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Psychiatric Times. Vol. 24 No. 13
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Depression and Cognitive Impairment in Older Adults

By Guy G. Potter, PhD and David C. Steffens, MD, MHS | November 1, 2007
Dr Potter is assistant clinical professor and Dr Steffens is professor and chief of the division of geriatric psychiatry in the department of psychiatry and behavioral sciences at Duke University Medical Center in Durham, NC. They report no conflicts of interest concerning the subject matter of this article.

Another widely used questionnaire is the Beck Depression Inventory (BDI-II),45 which was not developed specifically for older adults but is useful because it surveys suicidal ideation and has item content consistent with DSM-IV diagnostic criteria for depression. A score of 15 is often considered to be the lower range of mild but clinically significant depression.

One important but perhaps overlooked aspect of diagnosing either depression or cognitive impairment is a thorough review of risk factors and medical conditions that can be a primary cause or exacerbating element in both these conditions. This is particularly important in geriatric mental health because medical comorbidities are more common in older adults46 and may have treatable elements.

Cerebrovascular risk factors are influential in the pathogenesis of both depression and cognitive impairment. One study found that persons with 2 or more cerebrovascular risk factors (diabetes, hypertension, or atrial fibrillation) and lower scores on a neuropsychological measure of executive functions had significantly higher levels of depressive symptoms at baseline and at 18 months compared with persons who had fewer cerebrovascular risk factors and better cognitive performance.47

Other common medical conditions that can cause cognitive impairment include hypothyroidism, which often presents with deficits in memory, visual processing speed, and visuospatial/ constructional abilities48; obstructive sleep apnea, presenting with a cognitive profile of psychomotor slowing and deficits in memory, attention, and executive functions49; and vitamin B12 deficiency, which can produce deficits in processing speed and executive functions.50 Several of these conditions (eg, hypothyroidism) can produce depression or behaviors consistent with depression, such as lethargy and fatigue from B12 deficiency, and dysphoria, concentration deficits, and apathy in the context of sleep apnea.

Medication review is also important because depression symptoms have been associated with common medications including α-methyldopa, amantadine(Drug information on amantadine), β-blockers, β-interferon, calcium channel blockers, clonidine, metronidazole(Drug information on metronidazole), prazosin, reserpine, and steroids.51 Deficits in memory and information processing speed have also been associated with benzodiazepines52,53 and tricyclic antidepressants, particularly amitriptyline(Drug information on amitriptyline).54

Several features of the presentation and clinical history of depressed older adults can help clinicians differentiate between a major depressive episode and Alzheimer disease. Table 3 lists differences in the clinical and cognitive presentations of depression and dementia, including the core distinction that cognitive deficits associated with depression generally emerge and remit in concert with mood changes on a timeline of weeks to months. In contrast, cognitive changes in dementia are more independent of mood symptoms and become progressively worse over a timeline of months to years. Table 4 [Table restricted. Please see print edition for content.] summarizes the distinction between diagnostic criteria for a major depressive episode and depression in Alzheimer disease.

It is important to recognize that patients with depression may appear cognitively impaired because they tend to give up easily or produce "I don't know" responses to complex questions or those that require effortful recall. Alzheimer disease may be more likely if the quality of a patient's responses does not improve with increased time to respond or with memory cues. It is also important to carefully assess functional activities to determine whether deficits are caused more by loss of knowledge or ability (Alzheimer disease) or whether they are caused by loss of interest or motivation (depression and some dementia).

Given the possibility of impairments in reporting cognitive and functional behaviors, clinicians should try to obtain collateral information from family members, particularly with suspected dementia, where family is often the first to notice subtle cognitive changes. A quick and useful informant-based screening of cognitive decline and dementia is the Informant Questionnaire on Cognitive Decline in the Elderly.55,56

Clinical screening of cognition is important to identify depressed patients with overt cognitive impairment, but it presents a number of limitations for differential diagnosis and early detection of dementia. Many clinicians use a score of 24 or lower on the Mini-Mental State Examination (MMSE)57 to identify impairment, but this may miss many persons with milder impairment because the MMSE has a low ceiling of difficulty; a limited assessment of processing speed and executive functions; and differential sensitivity to age, education, and ethnicity.58

In our clinical experience, we have seen a number of high functioning, well-educated individuals with perfect MMSE scores and a diagnosis of mild cognitive impairment based on more extensive testing. However, we have also seen many individuals with low literacy and education levels for whom a score of 24 is a reflection of their normal function.

Deficits on cognitive screening or persistent patient or family reports of cognitive difficulty despite improved depression should be followed up with additional clinical assessment and often a neuropsychological evaluation to more fully characterize the severity and extent of cognitive deficits. Neuropsychological evaluations can be useful in distinguishing prefrontally mediated deficits in memory retrieval that characterize a cognitive syndrome of depression from those hippocampally mediated deficits in memory consolidation and storage that characterize early Alzheimer disease (Table 3).59 An evaluation can also help differentiate depression in Alzheimer disease from other dementias that commonly present with depressive symptoms.

Early detection of dementia with the aid of neuropsychological assessment helps promote early intervention and allows tracking of cognitive change in response to treatment. Serial neuropsychological assessments of cognitively impaired individuals can help estimate whether cognitive deficits have partially or fully resolved (as in depression and some medical conditions), have remained stable (as in cerebrovascular events), or have been progressive (as in Alzheimer disease or other dementing disorders).

Treatment options

Psychiatric treatment of individuals with both depression and cognitive impairment requires consideration of both the affective and cognitive elements. In the Depression in Alzheimer Disease Study, sertraline(Drug information on sertraline) was found to be effective in treating individuals with comorbid major depression and Alzheimer disease.60 In addition, individuals who responded well in mood also improved in activities of daily living and behavioral disturbances not associated with mood, but cognitive function did not improve in conjunction with mood.60,61

There is no current evidence to recommend treating cognitive impairment in MDD with medications for Alzheimer disease; in fact, starting both an antidepressant medication and a cognitive medication may complicate the clinician's ability to manage side effects and adverse events. Persistent or worsening memory deficits after several months of remission or mild depression raise suspicion of dementia, in which case prescription of cholinesterase inhibitors (eg, donepezil(Drug information on donepezil), galantamine(Drug information on galantamine), rivastigmine(Drug information on rivastigmine)) or an N-methyl-d-aspartic acid receptor antagonist (eg, memantine(Drug information on memantine)) may be beneficial.

Pharmacological treatment of geriatric depression with cognitive impairment is complicated by the fact that deficits in executive functions are associated with lower remission rates and higher recurrence of depression. Psychotherapy may mitigate some cognitive deficits associated with depression, as evidenced in a study that found a 12-week trial of problem-solving therapy was associated with higher remission and lower functional disability compared with supportive therapy when used with depressed older adults who had comorbid deficits in executive functions.62 What is interesting about this study is that the focus on practical problem-solving strategies appeared to be beneficial to individuals whose cognitive deficits compromised their ability to resolve psychosocial aspects of depression.

Cognitive impairment and depression are common among older adults, and the combination of these 2 conditions may lead to persistent difficulties with both cognition and mood. Clinicians can reduce the occurrence of complicating factors with a proactive approach to evaluation that includes effective detection of cognitive impairment and referral for more comprehensive assessment when indicated. Treatment approaches should be similarly proactive and may include a combination of pharmacological and psychotherapeutic interventions.

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  • Lyketsos CG, DelCampo L, Steinberg M, et al. Treating depression in Alzheimer disease: efficacy and safety of sertraline therapy, and the benefits of depression reduction: the DIADS. Arch Gen Psychiatry. 2003;60:737-746.
  • Sheline YI, Barch DM, Garcia K, et al. Cognitive function in late life depression: relationships to depression severity, cerebrovascular risk factors and processing speed. Biol Psychiatry. 2006;60:58-65.
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