neuropsychological Symptoms
Behavioral Disturbances
Global hypoactivity with abulia, and apathy,
and aspontaneity
Global hyperactivity with distractibility,
impulsivity, disinhibition
Perseveration, stereotyped behavior
Syndrome of environmental dependency
(imitation and utilization behavior)
}
Disturbances of emotion, social behavior
Anosognosia
Confabulation and reduplicative paramnesia
Disorders of sexual behavior, hyperorality
Highly
Suggestive
}
Supportive
Features
Common Neuropsychological Symptoms
Cognitive Disturbances
Response initiation
Response suppression
Focused attention
Rule deduction, shifting set
Problem solving, planning
}
Information generation
Sustained and divided attention
Working memory
Processes of Retrieval
“Theory of Mind”
}
Highly Suggestive
Supportive Deficits
Memory Deficits
Memory disorders after stroke common
Can occur following strokes to all cerebral arterial
territories
ACA
MCA
PCA
Deep Branches
Hemiparesis, aphasia typically overshadows
memory complaints
Over 50% of all stroke survivors complain of
memory difficulties
Memory Deficits
Memory is not a unitary capacity
Episodic memory – remembering personal experiences
Semantic memory – storage, retrieval of general
knowledge, facts
Procedural memory – learn activities, skills that will then
be performed automatically
Working memory
– governs ability to pay attention, concentrate
– holding information, manipulating information
Distribution of Functions
Although brain is symmetrical organ, there is a
lateralized distribution of functions
Left-Hemisphere
Organization of functions discreet
Sequential/analytic processing style
• Extract/process perceptual detail
• Temporal resolution of events (rapidly
changing speech sounds)
(L) Hemisphere Dominant for Verbal
Abilities
Oral and written language
Production and comprehension of
phonology/syntax
Motor planning
Gesture communication
Number processing
Calculation
Verbal memory (semantic memory)
(L) Hemispheric Cognitive Syndromes
(L) hemispheric vascular lesions
Aphasia
Reading/writing disorders
Learned skill - buccofacial, limb apraxia
Depression
Distribution of Functions
Right Hemisphere
Functions distributed in large scale networks
Has a more “configurational” processing style
• Integrate across inputs
• Process global percepts (faces, voices, music)
• Comprehension of metaphoric/emotional
components of language
• Better ability to handle new information
 (LH) superior in automatized processes
(reading, writing)
(R) Hemisphere Specializes in
Visuospatial Abilities
and other “non-verbal” (or difficult to verbalize) abilities
Capacity to orient
Engage and shift attention
Processing and recognition of complex visual
patterns
Visual learning
Typographic memory
Music
Emotions
(R) Hemispheric Cognitive Syndromes
(R) hemispheric vascular lesions
Unilateral spatial inattention or neglect
Transient mutism, abulia, akinesia
Alien hand syndrome
Production/comprehension emotional speech
Delusional misidentification syndrome
Agitation, anxiety, emotional incontinence,
mania
Hallucinations, apathy, anasognosia
Emotional Distress Accompanying Stroke
More than 100 years, recognition emotional disorders
accompany stroke
Causes viewed from two perspectives
Pathological changes produced by brain injury
Psychological responses to impairment
Neuropsychiatric symptoms
Depression
Mania
Anxiety
Psychosis
Catastrophic Reaction
- Apathy
- Disturbances of prosody
- Irritability
- Pathological laughing & crying
How Do We Classify Depression?
Is depression a continuum or are there distinct forms
Researchers distinguished between major depression and
minor depression
When viewed in this manner
During acute stroke period patients with
• Minor depression  posterior lesions of (L) hemisphere
• Major depression  anterior (L) hemisphere lesions
Depression related cognitive impairment associated with
major but not minor depression
What is Prevalence of Post Stroke Depression?
Most common/severe emotional disorder
Major depression can last average of almost 12 months
Few last three years or more
Minor depression
Few months to 24 months
Can develop into major depression
Risk developing post-stroke depression last for at least
2 years
Differences Between Post Stroke
Depression and Primary Mood Disorder?
Phenomenology of MDD w/stroke appears similar to
that found in patients with primary mood disorder
Post Stroke Depression
Provoked by injury to strategic areas of brain
By social, psychological factors
Is There a Remission of Depressive
Symptoms?
Two consistent findings:
Majority post stroke major depression over by 12 months
Remissions occur without treatment
Primary depressions (patients with no lesions), natural
course of approximately 9 months
Group of post stroke depressions
Do not remit within one year
Become chronic major depressions
Possible pre-morbid vulnerability
Family history of mood disorder
What is the Time of Onset?
Depression may develop
During acute post stroke period
Several months
Years following stroke
Some acute, some delayed depressions related to lesion
location
Depression and Lesion Location
During first two months
Frequency of MD 2x as great following:
• (L) Frontal or (L) Basal Ganglia Stroke, compared
• (R) Anterior Lesions or (L) Parietal/Occipital Lesions
Over 6 months
Severity of depression symptoms correlate with proximity of
lesion to L-frontal pole
Frontal-Basal Ganglia-Thalamic circuits mediate post stroke
depression
Areas of brain injury related to depression disorders
Basal Ganglia, compared with thalamic stroke
MCA compared to infarcts of posterior circulation (i.e.
vertebral-basilar arteries supplying brainstem, cerebellum,
thalamus, posterior hemisphere)
Depression and Lesion Location (cont’)
What about R-Hemisphere stroke?
Depression associated with family history of psychiatric
disorder
Anterior, posterior lesion locations
Insular Cortex
Depression not associated
Tiredness, amotivational states
Greater frequency depression/anxiety with
Lateral pre-frontal lesions vs. medial frontal lesions
Depression and Physical Impairment
Many investigations of this relationship
Motor impairment most common presenting symptom
• Acute hemispheric stroke
 Motor impairment = 70/80%
 Sensory Loss = 35%
 Visual Loss = 25%
Severity of depression in first few months after stroke
associated with impaired recovery in ADL’s at 1-2
year follow-up.
Depression and Social Functioning
Patients with,
Poor social support  develop depression
Depression  deteriorate in social functioning
Focus of concern change over time
Acute
• Impaired relationship with closest other
• Limited social activities prior stroke
3 to 6 months
• Fears of economic security
• Limited social activities
1 to 2 years
• Fear of loss of job satisfaction
Suicidal Thoughts and Stroke
Among stroke patients
SI relatively frequent, completed suicide rare
About 10% of patients with stroke develop suicidal thoughts
Strongest association with suicidal thoughts is
existence of MD
Typically go away when no longer depressed
Factors playing role in development of suicidal plan
Social isolation
Younger age
Prior alcohol abuse history
Cognitive/social impairment
Prior stroke
Causes of Post Stroke Depression
Should be considered in light of clinical findings
Cognitive impairment associated with major, not minor
depression
Following the left, but not right hemisphere stroke
Associated with (L) frontal, (L) basal ganglia lesions
MD associated with proximity lesion to frontal pole
Minor depression with posterior lesions of (L) hemisphere
Causes of Post Stoke Depression
Major debate in literature
Psychological response to impairment/loss
Neurophysiological response to brain injury
Etiology of PSD, like all depressive disorders, unknown
Serotonin depletion
• Metabolites of serotonin decreased in spinal fluid of
depressed stroke patients
• Serotonin receptors decreased in (L) temporal cortex
Cortical-thalamic circuits are disrupted
• Ischemic injury
• Altered serontonergic modulation
Causes of Post Stroke Depression
Recent work
Ischemic injury  increased production proinflammatory
cytokines  activates or inhibits enzymes  decreased
production of serotonin
Disruption of certain frontal-thalamic circuits  decreased
perception of emotional stimuli, perhaps by serotonergic
dysfunction
• i.e. inability to experience happy emotional feelings 
depression
Symptoms
Post Stroke Mania
Elevated mood
Decreased sleep
Increased talk
Increased activity
Grandiosity
 About 1%  higher frequency in
TBI
Risk Factors
Family history mood disorder
Right hemisphere lesions
• Orbitofrontal cortex
• Basotemporal cortex
• Basal ganglia
• Thalamus
Lithium remains first line of treatment
Post Stroke Anxiety Disorders
Frequency of experiencing anxiety with acute stroke
is 21%
50% will have Major Depression
33% will have Minor Depression
Correlates
Prior history alcohol abuse
Right hemisphere cortical lesions
Greater impairment ADL’s/social functioning
Natural course
Acutely after stroke = 1.5 months
Psychosis Following Stroke
Variety of presentations
No insight about the non-reality of hallucination/delusion
Retain awareness of reality in spite of existence of
hallucinations (Peduncular Hallucinosis)
Associated with (R) hemisphere lesions
Often affecting parietal temporo-occipital junction
Some subcortical, mostly cortical lesions
Seizures
Subcortical brain atrophy
Small vessel disease
Anosognosia and Denial
1.
2.
Anosognosia – failure of awareness of one’s own deficits/diseases
Denial – failure to acknowledge illness/deficits
– reported among patients with/without brain injury
Patient has brain injury
• Nature of brain injury  creates cognitive/sensory
impairments  deficits in awareness of impairment
No brain injury
• Unawareness  psychological response
Anosognosia and Denial
3.
Indifference Reaction – do not deny the existence of
impairment , but their unconcern seems clearly inappropriate to
severity to illness
4.
Alien Hand Syndrome – inability to recognize that one’s hand,
usually the left, is their own
Try to throw hand out of bed
Strike it with the right hand
Button shirt with (R) hand, (L) hand follows, undoing work
of (R) hand
Usually (R) hemisphere has sustained injury
Anosognosia and Denial
Attempts to Explain
Psychological etiologies
• Denial is a psychological defense mechanism
• Which attenuates the emotional impact of a catastrophic
reaction
Confusional state
Insufficient sensory feedback to brain that limb is weak
• Or, proprioceptive system is impaired
• Consequently, they do not sense an absence of motor
activity
Anosognosia and Denial
Attempts to Explain (cont’)
Hemispatial neglect
• If patient neglects their (L) visual field
• May be unaware there is no movement in their (L) arm
Disconnection syndrome
• With areas in (R) hemisphere disconnected from language
centers in (L) hemisphere
• Leading to language-mediated unawareness of
impairment
Anosognosia and Denial
Today…
Not associated with prior history of psychiatric disorder
Higher frequency of (R) hemisphere lesions
Dysfunction in pathways extending from
• (R) parietal/temporal lobe  basal ganglia 
thalamus  orbitofrontal cortex
• Could impede integration of sensory input
Catastrophic Reaction
Sudden onset – anxiety, tears, aggressive behaviors,
swearing, compensatory boasting
A response to the inability of person to cope
Emotional outbursts last only a few seconds
Usually associated with stressor
Prevalence estimates ranged from 4% to 19%
Clinical correlates
Impairment severity
Post stroke MD
Basal ganglia lesions
Reaction can be very disruptive families
Apathy
A lack of feeling or emotion, or lack of interest or
concern
27% of patients
Associated with lesions of many brain regions
Thalamus
Frontal
Sub-cortical
Cortical – basal ganglia – thalamic circuits implicated
Same circuit suspected in depression
Pathological Laughing, Crying
Outbursts of emotion which are out of proportion to
the underlying feelings of happiness and sadness
Occurs in approximately
15% patients during acute post stroke period
20% during first year
Socially Debilitating
May occur as frequently as 100 times a day
Last from few seconds to several minutes
Embarrassing for patient
Fears of uncontrollable emotion  social phobia,
withdrawal
Pathological Laughing, Crying
Most frequent clinical correlate:
Depression
Clinical pathological correlates:
Unilateral lesions of basal ganglia
Frontal or temporal cortex
Lesions of brain stem
Periventricular structures
Disturbance of Prosody
Melodic line of speech produced by variations of
pitch, rhythm, and stress of pronunciation
Two types:
Comprehension of affective prosody – recognizing
emotional intonation in a person’s affective expression
Expressive affective prosody – showing facial expression
consistent with their own mood
Comprehension of prosody
Associated with (R) temporoparietal, (R) basal ganglia
lesions
Patients unable to comprehend emotional
intonations appear able to recognize their own inner
emotional state
Irritability and Aggression
Common disorder associated with several
conditions:
Stroke
Dementia
TBI
Huntington's disease
Clinical correlates with stroke
Greater cognitive impairment
Greater frequency of depressive symptoms
Higher frequency of major depression
Generalized anxiety
Lesions closer to frontal pole