Depression has been associated with dementia. For example, the Framingham study followed 949 men and women (average age was 79) for 17 years. There was a 50% increased risk of developing a dementia in those reporting symptoms of depression during the study. Similar findings are evident from the Baltimore Longitudinal study of aging.

Depression robs motivation and enjoyment, drives poor self-esteem, adds to the discomfort of pain, and produces social isolation. Depression also distorts memory. In very severe depressions, one is so focused on inner feelings of despair that there are few memory resources left to process information from their surroundings. As if this weren’t enough, people who develop a depression in later life are more at risk of experiencing cognitive decline.

There are four explanations for the association of depression and cognitive decline. First, depression is a symptom of dementia. Second, depression may be a reaction to the loss of memory. Third, depression is a unique risk factor for developing dementia. Fourth, the apathy and loss of engagement or the blunted affect often seen in dementia may be mistaken for depression. Often antidepressant medications are used to treat the depression associated with dementia but until recently their effectiveness has been assumed rather than tested.

A study in Lancet (July 2011) raises questions regarding the effectiveness of the commonly used antidepressants Zoloft (sertraline) and Remeron (mirtazapine) in treating depression in patients with Alzheimer’s disease. Neither medication was more effective than a placebo and both increased unwanted side effects (GI distress for Zoloft and sedation for Remeron). Another study in the British Medical Journal (August 2011) indicates a significant association between adverse outcomes (e.g., stroke, falls, seizures, and mortality) for antidepressant use (including SSRIs, which may fare a bit worse than older tricyclic antidepressants but better than medications such as Remeron, Trazodone, and Effexor) in those over 65.

These findings indicate that use of antidepressants must be carefully considered for those with a diagnosis of dementia or milder forms of cognitive decline and closely monitored in anyone over 65 (include thorough memory evaluation which should assess mood issues). Adverse effects appear more often during the first month of use and weekly monitoring by a professional is essential. A limitation of the study is that it did not address the issues of agitation or aggressiveness. There is clinical lore that antidepressants may calm agitation and aggressiveness that is part of some with dementia. This treatment effect was not addressed and needs to be empirically resolved.

Alternatively, don’t reach for the medications too quickly in the treatment of depression. A first approach in those with cognitive decline may be to treat the depression with nonmedical interventions first and then add medications if needed. Start with cognitive therapy that addresses the lack of worth. Include a plan for exercise and socialization immediately. Whether the issue is apathy or depression, the treatment needs to follow a plan that promotes and structures re-engagement. The idea is to get activated even though you don’t want to.