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“Senile dementia”, “hardening of arteries” Multi-infarct dementia Used interchangeably with Vascular Dementia VaD VaD superseded by VCI Recognize dementias with mixed neurodegenerative (AD) and vascular features Step away from “Alzheimerization of dementia” Recognizing that memory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 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… 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 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 - 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 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

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

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 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 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

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