. 2021 Apr 15;89(8):757-765.

doi: 10.1016/j.biopsych.2020.06.017. Epub 2020 Jul 2.

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

R Scott Mackin¹, Philip S Insel², Susan Landau³, David Bickford⁴, Ruth Morin⁵, Emma Rhodes⁵, Duygu Tosun⁶, Howie J Rosen⁷, Meryl Butters⁸, Paul Aisen⁹, Rema Raman⁹, Andrew Saykin¹⁰, Arthur Toga¹¹, Clifford Jack Jr¹², Robert Koeppe¹³, Michael W Weiner¹⁴, Craig Nelson⁴; Alzheimer’s Disease Neuroimaging Initiative and the ADNI Depression Project

Affiliations

¹ Department of Psychiatry, University of California, San Francisco, California; Center for Imaging of Neurodegenerative Diseases, Veterans Administration Medical Center, San Francisco, California. Electronic address: scott.mackin@ucsf.edu.
² Department of Psychiatry, University of California, San Francisco, California; Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund, Sweden. Electronic address: philipinsel@gmail.com.
³ Helen Wills Neuroscience Institute, University of California, Berkeley, California.
⁴ Department of Psychiatry, University of California, San Francisco, California.
⁵ Center for Imaging of Neurodegenerative Diseases, Veterans Administration Medical Center, San Francisco, California.
⁶ Department of Radiology, University of California, San Francisco, California; Center for Imaging of Neurodegenerative Diseases, Veterans Administration Medical Center, San Francisco, California.
⁷ Memory and Aging Center, Department of Neurology, University of California, San Francisco, California.
⁸ Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
⁹ Department of Neurology, University of Southern California, San Diego, California; Alzheimer's Therapeutic Research Institute, San Diego, California.
¹⁰ Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana.
¹¹ Laboratory of Neuro Imaging, Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, California.
¹² Mayo Clinic, Rochester, Minnesota.
¹³ Department of Radiology, University of Michigan, Ann Arbor, Michigan.
¹⁴ Department of Psychiatry, University of California, San Francisco, California; Department of Radiology, University of California, San Francisco, California; Center for Imaging of Neurodegenerative Diseases, Veterans Administration Medical Center, San Francisco, California.

PMID: 32980132
PMCID: PMC10165941
DOI: 10.1016/j.biopsych.2020.06.017

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

R Scott Mackin et al. Biol Psychiatry. 2021.

. 2021 Apr 15;89(8):757-765.

doi: 10.1016/j.biopsych.2020.06.017. Epub 2020 Jul 2.

Authors

Affiliations

¹ Department of Psychiatry, University of California, San Francisco, California; Center for Imaging of Neurodegenerative Diseases, Veterans Administration Medical Center, San Francisco, California. Electronic address: scott.mackin@ucsf.edu.
² Department of Psychiatry, University of California, San Francisco, California; Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund, Sweden. Electronic address: philipinsel@gmail.com.
³ Helen Wills Neuroscience Institute, University of California, Berkeley, California.
⁴ Department of Psychiatry, University of California, San Francisco, California.
⁵ Center for Imaging of Neurodegenerative Diseases, Veterans Administration Medical Center, San Francisco, California.
⁶ Department of Radiology, University of California, San Francisco, California; Center for Imaging of Neurodegenerative Diseases, Veterans Administration Medical Center, San Francisco, California.
⁷ Memory and Aging Center, Department of Neurology, University of California, San Francisco, California.
⁸ Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
⁹ Department of Neurology, University of Southern California, San Diego, California; Alzheimer's Therapeutic Research Institute, San Diego, California.
¹⁰ Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana.
¹¹ Laboratory of Neuro Imaging, Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, California.
¹² Mayo Clinic, Rochester, Minnesota.
¹³ Department of Radiology, University of Michigan, Ann Arbor, Michigan.
¹⁴ Department of Psychiatry, University of California, San Francisco, California; Department of Radiology, University of California, San Francisco, California; Center for Imaging of Neurodegenerative Diseases, Veterans Administration Medical Center, San Francisco, California.

PMID: 32980132
PMCID: PMC10165941
DOI: 10.1016/j.biopsych.2020.06.017

Erratum in

Erratum.
[No authors listed] [No authors listed] Biol Psychiatry. 2021 Apr 15;89(8):836. doi: 10.1016/j.biopsych.2021.02.004. Biol Psychiatry. 2021. PMID: 33766240 No abstract available.

Abstract

Background: We evaluated the role of cortical amyloid deposition as a factor contributing to memory dysfunction and increased risk of dementia associated with late-life depression (LLD).

Methods: A total of 119 older adult participants with a current diagnosis of major depression (LLD) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) Depression Project study and 119 nondepressed (ND) cognitively unimpaired participants matched on age, sex, and APOE genotype were obtained from the ADNI database.

Results: Thirty-three percent of LLD participants met ADNI criteria for mild cognitive impairment. Compared with ND individuals, the LLD group exhibited less global amyloid beta (Aβ) accumulation (p = .05). The proportion of amyloid positivity in the LLD group was 19.3% compared with 31.1% for the ND participants (p = .02). Among LLD participants, global Aβ was not associated with lifetime number of depressive episodes, lifetime length of depression, length of lifetime selective serotonin reuptake inhibitor use, or lifetime length of untreated depression (p > .21 for all). Global Aβ was associated with worse memory performance (p = .05). Similar results were found in secondary analyses restricting comparisons to the cognitively unimpaired LLD participants as well as when comparing the LLD group with an ND group that included participants with mild cognitive impairment.

Conclusions: Contrary to expectation, the LLD group showed less Aβ deposition than the ND group and Aβ deposition was not associated with depression history characteristics. Aβ was associated with memory, but this relationship did not differ between LLD and ND. Our results suggest that memory deficits and accelerated cognitive decline reported in previous studies of LLD are not due to greater cortical Aβ accumulation.

Keywords: Alzheimer’s disease; Amyloid; Cognition; Depressive symptoms; Late-life depression; Mild cognitive impairment.

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Figures

**Figure 1.**
Global Aβ PET Uptake and Amyloid Positivity for LLD and ND groups (n=238)

**Figure 2.**
Regional differences in Aβ for LLD and ND groups (n=238) Estimated Aβ SUVR differences between LLD and ND groups for all regions are shown on the left. A value of −0.05, for example, indicates that the LLD group had 0.05 lower average SUVR compared to the ND group.

**Figure 3:**
Depression group differences in amyloid beta. Top Row: LLD n = 44, ND n = 119; Middle Row: LLD n = 44, ND n = 119; Bottom Row: LLD n = 80, ND n = 80. Not all LLD participants were included in all comparisons. CN, cognitively normal; FDR, false discovery rate; LLD, late life depression; MCI, mild cognitive impairment; ND, nondepressed

**Figure 4.**
Association of Aβ with Memory Performance (n=238) Delayed logical memory is plotted against global Aβ SUVR. Dashed lines show LLD and ND groups separately. The red curve shows both groups combined.

**Figure 5:**
Association of Aβ with Depression Characteristics and Treatment History (n=238) Global Aβ SUVR is plotted against depression characteristics. Time variables are depicted in days.

See this image and copyright information in PMC

Comment in

Reply to: Brain Amyloid Deposition in Late-Life Depression.
Mackin RS, Insel PS. Mackin RS, et al. Biol Psychiatry. 2021 Apr 15;89(8):e43-e44. doi: 10.1016/j.biopsych.2020.09.019. Epub 2020 Nov 11. Biol Psychiatry. 2021. PMID: 33189331 Free PMC article. No abstract available.
Brain Amyloid Deposition in Late-Life Depression.
Pomara N, Imbimbo BP. Pomara N, et al. Biol Psychiatry. 2021 Apr 15;89(8):e41-e42. doi: 10.1016/j.biopsych.2020.07.025. Epub 2020 Nov 11. Biol Psychiatry. 2021. PMID: 33189332 No abstract available.
Amyloid-Associated Depression-or Not?
van Dyck CH, O'Dell RS, Mecca AP. van Dyck CH, et al. Biol Psychiatry. 2021 Apr 15;89(8):737-738. doi: 10.1016/j.biopsych.2021.02.008. Biol Psychiatry. 2021. PMID: 33766236 Free PMC article. No abstract available.

References

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1. Chodosh J, Kado DM, Seeman TE, et al. : Depressive symptoms as a predictor of cognitive decline: MacArthur Studies of Successful Aging. Am J Geriatr Psychiatry 2007; 15:406–415 - PubMed
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Late-Life Depression Is Associated With Reduced Cortical Amyloid Burden: Findings From the Alzheimer's Disease Neuroimaging Initiative Depression Project

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

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