1. Cognitive and Neuropsychiatric Effects of Stroke
Thomas Sugalski, Ph.D.
Psychology Associates of Bethlehem
March 7, 2015
De Sales University

2. 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

3. 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VaD superseded by VCI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

4. Clinical Subtypes of Vascular Cognitive Impairment
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

5. 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

6. Conceptual Neuropathological Subtypes of VCI
Large Vessel Disease
Small Vessel Disease
Non-infarct Ischemic Changes

7. 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

8. 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

9. Neuropathological Subtypes
Small Vessel Disease – Most common cause VCI
Leukoaraiosis
Subcortical infarcts

10. 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

11. 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

12. Neuropathological Subtypes
Sub-cortical Ischemic Vascular Disease (SIVD)
Occurs through… Within…
 Small vessel infarct • Cerebral white matter
 Ischemia • Basal Ganglia
 Incomplete ischemia • Brainstem
• Prefrontal subcortical circuit
 Thalamo-cortical circuit

13. 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)

14. 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

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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)

22. (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)

23. (L) Hemispheric Cognitive Syndromes
(L) hemispheric vascular lesions
Aphasia
Reading/writing disorders
Learned skill - buccofacial, limb apraxia
Depression

24. 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)

25. (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

26. (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

27. 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 - Apathy
Mania - Disturbances of prosody
Anxiety - Irritability
Psychosis - Pathological laughing & crying
Catastrophic Reaction

28. 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

29. 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

30. 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

31. 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

32. 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

33. 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)

34. 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

35. 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.

36. 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

37. 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

38. 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

39. 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

40. 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

41. Post Stroke Mania Symptoms Risk Factors
Elevated mood
Decreased sleep
Increased talk
Increased activity
Grandiosity
Risk Factors
Family history mood disorder
Right hemisphere lesions
Orbitofrontal cortex
Basotemporal cortex
Basal ganglia
Thalamus
Lithium remains first line of treatment
Post Stroke Mania
 About 1%  higher frequency in TBI

42. 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

43. 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

44. Anosognosia and Denial
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

45. Anosognosia and Denial
Indifference Reaction – do not deny the existence of impairment , but their unconcern seems clearly inappropriate to severity to illness
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

46. 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

47. 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

48. 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

49. 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

50. 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

51. 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

52. 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

53. 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

54. 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