Association of Cortical and Subcortical β-Amyloid With Standardized Measures of Depressive and Anxiety Symptoms in Adults Without Dementia

Janina Krell-Roesch, Departments of Health Sciences Research (Krell-Roesch, Syrjanen, Rakusa, Kremers, Mielke, Vassilaki), Radiology (Vemuri, Lowe, Jack), Psychiatry and Psychology (Machulda), and Neurology (Mielke, Knopman, Petersen), Mayo Clinic, Rochester, Minn.; Institute of Sports and Sports Science, Karlsruhe Institute of Technology, Karlsruhe, Germany (Krell-Roesch); Department of Neurology, University Medical Center, Maribor, Slovenia (Rakusa); International Clinical Research Center, St. Anne Hospital, Brno, Czech Republic (Stokin); and Department of Neurology, Barrow Neurological Institute, Phoenix (Geda).
Jeremy A. Syrjanen, Departments of Health Sciences Research (Krell-Roesch, Syrjanen, Rakusa, Kremers, Mielke, Vassilaki), Radiology (Vemuri, Lowe, Jack), Psychiatry and Psychology (Machulda), and Neurology (Mielke, Knopman, Petersen), Mayo Clinic, Rochester, Minn.; Institute of Sports and Sports Science, Karlsruhe Institute of Technology, Karlsruhe, Germany (Krell-Roesch); Department of Neurology, University Medical Center, Maribor, Slovenia (Rakusa); International Clinical Research Center, St. Anne Hospital, Brno, Czech Republic (Stokin); and Department of Neurology, Barrow Neurological Institute, Phoenix (Geda).
Martin Rakusa, Departments of Health Sciences Research (Krell-Roesch, Syrjanen, Rakusa, Kremers, Mielke, Vassilaki), Radiology (Vemuri, Lowe, Jack), Psychiatry and Psychology (Machulda), and Neurology (Mielke, Knopman, Petersen), Mayo Clinic, Rochester, Minn.; Institute of Sports and Sports Science, Karlsruhe Institute of Technology, Karlsruhe, Germany (Krell-Roesch); Department of Neurology, University Medical Center, Maribor, Slovenia (Rakusa); International Clinical Research Center, St. Anne Hospital, Brno, Czech Republic (Stokin); and Department of Neurology, Barrow Neurological Institute, Phoenix (Geda).
Prashanthi Vemuri, Departments of Health Sciences Research (Krell-Roesch, Syrjanen, Rakusa, Kremers, Mielke, Vassilaki), Radiology (Vemuri, Lowe, Jack), Psychiatry and Psychology (Machulda), and Neurology (Mielke, Knopman, Petersen), Mayo Clinic, Rochester, Minn.; Institute of Sports and Sports Science, Karlsruhe Institute of Technology, Karlsruhe, Germany (Krell-Roesch); Department of Neurology, University Medical Center, Maribor, Slovenia (Rakusa); International Clinical Research Center, St. Anne Hospital, Brno, Czech Republic (Stokin); and Department of Neurology, Barrow Neurological Institute, Phoenix (Geda).
Mary M. Machulda, Departments of Health Sciences Research (Krell-Roesch, Syrjanen, Rakusa, Kremers, Mielke, Vassilaki), Radiology (Vemuri, Lowe, Jack), Psychiatry and Psychology (Machulda), and Neurology (Mielke, Knopman, Petersen), Mayo Clinic, Rochester, Minn.; Institute of Sports and Sports Science, Karlsruhe Institute of Technology, Karlsruhe, Germany (Krell-Roesch); Department of Neurology, University Medical Center, Maribor, Slovenia (Rakusa); International Clinical Research Center, St. Anne Hospital, Brno, Czech Republic (Stokin); and Department of Neurology, Barrow Neurological Institute, Phoenix (Geda).
Walter K. Kremers, Departments of Health Sciences Research (Krell-Roesch, Syrjanen, Rakusa, Kremers, Mielke, Vassilaki), Radiology (Vemuri, Lowe, Jack), Psychiatry and Psychology (Machulda), and Neurology (Mielke, Knopman, Petersen), Mayo Clinic, Rochester, Minn.; Institute of Sports and Sports Science, Karlsruhe Institute of Technology, Karlsruhe, Germany (Krell-Roesch); Department of Neurology, University Medical Center, Maribor, Slovenia (Rakusa); International Clinical Research Center, St. Anne Hospital, Brno, Czech Republic (Stokin); and Department of Neurology, Barrow Neurological Institute, Phoenix (Geda).
Michelle M. Mielke, Departments of Health Sciences Research (Krell-Roesch, Syrjanen, Rakusa, Kremers, Mielke, Vassilaki), Radiology (Vemuri, Lowe, Jack), Psychiatry and Psychology (Machulda), and Neurology (Mielke, Knopman, Petersen), Mayo Clinic, Rochester, Minn.; Institute of Sports and Sports Science, Karlsruhe Institute of Technology, Karlsruhe, Germany (Krell-Roesch); Department of Neurology, University Medical Center, Maribor, Slovenia (Rakusa); International Clinical Research Center, St. Anne Hospital, Brno, Czech Republic (Stokin); and Department of Neurology, Barrow Neurological Institute, Phoenix (Geda).
Val J. Lowe, Departments of Health Sciences Research (Krell-Roesch, Syrjanen, Rakusa, Kremers, Mielke, Vassilaki), Radiology (Vemuri, Lowe, Jack), Psychiatry and Psychology (Machulda), and Neurology (Mielke, Knopman, Petersen), Mayo Clinic, Rochester, Minn.; Institute of Sports and Sports Science, Karlsruhe Institute of Technology, Karlsruhe, Germany (Krell-Roesch); Department of Neurology, University Medical Center, Maribor, Slovenia (Rakusa); International Clinical Research Center, St. Anne Hospital, Brno, Czech Republic (Stokin); and Department of Neurology, Barrow Neurological Institute, Phoenix (Geda).
Clifford R. Jack, Departments of Health Sciences Research (Krell-Roesch, Syrjanen, Rakusa, Kremers, Mielke, Vassilaki), Radiology (Vemuri, Lowe, Jack), Psychiatry and Psychology (Machulda), and Neurology (Mielke, Knopman, Petersen), Mayo Clinic, Rochester, Minn.; Institute of Sports and Sports Science, Karlsruhe Institute of Technology, Karlsruhe, Germany (Krell-Roesch); Department of Neurology, University Medical Center, Maribor, Slovenia (Rakusa); International Clinical Research Center, St. Anne Hospital, Brno, Czech Republic (Stokin); and Department of Neurology, Barrow Neurological Institute, Phoenix (Geda).
David S. Knopman, Departments of Health Sciences Research (Krell-Roesch, Syrjanen, Rakusa, Kremers, Mielke, Vassilaki), Radiology (Vemuri, Lowe, Jack), Psychiatry and Psychology (Machulda), and Neurology (Mielke, Knopman, Petersen), Mayo Clinic, Rochester, Minn.; Institute of Sports and Sports Science, Karlsruhe Institute of Technology, Karlsruhe, Germany (Krell-Roesch); Department of Neurology, University Medical Center, Maribor, Slovenia (Rakusa); International Clinical Research Center, St. Anne Hospital, Brno, Czech Republic (Stokin); and Department of Neurology, Barrow Neurological Institute, Phoenix (Geda).
Gorazd B. Stokin, Departments of Health Sciences Research (Krell-Roesch, Syrjanen, Rakusa, Kremers, Mielke, Vassilaki), Radiology (Vemuri, Lowe, Jack), Psychiatry and Psychology (Machulda), and Neurology (Mielke, Knopman, Petersen), Mayo Clinic, Rochester, Minn.; Institute of Sports and Sports Science, Karlsruhe Institute of Technology, Karlsruhe, Germany (Krell-Roesch); Department of Neurology, University Medical Center, Maribor, Slovenia (Rakusa); International Clinical Research Center, St. Anne Hospital, Brno, Czech Republic (Stokin); and Department of Neurology, Barrow Neurological Institute, Phoenix (Geda).
Ronald C. Petersen, Departments of Health Sciences Research (Krell-Roesch, Syrjanen, Rakusa, Kremers, Mielke, Vassilaki), Radiology (Vemuri, Lowe, Jack), Psychiatry and Psychology (Machulda), and Neurology (Mielke, Knopman, Petersen), Mayo Clinic, Rochester, Minn.; Institute of Sports and Sports Science, Karlsruhe Institute of Technology, Karlsruhe, Germany (Krell-Roesch); Department of Neurology, University Medical Center, Maribor, Slovenia (Rakusa); International Clinical Research Center, St. Anne Hospital, Brno, Czech Republic (Stokin); and Department of Neurology, Barrow Neurological Institute, Phoenix (Geda).
Maria Vassilaki, Departments of Health Sciences Research (Krell-Roesch, Syrjanen, Rakusa, Kremers, Mielke, Vassilaki), Radiology (Vemuri, Lowe, Jack), Psychiatry and Psychology (Machulda), and Neurology (Mielke, Knopman, Petersen), Mayo Clinic, Rochester, Minn.; Institute of Sports and Sports Science, Karlsruhe Institute of Technology, Karlsruhe, Germany (Krell-Roesch); Department of Neurology, University Medical Center, Maribor, Slovenia (Rakusa); International Clinical Research Center, St. Anne Hospital, Brno, Czech Republic (Stokin); and Department of Neurology, Barrow Neurological Institute, Phoenix (Geda).
Yonas E. Geda, Departments of Health Sciences Research (Krell-Roesch, Syrjanen, Rakusa, Kremers, Mielke, Vassilaki), Radiology (Vemuri, Lowe, Jack), Psychiatry and Psychology (Machulda), and Neurology (Mielke, Knopman, Petersen), Mayo Clinic, Rochester, Minn.; Institute of Sports and Sports Science, Karlsruhe Institute of Technology, Karlsruhe, Germany (Krell-Roesch); Department of Neurology, University Medical Center, Maribor, Slovenia (Rakusa); International Clinical Research Center, St. Anne Hospital, Brno, Czech Republic (Stokin); and Department of Neurology, Barrow Neurological Institute, Phoenix (Geda).Follow

Document Type

Article

Abstract

OBJECTIVE: The purpose of this study was to test the hypothesis that subcortical β-amyloid (Aβ) deposition was associated with elevated scores on standardized measures of depressive and anxiety symptoms when compared with cortical (Aβ) deposition in persons without dementia. METHODS: The authors performed a cross-sectional study, derived from the population-based Mayo Clinic Study of Aging, comprising participants aged ≥70 years (N=1,022; 55% males; 28% apolipoprotein E [APOE] ε4 carriers; without cognitive impairment, N=842; mild cognitive impairment; N=180). To assess Aβ deposition in cortical and subcortical (the amygdala, striatum, and thalamus) regions, participants underwent Pittsburgh Compound B positron emission tomography (PiB-PET) and completed the Beck Depression Inventory-II (BDI-II) and the Beck Anxiety Inventory (BAI). The investigators ran linear regression models to examine the association between PiB-PET standardized uptake value ratios (SUVRs) in the neocortex and subcortical regions and depressive and anxiety symptoms (BDI-II and BAI total scores). Models were adjusted for age, sex, education level, and APOE ε4 carrier status and stratified by cognitive status (without cognitive impairment, mild cognitive impairment). RESULTS: Cortical PiB-PET SUVRs were associated with depressive symptoms (β=0.57 [SE=0.13], p<0.001) and anxiety symptoms (β=0.34 [SE=0.13], p=0.011). PiB-PET SUVRs in the amygdala were associated only with depressive symptoms (β=0.80 [SE=0.26], p=0.002). PiB-PET SUVRs in the striatum and thalamus were associated with depressive symptoms (striatum: β=0.69 [SE=0.18], p<0.001; thalamus: β=0.61 [SE=0.24], p=0.011) and anxiety symptoms (striatum: β=0.56 [SE=0.18], p=0.002; thalamus: β=0.65 [SE=0.24], p=0.008). In the mild cognitive impairment subsample, Aβ deposition, regardless of neuroanatomic location, was associated with depressive symptoms but not anxiety symptoms. CONCLUSIONS: Elevated amyloid deposition in cortical and subcortical brain regions was associated with higher depressive and anxiety symptoms, although these findings did not significantly differ by cortical versus subcortical Aβ deposition. This cross-sectional observation needs to be confirmed by a longitudinal study.

Medical Subject Headings

Aged; Aged, 80 and over; Amyloid beta-Peptides (metabolism); Anxiety (psychology); Apolipoprotein E4; Brain (diagnostic imaging, metabolism); Brief Psychiatric Rating Scale; Cognitive Dysfunction (metabolism); Cross-Sectional Studies; Depression (psychology); Female; Humans; Longitudinal Studies; Male; Positron-Emission Tomography

Publication Date

1-1-2021

Publication Title

The Journal of neuropsychiatry and clinical neurosciences

E-ISSN

1545-7222

Volume

33

Issue

1

First Page

64

Last Page

71

PubMed ID

33086924

Digital Object Identifier (DOI)

10.1176/appi.neuropsych.20050103

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