Cortical Atrophy is Associated with Accelerated Cognitive Decline in Mild Cognitive Impairment with Subsyndromal Depression

https://doi.org/10.1016/j.jagp.2017.04.011Get rights and content

Objectives

To investigate the association between cognitive decline and cortical atrophy in individuals with mild cognitive impairment (MCI) and chronic subsyndromal symptoms of depression (SSD) over a 4-year period.

Setting

Multicenter, clinic-based.

Participants

Within the Alzheimer's Disease Neuroimaging Initiative repository, the Neuropsychiatric Inventory was used to identify individuals with MCI and stable endorsement (SSD group N = 32) or no endorsement (non-SSD group N = 69) of depressive symptoms across time points.

Measurements

Repeated measures of cognitive outcomes, cortical atrophy, and their associations were evaluated with mixed effects models adjusting for age, education, sex, and APOE genotype.

Results

The SSD group demonstrated accelerated decline on measures of global cognition (Alzheimer Disease Assessment Scale; df = 421, t = 2.242, p = 0.025), memory (Wechsler Memory Scale-Revised Logical Memory II; df = 244, t = −2.525, p = 0.011), information processing speed (Trail Making Test Parts A [df = 421, t = 2.376, p = 0.018] and B [df = 421, t = 2.533, p = 0.012]), and semantic fluency (Category Fluency; df = 424, t = −2.418, p = 0.016), as well as accelerated frontal lobe (df = 341, t = −2.648, p = 0.008) and anterior cingulate (df = 341, t = −3.786, p < 0.001) atrophy. No group differences were observed for rate of decline on measures of attention, learning, and confrontation naming or for rate of atrophy in any other regions. Accelerated frontal lobe and anterior cingulate atrophy was associated with cognitive decline on measures of global cognition, information processing speed, and semantic fluency (all p < 0.05), but not memory.

Conclusions

Individuals with chronic SSD may represent an MCI subgroup that is highly vulnerable to accelerated cognitive decline, an effect that may be governed by frontal lobe and anterior cingulate atrophy.

Section snippets

Participants

Data for the current study were obtained from the September 24, 2015, version of the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). The ADNI study is conducted in accordance with the Declaration of Helsinki and procedures were approved by the institutional review boards of all participating sites. All participants provided written informed consent at enrollment.

From the larger ADNI database, the present study included individuals with baseline magnetic

Demographic Factors

The baseline study sample included 32 participants in the SSD group and 69 participants in the non-SSD group. Median follow-up time was 3 years, with a median of six neuropsychological assessments (with the exception of the WMS [median: 4]) and five MRI scans. As seen in Table 1, there were no baseline differences between SSD and non-SSD groups with regard to sociodemographics (age, sex, years of education), APOE status, or baseline MMSE score. The SSD group had significantly higher scores on

Discussion

This study evaluated the association between rate of cortical atrophy and cognitive decline in participants with MCI and chronic SSD over an extended 4-year period. Our results demonstrate that MCI participants with chronic SSD 1) display accelerated cognitive decline longitudinally on measures of global cognition, memory, information processing speed, and semantic fluency; 2) display accelerated rate of frontal lobe and anterior cingulate atrophy over time; and 3) show cognitive decline on

References (39)

  • R.S. Mackin et al.

    Patterns of reduced cortical thickness in late-life depression and relationship to psychotherapeutic response

    Am J Geriatr Psychiatry

    (2013)
  • J.N. Bae et al.

    Dorsolateral prefrontal cortex and anterior cingulate cortex white matter alterations in late-life depression

    Biol Psychiatry

    (2006)
  • D. Badre

    Cognitive control, hierarchy, and the rostro-caudal organization of the frontal lobes

    Trends Cogn Sci

    (2008)
  • Y. Dwivedi

    Involvement of brain-derived neurotrophic factor in late-life depression

    Am J Geriatr Psychiatry

    (2013)
  • M.A. Rapp et al.

    Increased neurofibrillary tangles in patients with Alzheimer disease with comorbid depression

    Am J Geriatr Psychiatry

    (2008)
  • N.D. David et al.

    Trajectories of neuropsychiatric symptoms and cognitive decline in mild cognitive impairment

    Am J Geriatr Psychiatry

    (2016)
  • L.L. Judd et al.

    Subsyndromal symptomatic depression: a new mood disorder?

    J Clin Psychiatry

    (1994)
  • R.S. Mackin et al.

    Longitudinal stability of subsyndromal symptoms of depression in individuals with mild cognitive impairment: relationship to conversion to dementia after 3 years

    Int J Geriatr Psychiatry

    (2012)
  • T. Gabryelewicz et al.

    The rate of conversion of mild cognitive impairment to dementia: predictive role of depression

    Int J Geriatr Psychiatry

    (2007)
  • Cited by (27)

    • Depression symptoms moderate the relationship between gray matter volumes and cognitive function in patients with mild cognitive impairment

      2022, Journal of Psychiatric Research
      Citation Excerpt :

      An increasing number of studies have revealed significantly positive correlations between the GMV of limbic structures, including the HIP and amygdala, and cognitive function measured by the Mini-Mental State Examination (MMSE) in elderly patients with MCI (Nickl-Jockschat et al., 2012; Zanchi et al., 2017; Roh et al., 2020). Additionally, evidence from one study focused on elderly MCI patients with subsyndromal symptoms of depression (SSD), defined as a Geriatric Depression Scale (GDS) score <5, indicated that the interaction effect between cortical atrophy and SSD on cognitive function was not significant (Gonzales et al., 2017). The generally recommended cut-point of ≥5 on the GDS-15 for screening depression can reach a specificity of 94% (Prakash et al., 2009).

    • Late-Life Depression Is Associated With Reduced Cortical Amyloid Burden: Findings From the Alzheimer's Disease Neuroimaging Initiative Depression Project

      2021, Biological Psychiatry
      Citation Excerpt :

      Taken together, we would conclude that the impact of depression on memory function, independent of amyloid, is likely a significant contributor to risk of future cognitive decline. This relationship could be a direct consequence of depressed mood on cognition and functional status, or it could stem from other factors such as cortical atrophy associated with depressive symptoms (51). Furthermore, for individuals with other concurrent neurodegenerative processes, including amyloid deposition, this additional effect of depression could contribute to accelerated rates of cognitive decline and faster conversion to dementia.

    • Clinical trial testing in-home multidisciplinary care management for older adults with cognitive vulnerability: Rationale and study design

      2020, Contemporary Clinical Trials
      Citation Excerpt :

      Often, patient complaints of memory problems and other cognitive impairment mask late life depression [2,15]. While the prevalence of co-occurring depression and cognitive impairment has long been recognized clinically [15], population-based studies attempting to determine causal pathways between depression and dementia in middle and later life have yielded mixed results, leading to speculation that depression and dementia may share common causes [16–19]. Moreover, depression in later life is often complicated by comorbid physical illnesses such as diabetes and heart failure [20].

    • Time course of neuropsychiatric symptoms and cognitive diagnosis in National Alzheimer's Coordinating Centers volunteers

      2019, Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
      Citation Excerpt :

      A meta-analysis estimated that depression affects overall almost one-third of persons with MCI (range: 25% in community samples to 40% in clinical samples) [10]. Depression has been associated with greater risk of progression to Alzheimer's disease, vascular dementia, and MCI of different etiologies [11,12], whereas subsyndromal depression has been associated with accelerated cognitive decline and frontal lobe and anterior cingulate atrophy that may reflect the underlying mechanism distinct from Alzheimer's pathology [13]. A UK cohort study of over 10,000 people found that the emergence of depressive symptoms in late life was associated with a higher risk for dementia [14].

    View all citing articles on Scopus
    1

    Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (www.loni.usc.edu/ADNI). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. The complete list of ADNI investigators is available at http://adni.loni.usc.edu/study-design/ongoing-investigations/.

    View full text