Differential Diagnosis Between Alzheimer's Disease-Related Depression and Pseudo-Dementia in Depression: A New Indication for Amyloid-β Imaging?

J Alzheimers Dis. 2022;88(3):1029-1035. doi: 10.3233/JAD-215619.

Abstract

Background: Alzheimer's disease and depression can start with combined cognitive and depressive symptoms [1, 2]. Accurate differential diagnosis is desired to initiate specific treatment.

Objective: We investigated whether amyloid-β PET imaging can discriminate both entities.

Methods: This retrospective observational study included 39 patients (20 female, age = 70±11years) with both cognitive and depressive symptoms who underwent amyloid-β PET imaging and in whom clinical follow-up data was available. Amyloid-β PET was carried out applying [18F]Florbetaben or [11C]PiB. The PET images were analyzed by standardized visual and relative-quantitative evaluation. Based on clinical follow-up (median of 2.4 years [range 0.3 to 7.0 years, IQR = 3.7 years] after amyloid PET imaging which was not considered in obtaining a definite diagnosis), discrimination ability between AD-related depression and pseudo-dementia in depression/depression with other comorbidities was determined.

Results: Visually, all 10 patients with pseudo-dementia in depression and all 15 patients with other depression were rated as amyloid-β-negative; 2 of 14 patients with AD-related depression were rated amyloid-β-negative. ROC curve analysis of the unified composite standardized uptake value ratios (cSUVRs) was able to discriminate pseudo-dementia in depression from AD-related depression with high accuracy (AUC = 0.92). Optimal [18F]Florbetaben discrimination cSUVR threshold was 1.34. In congruence with the visual PET analysis, the resulting sensitivity of the relative-quantitative analysis was 86% with a specificity of 100%.

Conclusion: Amyloid-β PET can differentiate AD-related depression and pseudo-dementia in depression. Prospective clinical studies are warranted to confirm this result and to potentially broaden the spectrum of clinical applications for amyloid-β PET imaging.

Keywords: Alzheimer’s disease; [18F]florbetaben; amyloid PET imaging; amyloid-β; depression; mild cognitive impairment; pittsburgh compound B; pseudo-dementia.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease* / complications
  • Alzheimer Disease* / diagnostic imaging
  • Amyloid beta-Peptides
  • Aniline Compounds
  • Cognitive Dysfunction* / diagnosis
  • Depression / diagnostic imaging
  • Diagnosis, Differential
  • Female
  • Humans
  • Middle Aged
  • Positron-Emission Tomography / methods
  • Prospective Studies

Substances

  • Amyloid beta-Peptides
  • Aniline Compounds