Anosognosia in Mild Cognitive Impairment: Lack of Awareness of Memory Difficulties Characterizes Prodromal Alzheimer's Disease

Abstract

While anosognosia is often present in Alzheimer's disease, the degree of awareness of cognitive difficulties in the earlier stages, such as Mild Cognitive Impairment (MCI), is less clear. Using a questionnaire and Feeling-of-Knowing tasks, the aims of this study were (1) to test the hypothesis that anosognosia is present specifically in prodromal AD stage in patients that, owing to a more severe AD neuropathology, will rapidly progress to overt dementia and (2) to assess the neural bases of self-awareness for memory functioning. A group of 44 patients with amnestic MCI and a group of 29 healthy older participants (CTRL) performed two Feeling-of-Knowing tasks (episodic and semantic FOK) and responded to the Functional Memory Scale (MARS), also completed by one of their relatives. They underwent FDG-PET and structural MRI. The participants were followed clinically for 4 years. At the end of follow-up, 23 patients with MCI developed Alzheimer's disease (converters) and 21 patients still presented symptoms of MCI without progression (non-converters). The analyses focused on the data from inclusion stratified according to clinical status 4 years later (converters, non-converters, CTRL). On the episodic FOK task, converters patients overestimated their ability to later recognize unrecalled words and they showed prediction accuracy (Hamann coefficient) at the level of chance. No difficulty was observed in any group with the semantic FOK task. On the MARS, converters patients had a higher anosognosia score than non-converters patients and CTRL, which did not differ from each other. Correlations between self-awareness scores and neuroimaging data using small volume correction analyses in a priori regions of interest in converters indicated that inaccurate episodic FOK judgments was related to changes in brain areas that might support interpretation of retrieved content for judging the likelihood of recognition. For the MARS, the association between anosognosia and decreased gray matter density of the left inferior prefrontal cortex in converters might indicate poor inhibition over outdated personal knowledge. In amnestic MCI, anosognosia could be an early sign of neurodegeneration in brain areas that would support control mechanisms over memory representations.

Neuropsychology of posteromedial parietal cortex and conversion factors from Mild Cognitive Impairment to Alzheimer’s disease: systematic search and state-of-the-art review

“…PMC hypoactivation appears to be significantly associated with an increased conversion rate from MCI to AD [9][10][11]. PMC is involved in VSWM [18], metamemory [50,67,69], and visuomotor control abilities [22][23][24]. Testing the integrity of this neuropsychological cluster could help clinicians to early discriminate MCI patients who are more likely to convert in probable AD from those who are not [12][13][14], thus orienting further investigations and/or preventive interventions.…”

“…As concerns the neurofunctional correlates of anosognosia for memory deficits, it has been recently proposed that decreased connectivity in the fronto-temporo-parietal network, including the medial temporal lobe, would prevent updating of the state of memory functioning, which depends on the experience-based knowledge accumulated through the continued exposure to memory successes or failures. Conversely, abnormal activity in medial-frontal and -parietal regions would affect online monitoring and evaluation of cognitive performance [67]. Recent neuroimaging studies showed that greater anosognosia for memory deficits in amnestic MCI was associated with (1) hypometabolism in posterior and middle cingulate cortices, inferior parietal lobule, precuneus, angular gyrus [50,69], hippocampus [49,50], and (2) reduced functional connectivity between the posterior cingulate cortex, orbitofrontal cortex and inferior parietal lobe [50].…”

“…Four studies [67][68][69][70] tested the hypothesis that anosognosia for memory deficits represented a risk factor for conversion to dementia (Table 2). The results of three out of the four studies [67,68,70] clearly supported this hypothesis. By bringing together the available data collected on a population of 153 patients with MCI (148 aMCI and 5 aMCI-md), 59 patients (38.56%) converted to dementia (57 AD, 1 FTD, 1 VaD) within about 2 years.…”

“…The presence of deficits in some or all three domains may suggest an early PMC alteration which has been, in turn, associated with a higher risk of conversion from MCI to AD [9][10][11]. Furthermore, VSWM and metamemory deficits were found to be individually and significantly associated with a higher risk of conversion [37,[66][67][68][69][70]. Consequently, their clinical importance is not at all negligible.…”

Metacognitive Performance on Memory and Visuospatial Tasks in Functional Cognitive Disorder

“…There is emerging evidence that metacognition may be affected even in the early stages of prodromal neurodegeneration. Those with mild cognitive impairment (MCI) and impaired metacognition are more likely to progress to future dementia than those with intact awareness [3]. How metacognition for different cognitive domains changes over the course of neurodegeneration is unclear, and is an understudied topic.…”