> Table of Contents > Dementia
Dementia
Umer Farooq, MD, MBBS
Wajiha Illyas, MD
image BASICS
DESCRIPTION
  • DSM-5 classifies dementias under neurocognitive disorders (major and mild).
  • Evidence of cognitive decline from previous level of performance in one of cognitive domains (attention, executive function, learning, and memory). The cognitive deficits interfere significantly with ADLs (for major only) and do not occur exclusively in the context of delirium or any other mental disorder.
  • DSM-5 specifies the cause of neurocognitive decline secondary to the following:
    • Alzheimer dementia (AD)
      • Progressive cognitive decline; most common in age >65 years
    • 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
    • Creutzfeldt-Jakob disease (CJD)
      • Very rare; rapid onset
    • HIV dementia
    • Substance-/medication induced neurocognitive disorder
EPIDEMIOLOGY
Prevalence
  • In patients age ≥71 years
    • AD: 5-10% up to 25% after 7th decade of life
    • VaD: 17%
    • Other: 13%
  • Estimated 5.4 million Americans had AD in 2010.
    • 5 million >65 years of age; 200,000 <65 years
    • Prevalence expected to double by 2030
ETIOLOGY AND PATHOPHYSIOLOGY
  • AD: involves &bgr;-amyloid protein accumulation and/or neurofibrillary tangles (NFTs), synaptic dysfunction, neurodegeneration, and eventual neuronal loss
  • Age, genetics, systemic disease, smoking, and other host factors may influence the &bgr;-amyloid accumulation and/or the pace of progression toward the clinical manifestations of AD.
  • VaD: cerebral atherosclerosis/emboli with clinical/subclinical infarcts
Genetics
  • AD: Positive family history in 50%, but 90% AD is sporadic: APOE4 increases risk but full role unclear.
  • Familial/autosomal dominant AD accounts for <5% AD: amyloid precursor protein (APP), presenilin-1 (PSEN-1), and presenilin-2 (PSEN-2)
RISK FACTORS
  • Age; sex: female > male
  • Genetic predisposition
  • Hypertension: AD; VaD
  • Hypercholesterolemia: AD; VaD
  • Diabetes: VaD
  • Cigarette smoking: VaD
  • Endocrine/metabolic abnormalities: hypothyroidism, Cushing syndrome, thiamine and vitamin B12 deficiency
  • Chronic alcoholism, other drugs
  • Lower educational status
  • Head injury early in life
  • Sedentary lifestyle
GENERAL PREVENTION
  • Treat reversible causes of dementia, such as drug-induced, alcohol-induced, and vitamin deficiencies.
  • Treat hypertension, hypercholesterolemia, and diabetes.
  • No evidence for statins (or any other specific medication) to prevent onset of dementia (1)[A]
  • BP control and low-dose aspirin may prevent or lessen cognitive decline in VaD.
COMMONLY ASSOCIATED CONDITIONS
  • Anxiety and major depression
  • Psychosis (delusions; delusions of persecution are common)
  • Delirium
  • Behavioral disturbances (agitation, aggression)
  • Sleep disturbances
image DIAGNOSIS
PHYSICAL EXAM
  • Often normal physical
  • No disturbances of consciousness
  • Cognitive decline demonstrated by standardized instruments, including the following:
    • Mini-mental state exam
    • Montreal Cognitive Assessment (MoCA) Test
    • ADAS-Cog
    • Clock draw test
    • Use caution in relying solely on cognition scores, especially in those with learning difficulty, language barriers, or similar limitations.
DIFFERENTIAL DIAGNOSIS
  • 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)
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • Used to rule out causes
    • CBC, CMP
    • Thyroid-stimulating hormone
    • Vitamin B12 level
  • Select patients
    • HIV, rapid plasma regain (RPR)
    • Erythrocyte sedimentation rate (ESR)
    • Folate
    • Heavy metal and toxicology screen
  • Research studies with cerebrospinal fluid (CSF) biomarkers in patient with confirmed AD have shown decreased A &bgr; (1 to 42) and increased tau and p-tau levels, which are specific features of AD, and CSF tau proteins are increased in CJD (3)[A].
  • Neuroimaging (CT/MRI of brain): cerebral atrophy
    • Early age of onset (<65 years), rapid progression, focal neurologic deficits, cerebrovascular disease risk, or atypical symptoms: neuroimaging (MRI/CT) to rule out other causes
    • Important findings
      • AD: diffuse cerebral atrophy starting in association areas, hippocampus, amygdala
      • VaD: old infarcts, including lacunar
Diagnostic Procedures/Other
PET scan is not routinely recommended; has been approved to differentiate between Alzheimer disease and frontotemporal dementia
Test Interpretation
AD
  • Neurofibrillary tangles: abnormally phosphorylated tau protein
  • Senile plaques: amyloid precursor protein derivatives
  • Microvascular amyloid
image TREATMENT
GENERAL MEASURES
  • Daily schedules and written directions
  • Emphasis on nutrition, personal hygiene, accident-proofing the home, safety issues, sleep hygiene, and supervision
  • Socialization (adult daycare)
  • Sensory stimulation (display of clocks and calendars) in the early to middle stages
  • Discussion with the family concerning support and advance directives
MEDICATION
  • Cognitive dysfunction
  • Medications for AD show a small, statistically significant improvement in some cognitive measures, but it remains unclear if the improvement is clinically significant (4)[A].
  • Cognitive dysfunction, mild
    • Cholinesterase inhibitors: donepezil (Aricept), 5 to 10 mg/day; rivastigmine (Exelon), 1.5 to 6 mg BID, transdermal system 4.6 mg/24 hr and 9.5 mg/24 hr; galantamine (Razadyne), 4 to 12 mg BID, extended release 8 to 24 mg/day
      • Adverse events: nausea, vomiting, diarrhea, anorexia, nightmares, bradycardia/syncope
      • P.265

      • Galantamine warning: associated with mortality in patients with mild cognitive impairment in clinical trial
      • Start drug with lowest acquisition cost; also consider adverse event profile, adherence, medical comorbidity, drug interactions, and dosing profiles.
  • Cognitive dysfunction, moderate to severe
    • Cholinesterase inhibitors OR
    • Memantine (Namenda), 5 to 20 mg/day
      • Adverse events: dizziness, confusion, headache, constipation
      • OR combination cholinesterase inhibitor and memantine
  • Commonly associated conditions
    • Psychosis and agitation/aggressive behavior
      • Look for precipitating factors (infection, pain, depression, medications).
      • Nonpharmacologic therapies (behavioral interventions, music therapy, etc.) are preferred as first-line treatment.
      • Mood stabilizers (valproic acid, carbamazepine) have been used, although evidence is lacking.
      • For moderate/severe symptoms; antipsychotics: Initiate low doses, risperidone 0.25 to 1 mg/day; olanzapine 1.25 to 5 mg/day; quetiapine 12.5 to 50 mg/day; aripiprazole 5 mg/day; ziprasidone 20 mg/day
      • Atypical antipsychotics associated with a better side effect profile: Quetiapine and aripiprazole are often first-line due to decreased extrapyramidal side effect.
  • Depression and insomnia
    • Depression
      • Selective serotonin reuptake inhibitors (SSRIs): Initiate low doses, citalopram (Celexa) 10 mg/day, escitalopram (Lexapro) 5 mg/day, sertraline (Zoloft) 25 mg/day.
      • Adverse events: nausea, vomiting, agitation, parkinsonian effects, sexual dysfunction, hyponatremia
      • Venlafaxine, mirtazapine, and bupropion are also useful.
    • Sleep disturbances
      • Low-dose antidepressants (e.g., Remeron) have significant sedative properties at 7.5 or 15 mg.
      • Trazodone 25 to 100 mg is frequently used because of better side effect profile.
    • Psychosis and agitation/aggressive behavior
      • Some data for SSRIs
      • Benzodiazepines if agitation with anxiety; in elderly, use PRN.
Geriatric Considerations
Initiate pharmacotherapy at low doses and titrate slowly up if necessary.
  • Benzodiazepine are potentially inappropriate for older adults; yet, their use persists.
  • Watch decreased renal function and hepatic metabolism.
ISSUES FOR REFERRAL
Neuropsychiatric evaluation particularly helpful in early stages or mild cognitive impairment
ADDITIONAL THERAPIES
Behavioral modification
  • Socialization, such as adult daycare, to prevent isolation and depression
  • Sleep hygiene program as alternative to pharmaceuticals for sleep disturbance
  • Scheduled toileting to prevent incontinence
COMPLEMENTARY & ALTERNATIVE MEDICINE
  • Vitamin E is no longer recommended due to lack of evidence.
  • Ginkgo biloba is not recommended due to lack of evidence.
  • NSAIDs, selegiline, and estrogen lack efficacy and safety data.
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
  • Worsening physical health issues
  • Psychiatry admission may be required because of safety concerns (self-harm/harm to others), self-neglect, aggressive behaviors, or other behavioral issues.
image 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: sleep, depression, psychosis
  • 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; legal guardianship, if necessary, to avoid capacity and competency issues
  • Advance directives
  • National Institute on Aging. About Alzheimer's disease: other dementias. http://www.nia.nih.gov/alzheimers/topics/other-dementias
PROGNOSIS
  • AD: usually steady progression leading to profound cognitive impairment
    • Average survival of AD is about 8 years.
  • VaD: incrementally worsening dementia, but cognitive improvement is unlikely
  • Secondary dementias: Treatment of the underlying condition may lead to improvement. Commonly seen with normal pressure hydrocephalus, hypothyroidism, and brain tumors.
REFERENCES
1. McGuinness B, Craig D, Bullock R, et al. Statins for the prevention of dementia. Cochrane Database Syst Rev. 2009;(2):CD003160.
2. Blass DM, Rabins PV. In the clinic. Dementia. Ann Intern Med. 2008;148(7):ITC4-1-ITC4-16.
3. van Harten AC, Kester MI, Visser PJ, et al. Tau and p-tau as CSF biomarkers in dementia: a meta-analysis. Clin Chem Lab Med. 2011;49(3):353-366.
4. Birks J. Cholinesterase inhibitors for Alzheimer's disease. Cochrane Database Syst Rev. 2006;(1):CD005593.
5. Softic A, Beganlic A, Pranjic N, et al. The influence of the use of benzodiazepines in the frequency falls in the elderly. Med Arch. 2013;67(4):256-259.
Additional Reading
&NA;
  • 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(7):561-572.
  • National Collaborating Centre for Mental Health. Dementia: The NICE-SCIE Guideline on Supporting People with Dementia and Their Carers in Health and Social Care. London, United Kingdom: British Psychological Society, Royal College of Psychiatrists; 2007. http://www.nice.org.uk/nicemedia/live/10998/30320/30320/pdf
  • Rabins PV, Blacker D, Rovner BW, 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(12)(Suppl):5-56.
See Also
&NA;
Algorithm: Dementia
Codes
&NA;
ICD10
  • F03 Unspecified dementia
  • G30.9 Alzheimer's disease, unspecified
  • F01.50 Vascular dementia without behavioral disturbance
Clinical Pearls
&NA;
  • Medications for AD show a small, statistically significant improvement in some cognitive measures, but it remains unclear if the improvement is clinically significant.
  • Do not forget the role of adult protective services in case of elderly abuse.
  • A particular concern in nursing homes relates to the use of physical restraints and antipsychotic medication, which are regulated in the United States by the Omnibus Reconciliation Act of 1987.