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 TerminologyUnderstanding of how syndrome has evolved

“Senile dementia”, “hardening of arteries”

Multi-infarct dementia

Used interchangeably with Vascular Dementia VaD

VaD superseded by VCIRecognize dementias with mixed neurodegenerative (AD) and vascular features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 DescriptionVascular 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 common1/3rd those with dementia show vascular pathology at autopsy

2nd most common form of impairment after ADPrevalence - 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 patientsPopulation 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 SubtypesLarge Vessel Disease

Dementia can occurSingle strategic infarct Multiple strokes/varying size and locations

• Angular gyrus Caudate Basal Ganglia

• Hippocampus Globis Pallidus Basal Forebrain

• Thalamus

Post-stroke dementia more commonOlder age

Low educational attainment

Pre-existing cognitive impairment

Neuropathological Subtypes

Small Vessel Disease – Most common cause VCILeukoaraiosis

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… Within…

Small vessel infarct • Cerebral white matter

Ischemia • Basal Ganglia

Incomplete ischemia • Brainstem

• Prefrontal subcortical circuit

Thalamo-cortical circuit

Neuropathological Subtypes

Pattern lesions associated with clinical syndromePre-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 syndromesDorsolateral (executive functions and impaired recall)

Orbitofrontal (behavior, emotional changes)

Anterior cingulate (ebulia, akinetic mutism)

Neuropathological Subtypes

Non-infarct Pathology in VCINot 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 DysfunctionCentral 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 DisturbancesGlobal 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 capacityEpisodic 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 - Apathy

Mania - Disturbances of prosody

Anxiety - Irritability

Psychosis - Pathological laughing & crying

Catastrophic Reaction

How Do We Classify Depression?

Is depression a continuum or are there distinct formsResearchers distinguished between major depression and minor depression

When viewed in this mannerDuring 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 disorderMajor depression can last average of almost 12 months

Few last three years or more

Minor depressionFew 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 DepressionProvoked 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 depressionsDo not remit within one year

Become chronic major depressions

Possible pre-morbid vulnerabilityFamily 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 CortexDepression not associated

Tiredness, amotivational states

Greater frequency depression/anxiety withLateral pre-frontal lesions vs. medial frontal lesions

Depression and Physical Impairment

Many investigations of this relationshipMotor 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 timeAcute

• 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 StrokeAmong 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 planSocial 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 literaturePsychological response to impairment/loss

Neurophysiological response to brain injury

Etiology of PSD, like all depressive disorders, unknownSerotonin 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 workIschemic 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

Post Stroke ManiaSymptoms

Elevated mood

Decreased sleep

Increased talk

Increased activity

Grandiosity

Risk FactorsFamily history mood disorder

Right hemisphere lesions• Orbitofrontal cortex• Basotemporal cortex• Basal ganglia• Thalamus

Lithium remains first line of treatment

About 1% higher frequency in TBI

Post Stroke Anxiety Disorders

Frequency of experiencing anxiety with acute stroke is 21%

50% will have Major Depression

33% will have Minor Depression

CorrelatesPrior history alcohol abuse

Right hemisphere cortical lesions

Greater impairment ADL’s/social functioning

Natural courseAcutely after stroke = 1.5 months

Psychosis Following Stroke

Variety of presentationsNo 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 junctionSome subcortical, mostly cortical lesions

Seizures

Subcortical brain atrophy

Small vessel disease

Anosognosia and Denial

1. Anosognosia – failure of awareness of one’s own deficits/diseases

2. 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 ExplainPsychological 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 ReactionSudden 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 correlatesImpairment 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 regionsThalamus

Frontal

Sub-cortical

Cortical – basal ganglia – thalamic circuits implicatedSame 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 DebilitatingMay 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 ProsodyMelodic 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 prosodyAssociated with (R) temporoparietal, (R) basal ganglia lesions

Patients unable to comprehend emotional intonations appear able to recognize their own inner emotional state

Irritability and AggressionCommon disorder associated with several conditions:

Stroke

Dementia

TBI

Huntington's disease

Clinical correlates with strokeGreater cognitive impairment

Greater frequency of depressive symptoms

Higher frequency of major depression

Generalized anxiety

Lesions closer to frontal pole