Introduction
Elderly people often experience cognitive decline with aging. The reasons for cognitive dysfunctions can range from physiological mild forgetfulness described by many older individuals to mild cognitive impairment until the severe effects of Alzheimer’s disease [
1]. Many patients with considerable subjective memory complaints (SMC) seek help at a memory outpatient clinic, and complaints increase from cognitive healthy elderly to patients with mild cognitive impairment (MCI) [
2]. On the other hand, many patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) do not recognize cognitive, functional or behavioral impairment [
3]. But this anosognosia [
4] can have serious effects on health, because patients eventually deny adequate treatment due to their unawareness of deficits. Daily functioning may be compromised, because they lack adequate judgement of situations [
5].
Subjective memory complaints (SMC) are supposed to be an early symptom of dementia and therefore are often applied in the diagnostic process [
6]. Cognitive decline is often accompanied by a change of awareness of deficits. Even in the earliest stages of AD and actually MCI, insight can be impaired and this lack of anosognosia is most common in severe AD [
4,
7]. Vogel et al. [
7] compared awareness of cognitive deficits in patients with MCI and mild AD and came to the conclusion, that impaired awareness was equally frequent in both groups with individual significant heterogeneity in the degree of impaired insight. Different studies regarding awareness in MCI demonstrate a great variability among this patient group. While some people with MCI show limited awareness, others seem to overestimate their dysfunction (also declared as reflecting heightened or hyper-awareness). Depressive symptoms may have negative influence on the expression of awareness and may increase negative attributions, making memory problems seem more severe than they are [
2,
8]. Sevush and Leve [
9] found, that denial of deficits might protect against depression in Alzheimer’s disease, because unawareness was inversely related to depressed mood. Therefore informants are often involved in diagnosis and assessment of subjective memory awareness [
10].
A review concerning self and informant reports in MCI patient illustrates that informant ratings display greater loss of cognitive competency and everyday functional ability and a greater correlation with objective measures of patient cognitive performance and characteristics of probable conversion to dementia [
10]. Ecklund-Johnson and Torres [
4] reviewed studies regarding unawareness of deficits in AD and found that unawareness of deficits progresses over time and awareness discrepancies between patients and their caregivers increase. Although informant reports might be influenced negatively by caregiver burden, informant ratings have turned out to be a strong predictor of an underlying dementia. The authors also conclude that memory deficits alone neither explain nor predict unawareness of deficits in AD. Brain correlates of unawareness in dementia were mainly detected in frontal and tempo-parietal regions, but further research is needed [
3].
The current research succeeds a recent cross-sectional study by Lehrner et al. [
11]. They concluded that awareness decreases along the nonamnestic MCI → amnestic MCI → AD continuum. The main objective of the present longitudinal study was to find out, whether awareness of subjective memory in patients with MCI has predictive value for future conversion to AD. The methods were based on precedent studies using additional informant ratings [
7]. The first aim was to explore correlations between subjective memory assessment and objective results of neuropsychological testing. Correlation analyses comprised neuropsychological test results and demographic data. Two variables measuring depressive symptoms were also included in order to examine the influence of depression on awareness [
2,
8]. The second aim was to figure out differences in awareness longitudinally. We hypothesized that small differences across time would indicate an intact awareness system, while large differences would reveal loss of awareness. It was assumed that decline of cognitive performance combined with decline of awareness between both times of assessment would imply anosognosia as observed in inherent dementia [
4]. The final intent was to find out, if unawareness of memory deficits could serve as a predictor of future AD in patients with MCI.
Discussion
The main intention of the present study was to explore awareness of subjective memory assessment in patients with MCI and AD and to determine if unawareness can serve as a predictor for future conversion to AD in MCI. For this purpose, objective performance measures were compared to patient and caregiver memory reports and to awareness scores on two times of assessment with a mean interval of two years. Awareness was assessed by subtracting informant-rating from self-rating scores of the FAI questionnaire. Whole-group comparisons of awareness with objective test data revealed one significant correlation concerning overall cognitive ability (MMSE), which became significant with large effect at follow-up (
r
s = 0.50). Patients with decline of cognitive performance overestimated their memory function compared to their caregivers. This outcome supports studies indicating that unawareness increases with cognitive decline [
4,
11]. Whole-group comparisons between self-assessment FAI scores and the results of the NTBV revealed significant correlations with subtests of the domains memory and language. At baseline self-ratings yielded two significant associations with moderate effect to the VSRT-subtests
Delayed Recall (
r
s = −0.43) and
Recognition (
r
s = −0.48) of the domain memory, revealing intact good accordance. The VSRT assesses loss of episodic memory, which is a core diagnostic criterion for later conversion to AD [
32]. Lehrner et al. [
11] used the subtest
Delayed Recall of the VSRT as a measure of objective memory in order to obtain awareness scores, because it is very sensitive to age related memory decline. Its association with self-assessment scores at baseline supports studies stating that memory complaints are supposed to be an early manifestation of memory impairment [
33]. At follow-up, this correlation was not significant anymore, instead self-report correlated significantly with the
Semantic Word Fluency Test (SWT,
r
s = −0.44) of the domain language. People who had worse performance on this test complained more about loss of memory. One reason might be a decline of insight for memory impairment in patients with proceeding MCI and those who converted to AD, while insight to dysfunctions in other cognitive domains remains relatively intact in early stages of dementia [
7]. Nevertheless, correlations with awareness scores, as observed in anosognosia, were not significant for these subtests of the NTBV [
4]. One probable explanation is that patients, who converted to dementia at follow-up, showed mild symptoms of AD because patients scoring 23 or less on the MMSE were excluded from the study. Unlike expected, informant memory appraisals did not correlate significantly with memory tasks at any time of assessment. As mentioned above, informant follow-up ratings rather reflected decline of overall cognitive ability. Besides, difference scores at group level showed that informant FAI scores revealed better memory appraisals for the AD group at follow-up than at the baseline. Nevertheless, discrepancy scores increased, because patients overestimated their memory functions even more [
7]. These findings might be influenced by several aspects like sample size, patient-informant relationship and characteristics of informants. Moreover, the current study did not include patients with moderate or severe AD, where memory deficits can easily be detected by caregivers. Neurocognitive memory tasks might identify subtle cognitive changes which might be beyond the competence of informants [
10].
In the field of non-cognitive factors, sex, age and education did not reveal any effect on awareness. Whole-group comparisons of the underlying sample could not reveal evident influence of depressive symptoms on awareness. More longitudinal studies are needed to investigate effects of hyper-awareness or underestimation [
8].
Another question of interest was, whether awareness changed over time in the total sample and each diagnostic group separately. Whole-group correlation analyses between baseline and follow-up showed that awareness of subjective memory assessment remained stable over time. Significant correlation coefficients with large effect (all
r
s ≥ 0.5) revealed that patients as well as their caregivers estimated patient-concerned memory functions consistently between baseline and follow-up. These results suggest that awareness of subjective memory assessment remains relatively stable in MCI and early AD patients. Separate group analyses also revealed that neither MCI nor AD-converted patients differed significantly across time regarding self, informant and awareness scores. These findings are supported by previous studies claiming that the level of awareness does not differ significantly between patients with MCI and mild AD [
7]. Subjective memory complaints increased in those people who maintained the MCI diagnosis and decreased those who converted to AD. The increase of discrepancy scores within the AD group indicates a decline of awareness in AD patients who tend to overestimate their memory functions. Although not significant, these findings correspond to the significant correlates of awareness with MMSE scores. They support precedent studies indicating that decline of overall cognitive ability is associated with decrease of awareness [
4,
11]. Regarding conversion rates within the MCI patient group, 11 of 13 people who turned to AD at follow-up, were diagnosed as aMCI at the baseline. Only 2 initial naMCI patients received the diagnosis of AD at the second time of assessment. These results are in line with previous studies claiming that people with aMCI are at higher risk of conversion to AD [
34,
35].
One major objective of the present study was to find out the predictive power of subjective memory assessment. FAI self, informant and awareness ratings of MCI patients who converted to AD or remained MCI were subject to ROC analyses. ROC curve analyses revealed that all ratings were close to random guessing (all AUC < 0.65). Therefore the present study could not confirm the hypothesis that awareness of subjective memory assessment serves as predictor for future dementia. Regarding the small sample size of self and awareness scores these results have to be interpreted with caution.
The present study has some limitations. First, the sample size was generally limited due to the design of the study. Patients with moderate or severe AD were not included in the study, because they are not capable of filling in the self-assessment questionnaires. Due to the small sample size only a limited number of patients converted to AD, thus, the study was probably statistically underpowered. However, the results of the study may generate new research questions using larger clinical sample sizes. Second, as this was a clinical study, its results may not be generalizable to the general population. Third, another limitation of the study was, that depressive symptoms/psychiatric diagnosis were not assessed by psychiatric (diagnostic) interview. Finally, information about cognitive trainings, drug or other treatments against probable progression to AD between both times of testing, that might have influenced the outcome [
34], was not assessed in the study.
The strengths of the study are the profound neuropsychological examination of all patients and the satisfactory sample size despite clinical limitations. Given the fact that cognitively well-preserved MCI patients usually come alone to the clinical assessment at the memory clinic, the number of participants plus informants performing pre- and post-tests is remarkable.
In conclusion, our study demonstrates that MCI patients have a relatively intact awareness of memory performance and a good self-estimation regarding episodic memory. In the longer term, cognitive decline leads to a decrease of complaints about memory loss, and to an increase of discrepancy scores between patients and their caregivers. Generally speaking, unawareness of subjective memory deficit increases to some extent in patients with incipient AD, but further long-term research is needed to clarify the relationship between awareness and AD.