Verbal memory formation across PET-based Braak stages of tau accumulation in Alzheimer's disease

Jaime Fernández Arias; Joseph Therriault; Emilie Thomas; Firoza Z Lussier; Gleb Bezgin; Cécile Tissot; Stijn Servaes; Sulantha S Mathotaarachchi; Dorothée Schoemaker; Jenna Stevenson; Nesrine Rahmouni; Min Su Kang; Vanessa Pallen; Nina Margherita Poltronetti; Yi-Ting Wang; Peter Kunach; Mira Chamoun; Kely M Quispialaya S; Paolo Vitali; Gassan Massarweh; Serge Gauthier; Maria N Rajah; Tharick Pascoal; Pedro Rosa-Neto

doi:10.1093/braincomms/fcad146

Verbal memory formation across PET-based Braak stages of tau accumulation in Alzheimer's disease

Brain Commun. 2023 May 18;5(3):fcad146. doi: 10.1093/braincomms/fcad146. eCollection 2023.

Authors

Jaime Fernández Arias^{1

2}, Joseph Therriault^{1

2}, Emilie Thomas^{1

2}, Firoza Z Lussier³, Gleb Bezgin^{1

2}, Cécile Tissot^{1

2

3}, Stijn Servaes^{1

2}, Sulantha S Mathotaarachchi^{1

2}, Dorothée Schoemaker⁴, Jenna Stevenson^{1

2}, Nesrine Rahmouni^{1

2}, Min Su Kang^{1

2}, Vanessa Pallen^{1

2}, Nina Margherita Poltronetti^{1

2}, Yi-Ting Wang^{1

2}, Peter Kunach^{1

2}, Mira Chamoun^{1

2}, Kely M Quispialaya S^{1

2}, Paolo Vitali², Gassan Massarweh⁵, Serge Gauthier^{2

6}, Maria N Rajah^{3

6}, Tharick Pascoal³, Pedro Rosa-Neto^{1

2

7}

Affiliations

¹ Faculty of Medicine, McGill University, Montreal, QC H3G 2M1, Canada.
² Department of Neurology and Neurosurger, McGill University Research Centre for Studies in Aging, Verdun, QC H4H 1R3, Canada.
³ Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15260, USA.
⁴ Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114, USA.
⁵ Department of Radiochemistry, Montreal Neurological Institute, Montreal, QC H3A 2B4, Canada.
⁶ Department of Psychiatry, Douglas Mental Health University Institute, Verdun, QC H4H 1R3, Canada.
⁷ Department of Neurology and Neurosurgery, Montreal Neurological Institute, Montreal, QC H3A 2B4, Canada.

Abstract

A classical early sign of typical Alzheimer's disease is memory decline, which has been linked to the aggregation of tau in the medial temporal lobe. Verbal delayed free recall and recognition tests have consistently probed useful to detect early memory decline, and there is substantial debate on how performance, particularly in recognition tests, is differentially affected through health and disease in older adults. Using in vivo PET-Braak staging, we investigated delayed recall and recognition memory dysfunction across the Alzheimer's disease spectrum. Our cross-sectional study included 144 cognitively unimpaired elderly, 39 amyloid-β+ individuals with mild cognitive impairment and 29 amyloid-β+ Alzheimer's disease patients from the Translational Biomarkers in Aging and Dementia cohort, who underwent [¹⁸F]MK6240 tau and [¹⁸F]AZD4694 amyloid PET imaging, structural MRI and memory assessments. We applied non-parametric comparisons, correlation analyses, regression models and voxel-wise analyses. In comparison with PET-Braak Stage 0, we found that reduced, but not clinically significant, delayed recall starts at PET-Braak Stage II (adjusted P < 0.0015), and that recognition (adjusted P = 0.011) displayed a significant decline starting at PET-Braak Stage IV. While performance in both delayed recall and recognition related to tau in nearly the same cortical areas, further analyses showed that delayed recall rendered stronger associations in areas of early tau accumulation, whereas recognition displayed stronger correlations in mostly posterior neocortical regions. Our results support the notion that delayed recall and recognition deficits are predominantly associated with tau load in allocortical and neocortical areas, respectively. Overall, delayed recall seems to be more dependent on the integrity of anterior medial temporal lobe structures, while recognition appears to be more affected by tau accumulation in cortices beyond medial temporal regions.

Keywords: Alzheimer’s disease; PET-Braak staging; delayed recall; recognition memory; tau PET.