The Interface of Depression and Dementia

By Malaz Boustani, M.D., M.P.H., and Lea Watson, M.D., M.P.H.
| March 1, 2004

Dr. Boustani is a research scientist at the Regenstrief Institute and assistant professor of medicine at the Indiana University School of Medicine. Dr. Watson is a fellow in geriatric psychiatry at Duke University.

Impact of Depression

In addition to decreasing functional and cognitive status, depression in dementia interacts with other behavioral and psychological symptoms (such as agitation, delusions and hallucinations, and wandering). In one clinical trial, improvement in depressive symptoms among community-dwelling patients with AD with major depression was associated with a decrease in the behavioral and psychological symptoms (Lyketsos et al., 2003).

Various cross-sectional studies conducted in long-term care have found that depression in dementia was associated with higher prevalence of wandering and verbal agitation (Dwyer and Byrne, 2000; Gruber-Baldini et al., 2003). Nursing home residents with dementia who manifested physical or verbal aggression had an approximately threefold increase in the prevalence of depression than those without such behaviors (Lyketsos et al., 1999; Menon et al., 2001). Finally, in a study of 303 community-dwelling patients with AD, the presence of depression was associated with an almost twofold increase in the risk of delusions (Bassiony et al., 2002).

Treating Depression

The goal of antidepressant treatment for depressive symptoms in dementia is to alleviate depressive suffering, improve cognitive performance and decrease the contribution of depression to the other health outcomes of dementia, such as behavioral and psychological symptoms and caregiver burden.

Pharmacological interventions, electroconvulsive therapy, and caregiver or care-recipient-based behavioral interventions are currently available for clinicians to manage depression among older adults. There is concern, however, that some of the antidepressants (such as the tricyclic antidepressants) and ECT might exacerbate the cognitive impairment of patients with dementia with depression. Furthermore, few data are available to confirm the efficacy of the previous interventions among this selected group of vulnerable older adults.

Two reviews of the literature have identified nine randomized, placebo-controlled trials that evaluated the efficacy of pharmacological interventions in reducing depression among patients with dementia (Bains et al., 2002; Olin et al., 2002). Five trials evaluated selective serotonin reuptake inhibitors (sertraline [Zoloft], fluoxetine(Drug information on fluoxetine) [Prozac] and citalopram(Drug information on citalopram) [Celexa]), three evaluated TCAs (clomipramine [Anafranil], imipramine [Tofranil] and maprotiline(Drug information on maprotiline) [Ludiomil]), and one trial evaluated moclobemide(Drug information on moclobemide) (Aurorix), a monoamine oxidase inhibitor not approved in the United States (Fuchs et al., 1993; Olin et al., 2002). These trials suggested that citalopram, sertraline(Drug information on sertraline), clomipramine(Drug information on clomipramine), maprotiline and moclobemide might help in the management of depression in patients with dementia. The findings from the Olin et al. (2002) study are summarized in Table 3.

However, patients enrolled in these trials were selected from both long-term care and community settings and had a spectrum of depressive disorders that ranged from major depression to mild depressive symptoms. Not surprisingly, the impact of medications was greater when treating major depression. None of the previous trials demonstrated any positive effects of antidepressants on cognition. Citalopram and sertraline appeared to be helpful in reducing the other behavioral and psychological symptoms related to dementia, and sertraline had some positive effect on the functional deficit of dementia.

In addition to pharmacological interventions, randomized, controlled trials also show that exercise and behavioral management reduce depressive symptoms in community-dwelling patients with dementia (Teri et al., 2003, 1997). More recently, Brodaty et al. (2003) conducted a 12-week, randomized, controlled trial in 11 Australian nursing homes. They found no efficacy differences among psychogeriatric case management, general practitioners with psychogeriatric consultation and standard care in managing 86 residents with dementia with depression, psychosis or both.

Clinical Implications

Due to the aging of the U.S. population, coexisting depression and dementia present a significant public health problem. Depending on the severity of dementia, using both caregiver and care-recipient-based depression screening instruments will help increase the recognition of depression in dementia. Treating depression adequately in mid- or late life may decrease the risk of the future development of dementia. Verbal agitation and physical aggression might be symptoms of depression among patients with severe dementia. Sertraline and citalopram improve major depression in those with dementia but their efficacy in milder depression is uncertain. Finally, behavioral interventions decrease depressive symptoms in community-dwelling patients with mild-to-moderate dementia. For clinicians treating patients with dementia, the most important message is to routinely assess for depression and to treat it, because successful treatment can improve many dementia-related outcomes.

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The Interface of Depression and Dementia

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