Memory deficits and β-amyloid prominent in elderly with treatment-resistant depression

Elderly patients with treatment-resistant depression have greater cognitive deficits and more brain β-amyloid than non-TRD patients, according to a study presented at CINP 2021 Virtual. These findings reinforce associations between amyloid burden, impaired cognition, depression and --- ultimately – possible dementia risk.

Depression is a risk factor for dementia and may even be a prodromal symptom. This is clearly shown by the recent Swedish study which followed large national cohorts of people with and without depression and looked for dementia occurring over the next 35 years.

Dementia risk was 10-20 times greater in the year after a depression diagnosis; and increased risk, although much diminished, was still evident after twenty years. Dementia risk was higher with severe than with moderate depression and remained after adjustment for familial and demographic factors.

Dementia risk raised even twenty years after depression diagnosis


Search for mediating factors

That said, it is clear that only some people with major depressive disorder (MDD) progress to dementia. So there is interest in whether other factors – notably β-amyloid burden – may play a part.

The presence of β-amyloid strongly predicts subsequent dementia in cognitively normal subjects.2 And findings in MDD patients support the hypothesis that a higher amyloid burden is associated with a poorer memory performance.3

These findings prompted a group of Taiwanese researchers to undertake a neuroimaging and cognition study looking specifically -- and for the first time -- at the role of treatment-resistant depression (TRD) in the elderly.

We need biomarkers that will reliably predict dementia in people with depression


Impaired verbal recall in TRD a marker of dementia risk?

The study involved Pittsburgh Compound-B PET (PiB-PET) amyloid imaging in 26 subjects aged 50 with TRD, 28 with non-treatment resistant depression, 26 healthy controls, and also a small group of patients with Alzheimer’s disease (AD).

Presenting the findings at CINP 2021 Virtual, Hsuan Lee (Taipei Veterans General Hospital, Taiwan) reported that elderly MDD patients globally had a higher amyloid burden than healthy controls.

In more detail,

  • The elderly patients with TRD had  greater amyloid deposits in the anterior and posterior cingulate cortex, parietal cortex, and occiptal cortex than either non-TRD patients or healthy controls. This was also true of patients with AD.
  • In terms of cognition, TRD patients had significantly more impaired immediate and delayed word-list memory than either non-TRD patients or healthy controls after controlling for age, gender, education, and depression scores.
  • TRD patients had lower scores on the MoCA (Montreal Cognitive Assessment) than control subjects but non-TRD patients were not different from healthy controls.

Posterior cingulate cortex amyloid deposits in TRD patients were strongly negatively correlated with the immediate recall of word lists (r=-0.93).

This finding, and evidence of a positive correlation between severity of geriatric depression and accumulation of PiB found by other workers,4 leads the Taiwanese group to suggest that a deficit in verbal recall may be a potential predictor of dementia risk in people with TRD.

Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.


1. Holmquist S et al. PLoS Med 2020;17(1): e1003016 

2. Lopez OL et al. Neurology 2018 May 22, 2018; 90 (21)

3. Wu K-Y et al. Eur J Nucl Med Mol Imaging 2016;43(6):1067-76

4. Yasuno F et al. Int J Geriatr Psychiatry 2016;31(8):920-8

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