CHAPTER 25

DEMENTIA

Miriam Rabkin, M.D.

            The dementias are a group of disorders involving multiple cognitive defects and the general loss of intellectual ability. Blancard’s 1726 definition, “extinction of the imagination and judgment,”[i] has been expanded into more formal diagnostic criteria, such as those of the Diagnostic and Statistical Manual of the American Psychiatric Association (Table 1), which emphasize the presence of memory loss, impairment in abstract thought, language, praxis or recognition, and disturbance of previous social or occupational functioning. Dementia is a prevalent problem, afflicting approximately 10 percent of 65-year olds and at least 40 percent of those over 85.[ii] While there are more than 60 different causes of dementia,[iii] this chapter will focus on the most common. Internists are often responsible for the diagnosis and care of persons with dementia, and it is important for them to recognize that management of such patients is improved with a “team” approach, utilizing occasional neurologic and psychiatric consultation, intensive social work and nursing care and the close involvement of family members. 

Table 1: DSM IV criteria for dementia

Reprinted and modified from the Diagnostic and Statistical Manual of Mental Disorders, 4th ed, APA 1994.

Diagnosis

            Patients and their families are often the first to note signs of dementia and “informant questionnaires” may be as diagnostically accurate as brief cognitive tests.[iv] Frequent early complaints involve changes in level of functioning, and common early symptoms include forgetting names and conversations, inability to manage finances and difficulty learning new skills. Behavioral changes such as personality change and agitation may also be evident. Overt dementia may be preceded by a three to five year period of mild but significant cognitive impairment in which subtle changes in cognition may be difficult to distinguish from the normal changes of aging. Mild cognitive impairment (MCI) has been studied in a national cohort of patients; 40 to 50 percent of patients progressed to Alzheimer’s disease within four years.

Symptoms that may indicate dementia are summarized in Table 2; the presence of any of these should trigger an assessment. Once the presence of dementia is suspected, history and physical exam should focus on four areas: determining if cognitive impairment is present, excluding delirium and depression, establishing the most likely cause of dementia and deciding if it is treatable or reversible.

Table 2: Symptoms that may indicate dementia

Reprinted and modified from source 10.

(1) Is cognitive impairment present?

            While some patients are obviously forgetful or disoriented, the presence of memory deficits may be subtle. An efficient, well-validated diagnostic tool is the Mini Mental State exam (appendix A), which takes five to ten minutes to perform in the office. A score of less than 24 points is 87 percent sensitive and 82 percent specific for dementia or delirium; conversely, a score of 26 or higher virtually excludes dementia. Other simple questions can be extremely helpful - a 1991 review by Siu[v] found that disorientation to day of the week has a high positive predictive value for the presence of dementia and ability to subtract serial sevens to 79 has a high negative predictive value. Patients with early dementia may have difficulty with prompted recall (remembering the president’s name) and with recognition (recognizing the president’s name). Of obvious importance is the need to take a patient’s level of education, hearing, vision and fluency in English into consideration when assessing cognitive ability. Providers also need to remember that short office-based screening instruments are unlikely to detect mild cognitive impairment (MCI).

(2) Is the patient delirious or depressed?

            As the DSM IV criteria indicate, the diagnosis of dementia should not be made in the presence of delirium or depression and these diagnoses should be carefully excluded in patients with new cognitive deficits. Both dementia and delirium can present with intellectual impairment, and both are common in older patients. Clues to the presence of delirium are rapid progression (over hours to days), reduced attention, incoherent speech, a fluctuating level of consciousness and a waxing and waning course.

            Depression and delirium are often mistaken for one another in elderly patients. Distinguishing the two is complicated by the fact that they can co-exist, that dementia can present as mood disturbance in the absence of significant memory deficits, and that depression can (infrequently) present as dementia or “depression-related cognitive dysfunction”.[vi] A careful clinical interview can be supplemented by using a self-report screening instrument such as the Geriatric Depression Scale, and psychiatric consultation can be extremely useful.

(3) What is the most likely cause of dementia?

            The most common etiologies of dementia are Alzheimer’s disease (AD), cerebrovascular disease and Parkinson’s disease (PD), accounting for approximately 60 percent, 10 percent and 3 percent of patients in clinical series respectively. Critical elements in distinguishing these from each other and from rarer causes include the history, mental status exam, physical exam and laboratory testing.

            HISTORY:

            It is impossible to overstate the importance of a detailed history in the evaluation of patients with dementia. Patients should be carefully interviewed in the language in which they are most fluent, and family members and caregivers surveyed for parallel history. In addition to focusing on aspects of the history which might implicate delirium and depression, specific issues that should be addressed include:

(1)   Time course: Did the symptoms begin abruptly or gradually? How quickly have they progressed?  Alzheimer’s disease typically presents insidiously with subtle defects of short term memory and progresses gradually. Abrupt onset or rapid progression points to another diagnosis - such as delirium.

(2)   Associated illness: Did symptoms present in the context of another medical disorder? Is there a diagnosis of systemic disease such as vasculitis, sarcoid, TB, SLE or diabetes? Has the patient suffered seizures? Strokes? Head trauma? A history of CVA implies that dementia is caused by cerebrovascular disease, but a recent study demonstrated that the presence of brain infarction increases the likelihood that patients with pathologic evidence of Alzheimer’s disease will be symptomatic.[vii]

(3)   Medications and alcohol use: As discussed below, these are among the most common causes of reversible dementia.

(4)   Dietary history: Is there a reason to suspect vitamin deficiency? In a 1988 series of 141 consecutive patients with neuropsychiatric symptoms due to cobalamin deficiency, Lindenbaum et al. found that 28 percent had neither anemia nor macrocytosis.[viii] 

(5)   Occupational history: Has the patient been exposed to heavy metals?

(6)   Social history: In addition to information about alcohol and drug use, patients should be asked about history of syphilis and risk factors for HIV infection. Physicians should have a clear and concrete sense of a patient’s ability to perform the activities of daily living, a key to planning care.

(7)   Family history: Early onset Alzheimer’s disease is clearly inherited, as are Huntington’s disease, several rare metabolic disorders such as Wilson’s disease and mitochondrial and lysosomal disorders.

            MENTAL STATUS TESTING:

            There are many well-validated tools used for cognitive testing. The goal of testing is to demonstrate a decline in intellectual function, to assess if depression may be a contributing factor, to make predictions about future functioning and to plan care. The Mini Mental Status Exam and the Geriatric Depression scale are easily administered by primary caregivers and should be performed on all patients with dementia. More detailed evaluation, such as the Wechsler Adult Intelligence Scale (WAIS), the Blessed Information-Memory-Concentration test, visuospatial testing and the Boston Diagnostic Aphasia Evaluation may also be helpful in making a diagnosis. Neuropsychiatric evaluation of this type can be performed at the Memory Disorders Clinic and should be considered if a patient’s presentation is atypical, a diagnosis is elusive or if dementia occurs before the age of 55.

            PHYSICAL EXAM:

            In addition to the history and mental status examination, a targeted physical exam should be performed on all patients with dementia. Signs of systemic disorders such as vasculitis, SLE, sarcoid, TB and hypothyroidism suggest further tailored evaluation is needed. Careful neurologic examination should include observation of gait and posture, cranial nerves, motor strength, sensation and reflexes:

(1)   Gait and posture: Stooped posture and shuffling gait are characteristic of Parkinson’s disease. A “magnetic” gait in a patient with dementia and incontinence should trigger suspicion of NPH. Patients with a broad-based gait and difficulty turning may have cerebellar dysfunction or posterior column disease (such as cobalamin deficiency). Bradykinesia and abnormal gait are seen late in the course of Alzheimer’s disease, if at all.

(2)   Cranial nerves: Focal abnormalities suggest cerebrovascular disease.

(3)   Motor strength: Focal abnormalities again suggest cerebrovascular disease. Rigidity and cogwheeling are typical symptoms of Parkinson’s disease.

(4)   Sensation: Peripheral neuropathy may be a clue to the presence of cobalamin deficiency, although it is also present in other unrelated disorders such as diabetes.

(5)   Reflexes: As well as looking for focal deficits and the delayed reflexes of hypothyroidism, examiners should test the more primitive “release” reflexes such as snout, glabellar, rooting and sucking which are more commonly found in neurodegenerative disorders. The presence of asterixis obviously points towards hepatic encephalopathy.

            LABORATORY TESTING:

            Further evaluation of the patient with dementia is a matter of some debate. Extensive evaluation, including lumbar puncture, was once standard practice. In 1987, a National Institutes of Health Consensus Conference recommended that all patients with dementia have a CBC, electrolyte panel, screening metabolic panel, thyroid function tests, vitamin B12 and folate levels, syphilis serology, urinalysis, electrocardiogram and chest Xray.[ix] Subsequent studies indicate that this list may be excessive, and the American Academy of Neurology practice parameters published in 1994[x] suggest that routine evaluation of the demented patient include:

                        (1) CBC

                        (2) serum electrolytes, including calcium

                        (3) glucose

                        (4) BUN/creatinine

                        (5) liver function tests

                        (6) thyroid function tests

                        (7) vitamin B12 level

                        (8) syphilis serology

The 1996 Clinical Practice Guideline on dementia published by the Agency for Health Care Policy and Research makes no specific recommendations about serologic evaluation, other than to refer to the American Academy of Neurology guidelines mentioned above and to caution that “a laboratory test should not be used as a screening procedure or as part of the initial assessment. Laboratory tests should be conducted only after (a) it has been established that the patient has impairments consistent with those used in this guideline (i.e. in multiple domains, not lifelong, representing a decline from a previous level); (b) delirium and depression have been excluded; (c) confounding factors such as educational level have been considered; and (d) it is relevant to rule out a medical condition.”[xi]

            In selected patients, further investigation is appropriate. Indications for lumbar puncture include suspicion of infection or vasculitis, positive syphilis serology, the presence of metastatic cancer, rapidly progressive dementia or dementia in a patient under the age of 55. Neuroimaging is indicated in patients with focal neurologic deficits, seizures, prominent gait disturbance, a history of head trauma or dementia at an early age. Risk factors for HIV should prompt serologic testing regardless of age.

            Several new diagnostic tests for AD have recently emerged. The best studied is the use of ApoE genotyping as a diagnostic (not screening) test.[xii] A 1998 report by Mayeux et al.[xiii] based on over 2,000 autopsied patients with dementia, examined the incremental diagnostic yield of knowing if patients had one or more E4 alleles. Clinical probabilities of having Alzheimer’s disease as the specific cause of dementia were computed based on age, sex, and a clinical assessment that included routine blood tests to exclude reversible causes of dementia and head imaging. Knowing the ApoE genotype improved the area under the ROC curve by about eight percent, mainly by reducing the false positive rate. The diagnostic strategy of clinical assessment followed by ApoE genotyping could not exclude other causes of dementia in a small number of subjects (about four percent in this study). Very few African-Americans or other minorities were in this study. The utility of ApoE genotyping in routine clinical practice will depend on the ability of the clinician to generate Bayesian probabilities, will require knowledge of pre- and post-testing genetic counseling, and should be preceded by evidence showing that a specific diagnosis of Alzheimer’s disease, rather than a strategy of excluding reversible causes of dementia, benefits patients, the health care system, or both. While it is likely that this test will become part of the accepted assessment of demented patients, based on these considerations, we do not recommend its use at this time.

(4) Is there a potentially reversible cause of dementia?

            When discussing dementia, the terms “treatable” and “reversible” are not interchangeable. While there is no curative therapy for most forms of dementia, such as Alzheimer’s disease, many symptoms are treatable and intervention can greatly improve quality of life. A potentially reversible dementia, however, is one in which a patient’s baseline intellectual function can be restored. It is critically important to consider reversible causes when evaluating a patient with dementia. However, clinicians should be aware that even if potentially reversible dementias exist, treatment may not be effective. In series of patients with dementia, potentially reversible causes are found in fewer than 20 percent. The most common of these are drug toxicity, alcohol abuse and depression. In one of the few papers to address follow-up after treatment, Clarfield analyzed 32 studies including 2889 patients and found that 13 percent had potentially reversible dementias but only 11 percent improved with treatment and only 3 percent had complete reversal.[xiv]

            The list of disorders causing potentially reversible dementia is extremely long (Table 3), raising the spectre of extensive and invasive evaluation of every patient with dementia. This is a low yield approach. Instead, careful attention should be paid to the history, remembering that it is often extremely useful to obtain history from caregivers as well as patients. Patients should bring all their medications to clinic (including all nonprescription drugs, supplements and vitamins). Many routinely prescribed medicines such as antihypertensives, H2-blockers and nonsteroidals can affect cognition in elderly patients, and polypharmacy is a particular concern.[xv] Appendix B reviews some of the medications that are known to cause cognitive impairment. Alcoholism among the elderly is increasingly common, and alcohol use should be reviewed.

            After medication side effects, alcohol use and depression, normal pressure hydrocephalus (NPH), metabolic disorders, hypothyroidism, neoplasm and trauma are less frequent etiologies of potentially reversible dementia. As noted above, recommendations for routine laboratory testing usually include thyroid function tests, syphilis serology and B12 levels.

Table 3: Causes of potentially reversible dementia

Reprinted and modified from source 10.

Treatment

            Treatment of dementia falls into two categories, cognitive and behavioral. Clearly, attempting to slow the progress of dementia will vary depending on diagnosis. Treatment of symptoms such as agitation, aggression, depression and incontinence, however, is similar no matter the underlying cause. As we learn more about Alzheimer’s disease, there is increasing interest in the possibilities of primary prevention. Diet and estrogen use are under intense scrutiny – and trials are ongoing - but data are not conclusive. At present, experts believe that there are no modifiable risk factors for Alzheimer’s disease.[xvi]

(1) Treatment of dementing diseases:

ALZHEIMER’S DISEASE:

            FDA-approved drug therapy for the treatment of the cognitive impairment of Alzheimer’s disease (AD) consists of hydergine, tacrine (Cognex^TM) and donepezil (Aricept^TM). Hydergine was initially conceptualized as a cerebral vasodilator, although this has subsequently been disproved; it does not appear to improve cognitive ability but instead may cause mild improvement in mood in those demented patients who are depressed. Tacrine and donepezil are central acetylcholinesterase inhibitors whose effects appear to be limited; they are best understood as weak palliative agents for AD.

            Although a 1986 trial[xvii] reported dramatic improvements in patients with AD treated with tacrine, result of this magnitude have not been reproduced, and the methods used in that study have been formally criticized by the FDA.[xviii] Five subsequent trials, including a 30-week randomized controlled trial in healthy patients with mild to moderate AD,[xix] have demonstrated slight improvements in cognitive function which disappear as soon as the drug is stopped.[xx] The half-life of tacrine is two to four hours and it must be given as a QID drug. Complications of tacrine include gastrointestinal side effects and transaminase elevation,[xxi] and dropout rates in clinical trials have been high (>50 percent). We do not recommend the use of this agent.

            Donepezil has also been tested in short trials of patients with mild to moderate AD and was associated with a slight improvement in cognitive function or lack of further deterioration compared to placebo. These trials had a drop-out rate of approximately 20 percent.[xxii]^,[xxiii] The agent has not been associated with LFT abnormalities, although nausea occurred in a small number of patients, and has a much longer half-life which permits once-daily dosing. At present, it is not known which patients are most likely to benefit from cholinesterase inhibitor therapy, which are most likely to suffer adverse effects and what effects might be observed in patients with intercurrent illness. The durability of cognitive improvement is similarly unclear. It may be appropriate to request neurologic consultation before initiating donepezil therapy.

            In addition to anticholinergic drugs, anti-inflammatory agents, estrogens and dietary antioxidants have all been studied in the treatment of Alzheimer’s disease.[xxiv] Studies of Ginkgo biloba suggest that it may produce a very small improvement in cognitive function; the clinical significance of this change is unknown.[xxv]   In one trial of 341 patients vitamin E (alpha-tocopherol) and selegiline, both dietary antioxidants, delayed nursing home placement in patients with AD when compared to placebo; they had no effect on cognitive function and were associated with more frequent falls.[xxvi] Estrogen therapy is not effective,[xxvii] and there are no data to support the use of NSAIDS, steroids or COX-2 inhibitors. It is most appropriate to refer patients interested in unconventional or untested AD therapies to the Sergeivsky Center at CPMC, where there are several clinical trials of these agents underway.

(2) Common clinical syndromes:

BEHAVIORAL PROBLEMS:

            Wandering, aggression, yelling, inappropriate sexual behavior and elopement are common in the demented, represent a burden to the caregiver both in the home and in institutions, and complicate the care of the cognitively impaired patient. Medical therapy can be effective, but there are no controlled trials demonstrating the superiority of either low dose neuroleptics or benzodiazepines. Both haldol 0.5-1 mg bid or ativan 0.5 mg bid are reasonable first-line interventions.[xxviii] Environmental measures - familiar caregivers, soft lighting, reassurance, music - may be as effective as pharmacologic treatment in some settings. Prior to therapy, any abrupt change in behavior in demented patients should spur a search for an underlying medical cause such as infection, drug toxicity or delirium.

            While it may be tempting to use physical restraints to prevent wandering or falls, data suggest that the use of posey vests, wrist restraints and other similar measures is actually associated with increased risk of injury and aspiration; there have been reports of deaths in patients restrained by posey vests. There are explicit guidelines governing the use of restraints in inpatient settings, and ethical guidelines have been published by the American Academy of Neurology.[xxix]

DEPRESSION:

            As discussed above, dementia and depression can co-exist and treatment of depression frequently improves cognitive ability.[xxx] Sleep disorders can also contribute to decreased quality of life in elders, and should be evaluated.[xxxi] Elderly patients tend to require lower doses of antidepressant medication - a starting dose of Prozac, for example, would be 5-10 mg rather than the usual 10-20 mg. Local resources include psychiatry consultation as well as the Geriatric Depression service. 

INCONTINENCE:

            As dementia progresses, urinary incontinence becomes more common and can complicate care and threaten patient dignity. Common causes of incontinence include confusion, inability to get to the bathroom, medication, fecal impaction, urinary tract infection, urge incontinence, stress incontinence and overflow incontinence. While patients and caregivers may feel that this problem is an inevitable result of “senility,” many forms of incontinence are treatable, and the problem should be formally evaluated. History can provide important clues to the differential and a diary (“bladder record”) can be particularly helpful. Behavioral interventions such as scheduled toileting, prompted voiding and habit training can alleviate the problem, and medication or surgical therapy is sometimes indicated. A thorough discussion of incontinence is beyond the scope of this chapter, but multiple resources are available, including a Practice Guideline published by the Agency for Health Care Policy and Research.[xxxii]

WEAKNESS:

            Deconditioning and weakness can compound problems with gait, balance and reflexes, predisposing demented patients to falls. Physical therapy can improve quality of life and should be considered for all mobile patients who can cooperate. Specific skill training (such as rising slowly, transferring from bed to chair or commode or using a walker) is appropriate, as is counseling about modifying the home environment. A family member or other caregiver should arrange the household to ensure adequate lighting, limited obstacles (stairs, throw-rugs, exposed electrical cords) and an easy way to call for assistance. 

Special Considerations

(1) Advance directives:

            Respect for a patient’s dignity and autonomy demands that the primary caregiver explicitly address the issue of end of life care. Ideally, such a conversation occurs before serious dementia sets in, while patients have the capacity to designate health care proxies and discuss their values and priorities. You should not assume that because a patient has Alzheimer’s disease s/he lacks decisional capacity – this must be assessed on an individual basis for each patient.[xxxiii] This issue is addressed at length in chapter 6. Family members of demented patients require education, counseling and support, particularly as they assume greater and greater responsibility for proxy decision-making.

(2) Palliative care:

            Decisions about withholding and withdrawing care from patients with dementia can be complex and challenging, particularly if patients cannot participate and have not previously discussed their wishes with their family or physician. In general, there is a consensus that the most appropriate care for patients with advanced dementia is comfort-oriented. Routine screening such as Pap smears and mammography is generally not performed and interventions are limited to the treatment of patients’ symptoms. Artificial hydration and nutrition are often avoided, as are diagnostic testing, hospitalization and resuscitation. These decisions must be carefully considered, discussed with the patient and proxy, individualized and explicitly documented.

(3) Caregiver support:

            Caring for a family member with dementia can be exhausting, frustrating and emotionally devastating and physicians should make a special effort to support the spouses, children and other caregivers of demented patients. Counseling and support groups can be very helpful, as can scheduled “holidays” when alternate care mechanisms are planned. Adult day care centers are available for patients who require supervision but not nursing care.

            Decisions about nursing home placement can be complicated. Caregivers are likely to feel guilt about “abandoning” family members, loss as they concede that they are no longer able to care for the patient at home and relief at being spared the burden of care. Financial concerns may also be prominent. Anticipating these decisions and making appropriate referrals to social work can ease the transition to nursing home care.

Acknowledgments

We thank Drs. Richard Mayeux and Mary Sano for their helpful comments and suggestions.