Comorbid disease in geriatric patients: dementia and depression

Comorbid disease in geriatric patients: dementia and depression – includes patient information

Rebecca S. Lundquist

Common concerns of primary care physicians working with geriatric patients include management of depression and dementia.[1] These disorders are major causes of morbidity and mortality in the elderly and present significant diagnostic challenges.

Dementia is a common geriatric disorder, affecting one in five persons over the age of 85 years. This disorder, which has many etiologies, represents a global impairment of intellect that interferes with all aspects of life, including social, cognitive and behavioral spheres. Alzheimer’s disease accounts for 75 percent of dementias, but all patients presenting with symptoms of a dementing illness require a thorough investigation to rule out reversible causes.

Depression affects approximately 15 percent of the geriatric population.[2,3] Recognition of depression in this age group is important because suicide rates are higher in the elderly, especially in white men and persons with debilitating chronic illnesses.[4] Although rare, suicide in patients with Alzheimer’s disease has been reported, and its risk should not be overlooked.[5] Depression is a disorder of mood that, like dementia, affects multiple spheres of functioning.[6]

Depression may be difficult to diagnose in elderly patients, for a variety of reasons. Sociocultural differences in beliefs about the meaning of dysphoria in the elderly may affect the willingness of patients to report symptoms to their physician. In addition, the higher prevalence of disabling and painful physical disorders in the elderly may make the somatic signs and symptoms of depression more difficult to elucidate and separate from those of medical illness. These somatic symptoms may include fatigue, sleep disturbance, weight change or constipation.


Memory loss, disinterest in surroundings and cognitive impairment are problems that need to be addressed because they are not signs of the normal aging process. Patients with mild dementia and patients with depression commonly complain about memory deficits, whereas patients with moderate to severe dementia may overestimate their memory.[6]

Coexistence of depression and dementing illness (especially mild to moderate dementia) is common, with an incidence ranging from 19 to 86 percent in some studies.[7,8] In some patients, depression can be mistaken for dementia when changes in cognition result directly from changes in mood. This reversible condition is referr-ed to as “pseudodementia.”

Elderly patients with Alzheimer’s disease who are admitted to a nursing facility or who experience some other change in their environment, such as a change in caregiver status, frequently respond negatively to the disruption. The resultant behavior problems are easily attributed to the dementing illness, and the diagnosis of depression can be missed. When depression is not recognized, these patients may not receive treatment and symptomatic relief.

Finally, and perhaps most intriguingly, late-onset depression may be a harbinger of dementia. In one study,[9] Alzheimer’s disease developed within two years in 39 percent of patients with late-onset depression. Studies that followed a group of patients with pseudodementia for three years[10] and eight years[11] found that Alzheimer’s disease developed in 89 percent of these patients. The exact relationship between depression and the progression toward dementia is unclear.


Since memory loss, cognitive deficit and lack of interest in surroundings are not part of the normal aging process, geriatric patients should be screened for both depression and dementia. In this context, the particular strengths of the primary care physician include a continuing relationship with the patient and the family, as well as a sense of the community in which the patient resides. These are extraordinary assets when working with elderly patients, particularly those with depression and dementia. Both dementia and depression affect not only cognition and behavior but also the activities of daily living. The physician’s knowledge of the patient, combined with data from the patient’s history, physical examination and laboratory studies, are invaluable in assessing both the presence and degree of depression and dementia.

It can be difficult to distinguish between depression with cognitive impairment and early Alzheimer’s disease with depressive symptoms (Table 1).[12] Memory deficits in major depression include problems with attention, concentration and speed of processing. Marked and profound memory deficits, visuospatial disorientation and wandering behavior are uncommon in primary depression. Likewise, neurologic signs of aphasia (speech impairment), apraxia (inability to use tools or execute purposeful movements) and acalculia (inability to perform simple calculations) are features of Alzheimer’s disease and are not seen in patients who have depression without dementing illness.[13]

TABLE 1 Differences Between Depression and Dementia


Family is usually aware of illness Onset dated and more acute Symptoms of short duration History of depression Patient complains of cognitive

deficits Patient is concerned Patient complains in detail Patient highlights failures Little effort at tasks No sundowning(*) “I don’t know” answers typical Variable performance on

psychologic tests No apraxia[dagger] or agnosia[double dagger] Corrects word intrusions Depressed mood often prominent Guilt feelings common


Family is unaware of illness in early

stage Insidious onset Symptoms of long duration No history of depression Patient unaware of cognitive deficits Patient is unconcerned Patient has vague complaints Patient delights in accomplishments Struggles with tasks Sundowning Frequent “near miss” answers Poor performance on psychologic

tests Apraxia or agnosia Has frequent word intrusions Mood typically not depressed No feelings of guilt (*) – Sundowning is disorientation at night or in unfamiliar surroundings. [dagger] – Apraxia is an inability to use tools or to execute purposeful movement. [double dagger] – Agnosia is an inability to recognize objects.

Adapted with permission from Wells CE. Pseudodementia. Am J Psychiatry 1979;136:895-900.

Depression may have an atypical presentation in moderately to severely depressed patients with Alzheimer’s disease. In such patients, a significant underlying depressive disorder may be manifested by the new onset of aggressive behavior, agitation, wandering, crying out or shouting, angry outbursts, apathy, insomnia, resistiveness, cursing, picking, or the refusal of food or medication.[14]

The new onset of agitation in patients with Alzheimer’s disease has a broad differential diagnosis, and other causes must be considered before a diagnosis of depression is made. These causes may include infectious illness, any pain syndrome, medication effects, cardiac ischemia and hypoxia. Furthermore, many patients with Alzheimer’s disease who have a change in environment or caregiver may demonstrate a brief period of agitation.

A change in the functional status of patients with Alzheimer’s disease may be the sign of a new illness, including depression. Caregivers of patients with Alzheimer’s disease need to be interviewed regularly for evidence of deterioration in the functions of feeding, dressing, grooming, toileting and ambulation.


A number of screening instruments for dementia and depression can may be used in the office setting. While screening tools are not diagnostic, they may assist in confirming the diagnostic impression. When used in combination with information from family members about a patient’s level of functioning at home, screening tools can be extremely helpful in unmasking dementia and depression.

Because of its ease of administration and proven validity, the Mini-Mental State Examination (MMSE) is perhaps the best dementia screening tool available to primary care physicians.[15,16] The MMSE has been criticized for being less useful in patients with low levels of education and for being based more on language skills than on visuospatial skills. Some of the bias of the MMSE toward language deficit can be overcome by adding a simple test in which the patient is asked to draw a clock and then number the clock face. The clock test helps to identify patients with the visuospatial deficits of dementia.[17] With periodic administration every three to six months, the MMSE (or a comparable screening test) may also be used to evaluate disease progression.

While a number of depression scales are available, many are too lengthy and time-consuming to be used in the office. The Geriatric Depression Scale (GDS) does have an easily administered short form that has been well validated in geriatric populations.[18,19] Furthermore, the GDS relies less on somatic symptoms, such as constipation and insomnia, that may also be present in elderly patients who do not have depression. Disagreement exists concerning the use of the GDS in demented patients. However, mild to moderate dementia (a MMSE score higher than 15/30) does not seem to affect the usefulness of the GDS, especially when the test is orally administered, rather than self-administered.[20,21]

Screening for depression often can be accomplished by asking the patient one simple question: “Do you often feel sad or depressed?”[22]

Interviewing the family is important in uncovering information and often adds clarity to the evaluation. In one study,[23] researchers interviewed 36 patients with Alzheimer’s disease and their caregivers. Based on information given by the patients alone, only 4.3 percent met the criteria for major depression as given in the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R).[24] When information from caregivers was used, 30.6 percent of patients met the criteria for depression. Other investigators have found similar discrepancies between patient and caregiver reports, underscoring the importance of involving caregivers and family members in the diagnostic process.[25]


The role of laboratory and imaging studies in the diagnosis of dementia and depression varies from patient to patient. Reversible causes for both disorders must be sought through the history and the physical examination, as well as through laboratory and imaging studies.[26] Among the reversible causes of dementia are drug toxicity, metabolic disorders, endocrine disorders, sensory deficits, nutritional disorders, intracranial pathology, infection and inflammatory complications. Many of these conditions can also produce an organic affective disorder with depressed mood (i.e., depression with an identifiable organic cause).

Laboratory tests used in the medical evaluation of depressed and demented elderly persons are listed in Table 2. Patients who are both demented and depressed may have a vascular lesion, such as subdural hematoma, cortical cerebrovascular accident, arteriosclerosis, lacunar infarction, or periventricular small-vessel disease from hypertension (Binswanger’s disease).


Laboratory Tests Used to Evaluate Depressed and Demented Patients

Standard tests

Complete blood count Blood chemistry profile Serum vitamin [B.sub.12] level Thyroid function tests VDRL test for syphilis

Potentially beneficial tests

Erythrocyte sedimentation rate Urinalysis Screening tests for alcohol and drug use Screening tests for heavy metals Screening test for human immunodeficiency

virus infection Electrocardiogram Chest radiograph Computed tomographic scan of the head Cardiac enzyme levels Lumbar puncture Electroencephalogram Magnetic resonance imaging of the head

Although it is not possible to diagnose dementia or depression with any currently available imaging study, many physicians believe that mass lesions, intracranial bleeding and hydrocephalus should be ruled out with either computed tomographic scanning or magnetic resonance imaging. It would be unusual, however, for a patient to be diagnosed with any of these conditions in the absence of localizing signs or other clues in the history or the physical examination.[27]


A variety of pharmacologic and nonpharmacologic treatments are used to manage Alzheimer’s disease, depression and related behavior problems. Although no currently available drug can reverse the dementia of Alzheimer’s disease, concurrent depression is amenable to treatment.


Once the diagnosis of depression is established in the patient with dementia, possible therapies should be discussed with family members and other caregivers, and a treatment plan should be formulated. Providing environmental stability and maintaining a structured daily routine can help reduce the patient’s fear and agitation.[28] Having familiar persons and mementos in the environment can help reduce the anxiety often experienced by a patient with Alzheimer’s disease and depression.

Caregivers must be educated about the dementing process, and they need to be instructed to change their expectations of the patient’s ability to perform tasks and respond to situations. Depression is often caused by the patient’s realization of his or her progressive functional impairment. Caregivers can help reduce the resulting despair and frustration by structuring the patient’s tasks and activities in ways that reduce the likelihood of failure and increase opportunities for success and satisfaction.[29,30]

Adult day care and outpatient psychiatric care can increase patient functioning and help relieve depression, as well as decrease caregiver burden. Cognitive behavior therapy has been shown to be useful in the patient with early-stage Alzheimer’s disease and concomitant depression. Caregivers must be monitored for burnout and depression, with support and referrals given when necessary.[30]


Antidepressant therapy is extremely beneficial in patients with concomitant dementia and depression. Drug treatment may actually be diagnostic of depression by improving depressed mood, decreasing agitation and sometimes lessening memory symptoms.[31] However, cognitive function improves only minimally and remains in the dementia range.[32] The correlation between the presence and severity of depression in patients with Alzheimer’s disease and a resulting decline in cognitive function has been recognized. Whether functional improvement can occur with antidepressant therapy has yet to be established.[33]

Drug therapy for Alzheimer’s disease has consisted of attempts to treat the dementing illness as well as accompanying disruptive behavior symptoms. The U.S. Food and Drug Administration has approved the use of tacrine (Cognex), a long-acting cholinesterase inhibitor, for the treatment of Alzheimer’s disease, even though some doubts exist about the drug’s efficacy for this indication.

One double-blind, placebo-controlled study- of tacrine in mildly to moderately impaired patients with Alzheimer’s disease found that treated patients had a smaller decline in both cognitive function and activities of daily living. However, physicians who independently evaluated these patients detected no global difference between the treated group and the control group.

Alzheimer’s disease appears to be a heterogeneous disorder in which the response to cholinesterase inhibition varies considerably. In patients who benefit from tacrine, clinically significant findings (recognized by both physician and caregiver) usually occur within 12 weeks of gradually increasing doses. Liver toxicity may occur, but it is reversible and is easily detected by monitoring alanine amino-transferase levels every other week for 16 weeks, monthly for two months and then quarterly. Tacrine does not appear to improve depressive symptoms in patients with Alzheimer’s disease. The length of time that this drug is useful for the individual patient has yet to be determined.[35]

Other classes of psychoactive drugs are often used to control the behavior effects of Alzheimer’s disease. The drug classes most commonly used for this purpose are the antipsychotics and the anxiolytics. While a full discussion of these drugs is beyond the scope of this article, it is important to note that antipsychotic and anxiolytic agents can have significant side effects, especially when they are used in large doses over long periods. These drugs do not alleviate depression in patients with Alzheimer’s disease.[36]

While antidepressant therapy is efficacious in patients with Alzheimer’s disease and concomitant depression, elderly patients are more susceptible to the most common and dangerous side effects of these medications, including central and peripheral anticholinergic effects (which can result in delirium), cardiovascular effects and sedative effects. Thus, in treating a geriatic patient with depression, it is very important to choose a drug that has a favorable side effect profile.

Lower doses of most antidepressants are effective in the elderly. Treatment is generally initiated at one half the recommended dose, and the patient is monitored for side effects as the dosage is titrated upward. Some physicians obtain an electrocardiogram and orthostatic blood pressures soon after a patient is started on an antidepressant medication.[37]

Antidepressants with greater anticholinergic effects, such as amitriptyline (Elavil, Endep), doxepin (Sinequan) and imipramine (Tofranil), generally are not favorable choices for elderly patients with dementia. Of the tricyclic antidepressants, nortriptyline (Pamelor) and desipramine (Norpramin) are considered to be more appropriate choices because of their decreased anticholinergic and sedative properties. Trazodone (Desyrel) is useful for its sedating effects, and it has been shown to reduce agitation.[37]

Tricyclic antidepressants do not change cognitive function in patients with Alzheimer’s disease. Furthermore, the beneficial effects of these drugs may not become apparent until patients have been receiving an effective dose for at least four weeks.

In recent years, a number of drugs with novel structures and mechanisms of action have become available.[38] Selective serotonin reuptake inhibitors (SSRIs), including fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil) and others, have been marketed heavily for use in geriatric populations. Although the SSRIs appear to have fewer anticholinergic and cardiac side effects, more work needs to be done to determine whether these agents are appropriate for patients with cognitive impairment and dementia. Preliminary studies in these patients tend to show equivalent efficacy for the various SSRIS. However, these agents may cause agitation, insomnia, gastrointestinal disturbance and weight loss. Other recently introduced drugs, such as nefazodone (Serzone) and venlafaxine (Effexor), show promise as alternative antidepressants with low side effect profiles.[39]

Referral to a psychiatrist should be considered for patients with intolerance of an antidepressant or nonresponse at six to eight weeks after the initiation of antidepressant drug therapy.

Final Comment

Numerous resources are available to primary care physicians who are managing patients with Alzheimer’s disease and depression. Local chapters of the Alzheimer’s Association can provide information on resources for patients and caregivers. Psychiatric consultation can be helpful when a patient is difficult to manage or has exhausted the resources and knowledge of the physician.


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The Authors

REBECCA S. LUNDQUIST, M.D. is a fourth-year resident in the Harvard Longwood psychiatry residency program and the Department of Psychiatry at Harvard Medical School, Boston. Dr. Lundquist received her medical degree from Wright State University School of Medicine, Dayton, Ohio.

ANTHONY BERNENS, M.D. is a fourth-year resident in the Department of Internal Medicine at the University of California, Davis, Medical Center, Sacramento. He graduated from Wright State University School of Medicine.

CYNTHIA G. OLSEN, M.D. is executive vice chair and associate professor in the Department of Family Medicine at Wright State University School of Medicine, where she earned her medical degree. Dr. Olsen completed a family practice residency at Good Samaritan Hospital, Dayton, and also earned a certificate of added qualifications in geriatric medicine.

Address correspondence to Cynthia G. Olsen, M.D., Department of Family Medicine, Wright State University School of Medicine, Franciscan Medical Campus of Dayton, 627 Edwin C. Moses Blvd., Dayton, OH 45408.

COPYRIGHT 1997 American Academy of Family Physicians

COPYRIGHT 2004 Gale Group