Beta-amyloid deposition and cognitive function in patients with major depressive disorder with different subtypes of mild cognitive impairment: 18F-florbetapir (AV-45/Amyvid) PET study
- 750 Downloads
The objective of this study was to evaluate the amyloid burden, as assessed by 18F-florbetapir (AV-45/Amyvid) positron emission tomography PET, in patients with major depressive disorder (MDD) with different subtypes of mild cognitive impairment (MCI) and the relationship between amyloid burden and cognition in MDD patients.
The study included 55 MDD patients without dementia and 21 healthy control subjects (HCs) who were assessed using a comprehensive cognitive test battery and 18F-florbetapir PET imaging. The standardized uptake value ratios (SUVR) in eight cortical regions using the whole cerebellum as reference region were determined and voxel-wise comparisons between the HC and MDD groups were performed. Vascular risk factors, serum homocysteine level and the apolipoprotein E (ApoE) genotype were also determined.
Among the 55 MDD patients, 22 (40.0 %) had MCI, 12 (21.8 %) non-amnestic MCI (naMCI) and 10 (18.2 %) amnestic MCI (aMCI). The MDD patients with aMCI had the highest relative 18F-florbetapir uptake in all cortical regions, and a significant difference in relative 18F-florbetapir uptake was found in the parietal region as compared with that in naMCI subjects (P < 0.05) and HCs (P < 0.01). Voxel-wise analyses revealed significantly increased relative 18F-florbetapir uptake in the MDD patients with aMCI and naMCI in the frontal, parietal, temporal and occipital areas (P < 0.005). The global cortical SUVR was significantly negatively correlated with MMSE score (r = −0.342, P = 0.010) and memory function (r = −0.328, P = 0.015). The negative correlation between the global SUVR and memory in the MDD patients remained significant in multiple regression analyses that included age, educational level, ApoE genotype, and depression severity (β = −3.607, t = −2.874, P = 0.006).
We found preliminary evidence of brain beta-amyloid deposition in MDD patients with different subtypes of MCI. Our findings in MDD patients support the hypothesis that a higher amyloid burden is associated with a poorer memory performance. We also observed a high prevalence of MCI among elderly depressed patients, and depressed patients with MCI exhibited heterogeneously elevated 18F-florbetapir retention as compared with depressed patients without MCI. The higher amyloid burden in the aMCI patients suggests that these patients may also be more likely to develop Alzheimer’s disease than other patients diagnosed with major depression.
KeywordsMajor depressive disorder Amyloid 18F-Florbetapir (AV-45/Amyvid) Alzheimer’s disease Dementia Mild cognitive impairment
We thank Avid Radiopharmaceuticals Inc. (Philadelphia, PA, USA) for providing the precursor for the preparation of 18F-florbetapir.
Compliance with ethical standards
This study was carried out with financial support from the National Science Council, Taiwan (NSC 101-2314-B-182-061-MY2, MOST103-2314-B-182-010-MY3, MOST 103-2314-B-182A-016-, MOST 104-2314-B-182A-034-, MOST 104-2314-B-182A-083-MY2) and grants from the Research Fund of Chang Gung Memorial Hospital (CMRPD1C0383, CMRPD1E0301).
Conflicts of interest
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 23.Wechsler D. Wechsler Adult Intelligence Scale (WAIS-III): administration and scoring manual. San Antonio, TX: Psychological Corporation; 1997.Google Scholar
- 24.Reitan RM, Wolfson D. The Halstead-Reitan neuropsychological test battery: theory and clinical interpretation. Tucson, AZ: Neuropsychology Press; 1985.Google Scholar
- 27.Benton A, Hamsher K, Sivan A. Multilingual aphasia examination. Iowa City: AJA Associates; 1989.Google Scholar
- 29.Sunrise Editors. Operating instructions for sunrise systems: continuous performance task. Washington: Sunrise Systems; 1995.Google Scholar
- 42.Braak H, Braak E. Staging of Alzheimer-related cortical destruction. Int Psychogeriatr. 1997;9 Suppl 1:257–61; discussion 269–72.Google Scholar
- 46.Storandt M, Mintun MA, Head D, Morris JC. Cognitive decline and brain volume loss as signatures of cerebral amyloid-beta peptide deposition identified with Pittsburgh compound B: cognitive decline associated with Abeta deposition. Arch Neurol. 2009;66:1476–81.CrossRefPubMedPubMedCentralGoogle Scholar
- 50.Sperling RA, Johnson KA, Doraiswamy PM, Reiman EM, Fleisher AS, Sabbagh MN, et al. Amyloid deposition detected with florbetapir F18 ((18)F-AV-45) is related to lower episodic memory performance in clinically normal older individuals. Neurobiol Aging. 2013;34:822–31.CrossRefPubMedPubMedCentralGoogle Scholar