CASE

Mr S is a 72-year-old man who told his primary care provider that he had depressed and low mood, poor sleep with the inability to sleep past 4.00 am, reduced appetite, and loss of interest in hobbies, all over the past 3 months. He was concerned that he had become more “forgetful.” He scored 11 out of 15 on the Geriatric Depression Scale (GDS), indicating severe depression. He scored 23 out of 30 on the Saint Louis University Mental Status Examination (SLUMS) indicating mild cognitive impairment; on cognitive testing, however, he seemed to give up easily and answered many questions with “I’m not sure.” Mr S had experienced a period of depression in his early 20s, which resolved without treatment after about 6 months. His other medical problems included hypertension, hyperlipidemia, and type 2 diabetes mellitus. His primary care provider diagnosed him as having a major depressive disorder and started the selective serotonin reuptake inhibitor (SSRI) sertraline. At an appointment 3 months later Mr S reported that his mood was improved and he had renewed interest in his hobbies. On the 15-point GDS his score was 3, indicating very few depression symptoms, and his SLUMS improved to 29 out of 30.

Current understanding of geriatric depression and the relationship between depression and cognitive impairment

The term depression is used both colloquially and medically, but in both instances indicates feeling blue, sad or unhappy. Medically the term is most often synonymous with major depressive disorder, a psychiatric illness characterized by persistent low mood and/or loss of pleasure and interest in normally enjoyable activities accompanied by changes in sleep and appetite, impaired concentration or difficulty with decision making, low energy, agitated or lethargic motor activity, feelings of worthlessness or inappropriate guilt, and thoughts of dying (see Box 5.1). These symptoms must be present for at least 2 weeks, and must negatively influence functioning or create disruption in the patient’s life. We will use the terms depression and major depressive disorder interchangeably. Researchers use the term subsyndromal depression to refer to mood disorders that do not meet full diagnostic criteria for major depressive disorder, either because the symptoms are present for less than 2 weeks or the patient experiences fewer depression symptoms. Yet patients with this seemingly less severe form of depression have negative outcomes similar to major depressive disorder including greater medical co-morbidity, diminished social activity, functional decline, and higher utilization of healthcare services. They are also at risk for developing major depressive disorder and suicidal ideation.

Box 5.1 DSM-IV-TR diagnostic criteria for major depressive disorder

Depressed mood

Anhedonia (loss of interest or pleasure in activities)

Changes in weight or appetite

Changes in sleep (insomnia or hypersomnia)

Psychomotor agitation or retardation

Low energy

Feelings of worthlessness or guilt

Poor concentration or difficulty making decisions

Recurrent suicidal ideation or thoughts of death

(five or more symptoms present for a 2-week period, including either depressed mood or anhedonia)

Depression is neither a normal nor expected development in old age. The prevalence of major depressive disorder in community-dwelling persons over the age of 65 is only 1%, less than that for middle-aged adults. However, the prevalence increases as the burden of age-related medical illness and functional impairments increases. For example, one study estimated the prevalence of major depression in elderly hospitalized patients to be 11.5%, and 13.5% in those who required home healthcare. Some depressive symptoms are ubiquitous in patients with Alzheimer’s disease, occurring in up to 87% of patients; prevalence estimates of major depression vary, though most reports estimate the prevalence to be 20–25%. In a study of long-term care residents, the incidence of major depressive disorder among those with Alzheimer’s disease was estimated at 6% over 1 year. Depression also complicates the course of less commonly occurring dementias, including, for example, vascular dementia, Parkinson’s disease dementia, and dementia due to Huntington’s disease.

Depression develops most commonly in the early and middle stages of Alzheimer’s disease. Aalten and co-investigators followed 199 patients with dementia, mostly Alzheimer’s disease, for 2 years and found that depression became less prevalent and less severe with disease progression while apathy and aberrant motor behavior, such as pacing, fidgeting, and inability to sit still, increased. Depression in patients with dementia is associated with a higher prevalence of other problematic behaviors, such as wandering and verbal agitation.

EVIDENCE AT A GLANCE

Depression becomes less prevalent and less severe with progression of dementia, while apathy and increased motor activity such as wandering and restlessness tend to increase.

The frequent co-occurrence of depression and dementia was first recognized in the 1880s, when the French psychiatrist Albert Mairet described melancholic depression, a disorder in which both poor mood and cognitive impairment were prominent. In 1952, the term “pseudodementia” was used by John Madden to describe older patients whose cognitive impairment developed and remitted with successful treatment of depression. Other geropsychiatrists have referred to this clinical presentation as “dementia syndrome of depression” and “depression related to cognitive dysfunction.” Despite decades of recognition and interest, researchers still do not agree on the clinical criteria for pseudodementia, yet describe similar characteristics.

In general, patients with pseudodementia complain of global memory decline, with emphasis on disability and subjective distress. They frequently exhibit slowed physical movement, anxiety, and neurovegetative symptoms of depression such as disrupted sleep, changes in appetite, and poor concentration. Their thoughts are marked by a sense of guilt and hopelessness that they will not improve or that any aspect of the future will be pleasurable. Scores on cognitive testing can be lower than expected for their level of function as a result of poor effort, for example, answering, “I don’t know” to even the simplest tests of cognition. In contrast to Alzheimer’s disease, sustained attention and motor speed are more impaired than delayed recall and object naming, and patients are typically capable of retaining information once learned.

TIPS AND TRICKS

Patients with pseudodementia often complain of memory impairment and show poor effort on cognitive examination. In these patients cognitive impairment may initially improve with depression treatment, but most will ultimately develop Alzheimer’s disease.

Pseudodementia is not always a benign condition. Several types of studies support the theory that a large subset of patients with pseudodementia in fact have early Alzheimer’s disease. For example, in a study employing functional neuroimaging, Cho and co-authors showed decreased cerebral blood flow in the temporoparietal region in patients with pseudodementia, similar to that of the Alzheimer’s disease comparators and different from the depressed study participants. Autopsy studies reveal that structural brain changes in patients with pseudodementia and Alzheimer’s dementia are similar. Prospective studies of patients with pseudodementia concur that cognition improves after depression treatment, yet up to 89% of patients subsequently develop dementia, usually Alzheimer’s dementia. Overall, these studies add strength to the finding that pseudodementia presages the development of dementia and, in fact, may represent early dementia, particularly Alzheimer’s disease.

Other associations exist between dementia and depression. Epidemiological studies reveal that depression occurring at any age is associated with an almost two-fold increase in risk of developing dementia, particularly Alzheimer’s disease. It is unclear whether depression represents an early symptom arising from common neuropathological processes or an independent risk factor for the development of dementia. The timing of depression onset, in early or late life, may help to determine the link between these two diseases. Depression occurring in the decades before the onset of dementia suggests depression as a risk factor, as it would be an unlikely early manifestation of dementia so many years in advance. Conversely, depression occurring in the 1–2 years before the onset of dementia suggests depression as an early symptom of dementia, particularly in an individual with no prior history of depression. Evidence exists in support of both hypotheses and there is no agreement at this point. Given what is known about the connection between depression and dementia, it is important to monitor cognition in older patients who have experienced depression at any point in their life.

EVIDENCE AT A GLANCE

Depression occurring at any age is associated with an almost two-fold increase in risk of developing dementia.

The biological basis for these associations remains hypothetical. Proposed pathways linking depression with dementia include vascular disease, hippocampal atrophy, and proinflammatory changes. Because hippocampal atrophy is a hallmark of Alzheimer’s disease, researchers have examined hippocampal volume in patients with depression. One study found reduced hippocampal size in patients with recurrent depression with a volume loss that was proportionate to the total duration of depressive symptoms.

One theory of depression is that the hypothalamic-pituitary axis is overactive, which results in chronically elevated levels of cortisol and damage to hippocampal neurons. In support of this theory, a recent study in rats demonstrated hippocampal neuronal damage associated with exogenous administration of corticosterone. Some studies in humans have shown a similar relationship between endogenous cortisol levels, hippocampal volume loss, and memory deficits. Though an appealing hypothesis, studies have been inconsistent in establishing these associations. An alternative hypothesis thus proposes that early amyloid deposition in the hippocampus due to Alzheimer’s disease leads to hippocampal atrophy and subsequent depressive symptoms, implicating depression as a prodromal symptom of dementia as opposed to a risk factor. Along these lines, depression may be directly linked to dementia through Alzheimer’s disease-specific pathology. Amyloid plaques and neurofibrillary tangles are present in higher amounts in the hippocampus of patients with Alzheimer’s disease with a history of major depressive disorder, compared with patients with Alzheimer’s disease without a history of depression.

As with depression and Alzheimer’s disease, the relationship between depression, vascular disease, and vascular dementia is complex. Vascular pathology has been shown to contribute to cognitive changes as well as dementia, offering support to the connected relationship between depression and dementia. The vascular depression hypothesis, first introduced in 1997 by George Alexopoulos, postulates that cerebrovascular disease is a major contributing factor in late onset depression through disruption of prefrontal systems or their modulating pathways. This can occur with a single lesion or an accumulation of lesions. Support for this hypothesis includes the high prevalence of depression in patients with vascular risk factors, such as diabetes and heart disease; the high prevalence of depression in patients with preexisting cerebrovascular disease, including those who have had symptomatic and asymptomatic strokes; and high prevalence of depression in those with substantial deep white matter lesions. Fujikawa et al. reported that clinically silent cerebral infarcts were found in 93.7% of patients with late onset depression.

In summary, no single process can yet fully explain the neurobiological association between depression and dementia. Depression is a heterogeneous disorder, with contributions from the biological, psychological, and social realms. The processes described are probably not mutually exclusive, and there may be yet undiscovered factors at play. The interaction may be synergistic, with the expression of cognitive impairment dependent on the mix of pathology present in each individual.

Biopsychosocial factors that may contribute to geriatric depression

As noted previously, medical conditions are risk factors for depression, particularly if functional impairment is present. Substance use disorders, such as alcohol dependence, are also associated with depression in old age. Genetic studies have not found any strong markers for late-life depression. No association has been found between the epsilon 4 allele of the apolipoprotein E gene and depressive symptoms. As with younger populations, female gender, a personal history of depression, and a family history of depression are risk factors for geriatric depression.

From a psychological perspective, individuals with a premorbid personality disorder are four times as likely to experience symptoms of depression as those without. In addition, studies that examine personality traits of older patients with and without depression have suggested that qualities such as hopelessness, rumination (repetitively focusing on a particular thought or set of thoughts), catastrophizing (viewing a situation as considerably worse than it is), less positive reappraisal (focusing on the good in what is happening or has happened), and perception of a lack of self-efficacy (the belief that one is capable of performing successfully in a particular situation) increase risk of depression. Depression may also occur as a result of receiving the diagnosis of Alzheimer’s disease or as a reaction to cognitive decline.

A variety of social factors are associated with an increased risk of depression and are prevalent in the aging population. Being unmarried, bereaved, poor, experiencing stressful life events or limited social support, and functional impairment are well-established risk factors for depression in late life.

Only gold members can continue reading. Log In or Register to continue