Dementia – Causes, Symptoms, Diagnosis, Treatment and Ongoing care

Basics

Description

Dementia is a decline in cognitive function potentially caused by a number of disorders:

  • Alzheimer dementia (AD):
    • Progressive deterioration of higher cortical functioning
  • Vascular dementia (VaD):
    • Usually correlated with a cerebrovascular event and/or cerebrovascular disease
    • Stepwise deterioration with periods of clinical plateaus
  • Lewy body dementia:
    • Fluctuating cognition associated with parkinsonism, hallucinations and delusions, gait difficulties, and falls
  • Frontotemporal dementia:
    • Language difficulties, personality changes, and behavioral disturbances

Epidemiology

Prevalence

  • In patients ≥71 years old:
    • AD: 70%
    • VaD: 17%
    • Other: 13%
  • AD 60–64 years: <1%, approximately doubles every 5 years after age 60
  • Estimated 5.2 million Americans had AD in 2008:
    • 5 million >65 years old; 200,000 <65 years

Risk Factors

  • Increasing age
  • Women > Men
  • Lower educational status
  • Genetic predisposition
  • Head injury early in life
  • Sedentary lifestyle
  • Hypertension: AD; VaD
  • Hypercholesterolemia: AD; VaD
  • Diabetes: VaD
  • Cigarette smoking: VaD

Genetics

  • Heterogenous: Sporadic AD, ApoE4 allele on chromosome 19
  • Familial: <0.1% AD, autosomal dominant

General Prevention

Data supporting specific preventative measures are limited and not conclusive:

  • Smoking cessation
  • Physical and mental activity
  • Treatment of hypertension, hypercholesterolemia, and diabetes

Etiology

  • AD:
    • Several mechanisms have been investigated.
    • Neurofibrillary tangles: Unable to support microtubules
    • Neuritic plaques (amyloid β-peptide):
      • Accumulation may lead to impaired cognitive function.
    • Other: Inflammatory mechanisms, oxidative:
      • Stress, mitochondrial dysfunction, apoptosis
  • VaD:
    • Cerebral atherosclerosis or emboli with clinical or subclinical infarcts

Commonly Associated Conditions

  • Anxiety and depression
  • Delirium
  • Behavioral disturbances (agitation, aggression)
  • Sleep disturbances
  • Caregiver stress

Alzheimer's disease, Magnetic resonance imaging, Senile plaques, neuritic plaques, genetic predisposition, cognitive function, hypercholesterolemia,

Diagnosis

History

Probable diagnosis AD (1)[A]:

  • Age between 40 and 90 (usually >65)
  • Progressive cognitive decline of insidious onset
  • No disturbances of consciousness
  • Deficits in >2 areas of cognition
  • No other explainable cause of symptoms
  • Specifically, rule out thyroid disease, vitamin deficiency (B12), grief reaction
  • Supportive factors: Family history

Physical Exam

  • No disturbances of consciousness
  • Cognitive decline demonstrated by standardized instruments, including:
    • Mini-Mental Status Exam
    • ADAS-Cog
    • Clock draw test
    • Change test
  • Deficits in >2 areas of cognition

Diagnostic Tests & Interpretation

Lab

Initial lab tests

  • Used to rule out other causes (1)[A]:
    • Comprehensive metabolic profile
    • Complete blood count
    • Thyroid stimulating hormone
    • Vitamin B12 level
    • Neuroimaging (preferably magnetic resonance imaging [MRI] of brain)
  • Select patients:
    • HIV
    • Rapid plasma reagin
    • Erythrocyte sedimentation rate
    • Folate
    • Heavy metal screen
    • Toxicology screen

Imaging

Tests that support the diagnosis:

  • Cerebral atrophy on neuroimaging
  • Normal lumbar puncture

Initial approach

  • Early age of onset (<65 years old), rapid progression, focal neurologic deficits, cerebrovascular disease risk, or atypical symptoms: Neuroimaging (MRI or computed tomography) to rule out other causes (1)[A]
  • Important findings:
    • AD: Diffuse cerebral atrophy starting in association areas, hippocampus, amygdala
    • VaD: Old infarcts, including lacunes

Diagnostic Procedures/Surgery

Positron emission tomography scan not routinely recommended; has been approved to differentiate between Alzheimer disease and frontotemporal dementia (2)[A]

Pathological Findings

AD:

  • Neurofibrillary tangles: Abnormally phosphorylated tau protein
  • Senile plaques: Amyloid precursor protein derivatives
  • Microvascular amyloid

Differential Diagnosis

  • Mild cognitive impairment
  • Major depression
  • Medication side effect
  • Chronic alcohol use
  • Delirium
  • Subdural hematoma
  • Normal pressure hydrocephalus
  • Brain tumor
  • Thyroid disease
  • Parkinson disease
  • Vitamin B12 deficiency
  • Toxins (aromatic hydrocarbons, solvents, heavy metals, marijuana, opiates, sedative-hypnotics)

Treatment

Medication

First Line

  • Cognitive dysfunction, mild (2)[A]:
    • Cholinesterase inhibitors: Donepezil (Aricept), 5–10 mg/d; rivastigmine (Exelon), 1.5–6 mg b.i.d., transdermal system 4.6 mg/24 hours and 9.5 mg/24 hours; galantamine (Razadyne), 4–12 mg b.i.d., extended release 8–24 mg/d:
      • Adverse events: Nausea, vomiting, diarrhea, anorexia, nightmares
      • Galantamine warning: Associated with mortality in patients with mild cognitive impairment in clinical trial
  • Cognitive dysfunction, moderate to severe (2)[A]:
    • Cholinesterase inhibitors OR
    • Memantine (Namenda) 5–20 mg/d:
      • Adverse events: Dizziness, confusion, headache, constipation
    • OR combination cholinesterase inhibitor and memantine
  • Commonly associated conditions:
    • Psychosis and agitation/aggressive behavior:
      • Antipsychotics: Initiate low doses, haloperidol 0.25–0.5 mg/d; risperidone 0.25–1 mg/d; clozapine 12.5 mg/d; olanzapine 1.25–5 mg/d; quetiapine 12.5–50 mg/d; aripiprazole 5 mg/d; ziprasidone 20 mg/d (2)[A]
      • Atypical antipsychotics associated with a better side effect profile; quetiapine and aripiprazole often 1st-line due to decreased extrapyramidal side effects

Alert

Support Tipsdiscover.com's development and hosting
  • Black box warning on atypical antipsychotics due to increased mortality found when used in elderly patients with dementia
  • Depression:
    • Selective serotonin reuptake inhibitors (SSRIs): Initiate low doses, citalopram (Celexa) 10 mg/d; escitalopram (Lexapro) 5 mg/d; sertraline (Zoloft) 25 mg/d (2)[A]
    • Adverse events: Nausea, vomiting, agitation, parkinsonian effects, sexual dysfunction, hyponatremia
    • Fluoxetine (Prozac) and paroxetine (Paxil) should be avoided in elderly patients.
  • Sleep disturbances:
    • Mirtazapine (7.5–60 mg) or trazodone (25–100 mg) at bedtime if also has depression (2)[A]
    • Atypical antipsychotics if psychotic symptoms present (2)[A]
    • Zolpidem (5–10 mg); zaleplon (5–10 mg) (2)[A]
    • Benzodiazepines only for short term if anxiety or as needed: Lorazepam 0.5–1.0 mg; oxazepam 7.5–15 mg (2)[A]

Second Line

Associated conditions:

  • Depression: Venlafaxine, mirtazapine and bupropion (2)[A]
  • Psychosis and agitation/aggressive behavior:
    • Some data for SSRIs (2)[A]
    • Benzodiazepines if agitation with anxiety; in elderly, use as needed (2)[A]

Geriatric Considerations

  • Initiate pharmacotherapy at low doses and titrate slowly up if necessary.
  • If benzodiazepines indicated for anxiety, choose drug with short half-life
  • Watch decreased renal function and hepatic metabolism.

Additional Treatment

Behavioral modification:

  • Socialization such as adult day care to prevent isolation and depression
  • Sleep hygiene program as alternative to pharmaceuticals for sleep disturbance
  • Scheduled toileting to prevent incontinence

General Measures

  • Daily schedules and written directions
  • Emphasis on nutrition, personal hygiene, accident-proofing the home, safety issues, sleep hygiene and supervision
  • Socialization (adult day care)
  • Sensory stimulation (display of clocks and calendars) in the early to mid stages
  • Discussion with the family concerning support and advance directives

Issues for Referral

  • Neuropsychiatric evaluation particularly helpful in early stages or mild cognitive impairment
  • Assessment and management of:
    • Cognitive problems
    • Mood disorders (e.g., depression, anxiety)
    • Psychosis
    • Behavioral problems (e.g., agitation, aggression)

Complementary and Alternative Medicine

  • Vitamin E is no longer recommended due to lack of evidence and possible association with an increase in mortality (2)[A].
  • Ginkgo biloba should not be recommended due to lack of evidence (2)[A].
  • Huperzine-A appears to have potential in small trials; however, until clinical evidence can firmly establish its role, it should not be recommended.
  • Use of nonsteroidal anti-inflammatory drugs, selegiline, and estrogen should not be recommended due to lack of efficacy and safety data (2)[A].

In-Patient Considerations

Admission Criteria

  • Patients who cannot be treated in an outpatient setting
  • Patients who may require geripsychiatric admission for aggressive behaviors

Ongoing Care

Follow-Up Recommendations

Patient Monitoring

  • Progression of cognitive impairment by use of standardized tool (e.g., MMSE, ADAS-Cog)
  • Development of behavioral problems
  • Adverse events of pharmacotherapy
  • Nutritional status
  • Caregiver evaluation of stress
  • Evaluate issues that may affect quality of life.

Patient Education

  • Safety concerns
  • Long-term issues: Management of finances, medical decision making, possible placement when appropriate
  • Advance directives

Prognosis

  • AD: Progressive disease (variable rates) leading to profound cognitive impairment:
    • Without treatment average decline on MMSE of 2 points per year
  • VaD: Less likely to be progressive, but cognitive improvement is unlikely
  • Secondary dementias: Treatment of the underlying condition may lead to improvement.

Complications

  • Wandering
  • Falls with injury:
    • Hip fracture
    • Head trauma
    • Subdural hematoma
  • Aspiration pneumonia in end stage
  • Caregiver burnout

References

1. Blass DM, Rabins PV. In the clinic. Dementia. Ann Intern Med. 2008;148:ITC4–1-ITC4–16.

2. APA Work Group on Alzheimer’s Disease and other Dementias, Rabins PV, Blacker D, et al. American Psychiatric Association practice guideline for the treatment of patients with Alzheimer’s disease and other dementias. Second edition. Am J Psychiatry. 2007;164:5–56.

Additional Reading

Birks J. Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst Rev. 2006;CD005593.

Blennow K, de Leon MJ, Zetterberg H. Alzheimer’s disease. Lancet. 2006;368:387–403.

Burns A, Iliffe S. Alzheimer’s disease. BMJ. 2009;338:b158.

Lleó A, Greenberg SM, Growdon JH. Current pharmacotherapy for Alzheimer’s disease. Annu Rev Med. 2006;57:513–33.

Lyketsos CG, Colenda CC, Beck C, et al. Position statement of the American Association for Geriatric Psychiatry regarding principles of care for patients with dementia resulting from Alzheimer disease. Am J Geriatr Psychiatry. 2006;14:561–72.

See Also (Topic, Algorithm, Electronic Media Element)

Algorithm: Dementia

Codes

ICD9

  • 290.0 Senile dementia, uncomplicated
  • 290.40 Vascular dementia, uncomplicated
  • 331.0 Alzheimer’s disease
  • 331.82 Dementia with Lewy bodies

Snomed

  • 52448006 Dementia (disorder)
  • 15662003 Senile dementia (disorder)
  • 6475002 Primary degenerative dementia of the Alzheimer type, presenile onset, uncomplicated (disorder)
  • 56267009 Multi-infarct dementia (disorder)
  • 429998004 vascular dementia (disorder)
  • 312991009 senile dementia of the Lewy body type (disorder)

Clinical Pearls

  • Dementia is loss of cognitive function in multiple areas.
  • Time is diagnostic; AD is a progressive disease that will manifest with continual decline over time.
  • Medications for AD show a small, statistically significant improvement in some cognitive measures, but it remains unclear if the improvement is clinically significant.

About the author

Many tips are based on recent research, while others were known in ancient times. But they have all been proven to be effective. So keep this website close at hand and make the advice it offers a part of your daily life.