Dementia

I. Background
Dementia is characterized by memory impairment along with the loss of other cognitive functions. Cognitive deficits may include difficulty with language (aphasia), common motor tasks (apraxia), the identification of common objects (agnosia), or complex and abstract thinking (executive functioning). These deficits must be severe enough that social behavior or independent living is impaired (1).
II. Pathophysiology
A. Etiology
Dementia is a syndrome rather than a disease, so etiology and pathophysiology can vary greatly. Most of the common dementias are progressive, but some are due to reversible causes.
  • Alzheimer's disease (AD) is multifactorial. There is both a familial predisposition and some evidence that AD has a significant vascular component, because there are many risk factors for progression in common with vascular dementia (2).
  • Vascular dementia can be due to multiple infarcts or small vessel disease.
  • Dementia syndromes can be found in connection with other degenerative neurologic diseases such as Parkinson's disease with dementia (PDD), frontotemporal dementia (FTD), Lewy body dementia (LBD), Huntington's disease and progressive supranuclear palsy (PSP).
  • Infectious diseases such as neurosyphilis, acquired immunodeficiency syndrome dementia, and Creutzfeldt-Jacob disease (CJD) can present with dementia. However any infection, such as urinary tract infection, can cause a patient with diminished reserve to decompensate and present with dementia.
  • Other dementias are found with metabolic diseases such as Gaucher's disease or with toxins such as alcohol-related dementia.
  • Normal pressure hydrocephalus is a potentially reversible dementia, which is characterized by the triad of dementia, gait instability, and urinary incontinence.
  • Other reversible dementias can be due to a variety of medical conditions such as hypothyroidism or vitamin B12 deficiency. Dementia can be due to electrolyte imbalance, hypoglycemia, hepatic, or renal dysfunction, hypoxia due to cardiac or pulmonary disease, depression, drugs, or trauma.
B. Epidemiology
  • The most common chronic dementia syndrome in the elderly is AD, accounting for an estimated 50% to 60% of dementias or over four million Americans (3).
  • Chronic dementia is due to vascular dementia in about 15% to 20% of cases. The other neurodegenerative dementias are less common (3).
  • Reversible dementias are more likely to be found in younger patients and may have a rapid onset measured in days or weeks rather than months or years.
III. Evaluation
A. History and physical examination
The history and physical findings make the diagnosis or help direct the workup of a potentially reversible dementia. A Mini-Mental State Examination (MMSE) (see Chapter 4.5), complete neurologic examination, and depression screen should be performed. A referral for formal neuropsychologic testing may be considered in patients who are difficult to evaluate because of a language barrier, suspected psychiatric diagnosis, education level, or upon request.
B. Testing
  • The American Academy of Neurology (AAN) recommends routine testing only for vitamin B12 deficiency and hypothyroidism as causes of dementia (4).
  • Other laboratory tests that may be helpful if clinically indicated due to a suspected medical condition contributing to dementia, include complete blood count, urinalysis, lipid panel, coagulation studies, comprehensive metabolic panel, toxicology, human immunodeficiency virus, Lyme disease titer, or Venereal Disease Research Laboratory test. A lumbar puncture is not routinely recommended.
  • A noncontrast head computed tomography or magnetic resonance imaging is recommended for initial evaluation. Positron emission tomography, single-photon emission computed tomography, and other imaging are investigational and are not recommended (4).
C. Genetics
The most studied genetic marker for dementia is apolipoprotein E epsilon 4 associated with AD. The AAN guidelines currently recommend against routine testing for any genetic markers for dementia syndromes except for specific cerebrospinal fluid proteins found in cases of suspected CJD (4).
IV. Diagnosis
A. Differential diagnosis
Any reversible dementias should be considered. The diagnosis of chronic dementia syndromes is based mainly on clinical manifestations.
  • The diagnosis of AD is clinically based on a slowly progressive dementia not due to other diseases, and not exclusively during a period of delirium.
  • A stroke syndrome or sudden or stepwise deterioration may suggest vascular dementia.
  • Findings of Parkinson's disease may indicate PDD or LBD. In PDD the motor features are most prominent, whereas in LBD the main features are sleep disturbance, syncope, falls, and hallucinations.
  • In FTD, also known as Pick's disease, patients have socially inappropriate uninhibited behavior or personality changes, but memory may be fairly well maintained.
  • Patients with PSP have downward gaze abnormalities and frequent falls.
  • Pseudodementia is common with depression, as well as with other psychiatric diagnoses.
B. Clinical manifestations
Dementia, whether mild, or advanced, often presents as a complaint from family. If a patient presents with the complaint of memory loss, it is important to consider depression, factitious disorders such as malingering, mild cognitive impairment, or normal age related cognitive decline (see Chapter 4.5). A high index of suspicion, a good history from those who know the patient well, and following serial examinations and MMSE scores help make the diagnosis.
References
1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th ed. Washington, DC: APA Press, 1994.
2. Sadowski M, Pankiewicz J, Scholtzova H, et al. Links between the pathology of Alzheimer's disease and vascular dementia. Neurochem Res 2004;29(6):1257 - 1266.
3. Adelman AM, Daly MP. Initial evaluation of the patient with suspected dementia. Am Fam Physician 2005;71(9):1745 - 1750.
4. Knopman DS, DeKosky ST, Cummings JL, et al. Practice parameter: diagnosis of dementia (an evidence-based review): report of the quality standards subcommittee of the American Academy of Neurology. Neurology 2001;56(9):1143 - 1153.