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Cited by 117Treatment of Major DepressionDementia and Cognitive Impairment ResearchAnxiety, Depression, Psychometrics, Treatment, Cognitive Processes

Neurocognitive Correlates of Response to Treatment in Late-Life Depression

Open access
Story, Tyler J., Potter, Guy G., Attix, Deborah K., Welsh-Bohmer, Kathleen A., Steffens, David C.·2008·The American Journal of Geriatric Psychiatry
DOI 10.1097/jgp.0b013e31817e739aPMC PMC2722450
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Abstract

Depression is often associated with neurocognitive deficits in older adults, particularly in the domains of information processing speed, episodic memory, and executive functions. Greater neurocognitive dysfunction while depressed is associated with a less effective treatment response; however, questions remain about the specific variables that characterize patients showing low treatment response and persistent cognitive deficiencies. OBJECTIVES The authors examined neurocognitive variables that differentiated patients who showed robust versus weak responses to antidepressant therapy. PARTICIPANTS The baseline sample included 110 women and 67 men, with a mean age of 69.1 years (SD = 6.9) and mean education of 14 years (SD = 3.3). DESIGN Patients enrolled in a treatment study completed both a structured diagnostic assessment for depression and neuropsychological testing at study entry and one-year follow-up. MEASUREMENTS Clinicians rated patient depression using the MADRS. Neuropsychological assessments consisted of prose recall and percent retention (WMS-III Logical Memory), word-list recall, attention and visuomotor processing speed (Trail Making A, Symbol-Digit Modalities), and mental flexibility (Trail Making B). INTERVENTIONS Patients underwent treatment for depression following the guidelines of the Duke STAGED approach. RESULTS Individuals who demonstrated the greatest improvement in mood symptoms at follow-up exhibited better prose recall and faster processing speed at baseline than individuals who demonstrated weaker treatment responses. These differences remained after controlling for depression severity at both time-points. CONCLUSION The current results suggest that better pre-treatment cognitive function, particularly in verbal memory, is associated with a greater treatment response in late life depression.

AI snapshot

Written from the paper’s full text.

TL;DR

In older adults with major depression, better baseline verbal memory and processing speed predicted greater one-year antidepressant treatment response, independent of baseline depression severity. Differences attenuated after controlling for follow-up depression severity, and effect sizes were small.

Key findings

  • High treatment responders showed better baseline delayed prose recall (LM delayed recall: F(1,97)=15.124, p=.001, η²=.135), prose percent retention (F(1,97)=9.56, p=.001, η²=.090), delayed word-list recall (F(1,97)=5.210, p=.025, η²=.051), and processing speed (SDMT: F(1,93)=5.951, p=.017, η²=.060) than low responders after covarying baseline depression.
  • Trail Making Test A and B did not significantly differ between response groups; TMT-B was in the expected direction but not significant (F(1,95)=3.026, p=.085, η²=.031).
  • Patients with moderate-to-severe baseline depression (MADRS ≥ 26, n=52) improved more at one year than those with mild-to-moderate depression (MADRS < 26, n=122; F(1,99)=25.27, p=.001, η²=.203).
  • At one-year follow-up, high responders’ cognitive advantages were maintained when controlling for baseline depression alone, but were no longer significant after covarying follow-up depression severity; TMT-B change was not significant (F(1,92)=.145, p>.05), though mean times suggested possible practice effects.

Methods

  • Baseline sample: 177 participants aged 60+ with DSM-IV major depressive disorder (110 women, 67 men; mean age 69.1 years, SD=6.9; mean education 14 years, SD=3.3); 103 returned for one-year follow-up.
  • Participants received depression treatment following the Duke STAGED algorithm and completed MADRS plus neuropsychological testing at study entry and one-year follow-up: WMS-R Logical Memory delayed recall and percent retention, CERAD word-list delayed recall, Trail Making A/B, and Symbol Digit Modalities Test.
  • Analyses used independent-samples t-tests for demographics and ANCOVA comparing high versus low treatment responders, with baseline depression as a covariate and follow-up depression covaried when follow-up cognition was analyzed; high response was defined as MADRS change greater than the baseline sample SD.

Limitations

  • The paper states there was no waitlist control group or single-agent design, so natural remission and cognitive functioning without treatment could not be assessed.
  • The naturalistic STAGED approach did not strictly control treatment agent or dosage, though it was intended to enhance external validity.
  • The paper notes that effect sizes were small (<.3) across measures, raising clinical-versus-statistical significance concerns, and that the brief battery was not a comprehensive neurocognitive assessment.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1097/jgp.0b013e31817e739a

Cites

56 of 56 references verified0 citation errors · 0 not checkable

Statistics

10 tests recomputed · 0 with the reported and recomputed p on opposite sides of .05

Claims the paper makes

0 of 13 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    In older adults with late-life depression, after covarying for depression severity at follow-up, the performance advantages for the high response group at 1-year follow-up were no longer significant, except for TMT-B.

    “These differences, however, were no longer significant after covarying depression severity at follow-up, with the exception of TMT-B.”
    Quote in the paperSubstantial claim
  • Findingown data

    In older adults with late-life depression, performance advantages for the high response group at 1-year follow-up were maintained when controlling for baseline depression alone.

    “Performance advantages for the high response group were maintained at 1-year follow-up when controlling for baseline depression alone.”
    Quote in the paperSubstantial claim
  • Findingown data

    In older adults with late-life depression, effect sizes were small (<.3) across all measures.

    “Although performances were significantly different between the two groups, effect sizes (<.3) were small across all measures.”
    Quote in the paperSubstantial claim
  • Findingown data

    In older adults with late-life depression, patients in the moderate-to-severe depression group at baseline showed more improvement in depressive symptoms at one-year follow-up than the mild-to-moderate group.

    “Patients in the moderate-to-severe group at baseline showed more improvement than the mild-to-moderate group in depressive symptoms at one-year follow-up (F (1, 99) = 25.27, p = .001, η2 = .203, see Table 1).”
    Quote in the paperSubstantial claim
  • Findingown data

    In older adults with late-life depression, high treatment responders had better baseline delayed word-list recall than low responders, after controlling for baseline depression severity.

    “better delayed word-list recall (F (1, 97) = 5.210, p = .025, η2 = .051)”
    Quote in the paperSubstantial claim
  • May combine two claims. 9
  • Classified as probably not a substantial claim. 9

  • May combine two claims.

    Findingown data

    In older adults with late-life depression, participants in the high response group on average had MADRS scores falling within the remitted range, while the low response group on average remained in the mildly depressed range.

    “Participants in the high response group on average had MADRS scores falling within the remitted range, while the low response group on average remained in the mildly depressed range.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In older adults with late-life depression, high and low treatment responders did not differ significantly on baseline TMT-B performance, though differences were in the expected direction.

    “In contrast, the two patient groups did not differ signficantly on TMT-A or TMT-B performances, though differences on the latter task were in the expected direction (F (1, 95) = 3.026, p = .085, η2 = .031).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In older adults with late-life depression, mean TMT-B differences suggested improved (faster) times on average for the high response group and worse (slower) times on average for the low response group.

    “the mean differences did suggest improved (faster) times on average for the high response group (M = −3.44, SD = 51.83) and worse (slower) times on average for the low response group (M = 7.88, SD = 39.18).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    In the study, chi-square analyses showed no differences between high and low response groups for current psychotropic medication use.

    “Chi-square analyses showed no differences between groups for current psychotropic medication use (χ2 (2) = .730, p > .05).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    In the study, 103 patients were available for a follow-up assessment after one year.

    “One-hundred three patients were available for a follow-up assessment after one year.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    In the study, those who did and did not return for follow-up did not differ in age, education, or baseline depression severity.

    “Those who did and did not return for follow-up did not differ in age (t {175} = 1.57, p = .106), education (t {175} = 1.29, p = .199), or baseline depression severity (t {172} = .229, p = .819).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductnone given

    The study included a 1-year follow-up interval, assessment of neuropsychological performance at both baseline and follow-up, and control for the effects of depression severity at both baseline and follow-up assessments.

    “The current study builds upon existing literature with the inclusion of a 1-year follow-up interval relative to previous 8–16 week intervals, assessment of neuropsychological performance at both baseline and follow-up, and control for the effects of depression severity at both baseline and follow-up assessments.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    In the study, high response and low response groups did not differ in age or education.

    “High response and low response groups did not differ in age (F (1, 98) = 2.79, p = .10, η2 = .028) or education (F (1, 98) =.348, p = .557, η2 = .004).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    In the study, rates of ECT did not differ between the high response and low response groups.

    “Rates of ECT did not differ between the high response and low response groups (χ2 (1) = .099, p > .05).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    In the study, baseline and 1-year MADRS scores were obtained from the treating psychiatrist, who was blind to neuropsychological performance for each patient.

    “Baseline and 1-year MADRS scores were obtained from the treating psychiatrist, who was blind to neuropsychological performance for each patient.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    In the study, the neuropsychological test battery was administered by a trained psychometrician who was blind to depression status.

    “The test battery was administered by a trained psychometrician who was blind to depression status.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    In the study, depression scores at 1-year follow-up were covaried when appropriate.

    “Similarly, depression scores at 1-year follow-up were also covaried when appropriate cognitive functioning at follow-up was included in analyses.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    In the study, baseline depression was treated as a covariate throughout analyses to control for variance associated with an acute mood disturbance.

    “Baseline depression was treated as a covariate throughout analyses to control for variance associated with an acute mood disturbance.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductreasoning

    The study design did not include a waitlist control group or single agent design, so the study does not have data concerning cognitive functioning and natural remission in LLD.

    “For instance, this design did not include a waitlist control group or single agent design, so we do not have data concerning cognitive functioning and natural remission in LLD.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Response inhibition predicts 8-week and 4-month treatment response.

    “One study found response inhibition to predict 8-week treatment (22–23) and 4-month treatment response (24)”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [22] Sneed, 2007, Response inhibition predicts poor antidepressant treatment response in very old depressed patients, Am J Geriatr Psychiatry source

      Not checked in the free run.

    • cites [23] Alexopoulos, 2005, Executive dysfunction and the course of geriatric depression, Biol Psychiatry source

      Not checked in the free run.

    • cites [24] Bogner, 2007, The effects of memory, attention, and executive dysfunction on outcomes of depression in a primary care intervention trial: the PROSPECT study, Int J Geriatr Psychiatry source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The MADRS is a 10-item scale of depression severity designed to be sensitive to symptom change in clinical trials.

    “The Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item scale of depression severity that is based on patient report and clinical observation. This measure was designed to be sensitive to symptom change in clinical trials (34).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [34] Montgomery, 1979, A new depression scale designed to be sensitive to change, Br J Psychiatry source

      Not checked in the free run.

16 of 16

  • The paper relies on this without support.

    The sample of older adults with late-life depression is representative of the broader LLD population.

    “The current results suggest that better pre-treatment cognitive function, particularly in verbal memory, is associated with a greater treatment response in late life depression.”

  • The paper relies on this without support.

    The one-year follow-up period is sufficient to capture treatment response in late-life depression.

    “Patients enrolled in a treatment study completed both a structured diagnostic assessment for depression and neuropsychological testing at study entry and one-year follow-up.”

  • The paper relies on this without support.

    The neuropsychological measures used are valid indicators of frontostriatal and hippocampal function.

    “We included measures of attention, processing speed, and mental flexibility that are associated with frontostriatal function, and measures of episodic memory that are associated with hippocampal function.”

  • The paper relies on this without support.

    The naturalistic treatment approach does not introduce confounding that would explain the association between baseline cognition and treatment response.

    “While we do not address natural symptom remission, the naturalistic treatment approach in this study was designed to enhance external validity and application in standard treatment settings.”

  • The paper relies on this without support.

    The exclusion of patients with dementia or low MMSE does not bias the sample in a way that affects the results.

    “Participants were excluded if they met clinical criteria for dementia at enrollment, or if they maintained a score below 25/30 on the Mini Mental State Examination (MMSE) across baseline and the initial 8 weeks of treatment.”
5 of 5

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • 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 Story et al., 2008

    The Discussion (page not provided) reports that depressed older adults with poorer baseline verbal memory and processing speed had less treatment response over one year. It does not establish that lingering dysfunction causes reduced intervention efficacy in people with treatment-resistant depression or measure functional outcomes. The sentence cites other sources, not Story et al., for the separate relapse claim. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • In adults with late-life major depressive disorder (n = 177), greater pretreatment verbal memory was associated with better treatment response.

    “In adults with late-life MDD (n = 177), greater pretreatment verbal memory was associated with better treatment response [75].”

    From Cognitive remission: a novel objective for the treatment of major depression? (2016) · cites this paper as [75]

Statistics that don’t add up

Each reported p-value recomputed from its test statistic and degrees of freedom.

  • p-value fits an unstated one-tailed test: F (1, 97) = 9.56, p = .001

    Minor

    The paper reports p = .001 here; recomputing from the test statistic and its degrees of freedom gives p = .003. The reported value is what a one-tailed test gives, but the paper does not say near this result that a one-tailed test was used.

    Reported p = .001 · recomputed p = .003

1 of 1

Statistics recomputed

Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.

  • Doesn’t add upF(1, 97) = 9.56reported p = .001 · recomputed p = .003

    “F (1, 97) = 9.56, p = .001”

  • ConsistentF(1, 99) = 25.27reported p = .001 · recomputed p < .001

    “F (1, 99) = 25.27, p = .001”

    The paper prints p at a floor (such as p < .001)

  • ConsistentF(1, 98) = 2.79reported p = .1 · recomputed p = .098

    “F (1, 98) = 2.79, p = .10”

  • ConsistentF(1, 98) = 0.348reported p = .557 · recomputed p = .557

    “F (1, 98) =.348, p = .557”

  • Consistentχ²(2) = 0.73reported p > .05 · recomputed p = .694

    “χ2 (2) = .730, p > .05”

  • Consistentχ²(1) = 0.099reported p > .05 · recomputed p = .753

    “χ2 (1) = .099, p > .05”

  • ConsistentF(1, 97) = 15.124reported p = .001 · recomputed p < .001

    “F (1, 97) = 15.124, p = .001”

    The paper prints p at a floor (such as p < .001)

  • ConsistentF(1, 97) = 5.21reported p = .025 · recomputed p = .025

    “F (1, 97) = 5.210, p = .025”

  • ConsistentF(1, 93) = 5.951reported p = .017 · recomputed p = .017

    “F (1, 93) = 5.951, p = .017”

  • ConsistentF(1, 95) = 3.026reported p = .085 · recomputed p = .085

    “F (1, 95) = 3.026, p = .085”

10 of 10

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Claim that all participants completed follow-up testing conflicts with attrition

    Minor

    The Methods say all participants completed testing at one-year follow-up, but the Results say only 103 of the 177 baseline participants were available for follow-up.

  • Logical Memory test version differs between sections

    Minor

    The abstract identifies the Logical Memory measure as WMS-III, whereas the Methods identify the administered measure as WMS-R.

2 of 2

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Schneider, 1996, Pharmacologic considerations in the treatment of late-life depression, Am J Geriatric Psychiatry, 4, S51

Cited by

Sorted by citations

Related

Authors
Story, T. J., Potter, G. G., Attix, D. K., Welsh-Bohmer, K. A., & Steffens, D. C.
Affiliations
Duke Medical Center (US)
Corresponding author
Story, Tyler J.
ORCID
Venue
The American Journal of Geriatric Psychiatry
Publisher
Elsevier BV
Published
2008-09
Volume
16
Issue
9
Pages
752-759
ISSN
1064-7481 (ISSN-L)
DOI
10.1097/jgp.0b013e31817e739a
PMC
PMC2722450
OpenAlex
W2150715444
Semantic Scholar
17f4982e2d35cae6f970c374ce8b5844cfc552d6
Cited by
117
References
56
Citations by year
2026: 3 · 2025: 5 · 2024: 4 · 2023: 2 · 2022: 9 · 2021: 7 · 2020: 8 · 2019: 3 · 2018: 7 · 2017: 9 · 2016: 4 · 2015: 14 · 2014: 6 · 2013: 13 · 2012: 8
FWCI
3.52
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • American Journal of Geriatric Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Mental Health (R01 MH-54846, K24MH070027, R01MH054846, K24-MH70027, P50MH60451, P50MH060451)
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
Keywords
geriatric depression, antidepressant response, neurocognitive function, verbal memory, processing speed, executive function, episodic memory, older adults, Symbol Digit Modalities Test, prose recall
MeSH terms
Aged, Antidepressive Agents, Attention, Brain, Cognition Disorders, Depressive Disorder, Major, Major Depressive Disorder, Female, Follow-Up Studies, Humans, Male, Memory Disorders, Motion Perception, Neuropsychological Tests, Surveys and Questionnaires, Reaction Time, Mental Recall, Visual Perception

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