Prefrontal Dysfunction and Treatment Response in Geriatric Depression

Kalayam, Balu; Alexopoulos, George S.

doi:10.1001/archpsyc.56.8.713

Cited by 244 publications

(196 citation statements)

References 42 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%

“…With regard to Kalayam and Alexopoulos' (1999) report that lower scores on the I/P scale from the Mattis Dementia Rating Scale (Mattis, 1989) were associated with poor treatment response, we found evidence for an effect of verbal perseveration, but not of verbal initiation or visual memory perseveration. These findings may add some clarity to the role of perseveration vs initiation as a predictor of treatment resistance, but are limited by the fact that different measures were used to assess the constructs of initiation and perseveration between the two studies.…”

Section: Discussionmentioning

confidence: 38%

“…Unlike previous treatment trial studies using a single pharmacologic agent (Kalayam and Alexopoulos, 1999), the current data reflect optimal treatment over a period of 3 months. We believe that the strength of this study is that it complements previous research based on treatment response to a single agent.…”

Section: Discussionmentioning

confidence: 85%

“…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

123

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: Discussionmentioning

confidence: 38%

Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Prefrontal Neuropsychological Predictors of Treatment Remission in Late-Life Depression

Potter

Kittinger

Wagner

et al. 2004

Neuropsychopharmacol

123

100

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Problem-Solving Therapy and Supportive Therapy in Older Adults With Major Depression and Executive Dysfunction

Alexopoulos¹,

Raue²,

Kiosses³

et al. 2011

Arch Gen Psychiatry

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177

189

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Context Older patients with depression and executive dysfunction represent a population with significant disability and high likelihood of failing pharmacotherapy. Objective To examine whether Problem Solving Therapy (PST) reduces disability more than Supportive Therapy (ST) in older patients with depression and executive dysfunction, and whether this effect is mediated by improvement in depressive symptoms. Design Randomized controlled trail, with participant recruitment from 12/02-11/07 and follow-up for 36 weeks. Setting Weill Cornell and University of California, San Francisco. Participants Adults (>59 years) with major depression and executive dysfunction. Intervention 12 sessions of either PST modified for older depressed adults with executive impairment, or ST. Main Outcome Measure Disability as quantified by the World Health Organization Assessment Schedule II (WHODAS II)-12 item form. Results 653 individuals were referred to this study, 221 of whom met criteria and were randomized to PST or ST. PST and ST led to comparable improvement of disability in the first 6 weeks of treatment, but a more prominent reduction in PST participants at weeks 9 and 12. The difference between PST and ST was greater in patients with greater cognitive impairment and higher number of previous episodes. Reduction in disability paralleled reduction in depressive symptoms. The therapeutic advantage of PST over ST in reducing depression was in part due to greater reduction of disability by PST. While disability increased during the 24 weeks following the end of treatment, the advantage of PST over ST-treated patients was retained. Conclusions This study suggests that PST is more effective than ST in reducing disability in older patients with major depression and executive dysfunction, and its benefits were retained after the end of treatment. The clinical value of this finding is that PST may be a treatment alternative in an older patient population likely to be resistant to pharmacotherapy.

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Executive Dysfunction and Long-term Outcomes of Geriatric Depression

Alexopoulos

Meyers²,

Young³

et al. 2000

Arch Gen Psychiatry

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431

257

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Executive dysfunction was found to be associated with relapse and recurrence of geriatric major depression and with residual depressive symptoms. These observations, if confirmed, will aid clinicians in identifying patients in need of vigilant follow-up. The findings of this study provide the rationale for investigation of the role of specific prefrontal pathways in predisposing or perpetuating depressive syndromes or symptoms in elderly patients.

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Prefrontal Dysfunction and Treatment Response in Geriatric Depression

Abstract: Background: This study investigated the relationship of clinical, neuropsychological, and electrophysiological measures of prefrontal dysfunction with treatment response in elderly patients with major depression.

Cited by 244 publications

References 42 publications

Prefrontal Neuropsychological Predictors of Treatment Remission in Late-Life Depression

Prefrontal Neuropsychological Predictors of Treatment Remission in Late-Life Depression

Problem-Solving Therapy and Supportive Therapy in Older Adults With Major Depression and Executive Dysfunction

Executive Dysfunction and Long-term Outcomes of Geriatric Depression

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