Alzheimer’s: when you don’t know that you know…

Alzheimer’s patients generally have a propensity to overestimate the strength of their episodic memory which is a category of memory that enables an individual to store and be aware of personally experienced events. A study conducted by researchers in the Cyclotron Research Center of the University of Liege, which was recently published in the magazine Cortex, found that the opposite was true in fact. In addition, they showed that the more the patients had a tendency to make inappropriate judgments, the less grey matter was contained in a particular region of their brain.

Anosognosia describes patients who have limited or no awareness of their physical, cognitive or behavioral deficits. (see also the article “self-unconsciousness”). Hemispatial neglect is a prime, almost caricatural example of a patient’s inability to have a clear knowledge of their state. Following a cerebrovascular accident (CVA) in the right hemisphere, some patients permanently behave as though their knowledge of the left side of space has been greatly reduced or in some cases, has disappeared completely. Those patients who are most affected by the condition bump into furniture and walls located on their left side, forget to shave or make up the left side of the face, or neglect to eat food on the left side of their plate... Some even have their head permanently turned to the right.

Anosognosia is particularly frequent in cases of dementia. Thus, in the case of Alzheimer’s disease, despite some discrepancies between different studies, it is estimated that 10 to 15% of patients in the early stages of the disease are anosognosic and this figure can be as high as 40 to 50% during the more severe stages of the disease.

Sarah Genon, a doctor of psychology and a scientific collaborator at the Cyclotron Research Center (CRC) of the University of Liege, is currently working on modelling the relationships between the brain and behavior. In addition, she has conducted a study (1) at the CRC which was published in October 2016 in the magazine Cortex. This research is not unrelated to anosognosia, because it deals with the metacognition skills of Alzheimer’s patients with regard to two types of   memory: episodic memory, which is a category of memory that enables an individual to store and be aware of personally experienced events, and semantic memory, which gives us our general knowledge of the world – this type of memory enables us to know that Rome is the capital of Italy or that Donald Trump is the new president of the United States… Metacognition defines the mental activity an individual uses to control his or her own mental processes. Imagine that on a given morning you don’t have to go to your usual place of work but you have to go to a different location. If, by some automatic reflex, you follow your usual route, you will eventually realize your mistake and rectify it. This awareness of poor performance in the above situation, concerning another mental process that is lower in hierarchical order, is an example of metacognition.

Unknown people and celebrities

Numerous works have shown that, in the case of Alzheimer’s, episodic memory is generally altered at an early stage, while semantic memory is preserved for a longer time. The reason for this is that episodic memory involves conscious and controlled processes which are underpinned by a large number of brain regions, while semantic memory is supported by more automatic processes. The question raised by the recent article in Cortex was: how do Alzheimer patients judge their memory processes? Sarah Genon dealt with this question by examining the way in which patients, who in this case were in the early stages of the disease, predicted their own memory performance in terms of their episodic or semantic memory. “We wanted to compare the processes of metacognition for these two types of memory by means of an identical task while using the same type of material”, explains Sarah Genon. This had never been done before. Moreover, the researchers wanted to use a relatively environmental task, one that resembled daily life as much as possible.

They showed 23 patients 80 photos of famous individuals and 80 photos of unknown individuals on a computer screen. They took care to ensure that the two samples matched each other in terms of age, gender, and ethnic origin, etc. With regard to the famous individuals, the psychologists conducted a pre-test on normal elderly individuals to ensure that the celebrities in question were very well-known. Alain Delon, for example. For the unknown individuals, a learning stage was required. The objective of the first step was to enable the patients to become familiar with the faces of the different individuals shown on the screen. “We showed the faces and then we asked the participants to indicate whether it was a man or a woman”, explains Sarah Genon. “We then began the stage of encoding the information in memory by giving the name of the person (Caroline Martin, for example) and in order to create an association between the face and the name in the patient’s memory, we asked questions such as "Do you think Caroline Martin is aptly named?”, and why”? Finally, we hid the name of the person on the computer screen where the photos appeared and asked the patient to recall  the name of the person immediately. In the case of a correct answer, we considered that the information was encoded and moved on to the next item; in the case of failure to provide a correct answer, we started the process again”.

A few minutes after the learning session, the participants in the experiment were again shown the photos of these fictional and famous individuals. On each occasion, four names were suggested to them. In order to avoid identifications that could be linked to a simple familiarity with regard to the phonology of the correct name, phonological distractors were introduced. For example, when the face of Alain Delon was presented, one of the four propositions was “Alain Seron”. In the same way, one of the suggestions for the “anonymous” Suzanne Firmin was Suzanne Quirtin. For each of the photos, the patients had to predict the possibility of a correct identification on a scale containing four levels: no chance (1), low likelihood (2), high likelihood (3) and certainty of success (4). “Level 1 referred to patients who considered that they definitely didn’t know the individual presented, as though they had never seen him or her”, says Sarah Genon. “In contrast, level 4 concerned patients who had direct access to the information in their memory and who were therefore capable of naming the face visible on the screen without any need whatsoever to give them a hint”. These two extreme categories, without any nuance, were not of any major interest to the researchers. They were interested in the two intermediate categories (low likelihood and high likelihood).

Failure

With regard to metacognition concerning episodic memory (fictional people), it emerged that, in relation to the group of elderly people unaffected by Alzheimer’s (a sample of 17 volunteers), the Alzheimer’s patients were more prone to pessimistic predictions (i.e. indicate low likelihood) of their ability to recognize the name, which they would in fact correctly identify a short time later – in a manner of speaking, they didn’t know that they knew. On the other hand, when metacognition concerned semantic memory (famous people), the patients knew that they had a good chance of recognizing the person. “They judged their semantic memory performance in a similar way to normal elderly individuals”, explains Sarah Genon.

In the field of metacognition linked with episodic memory, the results of the study published in Cortex came as a surprise to the authors themselves. Firstly, the results went against the notion of anosognosia, a neuropsychological disorder typically described in cases of Alzheimer’s disease. Secondly, they contradict a study (2) conducted previously by a Franco-English team at the University of Leeds, in which patients over-estimated the probability of being able to carry out an episodic memory task. In any event, the nature of the experiment was not the same. In the first place, the task to be completed was not environmental: it depended on the association of words without any particular connection (“chair” and “apple”, for example). The patient had to recall the second term of a pair the first term of which was suggested to him or her. Subsequently and most importantly, the test only included some twenty items. This led Sarah Genon to offer an explanatory hypothesis: “It is probable that the first reaction of Alzheimer’s patients instructed to complete a task which they were not used to, was to overestimate their ability. In the task we designed, they often failed during the learning stage, which was arduous. They were therefore confronted with their difficulties” The researcher adds: “Several studies have revealed that, even among anosognosic patients, it is possible to induce a very temporary awareness of their memory dysfunction during the execution of a task”.

In a study not yet published, the researcher comes to a conclusion that is contrary to the one she reached in her first work. But here, once again, the task was easier and involved only 20 items. The patients only needed to recall a first name, so the test was more ludic… In short, there were fewer failures during the learning phase. In her opinion, it should be concluded from the limited data available, that Alzheimer’s patients poorly judge their memory function, in accordance with the social environment and the circumstances.

Cortical stimulation?

The article which appeared in October 2016 in Cortex demonstrates the existence of a correlation between the number of inappropriate judgements and the volume of grey matter in Alzheimer’s patients measured by Structural MRI. The more the patients make mistakes concerning their memory skills, the less grey matter is present in a certain region of the brain: the right prefrontal lateral cortex, which is known to be involved in monitoring processes such as those that enable us to control our behavior and to select relevant information, or to “manage” our memory.

What is the significance of the work conducted by Sarah Genon? “It seems to me that our study is important in terms of understanding the beliefs of Alzheimer’s patients about their memory and also to develop neuropsychological strategies”, says the CRC collaborator. “In a wider context, the study will be extended to determine how Alzheimer’s patients form their beliefs about their memory and how to improve the awareness they have of their everyday functions. In this way, their care could be improved”.

An understanding of how to proceed in order to influence the judgement a patient has about his or her own memory capability still needs to be found. Failure could theoretically be a way to fight anosognosia and its corollary, overestimation of their memory skills as demonstrated by many patients when they assess their memory capabilities (or others). “This strategy would not be appropriate because different studies(3) have revealed that failure generates negative emotions and that, in spite of everything, this experience does not change anosognosia”, says Sarah Genon.

She adds that promising approaches could involve Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (TDCS). Work conducted on young subjects revealed that their predictions regarding their memory performance can be improved by such cortical stimulations administered to median prefrontal regions, but also, according to certain studies, to the prefrontal lateral regions. For the moment, the experiments undertaken are limited to highlighting the existence of improvements in metacognition over periods of a few hours. Can we consider that the effects are lasting? It remains a mystery for now. In addition, there is no available information relative to the efficacy of these stimulations in Alzheimer’s patients. For now, we’ll have to wait and see.

(1) Genon S, Simon J, Bahri MA, Collette F, Souchay C, Jaspar M, Bastin C, Salmon E, Relating pessimistic memory predictions to Alzheimer's disease brain structure, Cortex 2016. Pii: S0010-9452(16)30261-1. Doi: 10.1016/j.cortex.2016.09.014.

(2) Souchay, C., Isingrini, M., Gil, M. Alzheimer's disease and feeling-of-knowing in episodic memory. Neuropsychologia 40: 2386-2396, 2002.
(3) Mograbi, D.C., & Morris, R. G. On the relation among mood, apathy, and anosognosia in Alzheimer’s disease. Journal of the International Neuropsychological Society 20: 2-7, 2014.