Altered metamemory precedes cognitive impairment in subjective cognitive decline with positive amyloid-beta

Abstract

Subjective cognitive decline (SCD) as an indicator of preclinical Alzheimer's disease (AD) may precede mild cognitive impairment (MCI) over several decades. Self-reported cognitive decline as a typical clinical manifestation is critical in preclinical AD. Metacognition represents a person's ability to accurately assess cognition. Our study aimed to examine (1) the alternations of metamemory in a cohort across the Alzheimer's continuum, (2) the association between metamemory and cognition, and (3) the relationship of cortical thickness in four regions of interest (ROI) with metamemory scores. Six hundred ninety-seven participants were classified as 79 AD dementia, 161 aMCI, 261 SCD, and 196 cognitively unimpaired (CU) individuals, in which 418 participants aged above 65, 131 participants with Aβ+ after receiving positron emission tomography, and 602 participants received sMRI. The degree of confidence (DOC) was measured by calculating discrepancies between judgments and memory performance. We assessed the relationships between DOC tertiles and cognition and analyzed the screening power, then investigated the partial correlation between DOC and ROIs, controlled by age, sex, and cognition. In the Aβ+ subgroup, SCD showed significantly higher DOC scores than the CU group. There was an increasing trend of overconfidence with the decline of cognition across the AD spectrum (P for trend < 0.001). After adjusting for age, sex, and education, the lower degree of confidence-long-term delay recall (DOC-LD) tertiles were associated with lower odds ratio in SCD, aMCI, and AD in the Aβ+ subgroup (all P for trend < 0.05). The area under the curves of DOC scores for screening SCD from CU in the Aβ+ subgroup was better than that in all participants and the age ≥65 subgroup. Partial correlation showed that in the Aβ+ subgroup, DOC-SD (degree of confidence-short-term delay recall) was negatively correlated with the anterior cingulate cortex; DOC-LD was negatively correlated with the cortices of parahippocampal, anterior cingulate, posterior cingulate, and medial orbitofrontal. In individuals with Aβ+, SCD exhibited a detectable metamemory alternation before objective cognitive impairment could be tested, indicated by the overestimation in the memory performance. The pattern of an increasing trend of overconfidence across SCD, aMCI, and AD dementia supports the view of a continuum in Alzheimer's disease.

Keywords: Alzheimer’s continuum; Alzheimer’s disease; amyloid-beta; metacognition; metamemory; subjective cognitive decline.

FIGURE 1

A flowchart of participant selection.

FIGURE 2

An increasing trend of metamemory scores with the decline of cognitive state in all participants and two subgroups. ANCOVA analyses were performed on the metamemory scores, controlled by the influence of age and education years among four groups.

FIGURE 3

Receiver operating characteristic curve (ROC) curves of metamemory scores in all participants [(A) subjective cognitive decline (SCD) vs. cognitively unimpaired (CU); (B) amnestic mild cognitive impairment (aMCI) vs. CU; (C) Alzheimer’s disease (AD) vs. CU], Aβ+ subgroup [(D) SCD vs. CU; (E) aMCI vs. CU; (F) AD vs. CU], and age ≥65 subgroup [(G) SCD vs. CU; (H) aMCI vs. CU; (I) AD vs. CU].