Depression and Cognitive Impairment in Older Adults

Depression is primarily a mood disorder, but it can also be viewed as a cognitive disorder for many older adults. In community samples, the co-occurrence of depression and cognitive impairment doubles every 5 years after the age of 70 years, and they are estimated to co-occur among at least 25% of persons older than 85 years.¹ One of the clinical implications of the co-occurrence of depression and cognitive impairment is that there is a higher risk of adverse outcomes for physical health, functional status, and mortality than from each condition alone.² Moreover, research suggests that depression in late life may be a prodromal symptom of Alzheimer disease^3,4 or a risk factor for dementia in general.^5-7

The clinical challenge of treating geriatric depression with cognitive impairment is determining the extent to which cognitive changes are caused by depression versus underlying brain pathology. With the growing aging population in the United States and many other countries, it is important for mental health professionals to develop skills to diagnose and treat cognitive impairment in older patients with depression.

For the purposes of this article, our use of the term "depression" refers primarily to symptoms that occur in major depressive disorder (MDD), which is defined as 1 or more episodes of neg-ative mood and sadness sufficient to interfere with daily living.⁸ The prevalence of depression is nearly twice as high in women as it is in men.⁹ Community-based studies estimate that 30% of individuals first experience depression in later life (at approximately age 60 years), 40% first experience depression earlier in life, and 30% are difficult to categorize reliably because of problems with retrospective recall of past depressive symptoms.¹⁰

Late-onset depression is more frequently characterized by medical comorbidities, greater apathy, greater cerebrovascular pathology,^11,12 more extensive cognitive impairment, and a stronger association with dementia.³ Early-onset depression is more frequently associated with psychiatric comorbidities, family history of mood disorder,¹³ and volume loss in the hippo-campus when untreated or recurrent.^14,15

Although the assessment of cognitive impairment in geriatric depression is predicated on an accurate assessment of depression itself, a full discussion of the clinical assessment of depression is beyond the scope of this article. Table 1 provides a list of elements that are important to a comprehensive evaluation of geriatric depression. In this article, we focus on interviewing and screening for depression, the influence of medical comorbidities on cognitive impairment and depression, and the differentiation of cognitive impairment secondary to depression from comorbid depression and Alzheimer disease.

Research on the neurobiology of depression has provided important insights into the interrelationship between dysfunctions in mood and cognition. One neurobiological model proposes that a ventral neural system functions to guide affective responses based on the emotional significance and reward value of a stimulus, while a dorsal neural system functions to analyze, monitor, and regulate affective responses to internal thoughts and external events that have high emotional valence.^16,17

The ventral system includes the ventral regions of the anterior cingulate gyrus and prefrontal cortex, the amygdala, insula, and ventral striatum; the dorsal system includes the dorsolateral and dorsomedial prefrontal cortices, the hippocampi, and the dorsal anterior cingulate gyrus. Abnormality or damage in the ventral system can lead to decreased motivation and lack of reinforcement from positive experiences, whereas abnormality or damage in the dorsal system can produce dysregulation of emotional responses and exacerbation of negative affect. This broad neural system receives projections from 3 key neurotransmitters linked to depression: serotonin, dopamine(Drug information on dopamine), and noradrenaline.¹⁸ Emotional and cognitive processes are regulated by both systems, and dysfunction in one system may produce dysfunction in the other.

While many persons with depression experience slowed thinking and concentration difficulties, the presentation of cognitive deficits is more heterogeneous among older adults. Depressed elderly persons typically perform worse than nondepressed elderly on neuropsychological measures of informa- tion processing speed^19,20; cognitively demanding processes of selective attention, response inhibition, and performance monitoring (otherwise known as executive functions)^21,22; and the ability to learn and recall new information.^22,23 In many cases, these underlying deficits are reflected in a patient's subjective complaints (Table 2).

Neurocognitive deficits involving processing speed and executive functions are more common when first onset of depression occurs in late life, and even more so when apathy is a prominent symptom.^21,24 In many cases, the combination of slowed processing, executive dysfunction, and apathy are associated with underlying cerebrovascular pathology involving frontal and subcortical brain regions.^25,26 Other research suggests that older adults with a history of early chronic depression have a more selective deficit in memory,²⁷ probably caused by reductions in hippocampal volume.^14,28,29

Even though elderly persons who are depressed tend to demonstrate more cognitive deficits than nondepressed elderly, a smaller proportion of depressed individuals have impaired cognitive function. Mild cognitive impairment was first proposed to characterize a state of abnormal cognition with a high risk of progression to Alzheimer disease,³⁰ but it is increasingly used in depression to characterize depressed individuals with comorbid cognitive impairment in the absence of dementia.

The prevalence of mild cognitive impairment in depression ranges from approximately 25% to 50%,^31-33 which is substantially higher than the 3% to 6% prevalence of conventional mild cognitive impairment in studies of individuals who are not depressed where memory is the focal deficit.^31,34 An important clinical implication is that mild cognitive impairment or other cognitive impairment during an episode of depression may persist after improvement from the depression symptoms themselves, ranging from one third of individuals with persistent multiple cognitive deficits 1 year after the onset of depression³⁵ to a 4-fold likelihood for impairments in memory to persist 1 year later among individuals who are in remission.³³

With or without cognitive impairment, the occurrence of depression in later life is a clinical concern because it may be either a risk factor for or an early symptom of dementia. Several studies have found a higher risk of dementia among persons with a remote history of depression (10 to 25 years before onset of dementia),^7,36,37 but they also reveal an increased risk for dementia with decreased time between depression onset and dementia diagnosis, which suggests that onset of depression in later life is either a prodromal symptom or that it creates susceptibility for later dementia.

Symptoms consistent with a major depressive episode range from 10% to 30% in patients with mild and moderate Alzheimer disease,^38,39 with an additional 20% to 30% of individuals having other depression syndromes.⁴⁰ Higher rates of depression are seen in patients who have vascular dementia.⁴¹ It is likely that depression is a dementia risk factor for some individuals, while for others it is an early sign of dementia, particularly when the first onset of depression occurs later in life. The key question is which features of affect and cognition best identify which of these respective groups depressed patients fall into.

Clinical screening questionnaires should not be used to formally diagnose depression, but they do provide important information to help identify at-risk individuals by characterizing the nature and extent of symptoms that are associated with depression. The Geriatric Depression Scale (GDS) was developed and validated for use with older adults; as such, it avoids somatic and sexual symptoms, surveys subjective experiences of cognitive impairment, and uses simple yes/no items that decrease cognitive burden.^42,43 A 15-item version of the GDS requires 5 to 10 minutes to complete and is satisfactory for most screening purposes,⁴⁴ with a depression cut-off score of 5 or more.