Neurocognitive Disorders Notes

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
      • Days
    • Example: confusion, disorientation, attention, memory, and language deficits.
  • Diagnostic Criteria for Delirium (DSM-5):
    • A. Disturbance in attention and awareness.
    • B. The disturbance develops over a short period of time and tends to fluctuate in severity during the course of a day.
    • C. An additional disturbance in cognition.
    • D. The disturbances are not better explained by another preexisting, established, or evolving neurocognitive disorder.
    • E. Evidence from history, physical examination, or laboratory findings that the disturbance is a direct physiological consequence of another medical condition.
  • 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"
  • 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 was created to focus attention on the early stages of cognitive decline.
  • Diagnostic Criteria for Mild Neurocognitive Disorder (DSM-5):
    • A. Evidence of modest cognitive decline from a previous level of performance.
      • Concern of the individual, a knowledgeable informant, or the clinician.
      • A modest impairment in cognitive performance, preferably documented by standardized neuropsychological testing.
    • 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 the age of 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
  • 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 (DSM-5):
    • 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.
    • C. Criteria are met for either probable or possible Alzheimer's disease.
    • 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
  • 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 the most common cause
    • Memory loss is the 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 (DSM-5):
    • 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):
      • Behavioral variant:
        • Three or more behavioral symptoms (disinhibition, apathy, loss of empathy, etc.)
        • Prominent decline in social cognition and/or executive abilities.
      • Language variant:
        • Prominent decline in language ability.
    • 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 vs. Possible frontotemporal neurocognitive disorder, based on genetic mutation evidence or neuroimaging.

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 (DSM-5):
    • A. The criteria are met for major or mild neurocognitive disorder.
    • B. Evidence of traumatic brain injury with one or more indicators (loss of consciousness, posttraumatic amnesia, etc.).
    • C. The neurocognitive disorder presents immediately after the injury or 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 (DSM-5):
    • A. The criteria are met for major or mild neurocognitive disorder.
    • B. The disorder has an insidious onset and gradual progression.
    • C. Combination of core diagnostic features (fluctuating cognition, recurrent visual hallucinations, spontaneous parkinsonism) and suggestive diagnostic features (REM sleep behavior disorder, 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 (DSM-5):
    • 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.
  • Criteria for probable vs. possible 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
    • 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 (DSM-5):
    • 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.
    • 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 (DSM-5):
    • 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 based on family history/genetics.
    • 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 (DSM-5):
    • A. The criteria are met for major or mild neurocognitive disorder.
    • B. There is insidious onset, and rapid progression is common.
    • C. Motor features of prion disease 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 (DSM-5):
    • A. The criteria are met for major or mild neurocognitive disorder.
    • B. The neurocognitive impairments do not occur exclusively during delirium and persist beyond usual intoxication/withdrawal.
    • C. The substance and duration/extent of use are capable of producing the impairment.
    • D. The temporal course is consistent with the timing of substance use and 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 is 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

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
  • 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