Cognitive control, reward-related decision making and outcomes of late-life depression treated with an antidepressant
Open accessAbstract
Background.: Executive processes consist of at least two sets of functions: one concerned with cognitive control and the other with reward-related decision making. Abnormal performance in both sets occurs in late-life depression. This study tested the hypothesis that only abnormal performance in cognitive control tasks predicts poor outcomes of late-life depression treated with escitalopram. Method.: We studied older subjects with major depression ( N = 53) and non-depressed subjects ( N = 30). Executive functions were tested with the Iowa Gambling Test (IGT), Stroop Color-Word Test, Tower of London (ToL), and Dementia Rating Scale – Initiation/Perseveration domain (DRS-IP). After a 2-week placebo washout, depressed subjects received escitalopram (target daily dose: 20 mg) for 12 weeks. Results.: There were no significant differences between depressed and non-depressed subjects on executive function tests. Hierarchical cluster analysis of depressed subjects identified a Cognitive Control cluster (abnormal Stroop, ToL, DRS-IP), a Reward-Related cluster (IGT), and an Executively Unimpaired cluster. Decline in depression was greater in the Executively Unimpaired ( t = −2.09, df = 331, p = 0.0375) and the Reward-Related ( t = −2.33, df = 331, p = 0.0202) clusters than the Cognitive Control cluster. The Executively Unimpaired cluster ( t = 2.17, df = 331, p = 0.03) and the Reward-Related cluster ( t = 2.03, df = 331, p = 0.0433) had a higher probability of remission than the Cognitive Control cluster. Conclusions.: Dysfunction of cognitive control functions, but not reward-related decision making, may influence the decline of symptoms and the probability of remission of late-life depression treated with escitalopram. If replicated, simple to administer cognitive control tests may be used to select depressed older patients at risk for poor outcomes to selective serotonin reuptake inhibitors who may require structured psychotherapy.
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Positive functional outcomes of individuals with TRD are hampered by lingering neurocognitive dysfunction that decreases intervention efficacy and increases relapse.
“Positive functional outcomes of individuals with TRD are hampered by lingering neurocognitive dysfunction that decreases intervention efficacy (Alexopoulos et al., 2015;Gonda et al., 2015;Story et al., 2008) and increases relapse (Alexopoulos, 2021;Gonda et al., 2015;Manning et al., 2015).”
From Neurocognitive effects of theta burst stimulation for treatment-resistant depression in adults: A systematic review and recommendations for future research (2025) · cites this paper as Alexopoulos et al., 2015
The Discussion (page not provided) reports that older adults with major depression who performed poorly on cognitive-control tasks had less symptom improvement and a lower probability of remission during 12 weeks of escitalopram treatment. This supports the intervention-efficacy portion of the citation, but the study does not establish that lingering dysfunction impairs functional outcomes in people with treatment-resistant depression. The sentence cites other papers, not Alexopoulos et al. (2015), for relapse. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn older adults, executive functioning and neuroticism are separate factors that both raise risk for and maintain mood problems and cognitive decline.
“Converging neuropsychological and neuroimaging evidence indicates the cognitive process of executive functioning and the personality trait of neuroticism each individually and independently predispose and perpetuate mood disturbance and cognitive decline in older adults9–12.”
From State of the Science of Neural Systems in Late‐Life Depression: Impact on Clinical Presentation and Treatment Outcome (2018) · cites this paper as [10]
Scores on these tests are linked to structural and functional abnormalities in cognitive control areas including dorsolateral prefrontal cortex, dorsal and rostral anterior cingulate, and parietal association cortex.
“Performance on these tests correlates with structural and functional abnormalities in cognitive control regions, namely the dorsolateral prefrontal cortex (DLPFC), the dorsal and rostral regions of the anterior cingulate, and parietal association regions10, 11.”
From State of the Science of Neural Systems in Late‐Life Depression: Impact on Clinical Presentation and Treatment Outcome (2018) · cites this paper as [10]
One earlier study reported no link between reward-related decision making and three-month antidepressant response in older depressed adults.
“a prior study found no association between reward related decision making and antidepressant treatment response over three months in older adults with major depression (44).”
From Neuroticism Traits Selectively Impact Long Term Illness Course and Cognitive Decline in Late-Life Depression (2017) · cites this paper as [44]
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- Authors
- Alexopoulos, G. S., Manning, K., Kanellopoulos, D., McGovern, A., Seirup, J. K., Banerjee, S., & Gunning, F.
- Affiliations
- Weill Cornell Medicine (US)
- UConn Health (US)
- Corresponding author
- Alexopoulos, G. S.
- Venue
- Psychological Medicine
- Publisher
- Cambridge University Press (CUP)
- Published
- 2015-07-14
- Volume
- 45
- Issue
- 14
- Pages
- 3111-3120
- ISSN
- 0033-2917 (ISSN-L)
- 1469-8978
- PMC
- PMC4631680
- OpenAlex
- W2123297362
- Cited by
- 43
- References
- 67
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 2 · 2023: 10 · 2022: 2 · 2021: 4 · 2020: 8 · 2019: 2 · 2018: 5 · 2017: 2 · 2016: 3
- FWCI
- 2.40
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychological Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH079414, R01MH097735, R01MH065653, R01MH102252, T32MH019132)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- geriatric depression, cognitive control, executive function, escitalopram, selective serotonin reuptake inhibitors, treatment outcome prediction, depression remission, older adults, Stroop task, Tower of London, Mattis Dementia Rating Scale
- MeSH terms
- Aged, Aged, 80 and over, Antidepressive Agents, Anxiety, Cognition, Decision Making, Depression, Depressive Disorder, Major, Major Depressive Disorder, Female, Humans, London, Male, Middle Aged, Neuropsychological Tests, Psychiatric Status Rating Scales, Psychotherapy, Reward, Citalopram, Treatment Outcome, Executive Function
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