Neurocognitive Disorders

Perspectives on Neurocognitive Disorders

• Affect multiple cognitive processes:
  • Learning
  • Memory
  • Consciousness
• Most develop later in life.
• Three classes:
  • Delirium
  • Mild neurocognitive disorder
  • Major neurocognitive disorder
• DSM changes:
  • "Organic" vs. "Neurocognitive disorders"
  • Broad cognitive impairments:
    • Memory
    • Attention
    • Perception
    • Thinking
  • Profound changes:
    • Behavior
    • Personality

Delirium

• Clinical description:
  • Global impairments:
    • Consciousness
    • Cognition
  • Develops rapidly:
    • Several hours to days
  • Example: confusion, disorientation, attention, memory, and language deficits
• Diagnostic Criteria for Delirium:
  • A. Disturbance in attention and awareness.
  • B. Disturbance develops over a short period and tends to fluctuate in severity.
  • C. Additional disturbance in cognition (e.g., memory deficit, disorientation, language, visuospatial ability, or perception).
  • D. The disturbances are not better explained by another neurocognitive disorder and do not occur in the context of a severely reduced level of arousal.
  • E. Evidence from history, physical examination, or lab findings that the disturbance is a direct physiological consequence of another medical condition, substance intoxication or withdrawal, exposure to a toxin, or multiple etiologies.
• Statistics:
  • 20% of older adults in acute care (ER)
  • Highest prevalence:
    • Older adults
    • AIDS patients
    • Cancer patients
    • Medical patients
  • Full recovery = several weeks
    *Vital signs to be checked
• Subtypes of delirium:
  • Delirium due to a general medical condition
  • Substance-induced delirium
  • Delirium due to multiple etiologies
  • Delirium not otherwise specified
• Causes:
  • Drug intoxication
    • Medications
    • Illicit drugs
      • Ecstasy (methylene-dioxymethamphetamine)
    • Poisons
  • Withdrawal from drugs
  • Infections
  • Head injury
  • High fever
  • 50% of people with dementia suffer at least one episode of delirium
  • Age
  • Infections
  • Head injury/brain trauma
  • Sleep deprivation
  • Immobility
  • Excessive stress
  • fMRI scanning - Ethical concerns
• Treatment:
  • Treat underlying medical or withdrawal problems.
  • Acute delirium:
    • Haloperidol or olanzapine
      • First line of treatment
  • Psychosocial interventions:
    • Education
    • Reassurance
    • Coping strategies
• Prevention:
  • Proper medical care
  • Proper medication use

Major and Mild Neurocognitive Disorders

• Major neurocognitive disorder (previously labeled dementia) is a gradual deterioration of brain functioning that affects:
  • Memory
  • Judgment
  • Language
  • Other advanced cognitive processes
• Mild neurocognitive disorder is a new DSM-5 disorder that focuses attention on the early stages of cognitive decline.
• Diagnostic Criteria for Mild Neurocognitive Disorder:
  • A. Evidence of modest cognitive decline from a previous level of performance in one or more cognitive domains.
    • Concern of the individual, a knowledgeable informant, or the clinician that there has been a mild decline in cognitive function; and
    • A modest impairment in cognitive performance, preferably documented by standardized neuropsychological testing or, in its absence, another quantified clinical assessment.
  • B. The cognitive deficits do not interfere with capacity for independence in everyday activities.
  • C. The cognitive deficits do not occur exclusively in the context of a delirium.
  • D. The cognitive deficits are not better explained by another mental 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
    • Multiple etiologies
    • Unspecified
• Clinical description:
  • Gradual deterioration of brain functioning
  • Affects multiple domains:
    • Judgment
    • Memory
    • Language
    • Advanced cognitive processes
  • Multiple etiologies
• Initial symptoms:
  • Memory impairment
  • Visuospatial skills deficits
  • Agnosia
    • Facial agnosia
  • Delusions
  • Depression
  • Agitation
  • Aggression
  • Apathy
• Later symptoms:
  • Continued cognitive decline
  • Assistance with activities of daily living
  • Death = inactivity + other illnesses
    • Pneumonia
• Statistics:
  • Onset:
    • Any age
    • Most common in the elderly
  • Prevalence:
    • New case every seven seconds
    • 5% older than 65
    • 20-40% over age 85
    • Rates double with every 5 years after age 75
    • Alzheimer’s in centenarians = 100%
    • Longer lifespan
  • Mild neurocognitive disorder
    • 10% over 70
    • Black men and women at higher risk
  • Cost of caring for 1 year $100$ billion

DSM-5 Classes of Neurocognitive Disorder

• Etiology
  • Dementia of the Alzheimer’s type
  • Vascular injury
  • Frontotemporal degeneration
  • Traumatic brain injury
  • Lewy body disease
  • Parkinson’s disease
  • HIV infection
  • Substance use
  • Huntington’s disease
  • Prion disease
  • Another medical condition

Neurocognitive Disorder Due to Alzheimer’s Disease

• Clinical description
  • Multiple cognitive deficits
    • Memory
    • Orientation
    • Judgment
    • Reasoning
  • Develop gradually and steadily
  • Confusion
  • Agitation / combativeness
  • Depression
  • Anxious
  • Sundowner syndrome
• Range of cognitive deficits
  • Aphasia
  • Apraxia
  • Agnosia
  • Executive function
• Significant social and occupational impairments
• Definitive diagnosis = Autopsy
• Brain scans
• Spinal fluid
• Mental status exam
• Testing for Neurocognitive Disorder due to Alzheimer's Disease
  • The examination also includes an assessment of the patient's level of consciousness: alert, drowsy, stupor, or coma.
  • Note: One part of the diagnosis of the neurocognitive disorder due to Alzheimer's disease uses a relatively simple test of the patient's mental state and abilities, like this one, called the Mini Mental State Inpatient Consultation Form. A low score on such a test does not necessarily indicate a medical diagnosis of the disorder.
• Statistics
  • Nature and progression of the disease
    • “Nun study”
    • Deterioration
      • Early and later stages = slow
      • During middle stages = rapid
    • Post-diagnosis survival = 8 years
    • Onset = 60s or 70s
      • Early onset = 40s to 50s
    • 50% of the cases of neurocognitive disorder are found to be the result of Alzheimer’s disease
  • Prevalence
    • 5 million Americans, several million worldwide
    • Higher :
      • Poorly educated
      • Women
        • Estrogen?
    • Lower:
      • Higher education
      • Cognitive reserve theory
      • American Indians - lower
• Diagnostic Criteria for Major or Mild Neurocognitive Disorder due to Alzheimer's Disease
  • A. The criteria are met for major or mild neurocognitive disorder.
  • B. There is insidious onset and gradual progression of impairment in one or more cognitive domains (for major neurocognitive disorder, two domains must be impaired).
  • C. Criteria are met for either probable or possible Alzheimer's disease as follows:
    • For major neurocognitive disorder:
      • Probable Alzheimer's disease is diagnosed if either of the following is present; otherwise, possible Alzheimer's disease should be diagnosed.
        • 1. Evidence of a causative Alzheimer's disease genetic mutation from family history or genetic testing
        • 2. All three of the following are present:
          • a. Clear evidence of decline in memory and learning and at least one other cognitive domain (based on detailed history or serial neuropsychological testing).
          • b. Steadily progressive, gradual decline in cognition, without extended plateaus.
          • c. No evidence of mixed etiology (i.e., absence of other neurodegenerative or cerebrovascular disease, or another neurological, mental, or systemic disease or condition likely contributing to cognitive decline).
    • For mild neurocognitive disorder:
      • Probable Alzheimer's disease is diagnosed if there is evidence of a causative Alzheimer's disease genetic mutation from either genetic testing or family history.
      • Possible Alzheimer's disease is diagnosed if there is no evidence of a causative Alzheimer's disease genetic mutation from either genetic testing or family history, and all three of the following are present:
        • 1. Clear evidence of decline in memory and learning.
        • 2. Steadily progressive, gradual decline in cognition, without extended plateaus.
        • 3. No evidence of mixed etiology (i.e., absence of other neurodegenerative or cerebrovascular disease, or another neurological or systemic disease or condition likely contributing to cognitive decline).
  • D. The disturbance is not better explained by cerebrovascular disease, another neurodegenerative disease, the effects of a substance, or another mental, neurological, or systemic disorder.

Vascular Neurocognitive Disorder

• Vascular neurocognitive disorder is a progressive brain disorder that is a common cause of neurocognitive deficits
• Clinical description
  • Progressive brain disorder
  • Blockage or damage to blood vessels
  • Onset is often sudden
    • Stroke
  • Variable impairments
• DSM-5 Criteria
  • Cognitive disturbances
    • Speed of information processing and executive functioning
  • Greater motor problems
    • Weakness in limbs
  • Significant impairments
• Diagnostic Criteria for Major or Mild Vascular Neurocognitive Disorder
  • A. The criteria are met for major or mild neurocognitive disorder.
  • B. The clinical features are consistent with a vascular etiology as suggested by either of the following:
    • 1. Onset of the cognitive deficits is temporally related to one or more cerebrovascular events.
    • 2. Evidence for decline is prominent in complex attention (including processing speed) and frontal-executive function.
  • C. There is evidence of the presence of cerebrovascular disease from history, physical examination, and/or neuroimaging considered sufficient to account for the neurocognitive deficits.
  • D. The symptoms are not better explained by another brain disease or systemic disorder.
    • Probable vascular neurocognitive disorder is diagnosed if one of the following is present, otherwise, possible vascular neurocognitive disorder should be diagnosed:
      • 1. Clinical criteria are supported by neuroimaging evidence of significant parenchymal injury attributed to cerebrovascular disease (neuroimaging-supported).
      • 2. The neurocognitive syndrome is temporally related to one or more documented cerebrovascular events.
      • 3. Both clinical and genetic (e.g., cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) evidence of cerebrovascular disease is present.
    • Possible vascular neurocognitive disorder is diagnosed if the clinical criteria are met but neuroimaging is not available and the temporal relationship of the neurocognitive syndrome with one or more cerebrovascular events is not established.
• Prevalence
  • $1.5\%$ in age 70 to 75
  • $15\%$ in age 80 or older
  • Men>Women
    • Higher rates of cardiovascular disease
  • Most will require formal nursing care
  • Death from infection
    • Pneumonia
    • Weak immune system

Other Medical Conditions That Cause Neurocognitive Disorder

• Frontotemporal degeneration
• Traumatic brain injury
• Lewy body disease
• Parkinson’s disease
• HIV infection
• Substance use
• Huntington’s disease
• Prion disease
• Normal pressure hydrocephalus (excessive water in the cranium, resulting from brain shrinkage)
• Hypothyroidism (an underactive thyroid gland)
• Brain Tumor
• Vitamin B12 deficiency
• Head trauma
  • Accidents are most common cause
  • Memory loss is primary symptom
  • Chronic Traumatic Encephalopathy (CTE)

Frontotemporal Neurocognitive Disorder

• Damage the frontal or temporal regions of the brain affecting
  • Personality
  • Language
  • Behavior
• Two types
  • Declines in appropriate behavior
  • Declines language
• Diagnostic Criteria for Major or Mild Frontotemporal Neurocognitive Disorder
  • A. The criteria are met for major or mild neurocognitive disorder.
  • B. The disturbance has insidious onset and gradual progression.
  • C. Either (1) or (2):
    • 1. Behavioral variant:
      • a. Three or more of the following behavioral symptoms:
        • i. Behavioral disinhibition.
        • ii. Apathy or inertia.
        • iii. Loss of sympathy or empathy.
        • iv. Perseverative, stereotyped, or compulsive/ritualistic behavior.
        • v. Hyperorality and dietary changes.
      • b. Prominent decline in social cognition and/or executive abilities.
    • 2. Language variant:
      • a. Prominent decline in language ability, in the form of speech production, word finding, object naming, grammar, or word comprehension.
  • D. Relative sparing of learning and memory and perceptual-motor function.
  • E. The disturbance is not better explained by cerebrovascular disease, another neurodegenerative disease, the effects of a substance, or another mental, neurological, or systemic disorder.
  • Probable frontotemporal neurocognitive disorder is diagnosed if either of the following is present; otherwise, possible frontotemporal neurocognitive disorder should be diagnosed:
    • 1. Evidence of a causative frontotemporal neurocognitive disorder genetic mutation, from either family history or genetic testing.
    • 2. Evidence of disproportionate frontal and/or temporal lobe involvement from neuroimaging.
  • Possible frontotemporal neurocognitive disorder is diagnosed if there is no evidence of a genetic mutation, and neuroimaging has not been performed.

Pick’s Disease

• Rare neurological condition
• $5\%$ of all dementias
• Cortical impairment pattern
• Early onset = 40s or 50s

Traumatic Brain Injury

• Neurocognitive disorder due to traumatic brain injury - includes symptoms that persist for at least a week following the trauma, including executive dysfunction
• Diagnostic Criteria for Major or Mild Neurocognitive Disorder due to Traumatic Brain Injury
  • A. The criteria are met for major or mild neurocognitive disorder.
  • B. There is evidence of a traumatic brain injury-that is, an impact to the head or other mechanisms of rapid movement or displacement of the brain within the skull, with one or more of the following:
    • 1. Loss of consciousness.
    • 2. Posttraumatic amnesia.
    • 3. Disorientation and confusion.
    • 4. Neurological signs (e.g., neuroimaging demonstrating injury; a new onset of seizures; a marked worsening of a preexisting seizure disorder; visual field cuts; anosmia; hemiparesis).
  • C. The neurocognitive disorder presents immediately after the occurrence of the traumatic brain injury or immediately after recovery of consciousness and persists past the acute post-injury period.

Lewy Body

• Neurocognitive disorder due to Lewy body disease
  • Lewy bodies are microscopic deposits of a protein that damage brain cells over time
• Diagnostic Criteria for Major or Mild Neurocognitive Disorder with Lewy Bodies
  • A. The criteria are met for major or mild neurocognitive disorder.
  • B. The disorder has an insidious onset and gradual progression.
  • C. The disorder meets a combination of core diagnostic features and suggestive diagnostic features for either probable or possible neurocognitive disorder with Lewy Bodies.
    • For probable major or mild neurocognitive disorder with Lewy Bodies, the individual has two core features, or one suggestive feature with one or more core features.
    • For possible major or mild neurocognitive disorder with Lewy Bodies, the individual has only one core feature, or one or more suggestive features.
    • 1. Core diagnostic features:
      • a. Fluctuating cognition with pronounced variations in attention and alertness.
      • b. Recurrent visual hallucinations that are well formed and detailed.
      • c. Spontaneous features of parkinsonism, with onset subsequent to the development of cognitive decline.
    • 2. Suggestive diagnostic features:
      • a. Meets criteria for rapid eye movement sleep behavior disorder.
      • b. Severe neuroleptic sensitivity.
  • D. The disturbance is not better explained by cerebrovascular disease, another neurodegenerative disease, the effects of a substance, or another mental, neurological, or systemic disorder.

Parkinson’s Disease

• Degenerative brain disorder
• Dopamine pathway damage
• 1 out of 1,000 people worldwide
• Motor problems
  • Tremors
  • Posture
  • Walking
  • Speech
• Sub-cortical impairment pattern
• Not all with PD will develop dementia
• Diagnostic Criteria for Neurocognitive Disorder due to Parkinson's Disease
  • A. The criteria are met for major or mild neurocognitive disorder.
  • B. The disturbance occurs in the setting of established Parkinson's disease.
  • C. There is insidious onset and gradual progression of impairment.
  • D. The neurocognitive disorder is not attributable to another medical condition and is not better explained by another mental disorder.
  • Major or mild neurocognitive disorder probably due to Parkinson's disease should be diagnosed if 1 and 2 are both met. Major or mild neurocognitive disorder possibly due to Parkinson's disease should be diagnosed if 1 or 2 is met:
    • 1. There is no evidence of mixed etiology (i.e., absence of other neurodegenerative or cerebrovascular disease or another neurological, mental, or systemic disease or condition likely contributing to cognitive decline).
    • 2. The Parkinson's disease clearly precedes the onset of neurocognitive disorder.

Human Immunodeficiency Virus-Type 1 (HIV-1)

• Clinical description
  • HIV causes neurological impairments and dementia
  • Cognitive slowness
  • Impaired attention
  • Forgetfulness
  • Clumsiness
  • Repetitive movements
  • Tremors/leg weakness
  • Apathy
  • Social withdrawal
• Clinical description
  • Later stages of HIV infection
  • Fewer with HAART medications
  • $10\%$ patients now experience neurocognitive disorder
  • Sub-cortical dementia
    • Motor skill impairments
    • Slowing
    • Anxiety
    • Depression
    • No aphasia
• Diagnostic Criteria for Major or Mild Neurocognitive Disorder due to HIV Infection
  • A. The criteria are met for major or mild neurocognitive disorder.
  • B. There is documented infection with human immunodeficiency virus (HIV).
  • C. The Neurocognitive Disorder is not better explained by non-HIV conditions, including secondary brain diseases. such as progressive multifocal leukoencephalopathy or cryptococcal meningitis.
  • D. The neurocognitive disorder is not attributable to another medical condition and is not better explained by a mental disorder.

Huntington’s Disease

• Genetic autosomal dominant disorder
  • Chromosome 4
• Early onset = 40s or 50s
• Motor symptoms
  • Chorea
• Sub-cortical dementia pattern
• Diagnostic Criteria for Major or Mild Neurocognitive Disorder due to Huntington's Disease
  • A. The criteria are met for major or mild neurocognitive disorder.
  • B. There is insidious onset and gradual progression.
  • C. There is clinically established Huntington's disease, or risk for Huntington's disease based on family history or genetic testing.
  • D. The neurocognitive disorder is not attributable to another medical condition and is not better explained by another mental disorder.

Prion Disease

• Always fatal
• Not contagious in humans
  • Cannibalism
  • Blood transfusions
• Linked to mad cow disease
• Diagnostic Criteria for Neurocognitive Disorder due to Prion Disease
  • A. The criteria are met for major or mild neurocognitive disorder.
  • B. There is insidious onset, and rapid progression of impairment is common.
  • C. There are motor features of prion disease, such as myoclonus or ataxia, or biomarker evidence.
  • D. The neurocognitive disorder is not attributable to another medical condition and is not better explained by another mental disorder.

Creutzfeldt-Jakob Disease

• Type of Prion disease
• 1 in 1,000,000
• Linked to mad cow disease
• 10 new cases of variant Creutzfeldt-Jakob Disease - United Kingdom

Substance/ Medication-Induced Neurocognitive Disorder

• Substance-induced persisting dementia
  • Drug use plus poor diet
    • Alcohol, inhalants, sedatives, hypnotics, anxiolytics
  • Brain damage may be permanent
  • Symptoms similar to other neurocognitive disorders
    • Aphasia
    • Apraxia
    • Agnosia
    • Executive function impairments
• Diagnostic Criteria for Substance/Medication-Induced Major or Mild Neurocognitive Disorder
  • A. The criteria are met for major or mild neurocognitive disorder.
  • B. The neurocognitive impairments do not occur exclusively during the course of a delirium and persist beyond the usual duration of intoxication and acute withdrawal.
  • C. The involved substance or medication and duration and extent of use are capable of producing the neurocognitive impairment.
  • D. The temporal course of the neurocognitive deficits is consistent with the timing of substance or medication use and abstinence (e.g., the deficits remain stable or improve after a period of abstinence).
  • E. The neurocognitive disorder is not attributable to another medical condition and is not better explained by another mental disorder.

Causes of Neurocognitive Disorder

• Early, unsupported views
  • Smoking
• Alzheimer’s disease the most common cause of neurocognitive disorder
• Neurobiological influences
  • Neurofibrillary tangles
    • Tau
  • Amyloid plaques
    • Neuritic or senile plaques
    • Spinal fluid
      • $β$-amyloid peptides
  • Cortical atrophy
• Genetic influences
  • Polygenetic
  • Chromosomes 21, 19, 14, 12, 1
    • Chromosome 14—early onset
    • Chromosome 19—late onset
• Deterministic genes
  • Preseniln-1, Preseniln-2
  • $β$-amyloid precursor protein
    • APP gene on chromosome 21
    • APP produces amyloid in plaques
    • Down syndrome and Alzheimer incidence
• Two mechanisms that may account for amyloid protein buildup
  • Amyloid precursor protein (APP)
    • Chromosome 21
  • Apolipoprotein E (apo E)
• Susceptibility genes
  • apoE2
  • apoE3
  • apoE4
    • Chromosome 19
    • Late-onset Alzheimer’s
    • Higher prevalence in families with Alzheimer’s
    • Interaction with head injuries
• Diagnostic Criteria for Substance/Medication-Induced Major or Mild Neurocognitive Disorder
  • A. The criteria are met for major or mild neurocognitive disorder.
  • B. The neurocognitive impairments do not occur exclusively during the course of a delirium and persist beyond the usual duration of intoxication and acute withdrawal.
  • C. The involved substance or medication and duration and extent of use are capable of producing the neurocognitive impairment.
  • D. The temporal course of the neurocognitive deficits is consistent with the timing of substance or medication use and abstinence (e.g., the deficits remain stable or improve after a period of abstinence).
  • E. The neurocognitive disorder is not attributable to another medical condition and is not better explained by another mental disorder.

Psychosocial and Social Influences

• Not direct causes
• Influence onset and course
• Lifestyle factors
  • Drug use
  • Diet
  • Exercise
  • Stress
• Cultural factors
  • Variable risk for diseases and accidents
  • Ethnicity
  • Economic conditions
• Psychosocial factors

Treatment

• Early intervention is critical
• Three areas of focus
  • Prevent certain conditions
  • Delaying onset
  • Cope with the advancing deterioration
• Multidimensional treatment
• Focus on slowing the progression
• Caregivers
  • Anxiety disorders
  • Psychotropic medications use
• Biological treatment
  • Neuronal preservation and restoration
    • Glial cell-derived neurotrophic factor
    • Transplanting fetal brain tissue
  • Cholinesterase-inhibitors
    • Aricept, Exelon, Reminyl
  • New drugs that target the beta amyloid (plaques)
• Ginkgo biloba
  • Studies not replicated
• Antioxidants
  • Vitamin E dangerous in high dose
• Antidepressants
  • SSRIs
• Antipsychotics
• All are only modestly effective for short periods
• Immune system
  • Transgenic mice
• Psychosocial treatments
  • Focus on enhancement
    • Dementia patients
    • Families
    • Caregivers
  • Cognitive stimulation
  • Teach adaptive skills
  • Memory enhancement prosthetic devices
    • Memory wallet
• Psychosocial treatments
  • Main emphasis
    • Coping strategies
    • Behavioral interventions
    • Implementing technology
      • Wandering
      • “Smart home”
    • Stress reduction
    • Dealing with depression
    • Preventing elder abuse
    • Supportive counseling for family

Prevention

• Reducing risk of dementia
  • Controlling blood pressure
  • Do not smoke
  • Staying socially active
  • Staying physically active
• New and hopeful research continues