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The impact of amyloid burden and APOE on rates of cognitive impairment in late life depression

Rhodes, Emma ; Insel, Philip S. LU ; Butters, Meryl A. ; Morin, Ruth ; Bickford, David ; Tosun, Duygu ; Gessert, Devon ; Rosen, Howie J. ; Aisen, Paul and Raman, Rema , et al. (2021) In Journal of Alzheimer's Disease 80(3). p.991-1002
Abstract

Background: Cognitive impairment (CI) is a key feature of late life depression (LLD), but the contribution of underlying neurodegenerative pathology remains unclear. Objective: To evaluate cognitive dysfunction in LLD relative to a sample of nondepressed (ND) older adults with matched levels of memory impairment and amyloid-β (Aβ) burden. Methods: Participants included 120 LLD and 240 ND older adults matched on age, education, sex, Mini-Mental State Exam, mild cognitive impairment diagnosis, and PET Aβ burden. Results: LLD showed higher rates of impairment relative to ND with 54.6% of the LLD sample demonstrating impairment in at least one cognitive domain compared to 42.9% of controls (H = 7.13, p = 0.008). LLD had poorer performance... (More)

Background: Cognitive impairment (CI) is a key feature of late life depression (LLD), but the contribution of underlying neurodegenerative pathology remains unclear. Objective: To evaluate cognitive dysfunction in LLD relative to a sample of nondepressed (ND) older adults with matched levels of memory impairment and amyloid-β (Aβ) burden. Methods: Participants included 120 LLD and 240 ND older adults matched on age, education, sex, Mini-Mental State Exam, mild cognitive impairment diagnosis, and PET Aβ burden. Results: LLD showed higher rates of impairment relative to ND with 54.6% of the LLD sample demonstrating impairment in at least one cognitive domain compared to 42.9% of controls (H = 7.13, p = 0.008). LLD had poorer performance and higher rates of impairment on Rey Auditory Verbal Learning Test learning and memory compared to controls. In the overall sample, Aβ positivity was associated with worse performance on Logical Memory I (p = 0.044), Logical Memory II (p = 0.011), and Trail Making Test -B (p = 0.032), and APOE ϵ4 genotype was associated with worse performance on Logical Memory I (p =0.022); these relationships did not differ between LLD and ND. Conclusion: LLD showed higher rates of CI driven by focal deficits in verbal learning and memory. Alzheimer's disease (AD) biomarkers were associated with worse performance on timed set-shifting and story learning and memory, and these relationships were not impacted by depression status. These findings suggest that AD may account for a portion of previously reported multi-domain CI in LLD and highlight the potential for AD to confound studies of cognition in LLD.

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author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Amyloid, Apolipoprotein E, Cognitive impairment, Late life depression
in
Journal of Alzheimer's Disease
volume
80
issue
3
pages
12 pages
publisher
IOS Press
external identifiers
  • scopus:85103974095
  • pmid:33682706
ISSN
1387-2877
DOI
10.3233/JAD-201089
language
English
LU publication?
yes
id
61be4622-e5e2-4dc9-8bd4-8c396449a2e8
date added to LUP
2021-04-23 07:15:15
date last changed
2024-06-15 10:16:16
@article{61be4622-e5e2-4dc9-8bd4-8c396449a2e8,
  abstract     = {{<p>Background: Cognitive impairment (CI) is a key feature of late life depression (LLD), but the contribution of underlying neurodegenerative pathology remains unclear. Objective: To evaluate cognitive dysfunction in LLD relative to a sample of nondepressed (ND) older adults with matched levels of memory impairment and amyloid-β (Aβ) burden. Methods: Participants included 120 LLD and 240 ND older adults matched on age, education, sex, Mini-Mental State Exam, mild cognitive impairment diagnosis, and PET Aβ burden. Results: LLD showed higher rates of impairment relative to ND with 54.6% of the LLD sample demonstrating impairment in at least one cognitive domain compared to 42.9% of controls (H = 7.13, p = 0.008). LLD had poorer performance and higher rates of impairment on Rey Auditory Verbal Learning Test learning and memory compared to controls. In the overall sample, Aβ positivity was associated with worse performance on Logical Memory I (p = 0.044), Logical Memory II (p = 0.011), and Trail Making Test -B (p = 0.032), and APOE ϵ4 genotype was associated with worse performance on Logical Memory I (p =0.022); these relationships did not differ between LLD and ND. Conclusion: LLD showed higher rates of CI driven by focal deficits in verbal learning and memory. Alzheimer's disease (AD) biomarkers were associated with worse performance on timed set-shifting and story learning and memory, and these relationships were not impacted by depression status. These findings suggest that AD may account for a portion of previously reported multi-domain CI in LLD and highlight the potential for AD to confound studies of cognition in LLD.</p>}},
  author       = {{Rhodes, Emma and Insel, Philip S. and Butters, Meryl A. and Morin, Ruth and Bickford, David and Tosun, Duygu and Gessert, Devon and Rosen, Howie J. and Aisen, Paul and Raman, Rema and Landau, Susan and Saykin, Andrew and Toga, Arthur and Jack, Clifford R. and Weiner, Michael W. and Nelson, Craig and MacKin, R. Scott}},
  issn         = {{1387-2877}},
  keywords     = {{Amyloid; Apolipoprotein E; Cognitive impairment; Late life depression}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{991--1002}},
  publisher    = {{IOS Press}},
  series       = {{Journal of Alzheimer's Disease}},
  title        = {{The impact of amyloid burden and APOE on rates of cognitive impairment in late life depression}},
  url          = {{http://dx.doi.org/10.3233/JAD-201089}},
  doi          = {{10.3233/JAD-201089}},
  volume       = {{80}},
  year         = {{2021}},
}