ORLANDO – Elderly patients with acute depression who show deficits on brief structured tests of memory and executive function are at high risk for developing Alzheimer’s disease within the next few years, mounting evidence indicates.
"Our study suggests that late-life depression with documented memory and executive function impairment is just the tip of a very bad neuropsychiatric iceberg and that there is more to come," Dr. David C. Steffens said at the annual meeting of the American Association for Geriatric Psychiatry (AAGP).
Dr. David C. Steffens
It’s unclear as yet whether depression in the elderly is a risk factor for dementia or a prodrome of the disorder. That’s an ongoing debate in the field. The two possibilities are not mutually exclusive, according to Dr. Steffens, professor and chairman of the psychiatry department at the University of Connecticut, Farmington.
What is clear is that the subsequent course of elderly depressed patients with comorbid mild cognitive impairment is highly variable, as illustrated in a study in which Dr. Steffens and his colleagues followed 69 such patients for 2 years. Seventeen ended up cognitively unimpaired, 6 developed subsyndromal Alzheimer’s disease, 6 had possible Alzheimer’s disease, 2 had probable Alzheimer’s, 2 had dementia of undetermined etiology, 13 still met criteria for mild cognitive impairment without dementia, and 23 had cognitive impairment which during follow-up became attributable to a more specific cause, such as cerebrovascular disease or another medical condition (J. Geriatr. Psychiatry Neurol. 2009;22:52-61).
In an effort to find a means of predicting which patients with late-life major depressive disorder are most likely to go on to develop dementia, the investigators turned to baseline neuropsychologic testing. Dr. Steffens presented recently published highlights of the NCODE (Neurocognitive Outcomes of Depression in the Elderly) trial, a longitudinal outpatient depression treatment study. In this phase of NCODE, 179 nondemented, acutely depressed older adults underwent baseline neuropsychologic testing, received active treatment for their depression, and were followed for a mean of 5.5 years. During follow-up, Dr. Steffens and his coinvestigators diagnosed 30 subjects as having incident dementia, while the other 149 were deemed cognitively normal.
Of course, completing an extensive battery of neuropsychologic tests is a lot to ask of an elderly patient with late-life depression. Fortunately, two of the neuropsychologic tests – the CERAD (Consortium to Establish a Registry of Alzheimer’s Disease) Recognition Memory and the Trail Making B – proved to be the best predictors of subsequent conversion to dementia. That’s good news, because focusing on just two tests for prognostication is practical in everyday clinical practice, whereas administering a lengthy battery of neuropsychologic tests really isn’t, observed Dr. Steffens, who is AAGP president.
In a multivariate analysis, deficits on CERAD Recognition Memory and Trail Making B were associated with a 6.8-fold increased risk of developing dementia during follow-up, compared with elderly acutely depressed patients who scored in the normal range. The two tests correctly classified 91.6% of NCODE participants, with false-positive and false-negative rates of 5.9% and 8.6%, respectively (Am J. Geriatr. Psychiatry 2013;21:297-306).
"As more and more data accumulate, I think the field is moving to a point where we can say that as part of our assessment, if you focus on one or two tests, that may actually prognosticate better," the psychiatrist observed.
The NCODE study was supported by the National Institute of Mental Health. Dr. Steffens reported having no financial conflicts of interest.