Table 1 Research questions and outcome data to be used to address the study objectives

1

Hippocampal atrophy associated with SD?

MRI: 3D T1 BRAVO & 3D T2 (morphometry & PET pre-processing)

PET: ¹¹C-UCB-J PET (SV2a: SD)

Hippocampal volume

¹¹C-UCB-J SUVR

2

Tau associated with SD in hippocampus?

MRI: 3D T1 BRAVO & 3D T2 (as above)

PET: ¹⁸F-MK-6240 (tau)

Hippocampal volume

¹⁸F-MK-6240 SUVR

3

ECT-induced ΔGM in hippocampus associated with ΔSD?

MRI: 3D T1 & 3D T2 (as above + post ECT)

PET: ¹¹C-UCB-J PET (SD)

Δ Hippocampal volume

Δ¹¹C-UCB-J

4

Tau associated with MTL WM damage?

MRI: 3D FLAIR (to define + quantify WML) SWI & ASL (perfusion/vascular pathology) multi-shell diffusion (DKI, NODDI + tractography)

PET: ¹⁸F-MK-6240 (tau)

Total + regional cerebral WML volume

¹⁸F-MK-6240 SUVR

WM microstructural damage (e.g. MK, FA, ND), MTL WM fibre bundles

5

Pathological brain ageing mediated by CV risk factors?

MRI: 3D T1 & T2 (as above)

MRI: 3D FLAIR (to define + quantify WML) SWI & ASL (perfusion/vascular pathology)

PET: ¹¹C-UCB-J PET (SD)

PET: ¹⁸F-MK-6240 (tau)

Doppler ultrasound (carotid artery)

Blood biomarkers (lipids, glucose)

GM volume/cortical thickness

Total + regional cerebral WML volume

¹¹C-UCB-J & ¹⁸F-MK-6240 SUVR

Intima-media thickness

Serum lipids (HDL, LDL), glucose (HbA1c)

Motor function metrics

6

Stress ➔ ↑tau & ↓SD ➔ MTL functional connectivity?

MRI: resting-state fMRI (fc connectivity)

3D T1 (as above)

PET: ¹¹C-UCB-J PET (SD)

PET: ¹⁸F-MK-6240 (tau)

Stress measures/EMA

Hippocampal +amygdala volume

¹¹C-UCB-J & ¹⁸F-MK-6240 SUVR

fc in MTL associated resting-state networks

physiological stress metrics / EMA response