The present study highlights that subjective cognition may be associated with the neuropathological hallmark of AD, i.e. Aβ deposition, as measured with PiB PET imaging. Our findings show that community-dwelling cognitively normal older subjects with high amyloid load tend to be less confident than those with lower amyloid load about their general memory abilities when they compare their abilities to those of other people of the same age. Nevertheless, our high PiB subjects cannot be simply classified as “complainers” because they did not report that they were significantly “worse than other people”, but they are clearly dissimilar to their low PiB peers on their degree of self-confidence about memory abilities. Our results show that this more cautious self-report is not related to depressive affect or higher education. However, this feeling could reflect the experience of subtle memory limitations, which may indeed correspond to an objective memory weakness since subjects with high PiB uptake have lower performance than low PiB subjects on an episodic memory measure.
While the metacognition literature has repeatedly confirmed the multidimensional nature of monitoring processes[47
], an unexpected result is that PiB uptake was not significantly related to the other subjective cognition measures. In particular, it is surprising that subjects responded rather differently to the other off-line monitoring measure, when participants have to assess their memory abilities relative to 20 years ago. It is possible that the insidious and gradual occurrence of subtle cognitive problems may make an accurate monitoring of one’s abilities over time difficult in comparison to memory monitoring based on the present. For the on-line monitoring measure, subjects could be less prone to experience subtle cognitive limitations when they have to assess their ongoing performance in unfamiliar laboratory tasks.
Additionally, we found that regional PiB in the right medial PFC/ACC and precuneus/PCC/ICC was significantly related to general memory self-reports. These regions correspond precisely to those where amyloid load is typically the highest and the earliest, which confirms the consistency of the association of subjective cognition with the neuropathological signs of AD. Interestingly, these regions and their right hemispheric location are also commonly associated with the self and metacognitive processes[50
]. Nevertheless, the presence of amyloid in medial PFC/ACC and precuneus/PCC/ICC regions does not have detrimental effects on subjects’ insight about their cognition. Related to this, the impact of the regional amyloid load on local regional function is unclear in the literature.
The significant relationship observed between PiB uptake and subjective cognition measured with general memory self-reports relative to age-equivalent peers echoes previous studies showing that memory complaints in healthy people were related to genetic risks[25
]and brain structural and functional features of AD[18
]. In reference to the biomarker cascade model of AD proposed by Jack et al.[11
]Aβ deposition measure in cognitively intact older subjects may be the most appropriate measure to detect the earliest manifestation of AD. While the two previous PiB studies involving SCI subjects were not conclusive about the association of PiB with SCI[28
], our results are consistent with findings from postmortem investigations showing a relationship between memory complaints and AD pathology (including amyloid) in older people without dementia[26
Our study provides new evidence that cognitively normal and non depressed older subjects with less confidence about their memory abilities may have neuropathological signs of AD. By extension, this observation is consistent with the idea that SCI may represent a very early clinical manifestation of incipient dementia, which supports the predictive validity of memory complaints for AD and the claim that SCI may constitute a “pre-MCI” stage[1
]. Interestingly, a recent study[29
]enriches the cascade model of AD proposed by Jack et al.[11
]by showing that elevated PiB uptake was strongly related to brain atrophy in SCI, but not in MCI or in AD. Therefore, at the initial stage of AD development when amyloid accumulates and subtle neurodegeration begins, cognitive changes may be functionally compensated for and remain undetectable whereas subjective complaints may be present, i.e. the SCI stage. A probable duration of 15 years for the SCI stage has been proposed[53
]. Then, amyloid deposition may reach a plateau, atrophy rates may accelerate and MCI may appear[11
With regard to the interpretation of SCI in aging (SCI is often associated with affective or personality traits rather than dementia[54
]), our results suggest that lower confidence about one’s memory in older subjects with intact cognition may not be a benign symptom and should be evaluated carefully since it may reflect an underlying degenerative process. These conclusions should be considered cautiously for several reasons. The present study is amongst the first to test the relationship between subjective cognition and an AD neuropathological hallmark, thus, replication studies are warranted. Whereas our high PiB subjects are less confident about their memory than low PiB subjects, they cannot be identified as “complainers”, and it is unclear whether similar results would be identified in SCI subjects. Furthermore, we did not assess the influence of personality features on metacognition, which may weight these relationships. Overall, relationships between subjective cognition and AD development should be clarified considering these limitations and with longitudinal follow-up of participants.