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Special Focus: Dementia

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From the June ACP Observer, copyright © 2007 by the American College of Physicians.

It's a challenging and increasingly common scenario: Patients say their memory just isn't what it used to be. But does it turn out that they need to repeat a phone number three times instead of two to remember it, or are they losing their keys, wallet and glasses five times a day and can't remember the names of their children? Thorough information gathering and evaluation will help determine what's really happening and the best course of action. It can turn what can be a frustrating situation into one with clear and achievable goals.

DementiaAs the baby boomer population ages, the prevalence of these cases will increase because the incidence of dementia increases with age. In 2000, there were 4.5 million people with Alzheimer disease; that number is expected to increase to 13.2 million by 2050, especially because of the increase in patients age 85 and older (Arch Neurol. 2003 Aug;60(8):1119-22). As a result, internists are becoming more aware that symptoms that used to be considered just "a part of getting old" might indicate dementia, said David M. Blass, MD, Assistant Professor of Psychiatry, Department of Psychiatry and Behavioral Sciences, Division of Geriatric Psychiatry and Neuropsychiatry at Johns Hopkins University School of Medicine and editorial consultant for the PIER module on dementia.

"The job of the physician in evaluating patients with dementia is to identify the specific etiology of the condition, and to implement treatment strategies to delay or reduce further worsening, based on the type of dementia," said Dr. Blass, who also is attending psychiatrist at Abarbanel Mental Health Center, Bat Yam, Israel. But having adequate time and resources can be a stumbling block. “If a patient hasn't been scheduled for a long enough visit—at least one hour—he may need to return for a more complete evaluation,” he said.

At the beginning of care, families of patients with dementia often are confused and uninformed about the disease, which is marked by deterioration of memory, concentration and judgment, and often also includes psychiatric disturbances such as depression, anxiety, delusions, hallucinations, aggression, and other behavior disturbances, as well as personality changes. Patients may be unsafe or depressed, be unable to formulate and implement even rudimentary daily plans for themselves and potentially be putting their financial resources at risk. A comprehensive approach including drug therapy, psychosocial interventions, and family education and counseling can improve safety, the family's and patient's emotional state, and the patient's quality of life.

Moreover, it is important for the physician to view treatment results in the same way as managing any patient with a chronic disease. "If you treat a person with diabetes and define success as curing diabetes, you'll feel frustrated and demoralized. But if you define success more realistically to maximize function and quality of life, you'll feel like you accomplished something," Dr. Blass said. "Even though there's no cure for dementia, you can have realistic goals about what can and can't be accomplished, and that can be very rewarding."

PREVENTION

Studies linking hypertension and hypercholesterolemia in middle age to developing both Alzheimer disease and vascular dementia later in life give yet another reason to treat these conditions proactively. Randomized trials have found that treating older patients with hypertension reduces the incidence of both types of dementia, and observational studies have shown that treatment of patients with hypercholesterolemia with statins has similar effects. Specific blood pressure and serum cholesterol targets to achieve this effect are not yet known, but it is reasonable to establish blood pressure and lipid goals based on the patient’s comorbidities.

Counsel patients to stop smoking, increase physical activity and avoid head trauma, all of which are risk factors for Alzheimer disease and vascular dementia. Because several large longitudinal cohort studies show the incidence of vascular dementia is significantly higher in patients with diabetes, aim to reduce hemoglobin A1C levels to <7%. Note, however, that there is as yet no direct evidence that modifying these risk factors is effective in decreasing the incidence of dementia.

Similarly, hyperhomocysteinemia has been shown to be an independent risk factor for development of dementia. In a cohort of 1,092 dementia-free, older subjects from the Framingham Study followed for eight years, elevated homocysteine levels were associated with an increased incidence of dementia of all types, as well as Alzheimer disease specifically. However, as in the case of cardiovascular disease, lowering homocysteine levels with folic acid has not as yet been shown to reduce the incidence of dementia.

Do not recommend either NSAIDs, which have significant side effects, or estrogen to prevent dementia. Early trial data suggesting that they might be protective has not been supported by recent more conclusive evidence.

SCREENING

There are as yet no randomized prospective studies showing the benefits of routine population screening for dementia, and the U.S. Preventive Services Task Force concluded that evidence is insufficient to recommend for or against routine screening for dementia in older adults. Treatment options remain limited, and there is no cure for the disease.

On the other hand, dementia is common, represents a growing problem and causes significant morbidity and expense. It is significantly under-diagnosed, which creates safety problems and hazardous situations. Early diagnosis allows families to engage in advance care planning before the disease progresses. Available treatment may at least delay its progression in many cases and address risk factors for important comorbid diseases.

In general, consider screening patients over age 70 and younger patients with risk factors for cardiovascular disease and those with other neurologic conditions.

Use a standardized cognitive screening test, such as the mini mental status examination (MMSE), a well-known and quick test that covers areas of cognitive function such as memory, orientation, and language. Also, consider other easy-to-administer screening tests like the Mini-Cog, which combines short-term recall and clock drawing. Testing clock-drawing alone is insufficient. Quick, simple tests like these enable the clinician to identify which patients need a more detailed evaluation.

DIAGNOSIS

In patients with a positive screening test, interview the patient and a family member or caregiver to get a detailed history. Ask about:

  • memory loss
  • getting lost
  • word-finding difficulties
  • impaired activities of daily living (eating, bathing, dressing, toileting, transferring or walking and continence)
  • changes in personality, mood, energy level, enjoyment of activities
  • appetite, sleep pattern, sexual activity
  • neurologic changes including gait abnormalities, falls, weakness, clumsiness, abnormal movements, incontinence
  • comorbid conditions that may underlie dementia
  • a complete medication and substance history including benzodiazepines, anticholinergics, barbiturates and other sedative hypnotics as well as alcohol

Family members can provide useful information. Note that memory loss may not be the presenting problem, and patients with early dementia may only appear to be depressed. Sometimes memory difficulties may be the presenting problem of neurologic conditions.

Perform an examination that includes mental status, neurologic and general physical components. In the mental status examination, evaluate:

  • level of alertness
  • short- and long-term memory
  • orientation to time, place and person
  • concentration
  • abstract reasoning
  • use of language, (vocabulary, fluency, repetition, comprehension)
  • visuospatial abilities (clock drawing or design copy)
  • cortical-sensory integrative function (neglect, left-right differentiation stereognosis, graphesthesia)
  • praxis
  • mood
  • presence of hallucinations or delusions

Order certain lab studies (e.g., CBC, TSH, RPR, Vitamin B12,) to look for underlying causes of dementia. Consider testing specific patients with certain risk factors, such as exposure to HIV, exposure to toxic materials such as heavy metals, or substance abuse.

Obtain neuroimaging such as MRI or CT scan, especially if symptoms have been present for less than three years, there has been rapid progression or early age of onset, risk factors for cardiovascular disease or focal neurologic deficits are present or if there is a recent history of head trauma, CNS infection, symptoms atypical for Alzheimer disease or unexplained altered level of consciousness. Note that neuroimaging is required to make the diagnosis of vascular dementia.

If clinical evaluation suggests a specific underlying disease or unusual course of disease, consider other studies such as lumbar puncture when, for example, there is a positive RPR, even if a definitive syphilis test is negative. Also consider lumbar puncture if there is rapidly progressive dementia; immunosuppression; or suspicion of CNS metastatic cancer, CNS infection, CNS vasculitis, hydrocephalus, or Creutzfeldt-Jakob disease.

Consider obtaining an EEG when there is a suspicion of unexplained ongoing delirium, encephalitis, seizures or Creutzfeldt-Jakob disease. Consider neuropsychologic testing to:

  • clarify an uncertain diagnosis, especially to differentiate between mild depression and early dementia
  • identify and characterize the patient's impairment to formulate specific recommendations, and
  • document disease progression over time.

Do not routinely pursue genetic testing (including apolipoprotein E genotyping) in patients with dementia as it does not contribute to the diagnosis of Alzheimer disease or other forms of dementia.

Although memory complaints may not be the presenting symptom in all patients with dementia, they are among the most common. The differential diagnosis of cognitive dysfunction is broad and includes not only the common neurodegenerative dementias (see table) but a number of other disorders affecting brain function including:

  • delirium
  • drugs
  • normal pressure hydrocephalus
  • subdural hematoma
  • traumatic brain injury
  • vitamin B12 deficiency
  • hypo- and hyperthyroidism
  • neurosyphilis
  • HIV disease
  • progressive supranuclear palsy
  • Huntington disease
  • Parkinson disease
  • Creutzfeldt-Jakob disease
  • alcohol abuse
  • toxins including hydrocarbons, solvents, heavy metals, opiates, cocaine
  • systemic diseases affecting the CNS, including vasculitis, infections, renal disease, liver disease, electrolyte abnormalities, Wilson disease

In approaching the differential diagnosis of patients with memory loss and suspected dementia, it is important to appreciate that, unlike patients with delirium, those with dementia generally do not present with an altered level of consciousness. After establishing the presence of dementia, a good history, supplemented by a physical examination and limited use of laboratory studies usually provides the diagnosis.

CONSULTATION

Consider consulting with a specialist (e.g., neurologist, geriatric psychiatrist or geriatrician specializing in dementia) if you don't have enough time to do a complete assessment, if you don't feel you have the knowledge to do so, or if patients have multiple problems, are on multiple medications or have other psychiatric symptoms—depression, psychosis, behavioral disturbances, for example—that complicate the cognitive exam (see "Differential Diagnosis of Memory Dysfunction").

The differentiation between major depression and Alzheimer disease or vascular dementia can be difficult. A specialist can help do this, as well as differentiate medication side effects from symptoms of an illness such as Parkinson's disease. Finally, consider a consult if the patient has atypical features such as early age of onset, rapid decline, focal neurological deficits, strong family history, depression, or if you are uncertain of the diagnosis.

TREATMENT

Non-drug therapy

Non-drug treatment, which can maximize a patient's functional status, is a critical part of a comprehensive approach to treating patients with dementia, especially in treating behavior and later manifestations such as depression, anxiety, hallucinations and delusions.

Address general health and hygiene with the patient and the caregiver. Pay specific attention to dental or denture care, bathing and skin care and toileting. In addition, checking on visual aids such as glasses and hearing aids can go a long way in improving the patient's quality of life.

Address the patient's driving ability with the patient and caregiver. The risks of driving increase with dementia patients and eventually all patients with progressive dementia will lose the ability to drive safely. Patients who have been diagnosed with dementia should undergo a driving evaluation, which is usually available at the local motor vehicle agency or hospital department of occupational therapy. State law varies about whether physicians have to report patients with dementia so be familiar with your local regulations. For those patients still able to drive, repeat the driving assessment every six months.

A number of recommendations regarding lifestyle can be made. For example, counsel patients with vascular dementia to stop smoking. For patients with sleep problems, recommend use of behavior interventions such as sleep scheduling, nap restriction and caffeine restriction. To improve general health and functional independence, exercise can be recommended, an area that is still being studied.

DRUG THERAPY

Current guidelines recommend using acetylcholinesterase inhibitors—donepezil (start at 5 mg/d, increase to 10 mg/d if tolerated after one month), rivastigmine (start at 1.5 mg bid, increase by 1.5 mg bid every month until reaching a target dose range of 6-12 mg/d) or galantamine (start at 4 mg bid, increase by 4 mg bid every month until reaching a target total daily dose of 24 mg)—which can delay cognitive decline in Alzheimer disease, and dementia with Lewy bodies and mixed Alzheimer disease by six to 18 months. Rivastigmine was also recently approved by the FDA for treatment of mild-to-moderate dementia in patients with Parkinson’s disease. Tacrine is no longer used.

Use the N-methyl-D-aspartate receptor inhibitor memantine to delay cognitive decline in patients with moderate to advanced Alzheimer disease. Begin with 5 mg/d, increase doses weekly by 5 mg/d until the target dose of 10 mg twice daily is reached. Use this in addition to a cholinesterase inhibitor, not as a substitute. Do not use high-dose vitamin E to slow the progression of symptoms in Alzheimer disease. Although at one time this seemed safe despite weak evidence, further studies question not only its efficacy but whether it may have led to increased mortality. Also avoid estrogen in women or NSAID treatment, and a new study shows that Ginkgo biloba extract is not as effective as once thought.

At this time, the FDA has not approved any agents for treating vascular dementia due to mixed evidence from clinical trials. There are significant safety concerns about using any medications in patients with vascular dementia although there may be reasons to consider using them in individual circumstances. However, aspirin 325 mg/d may prevent further cerebrovascular events and improve cerebral blood flow and thus can be used in patients with vascular dementia, unless there are general medical reasons to avoid its use. One small, randomized, prospective, double-blind (but not placebo-controlled) study published in the 1989 Journal of the American Geriatric Society has shown significant cognitive improvement, as measured by the Cognitive Capacity Screening Exam, in patients with vascular dementia followed over one to three years.

In addition, treat all underlying conditions, and in particular, use appropriate drugs to modify risk factors for CVD in men and women. Treat hypertension and hypercholesterolemia with adequate doses of appropriate drugs. Control serum glucose in patients with diabetes—lower hemoglobin A1C to <7%, which may improve cognition in patients with diabetes mellitus.

Replace thyroid hormone in patients with memory problems and hypothyroidism. Use monthly intramuscular injections of vitamin B12, 1 mg or oral vitamin B12 2 mg/d in patients with evidence of deficiency as soon as possible, as the earlier it is treated, the greater the chances for cognitive deficit improvement. Treat major depression, which can complicate dementia, with antidepressant drugs. Consider using sertraline, paroxetine, citalopram, fluoxetine, venlafaxine or nortriptyline depending on the individual circumstances. Avoid drugs with the most anticholinergic side effects.

Atypical antipsychotic medications—aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone—have been used to treat psychotic symptoms, such as hallucinations and delusions, or behavioral disturbances such as aggression, severe irritability, agitation and explosiveness, if there is risk of harm to the patients or others or if non-drug treatments have not worked and the patient is in significant distress. However, the FDA has issued a black box warning for all of these agents in response to reports of increased deaths due to cardiovascular events or infections. All of these agents, in particular risperidone, have been associated with increased rate of stroke. Many of these agents have also been associated with increased incidence of diabetes.

Carefully weigh the risks and benefits before prescribing these drugs, use the lowest effective doses, and monitor patients closely. Do not use them to treat insomnia or anxiety. For behavioral symptoms such as aggression, severe irritability, agitation or explosiveness that do not include psychotic features, a trial of carbamazepine or divalproex sodium could be considered before an antipsychotic.

Consider pharmacotherapy for patients with sleep difficulties only if non-drug interventions fail. Trazodone is preferred; zolpidem is a second-line choice. In general, avoid sedative-hypnotics, antihistamines or benzodiazepines in patients with dementia because of the side effects and hazards.

Hospitalization

While hospitalization typically is not necessary to establish the diagnosis of dementia, consider it when the patient cannot complete a full diagnostic evaluation on an outpatient basis because of dangerous behavior, unsafe living conditions, neglected medical conditions or other reasons. Also consider hospitalization, sometimes involuntary, for patients who exhibit behavioral disturbances (e.g., wandering, aggression and calling out) that are dangerous or disturbing to others and cannot be treated successfully outside of the hospital, or for psychosis when others need to be protected and the patient needs to be treated safely and effectively.

Hospitalization should also be considered for patients with severe depression and risk for suicide, decreased food and fluid intake, inability to attend to other serious medical conditions and need for electroconvulsive therapy.

FOLLOW-UP

See patients every six to 12 months to address follow-up issues and to keep abreast of new problems that emerge as the dementia progresses. Follow-up issues include behavior, general medical/dental care, medication administration, safety, driving, nutrition/hydration, hygiene, ADL/daily routine, sleep, mood and/or emotional well being, sensory aids, need for residential placement, and caregiver well-being. Given the high rate of progression to dementia, see patients even with mild cognitive impairment every six to 12 months to reassess cognitive function.

When a family member has dementia, caregivers commonly experience grief, anger, demoralization, guilt and fatigue. Refer them to appropriate psychoeducational programs and educate them about dementia and the challenges it poses. Studies show this can reduce caregiver distress and improve patient mood.

Focus initially on accepting the diagnosis, managing grief and developing a plan to cope with current difficulties as well as safety concerns. Consult with the caregiver before talking to the patient about the diagnosis. When the family is ready, support long-term planning, including finances, medical decision-making and possible placement issues.

Read more on consultation, hospitalization and follow-up in the PIER module "Dementia."


The information included herein should never be used as a substitute for clinical judgment and does not represent an official position of ACP.

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Safety Issues for Patients with Dementia

Expert guidelines suggest that patients not be left alone if they:

  • Cannot use the phone
  • Do not know their full name, address, telephone number, or directions to their home
  • Would not know what to do if they became ill, fell down, or had a fire
  • Cannot distinguish between people who should or should not enter the home
  • Have wandered out of the home
  • Become lost in the neighborhood
  • Say they “want to go home” when they are already there
  • Smoke
  • Misidentify family members

Emphasize to caregivers the importance of being vigilant in the patient's medical care:

  • Supervision of medication administration, because the patient may forget to take the medication, take extra doses, or become confused as to the proper way to take them
  • Notification of the primary care physician of suspected symptoms, including changes in behavior, confusion, or significant worsening of cognition
  • Give patients information about medical alert and safe return bracelets. The Alzheimer's Association Safe Return registration can be reached at:
    Safe Return
    P.O. Box 9307
    St. Louis, MO 63117-0307
    888-572-8566

Refer caregivers to local and national resources for information and support for caregivers, such as the Alzheimer's disease and Related Disorders Association and encourage ongoing participation.

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