Amygdala tau deposition best discriminates between stages of memory impairment

Abstract

AbstractBackgroundThe recent development of positron emission tomography (PET) radiotracers for tau aggregates allows quantifying the regional tau burden in‐vivo. We aimed to investigate the associations between regional tauopathy and episodic memory outcomes in the AD spectrum from clinically normal to the dementia stage.MethodWe recruited 111 participants between 2019 and 2023 at the Memory Clinic of Saint‐Luc University Hospital. Each participant underwent [F18]‐MK6240 tau‐PET, 3DT1 MRI, cognitive assessment, and either lumbar puncture or [F18]‐Flutemetamol PET for amyloid status. Tau burden was quantified using Freesurfer by referring to the Desikan‐Kiliany lobe cortical parcellation, as well as in several medio‐temporal regions (MTL; i.e., entorhinal cortex, amygdala, hippocampus). Memory was assessed using three Z‐scores from the FCSRT: Sum of Free Recall (SFR), Sum of Total Recall (STR), and Sum of Delayed Free Recall (DFR). The average of these scores forms the Memory Composite Score (MCS). Participants were classified in three groups (Table 1): amyloid‐negative clinically normal participants (n = 44); non‐demented participants with AD pathology (early AD, n = 45); and AD dementia participants (n = 22). Based on their SFR and STR scores, subjects were also classified as having retrieval and/or encoding memory deficits according to a Stage of Objective Memory Impairment (SOMI) classification, inspired from Grober and colleagues (2018). Analyses were corrected for multiple comparisons.ResultIn early AD, SFR and DFR correlated with tauopathy in the bilateral entorhinal cortex (EC) and amygdala (Fig.1). MCS correlated with tauopathy in the bilateral amygdala, and the right frontal lobe. Tau levels did not correlate with STR in any regions. Moreover, MTL tauopathy differed between SOMI stages: Specifically, amygdala tauopathy gradually increased with retrieval deficits (SOMI1‐2) and encoding deficits (SOMI3‐4). In contrast, tauopathy in the EC, the temporal lobe, and the parietal lobe was elevated in all participants with memory deficits, but did not distinguish between retrieval and encoding deficits (Table 2).ConclusionTauopathy in the MTL ROIs is predictive of retrieval deficits in early stage of AD. SFR is a more sensitive measure of this early decline compared to STR. Amygdala tauopathy differs between patients with retrieval and encoding deficits.