Executive Dysfunction and Long-term Outcomes of Geriatric Depression

Alexopoulos, George S.; Meyers, Barnett S.; Young, Robert C.; Kalayam, Balu; Kakuma, Tatsuyuki; Gabrielle, Michelle; Sirey, Jo Anne; Hull, James W.

doi:10.1001/archpsyc.57.3.285

Cited by 435 publications

(280 citation statements)

References 52 publications

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“…In particular, MRI findings of deep white matter hyperintensities involving frontal-subcortical pathways are associated with both chronicity and cognitive impairment in late-life depression (Krishnan et al, 1998;Steffens et al, 2000;Lesser et al, 1996). These results are consistent with neurophysiological and neuropsychological data that associate prefrontal dysfunction with treatment resistance in depressed older adults (Alexopoulos et al, 2000;Kalayam and Alexopoulos, 1999), which is estimated to occur in up to one-third of this population (Schneider, 1996). As underlying deficits in prefrontal cortex appear to be associated with more intractable depression, assessment of prefrontal functions may improve treatment efficacy through early identification of individuals most likely to be refractory to routine clinical intervention.…”

Section: Introductionsupporting

confidence: 89%

“…Although that study is limited by a small sample size (n ¼ 14), it does suggest that perseverative tendencies contribute to poor treatment across a broad age spectrum. These results, in addition to those of the current study and others with geriatric samples (Kalayam and Alexopoulos, 1999;Alexopoulos et al, 2000), suggest that further research is needed to identify the types of perseveration that are associated with poor treatment response, with particular attention to age effects.…”

Section: Discussionsupporting

confidence: 62%

“…Alexopoulos and co-workers found among a group of older depressed individuals enrolled in a pharmacologic treatment study that lower performance on a neuropsychological measure of prefrontal initiation/preservation (I/P) was associated with poorer acute treatment response (Kalayam and Alexopoulos, 1999) and higher rates of recurrence over a 2-year follow-up period (Alexopoulos et al, 2000). The fact that they did not report the extent to which initiation and perseveration differentially contributed to their findings reflects the primary limitation of these studies, which is that the findings from a single brief measure are generalized to the multiple neurocognitive processes that are mediated by the prefrontal cortex.…”

Section: Introductionmentioning

confidence: 99%

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Prefrontal Neuropsychological Predictors of Treatment Remission in Late-Life Depression

Potter

Kittinger

Wagner

et al. 2004

Neuropsychopharmacol

125

100

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Recent studies suggest that neuropsychological measures involving the prefrontal cortex are associated with treatment remission in latelife depression. To further explore this issue, we studied the neuropsychological performance of 110 depressed individuals aged 60 years and over who are participating in an ongoing pharmacologic treatment study. Participants were clinically depressed at entry to the study as rated by the Montgomery-Asberg Depression Rating Scale (MADRS X15), at which time they also completed a neuropsychological assessment that included measures of prefrontal/executive functions. A geriatric psychiatrist treating the participant using a standardized pharmacologic treatment algorithm evaluated the participant at baseline and 3-month follow-up, completing a MADRS at both visits. Using logistic discriminative procedures to predict depression remission at 3 months while controlling for age, gender, education, ethnicity, and baseline MADRS severity, we found that perseverative responses during verbal initiation tasks significantly predicted remission status (MADRS o7). This finding is consistent with previous single-agent treatment studies suggesting a relationship between prefrontal neuropsychological function and treatment response in late-life depression. The current results, however, appear to differentiate verbal perseveration from verbal initiation as the cognitive process that is most associated with poor treatment response. By extension, we suggest that orbitofrontal prefrontal cortex may play a role in sustaining perseverative processing in geriatric depression.

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Section: Introductionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 62%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Prefrontal Neuropsychological Predictors of Treatment Remission in Late-Life Depression

Potter

Kittinger

Wagner

et al. 2004

Neuropsychopharmacol

125

100

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“…In addition, cognitive impairment, especially executive dysfunction (Alexopoulos et al, 2000), comorbid anxiety (Mulsant et al, 1996;Lenze et al, 2002;Alexopoulos et al, 2005;Andreescu et al, in press), low selfesteem (Gildengers et al, 2005), lower social support and adverse life events (Dew et al, 1997), and residence in low-income communities (Cohen et al, 2006) have all been cited as predictors of delayed or partial treatment response. This study builds upon these findings in order to identify predictors of partial and non-response to initial 6-week pharmacotherapy of major depression in old age.…”

Section: Introductionmentioning

confidence: 99%

Predicting 6‐week treatment response to escitalopram pharmacotherapy in late‐life major depressive disorder

Saghafi

Brown

Butters

et al. 2007

Int J Geriat Psychiatry

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SUMMARYObjective-Approximately half of older patients treated for major depressive disorder (MDD) do not achieve symptomatic remission and functional recovery with first-line pharmacotherapy. This study aims to characterize sociodemographic, clinical, and neuropsychologic correlates of full, partial, and non-response to escitalopram monotherapy of unipolar MDD in later life.Methods-One hundred and seventy-five patients aged 60 and older were assessed at baseline on demographic variables, depression severity, hopelessness, anxiety, cognitive functioning, coexisting medical illness burden, social support, and quality of life (disability). Subjects received 10 mg/d of open-label escitalopram and were divided into full (n =55; 31%), partial (n =75; 42.9%), and non-responder (n =45; 25.7%) groups based on Hamilton depression scores at week 6. Univariate followed by multivariate analyses tested for differences between the three groups.Results-Non-responders to treatment were found to be more severely depressed and anxious at baseline than both full and partial responders, more disabled, and with lower self-esteem than full responders. In general partial responders resembled full responders more than they resembled nonresponders. In multivariate models, more severe anxiety symptoms (both psychological and somatic) and lower self-esteem predicted worse response status at 6 weeks.Conclusion-Among treatment-seeking elderly persons with MDD, higher anxiety symptoms and lower self-esteem predict poorer response after six weeks of escitalopram treatment.

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“…Impairment in some executive functions has been found to predict nonresponse to fluoxetine in major depression among a sample of 14 young and middle aged women who participated in a randomized, double-blind, placebo-controlled trial of the effectiveness of fluoxetine in treating major depression (Dunkin et al, 2000). Among older psychiatric patients with major depression, abnormal performance in tasks of response inhibition (Stroop Color-Word), initiation/perseveration, and other executive functions (Potter et al, 2004) appear to predict poor or delayed response to antidepressant drugs (Kalayam and Alexopoulos, 1999;Alexopoulos et al, 2004;Alexopoulos et al, 2005b) and early relapse and recurrence of major depression (Alexopoulos et al, 2000). However, an analysis of psychiatric patients in two independent intervention trials failed to replicate these findings (Butters et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

The effects of memory, attention, and executive dysfunction on outcomes of depression in a primary care intervention trial: the PROSPECT study

Bogner

Bruce

Reynolds

et al. 2007

Int J Geriat Psychiatry

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OBJECTIVE-To describe the influence of domains of cognition on remission and response of depression in an intervention trial among older primary care patients.METHODS-Twenty primary care practices were randomly assigned to Usual Care or to an Intervention consisting of a depression care manager offering algorithm-based care for depression. In all, 599 adults 60 years and older with a depression diagnosis were included in these analyses. Depression severity and remission of depression were assessed by the 24-item Hamilton Depression Rating Scale. The Mini-Mental State Examination (MMSE) was our global measure of cognitive function. Verbal memory was assessed with the memory subscale of the Dementia Rating Scale. Attention was measured with the digit span from the Weschler Adult Intelligence Test. Response inhibition, one of the executive functions, was assessed with the Stroop Color-Word test. RESULTS-The intervention was associated with improved remission and response rates regardless of cognitive impairment. Response inhibition as measured by the Stroop Color-Word test appeared to significantly modify the intervention versus usual care difference in remission and response at 4 months. Patients in the poorest performance quartile at baseline on the Stroop ColorWord test in the Intervention Condition were more likely to achieve remission of depression at 4 months than comparable patients in Usual Care (odds ratio (OR) = 17.76, 95% confidence interval (CI) [3.06, 103.1]).CONCLUSIONS-Depressed older adults in primary care with executive dysfunction have low remission and response rates when receiving usual care but benefit from depression care management.

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Executive Dysfunction and Long-term Outcomes of Geriatric Depression

Cited by 435 publications

References 52 publications

Prefrontal Neuropsychological Predictors of Treatment Remission in Late-Life Depression

Prefrontal Neuropsychological Predictors of Treatment Remission in Late-Life Depression

Predicting 6‐week treatment response to escitalopram pharmacotherapy in late‐life major depressive disorder

The effects of memory, attention, and executive dysfunction on outcomes of depression in a primary care intervention trial: the PROSPECT study

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