Functional and Pathological Correlates of Judgments of Learning in Cognitively Unimpaired Older Adults

Author:

d’Oleire Uquillas Federico1,Jacobs Heidi I L23,Schultz Aaron P14,Hanseeuw Bernard J25,Buckley Rachel F167,Sepulcre Jorge48,Pascual-Leone Alvaro910,Donovan Nancy J1112,Johnson Keith A2411,Sperling Reisa A1411,Vannini Patrizia1411

Affiliation:

1. Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA

2. Division of Nuclear Medicine, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA

3. School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, Maastricht 6200 MD, Limburg, The Netherlands

4. Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA

5. Department of Neurology, Saint-Luc University Hospital, Institute of Neuroscience, Université Catholique de Louvain, 1200 Brussels, Belgium

6. Florey Institutes of Neuroscience and Mental Health, University of Melbourne, 3010 Melbourne, Australia

7. Melbourne School of Psychological Science, University of Melbourne, 3010 Melbourne, Australia

8. Department of Radiology, Gordon Center for Medical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA

9. Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA

10. Hinda and Arthur Marcus Institute for Aging Research and the Center for Memory Health at Hebrew SeniorLife, Boston, MA 02131, USA

11. Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA

12. Division of Geriatric Psychiatry, Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA

Abstract

Abstract Judgments of learning (JOL) pertain to introspective metamemory processes evaluating how well information is learned. Using a functional magnetic resonance imaging (fMRI) task, we investigated the neural substrates of JOL predictions in a group of 105 cognitively unimpaired older adults from the Harvard Aging Brain Study. Associations of JOL performance and its neural correlates with amyloid-β (Aβ) and tau pathology, two proteinopathies associated with Alzheimer’s disease (AD) and aging, were also examined. We found that trials judged as learned well relative to trials judged as learned less well (high JOL > low JOL) engaged the ventromedial prefrontal cortex and precuneus, among other midline regions, in addition to bilateral hippocampi. In this cohort of older adults, greater levels of entorhinal tau deposition were associated with overestimation of memory performance and with lower fMRI signal in midline regions during predicted memory success. No associations with Aβ were found. The findings suggest that tau pathology in unimpaired older adults may play a role in altered metamemory processes. We discuss our findings in light of the hypothesis that JOLs are partially dependent on a process involving attempts to retrieve a correct answer from memory, as well as implications for clinical research investigating unawareness of memory performance (i.e., anosognosia) in patients with AD dementia.

Funder

European Union’s Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie Grant agreement

Alzheimer’s Association

National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

Cellular and Molecular Neuroscience,Cognitive Neuroscience

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