I. Problem/Condition.

Dementia is the progressive impairment of memory and cognition that interferes with a patient’s work and social relationships. The level of consciousness and attention are preserved in dementia. Evaluating a person for dementia involves determining whether there has been a loss of cognition relative to a previous level of performance. Typically, evidence is obtained through the clinical history from a knowledgeable informant such as a family member or close friend and should be documented by mental status testing.

It is important to recognize that although Alzheimer’s disease is the most common form of dementia, there are many other types that can be diagnosed by careful clinical evaluation.

II. Diagnostic Approach

A. What is the differential diagnosis for this problem?

The differential diagnosis of dementia should emphasize common conditions, such as dementia associated with strokes (multi-infarct dementia) or Lewy bodies, and potentially treatable disorders that may cause, or exacerbate, dementia. Although reversible disorders are uncommon, their importance justifies a thorough evaluation of each patient.

This a list of the causes of dementia by category:

Trauma with concussion, chronic subdural hematoma

Infectious: human immunodeficiency virus (HIV) dementia, syphilis, post-herpetic encephalitis, focal cerebritis/abscess

Neoplastic: benign or malignant tumor, primary or metastatic

Metabolic: hypothyroidism, vitamin B12 deficiency, uremia, chronic hepatic encephalopathy, adrenoleukodystrophy

Vascular: multi-infarct dementia, Binswanger’s encephalopathy, diffuse hypoxic/ischemic injury

Drugs and toxins: medications (beta-blockers, neuroleptics, antidepressants, anticonvulsants), substance abuse, toxins such as lead, mercury and arsenic

Demyelinating such as multiple sclerosis, progressive multifocal leukoencephalopathy, sarcoidosis

Obstructive: normal pressure hydrocephalus, obstructive hydrocephalus

Degenerative: Alzheimer’s disease, Pick’s disease, Parkinson’s disease, Huntington’s disease, frontotemporal dementia, progressive supranuclear palsy, Lewy body disease, Wilson’s disease

B. Describe a diagnostic approach/method to the patient with this problem

Once it has been established that the patient meets the criteria for dementia, the history of the present illness should be directed towards soliciting the presenting symptoms and associated medical conditions that suggest a specific diagnosis. These include the symptoms noted below, as well as speed of progression, mode of onset, associated focal neurologic deficits, presence or absence of headache, and incontinence. A thorough review of the patient’s medications, assessment of the patient’s vascular and HIV risk factors, alcohol use, and family history of dementia should be obtained. A review of systems that includes complaints that suggest associated medical illnesses is useful. Symptoms vary depending on the cause of dementia.

1. Historical information important in the diagnosis of this problem.

In Lewy body disease, dementia precedes appearance of parkinsonism by months to years. Early visual hallucinations occur in up to 80% of patients and are the major differentiating feature from Alzheimer’s disease. Fluctuations in performance, especially with regards to attention and alertness, are another key feature of the presentation.

Creutzfeldt-Jakob disease (CJD) is usually more rapidly progressive. It can have cerebellar signs and symptoms, and often has distinctive electroencephalogram (EEG) abnormalities.

Atypical parkinsonian syndromes (multiple systems atrophy, progressive supranuclear palsy, corticobasal degeneration) have other features such as cerebellar degeneration, supranuclear gaze palsy, or asymmetrical limb apraxia.

2. Physical Examination maneuvers that are likely to be useful in diagnosing the cause of this problem.

A general physical examination including a detailed neurologic and mental examination can sometimes help clinicians exclude certain diagnoses.

3. Laboratory, radiographic and other tests that are likely to be useful in diagnosing the cause of this problem.

Initial evaluation should include complete blood count (CBC), liver function tests, and sodium, calcium, thyroid stimulating hormone, rapid plasma reagent (RPR), and vitamin B12 levels. In appropriate circumstances, consider HIV testing or Lyme serology. Tests for cholesterol and diabetes mellitus are often checked for risk modification.

Atypical presentations of dementia may require one of the following: ceruloplasmin and copper level (Wilson’s disease), plasma levels of very long chain fatty acids (adrenoleukodystrophy), vitamin E and B1 levels, porphyrins, blood gas, hemoglobin A1c, tumor markers (anti-Hu, anti-Yo, anti-Ri), antinuclear antibody (ANA)/vasculitis work up, urinary heavy metals, thyroid antibodies, and toxicology screen.

Brain magnetic resonance imaging (MRI) is indicated mostly to look for multiple prior strokes suggestive of vascular dementia.

C. Criteria for Diagnosing Each Diagnosis in the Method Above.

Vascular dementia

This includes all dementia syndromes resulting from ischemic, anoxic, or hypoxic brain damage. A history of multiple strokes, an abnormal physical examination with focal neurologic findings, and the presence of vascular risk factors in a person with dementia are all suggestive of vascular disease, but they do not prove that the dementia is related to cerebrovascular disease. Many persons with dementia with white matter changes on MRI or computerized tomography (CT) have Alzheimer’s disease at autopsy. Therefore, although the presence of vascular dementia should be supported by evidence of vascular disease on CT or MRI, the presence of these lesions does not necessarily indicate that the dementia is of vascular origin. Careful control of vascular risk factors such as hypertension, diabetes mellitus, hyperlipidemia, and cigarette smoking may alter the natural history of this illness.

Parkinson's disease

People with well-established Parkinson’s disease (PD) who subsequently develop dementia are often simply referred to as having Parkinson’s disease with dementia. Patients with PD also can develop a dementia that appears to be the result of the invasion of the limbic system and neocortex with Lewy bodies.

In some situations, the dementia and parkinsonian signs appear to develop simultaneously. Patients in these cases are often referred to as having dementia with Lewy bodies (DLB). In addition to dementia and parkinsonian signs, DLB patients have fluctuating cognition, depression, REM (rapid eye movement) sleep disturbances, and hallucinations. These patients may be subject to onset of parkinsonian signs and symptoms with modest doses of neuroleptic medications, and use of neuroleptics should be limited.

Mass lesions

Although rare, brain tumors in the “silent” areas of the brain may present exclusively as a change of personality and intellectual decline. Subtle focal findings usually can be demonstrated on the neurologic examination, but they occasionally are lacking. Similar comments may be applied to subdural hematomas, especially in the geriatric age group. Thus, some type of neuroimaging procedure remains warranted for all patients being evaluated for dementia.

Frontotemporal dementia

This is a rare group of conditions that includes Pick’s disease, primary progressive aphasia, and motor neuron disease with dementia. Patients present with neurobehavioral features of frontal and/or temporal lobe dysfunction, such as socially inappropriate behavior or a progressive language deficit, as opposed to the amnestic syndrome that characterizes Alzheimer’s disease. Patients are typically younger than those with Alzheimer’s disease. Patients also frequently have parkinsonian signs. Families with autosomal dominant frontotemporal dementias with parkinsonism and amyotrophy have been linked to mutations in the tau gene on chromosome 17.

Prion diseases

Prion diseases are a heterogeneous group of fatal neurodegenerative conditions of sporadic, infectious, or genetic origin. The transmissible agent appears to be composed solely of the prion protein, encoded by a gene on chromosome 20, without any nucleic acid, making it unlike any other known viral or bacterial agent. Prion protein is a normal glycoprotein. The most common prion disease is Creutzfeldt-Jakob disease (CJD). Sporadic CJD presents as a rapidly progressive dementia with myoclonus, cerebellar dysfunction, parkinsonian signs, and pyramidal tract signs. Iatrogenic CJD can follow corneal or dural transplants or use of implanted stereotactic electrodes or human growth hormone.

Hydrocephalic dementia

The classic syndrome of hydrocephalic dementia (from normal pressure hydrocephalus) consists of gait disturbance, dementia, and urinary incontinence, although this triad also is seen commonly in Alzheimer’s disease and other degenerative dementias. The onset can progress over months or years. The dementia is mild without the profound episodic memory deficit typical of Alzheimer’s disease. Brain scans typically demonstrate hydrocephalus with enlargement of ventricles out of proportion to sulci.

Numerous studies have attempted without much success to determine predictors of improvement following ventricular shunting. Some patients with gait problems or dementia improve with cerebrospinal fluid (CSF) shunting procedures. However, the insertion of a shunt is not a benign procedure, especially in geriatric patients.

D. Over-utilized or “wasted” diagnostic tests associated with the evaluation of this problem.

Routine brain imaging in the diagnostic evaluation of a patient with cognitive impairment or dementia is controversial.

III. Management while the Diagnostic Process is Proceeding

A. Management of dementia

Cholinesterase inhibitors (ChEI) (also known as acetylcholinesterase inhibitors) have been shown to be effective in the treatment of dementia. Clinical studies have demonstrated small improvements in memory, language, and the ability to perform activities of daily living. Treatment with ChEI may also help to reduce symptoms of agitation and aggressiveness, slow functional decline, and lessen caregiver stress. At present there are no data supporting superiority of one cholinesterase inhibitor over another. Recent data suggest ChEI may be of some benefit in moderate to severe Alzheimer’s disease. See the Alzheimer’s disease chapter for more information on the management of this condition.

B. Common Pitfalls and Side-Effects of Management of this Clinical Problem

About 40% of elderly medical patients lose independence in one or more instrumental activities of daily living (ADL) after discharge. Interventions designed to reduce the risks of functional decline in elderly hospitalized patients have shown modest benefits in terms of functional status, length of hospital stay, and skilled nursing home admissions, although mortality has not been reduced. Delirium in at-risk, medically ill, hospitalized elderly patients can be reduced by 40 percent with a multicomponent targeted risk factor intervention.

Protein-energy malnutrition (PEM) is common in chronically ill elderly patients who are hospitalized for treatment of acute exacerbations of chronic diseases. These are frequently unrecognized or unaddressed early in the patient’s hospital course, often delaying recovery from an acute illness or the healing of wounds and pressure ulcers. Prolonged bed rest or immobility reduces a patient’s ability to transfer from bed to chair or to stand without assistance, and is associated with postural hypotension, falls, skin tears, pressure ulcers, and venous thromboses.

The optimal care of seriously ill patients is often best understood by taking into account their treatment preferences. A review of the patient’s advance directives, either in a living will or through a durable power of attorney for health care, will help guide clinical decision making when the patient is unable to make informed decisions. When discussing advance directives with capable patients, hospitalists should also seek their wishes for end-of-life care, including cardiopulmonary resuscitation, intensive care, or nutritional support during acute or end-stage illness.

When prescribing for older patients, it is important to consider pharmacokinetic and pharmacodynamic changes observed in normal aging and any current diseases, as well as the evidence for therapeutic efficacy and safety. Normal aging is one of many factors that may influence hepatic and renal clearance. Decreased albumin level and reduced phase one metabolism is common. Serum creatinine is not helpful because creatinine production is reduced in elderly patients, which explains why creatinine clearance is a better measurement of renal function in this population.

Discharge planning is facilitated by an interdisciplinary process that identifies patients who will need nursing home placement or home care services. It also serves to estimate the patient’s hospital length of stay, to review with the patient and family the patient’s diagnosis, prognosis, and choices for discharge location, and to review medications, home safety and the promotion of self-care.

Patient safety, including risks associated with impaired driving, wandering behavior, leaving stoves unattended, and accidents, must be addressed with the patient and family early, and appropriate measures implemented.