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Inability to Self-Monitor Memory May Be Preclinical Sign of Alzheimer's Disease

Key findings

  • Meta-memory—the ability to monitor one's memory accurately and engage in compensatory strategies when necessary—is known to decline in patients with Alzheimer's Disease (AD), but the pathological processes are not well understood
  • In this study of 102 cognitively unimpaired older adults, participants displayed lower accuracy of meta-memory for recently acquired episodic information than for semantic information
  • Lower meta-memory for episodic information was related to deposition of tau in the medial temporal lobe, which is vulnerable to pathologic changes in early AD
  • Deterioration of a cognitively intact patient's ability to judge their memory accurately may be a sensitive clinical indicator of presymptomatic AD

Metamemory—the ability to monitor one's memory accurately and engage in compensatory strategies when necessary—is known to decline with normal aging, and the deterioration is worse in patients with Alzheimer's Disease (AD). However, little is known about the pathological processes that underlie these changes.

Patrizia Vannini, PhD, investigator in the Athinoula A. Martinos Center for Biomedical Imaging, and Reisa A. Sperling, MD, director of the Neuroimaging Program at the Massachusetts Alzheimer's Disease Research Center at Massachusetts General Hospital, and colleagues have determined that decreased metamemory in cognitively unimpaired older adults is associated with accumulation of tau protein in the brain (neurofibrillary tangles), one of the hallmarks of AD.

In NeuroImage: Clinical, they suggest that impaired metamemory may be a "red flag" of preclinical AD in older adults.

Study Methods

The researchers studied 102 cognitively unimpaired older adults from the Harvard Aging Brain Study who participated in a functional magnetic resonance imaging (fMRI) "feeling of knowing" task, a way of testing metamemory in which participants predict the likelihood of subsequently recognizing currently non-recalled information. The task had four phases:

  • Encoding — In each of three runs inside the MRI scanner, participants viewed 25 photographs of faces of non-famous individuals, with a fictional first name printed underneath
  • Recall — After each encoding run, while still in the scanner, participants were asked to recall the names of the 25 previously encoded items (episodic information). They were also shown photographs of the faces of 25 famous people (semantic information) and were asked to state their names
  • Judgment — Outside the scanner, all non-remembered faces (both famous and non-famous) were presented again. The participants were asked to rate their feeling of knowing—their likelihood of recognizing the name later—from 1 to 3
  • Recognition — The accuracy of each participant's feeling of knowing was tested using a forced-choice recognition test (three choices plus a "don't know" option)

Within six months of the fMRI task, participants underwent positron emission tomography of the brain to measure the deposition of tau as well as amyloid-beta, the other major proteinopathy in AD.

Accuracy of Judgments

On average, participants scored above chance accuracy on both metamemory processes (episodic and semantic). However, metamemory was significantly better for semantic information than for episodic information.

Association Between Metamemory and AD Pathology

  • Lower metamemory for episodic information was related to greater deposition of tau in the medial temporal lobe, including the temporal pole and entorhinal cortex, in addition to the superior temporal cortex
  • Lower metamemory for semantic information was related to greater deposition of tau in several regions of the neocortex, including the superior and inferior parietal lobe
  • There was no significant association between deposition of amyloid-beta and metamemory for either episodic or semantic information

Brain Regions of Interest

  • Whole-brain mapping confirmed a negative association between metamemory for episodic information and tau deposition in the right hemisphere, including the temporal pole, right entorhinal cortex and right superior temporal cortex
  • The association between metamemory for semantic information and tau burden in the neocortex was not confirmed

What Clinicians Should Know

The medial temporal lobe, especially the entorhinal cortex, is vulnerable to pathologic changes in early AD. This study suggests that tau pathology in these regions reduces the accuracy of metamemory for episodic information. In the absence of cognitive impairment, a decline in an individual's ability to accurately monitor their own memory may be a sensitive indicator of presymptomatic AD.

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Neuroscientists at Massachusetts General Hospital have developed advanced methods to analyze and visualize publicly available gene expression and genome-wide association data relevant to Alzheimer's disease—and are sharing them free online.


Functional MRI may someday be able to distinguish the neurodegenerative changes related to early Alzheimer's disease from those of normal aging.