Basics
Description
- Progressive deterioration in cognition, behavior, or both without impaired consciousness that is severe enough to interfere with activities of daily living due to alteration in cortical brain function. A chronic and progressive form of organic brain syndrome.
- Over 50 different causes, but >60% caused by Alzheimer disease
- Involves increased neurofibrillary tangles and elevated beta amyloid plaques
- Prevalence 1% at age 60 yr to 30-50% by age 85 yr
- Characterized by gradual decline in cognitive functioning:
- Generally evolves over period of years
- Course is highly variable, months to years in duration
- Rapid decline indicative of other causes, or rare rapid onset causes of dementia (prion diseases, progressive supranuclear palsy)
- Variable hereditary
- Increased risk of Alzheimer disease in 1st-degree relatives of patients with Alzheimer
- Apolipoprotein ε4 is the only well-established mutation with late-onset Alzheimer
Etiology
- Primary dementia:
- Cortical (Alzheimer disease, frontotemporal dementia)
- Subcortical (Huntington disease, Parkinson disease, progressive supranuclear palsy)
- Secondary dementia:
- Cerebrovascular disease (multi-infarct dementia)
- Toxic, metabolic, nutritional derangements
- Prion disorders (Creutzfelt-Jakob or bovine spongiform encephalopathy and variants)
- Infectious agents (HIV, syphilis, encephalitis)
- Vasculitis (systemic lupus erythematosus, thrombotic thrombocytopenic purpura)
- Traumatic (chronic subdural hematomas, pugilistic dementia)
- Structural (normal pressure hydrocephalus, brain masses)
- Binswanger disease
- Reversible (~15%) causes include normal pressure hydrocephalus, medications, intracranial masses, and alcohol abuse syndromes
- Pseudodementia:
- Depression in elderly can present with dementia-like symptoms
- Common in mildly demented patients, look for pin-point event with short duration of symptoms
- Generally with history of psychiatric conditions, emphasis on failures and disabilities
Diagnosis
Signs and Symptoms
- Insidious onset, with initial complaints of anxiety, depression, frustration, increased forgetfulness
- Generally preceded by "mild cognitive impairment,"� an intermediate state of cognitive function between normal aging and those meeting criteria for dementia
- Can be grouped into 3 categories:
- Early: Difficulty concentrating, memory deficits, difficulty with complex tasks, social withdrawal
- Moderate: Major memory difficulties, need assistance with activities of daily living
- Severe: Minimal ability to speak or communicate, difficulty eating, loss of psychomotor skills
- Diagnostic criteria (from American Psychiatric Association):
- Development of multiple cognitive deficits manifested by both:
- Memory impairment
- One (or more) of the following cognitive disturbances: Aphasia, apraxia, agnosia, disturbance in executive functioning
- Cognitive deficits that cause significant impairment in social or occupational functioning and are a decline from prior levels of functioning
- Deficits do not occur during course of delirium
History
- Must include input from family and friends
- Complete list of medications
- Comorbid diseases
- Prior history of similar behavior
- Onset and progression
- Consider use of Montreal Cognitive Assessment, Short Test of Mental Status (alternative to mini-mental status exam)
Physical Exam
Full and complete physical exam: �
- Head-to-toe evaluation, all organ systems
- Meticulous neurologic exam:
- Mental status evaluation
- Cranial nerves
- Reflexes
- Motor, sensory, cerebellar, gait
Essential Workup
- Must eliminate acute reversible or exacerbating factors
- Extent of workup is related to history and course of illness:
- Extensive evaluation for new diagnosis
- Directed evaluation for sudden change of dementia
- Limited evaluation for stable disease previously assessed
- Must be able to identify signs and symptoms of the reversible causes of dementia
Diagnosis Tests & Interpretation
Lab
- Extent of evaluation dependent on patient condition and suspected cause
- New diagnosis or sudden deterioration:
- CBC
- ESR/CRP
- CMP
- Ammonia
- Urinalysis
- Toxicology screen
- Thyroid-stimulating hormone
- Vitamin B12 level
- Syphilis serology (RPR)
- HIV
- Blood cultures if fever present
- Urine cultures if fever present
- Antinuclear antibody if SLE suspected
- Established diagnosis with stable disease: No tests may be required.
Imaging
- New diagnosis or sudden deterioration in established dementia:
- CXR if infection considered
- Head CT, without and with contrast
- EEG if suspicion of seizure disorder
- Brain MRI/MRA in selected cases
- More advanced imaging (PET, etc.) should be reserved for use by specialists
- Established diagnosis with stable disease: Studies may not be required.
Diagnostic Procedures/Surgery
- Lumbar puncture and CSF analysis, syphilis serology
- EEG if seizure suspected
Differential Diagnosis
- Toxic, metabolic, nutritional abnormalities:
- Narcotics, sedatives, hypnotics
- Alcohol
- Heavy metals
- Dehydration
- Electrolyte abnormalities
- Pseudodementia
- Delirium (high suspicion for UTI and pneumonia in febrile patients)
- Senescent aging
Treatment
Pre-Hospital
- Obtain history from friends, family
- Provide for patient and staff safety
- Manage agitation
- Attentiveness to comorbid conditions
- Treat acute toxic and metabolic disorders:
- Hypoglycemia
- Hypothermia
- Hyperthermia
Initial Stabilization/Therapy
- Ensure adequate airway
- Administer O2 if hypoxic
- Ensure normal vital signs
- Establish IV access if required
- In agitated patients, provide for patient and staff safety
Ed Treatment/Procedures
- Must determine if patient presents with acute change in mental status
- Consider full differential diagnosis-evaluate and treat appropriately:
- Treat hypoglycemia with PO or IV dextrose.
- Treat narcotic overdose or excess with naloxone.
- Rewarm if hypothermic.
- Antipyretic for hyperthermia
- IV fluids for dehydration
- Correct electrolyte abnormalities
- Administer antibiotics for infection:
- UTI and pneumonia most common occult infections; look for wounds and decubitus ulcers
- Treat seizures:
- Lorazepam, other agents as needed
- Long-term management in conjunction with neurology
- Sedation for agitation:
- Start with low doses and increase as necessary to achieve clinical result.
- Neuroleptics: Haloperidol, risperidone, ziprasidone
- Benzodiazepines: Lorazepam, midazolam
- Soft restraints if chemical sedation ineffective
- Attempt to limit number of medications:
- Reduced likelihood of toxicity
- Reduced likelihood of drug-drug interaction
- If agitation not an issue, eliminate all sedative-hypnotics
- Treat depression
Medication
- Alzheimers agents: Always start at lowest dose:
- Donepezil: 5-10 mg PO at bedtime
- Rivastigmine: 1.5-6 mg PO BID
- Galantamine: 4-12 mg PO BID
- Above 3 anticholinergics without clear superior agent, watch for side effects including nausea, vomiting, diarrhea
- Consider memantine (NMDA receptor antagonist) in those with poor response to anticholinergics: 5 mg PO QID-10 mg PO BID
- Effects generally modest, best started, and changed by primary provider
- Numerous trials showing inconsistent or negative benefit of anti-inflammatory agents, estrogens, and statins for Alzheimer
- Antidepressants: Start with lowest dose:
- Oversedation a problem
- May worsen dementia
- Useful in patients who cannot sleep
- Sedative agents: Always start with lowest dose
- Droperidol: 0.625-2.5 mg IV-advantage, rapid onset; disadvantage, risk for QT prolongation
- Haloperidol: 0.5-2 mg PO BID; start with lowest dose 0.5-2.5 mg IM or IV if rapid onset required
- Lorazepam: 0.5-1 mg IV, 0.5-2 mg PO
- Midazolam: 0.5-2 mg IV slow push
- Naloxone: 0.4-2 mg IVP
- Risperidone: 0.5-2 mg PO BID; start with lowest dose
- Ziprasidone: 20-80 mg PO BID, 10-20 mg IM q4h; start with lowest dose
Follow-Up
Disposition
Admission Criteria
- Unstable vital signs
- Significant comorbid condition requiring parenteral medications:
- Pneumonia
- UTI
- Fluid and electrolyte disorder
- Uncertain diagnosis requiring evaluation and management that is not suitable for outpatients
- Inadequate home support coupled with inability to arrange suitable placement from ED
Discharge Criteria
- Stable vital signs
- No significant unstable comorbid conditions
- Secure diagnosis or elimination of life-threatening organic disease
- Adequate home support, watch for caregiver burnout
- Reliable access to follow-up care
Issues for Referral
- Patients may need assistance with transportation, finances, etc.
- Patients with other comorbidities need referral to appropriate specialists.
Follow-Up Recommendations
- Primary care
- Geriatrician
- Psychiatrist
- Neurologist
Pearls and Pitfalls
- Primary dementia is characterized by slow, steady progression:
- Course is generally 5-10 yr from diagnosis to death.
- Can fluctuate as consequence of intervening illness and comorbid conditions
- Cholinesterase medications can improve functional status in patients with Alzheimer disease.
- Careful attention to medications, secondary illnesses, and prompt intervention for infections can improve quality of life and longevity.
- Death is generally consequence of infection, cardiovascular disease, or injury.
Additional Reading
- Holsinger �T, Deveau �J, Boustani �M, et al. Does this patient have dementia? JAMA. 2007;297:2391-2404.
- Langa �KM, Foster �NL, Larson �EB. Mixed dementia: Emerging concepts and therapeutic implications. JAMA. 2004;292:2901-2908.
- Mayeux, �R. Clinical practice. Early Alzheimers disease. N Engl J Med. 2010;362:2194-2201.
- Mitchell �SL, Teno �JM, Kiely �DK, et al. The clinical course of advanced dementia. N Engl J Med. 2009;361:1529-1538.
- Petersen �RC. Mild cognitive impairment. N Engl J Med. 2011;364:2227-2234.
- Savva �GM, Wharton �SB, Ince �PG, et al. Age, neuropathology, and dementia. N Engl J Med. 2009;360:2302-2309.
See Also (Topic, Algorithm, Electronic Media Element)
- Altered Mental Status
- Delirium
Codes
ICD9
- 294.10 Dementia in conditions classified elsewhere without behavioral disturbance
- 294.20 Dementia, unspecified, without behavioral disturbance
- 331.0 Alzheimers disease
- 294.21 Dementia, unspecified, with behavioral disturbance
- 290.40 Vascular dementia, uncomplicated
- 290.41 Vascular dementia, with delirium
- 290.42 Vascular dementia, with delusions
- 290.43 Vascular dementia, with depressed mood
- 290.4 Vascular dementia
- 294.11 Dementia in conditions classified elsewhere with behavioral disturbance
- 294.1 Dementia in conditions classified elsewhere
- 294.2 Dementia, unspecified
ICD10
- F02.80 Dementia in other diseases classified elsewhere without behavioral disturbance
- F03.90 Unspecified dementia without behavioral disturbance
- G30.9 Alzheimers disease, unspecified
- F03.91 Unspecified dementia with behavioral disturbance
- F01.50 Vascular dementia without behavioral disturbance
- F01.51 Vascular dementia with behavioral disturbance
- F01.5 Vascular dementia
- F02.81 Dementia in oth diseases classd elswhr w behavioral disturb
- F03.9 Unspecified dementia
- F03 Unspecified dementia
SNOMED
- 52448006 Dementia (disorder)
- 1581000119101 Dementia of the Alzheimer type with behavioral disturbance (disorder)
- 191519005 Dementia associated with another disease (disorder)
- 1591000119103 Dementia with behavioral disturbance (disorder)
- 10349009 Multi-infarct dementia with delirium (disorder)
- 14070001 Multi-infarct dementia with depression (disorder)
- 25772007 Multi-infarct dementia with delusions (disorder)
- 56267009 Multi-infarct dementia (disorder)
- 70936005 Multi-infarct dementia, uncomplicated (disorder)