Therefore, whether cognitive dysfunction is associated with the overall syndrome of MDD may be less relevant than whether cognitive dysfunction identifies a more biologically homogeneous subset of people with the MDD syndrome.
Cognitive dysfunction in adult MDD
The definition of MDD includes subjective complaints of impaired ability to think or concentrate. It is common for people with MDD to perceive decreased ability to focus attention and to experience forgetfulness. When formal cognitive testing was undertaken in adult patients with MDD, modest degrees of abnormalities in explicit verbal and visual memory, attention, verbal learning, speed of task performance, and executive processes were found. The largest effect sizes across studies were seen in the domains of encoding and retrieval of episodic memory, although the magnitude of these abnormalities is less than in patients with dementia, bipolar disorder, or schizophrenia.17
The literature on cognitive deficits associated with MDD is extensive but somewhat inconsistent on many critical points. While the vast majority of studies have found cognitive abnormalities, some studies in adults younger than 50 years have found only mild abnormalities or normal cognitive function.18 In a large European study of 8229 younger (mean age, 48 years) outpatients with MDD, about 2.5% were classified as normal or better than normal on a delayed recall memory test; 15.5% were rated as mildly impaired, 41% as mildly to moderately impaired, 35% as moderately to severely impaired, and only 6% as severely impaired.4
Cognitive deficits are generally worse and more frequently present in patients who:
• Are older
• Have more severe MDD symptoms or psychotic or melancholic features
• Present with co-occurring fibromyalgia, cardiovascular disease, or diabetes
• Have clinical features associated with a greater risk of bipolar disorder
Recent work suggests that hypercortisolemia may be associated with impaired memory and executive dysfunction in younger adults with MDD. Processing speed is more dependent on depression symptom severity.19
Many important questions remain. There continues to be some degree of uncertainty about whether cognitive symptoms are trait-related or state-related.20 While many studies have found cognitive dysfunction in patients with MDD who are in remission, many treatment studies show substantial improvement of cognitive measures in most patients. The question also remains as to how much reduced motivation, slowing, and inattention contribute to the broader set of cognitive abnormalities seen in patients with MDD.21
Furthermore, while some studies suggest that longer duration of illness or a greater number of prior episodes are associated with more severe cognitive dysfunction, other studies have failed to find these associations.
Cognitive dysfunction in geriatric MDD
The most robust and consistent abnormalities in cognition have been identified in older patients with MDD.5 This is perhaps not surprising in that most of the cognitive impairments seen in patients with MDD are remarkably similar to those that are found with normal aging, including slowed performance, attention problems, and short-term memory deficits.22 However, studies that have used same-age controls with similar degrees of risk factors for cardiovascular disease generally find that the MDD group has greater cognitive impairment.4,23
Within the geriatric MDD group, patients with a greater volume of deep white matter hyperintensities on MRI scans have the worst cognitive function.10,24 White matter hyperintensities are common in old age and occur in up to 60% of healthy older adults.25 However, older patients with MDD generally have a greater number of deep white matter hyperintensities than age-matched controls, and the presence of these lesions is associated with worse cognitive performance, particularly in domains of executive function.15,26
