Tau Pathology Linked to Alterations in Memory Self-Appraisal in Healthy Older Adults

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As people age and experience memory decline, accurate metamemory becomes increasingly important. Metamemory refers to the introspective knowledge of one's own memory capabilities, which plays a crucial role in learning and in using memory. Metamemory includes self-appraisal of memory performance; for example, it helps a person decide whether information has been learned well enough for successful recall later.

The accuracy of self-appraised memory performance is often evaluated by asking an individual to judge how well they will remember a set of particular items on a future examination. This approach is known as "judgments of learning" (JOL). In healthy young individuals, functional MRI (fMRI) has demonstrated that activity in the medial prefrontal and posteromedial cortices relates to accuracy on JOL tests.

Researchers at Massachusetts General Hospital recently conducted the first fMRI study to measure neural patterns of activity related to JOL in cognitively unimpaired older individuals. The results are reported in Cerebral Cortex by Federico d'Oleire Uquillas, former research assistant at the Mass General Department of Neurology, Patrizia Vannini, PhD, investigator, Athinoula A. Martinos Center for Biomedical Imaging and Brigham and Women's Center for Alzheimer Research and Treatment, and colleagues.

Study Methods

The researchers studied 105 adults in the Harvard Aging Brain Study (led by Dr. Reisa Sperling), ages 65 to 92, who had a score of 0 on the Clinical Dementia Rating scale. They participated in an fMRI task in which they viewed 75 face–name pairs (photographs of faces with a fictional name written underneath each one). Twenty-five faces were presented three times during each of three runs. Halfway through each run, participants were asked to indicate how well they had learned the name for each face: "learned the name well" (JOL1), "did not learn the name well" (JOL2) or "learned the name poorly" (JOL3).

Once outside the MRI scanner, participants were asked to choose from three name choices or an "I don't know" option for each face. A score called Absolute Accuracy, developed in previous research was calculated by subtracting the percentage of correct responses from the percentage of JOL1 predictions. A score of 0 indicated overall accurate memory self-appraisal, >0 indicated overall memory overestimation and <0 indicated overall memory underestimation.

Participants were also examined by positron emission tomography for the deposition of amyloid-beta and tau, the two pathologic hallmarks of Alzheimer's disease (AD).

Absolute Accuracy and fMRI

On average across all participants, 27 items were judged as "learned well," 23 were judged as "not learned well" and 17 were judged on average as "learned poorly." Some responses weren't captured during the time allotted.

The range of Average Accuracy values was −52% to 89%, and the average was −1.22%. However, Absolute Accuracy was statistically similar to zero, indicating that predicted memory performance was generally accurate. Men were more likely than women to overestimate their memory performance.

Confirming previous research in young individuals, neural substrates of JOL in older adults comprised a network of regions: the anterior and posterior cingulate cortex, ventromedial prefrontal cortex and precuneus. Activity in these regions, measured by fMRI, was greater for JOL1 trials than for JOL3 trials.

Absolute Accuracy and AD Pathology

Controlling for the effects of age and sex, overestimation of memory performance was associated with greater tau deposition in the entorhinal cortex, known to be an early site of tauopathy in aging and AD. Increased tau pathology was also related to decreased fMRI activity during JOL1 trials, suggesting functional alterations in the network that underlies predicted memory success.

There was no association between the estimation of memory performance and neocortical amyloid-beta.

Relevance to AD Research

Deficits in memory self-appraisal have been found across the AD continuum. In fact, two previous studies led by Dr. Vannini and published in The American Journal of Geriatric Psychiatry and Annals of Neurology have shown that awareness about memory performance predict whether mild cognitive impairment will progress to AD dementia.

The finding of a link between memory self-appraisal and tau deposition in cognitively unimpaired older adults has clear implications for clinical research into anosognosia (unawareness of memory performance) in patients with AD dementia.

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