Subjective Cognitive Complaints Contribute to Misdiagnosis of Mild Cognitive Impairment

Abstract

Subjective cognitive complaints are a criterion for the diagnosis of mild cognitive impairment (MCI), despite their uncertain relationship to objective memory performance in MCI. We aimed to examine self-reported cognitive complaints in subgroups of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) MCI cohort to determine whether they are a valuable inclusion in the diagnosis of MCI or, alternatively, if they contribute to misdiagnosis. Subgroups of MCI were derived using cluster analysis of baseline neuropsychological test data from 448 ADNI MCI participants. Cognitive complaints were assessed via the Everyday Cognition (ECog) questionnaire, and discrepancy scores were calculated between self- and informant-report. Cluster analysis revealed Amnestic and Mixed cognitive phenotypes as well as a third Cluster-Derived Normal subgroup (41.3%), whose neuropsychological and cerebrospinal fluid (CSF) Alzheimer’s disease (AD) biomarker profiles did not differ from a “robust” normal control group. This cognitively intact phenotype of MCI participants overestimated their cognitive problems relative to their informant, whereas Amnestic MCI participants with objective memory impairment underestimated their cognitive problems. Underestimation of cognitive problems was associated with positive CSF AD biomarkers and progression to dementia. Overall, there was no relationship between self-reported cognitive complaints and objective cognitive functioning, but significant correlations were observed with depressive symptoms. The inclusion of self-reported complaints in MCI diagnostic criteria may cloud rather than clarify diagnosis and result in high rates of misclassification of MCI. Discrepancies between self- and informant-report demonstrate that overestimation of cognitive problems is characteristic of normal aging while underestimation may reflect greater risk for cognitive decline.

Neuropsychological Criteria for Mild Cognitive Impairment in the Framingham Heart Study’s Old-Old

“…Furthermore, both of the MCI criteria examined by Hong and colleagues required impairment on only one cognitive measure, which differs from the Jak/Bondi neuropsychological MCI criteria that require at least 2 impaired test scores within a cognitive domain in order to balance sensitivity with reliability given the high base rates of one impaired neuropsychological scores within normative samples [8, 36]. Last, the neuropsychological criteria used by Hong et al[11] were confounded by inclusion of subjective cognitive impairment as a criterion, which has been associated with misdiagnosis of MCI [22]. …”

“…For both criteria, participants were also classified as amnestic MCI when memory was impaired and non-amnestic MCI when memory was intact and one or more non-memory domains were impaired. Although subjective memory complaint is typically included in the Petersen/Winblad criteria, it has been associated with elevated misclassification rates, even when considered in the context of neuropsychological performance and clinician judgement [22], and is more likely to be associated with depression and personality traits than cognitive impairment [23]. Therefore, subjective memory/cognitive complaint was not included in the diagnostic criteria in this study.…”

Prevalence and predictors of subjective memory complaints in adult male carriers of the FMR1 premutation

“…Further limitations relate to the lack of an informant-rated measure of subjective memory complaints, which may provide a more accurate assessment in the presence of objective memory impairment (edmonds, Delano-Wood, Galasko, Salmon, & Bondi, 2014;Slavin et al, 2010), and the cross-sectional study design which did not allow for the assessment of objective memory decline. Although the measure of subjective memory complaints included in the current study assessed perceived decline in memory over a period of the preceding five years, objective memory measures were administered at only a single time point.…”

Subjective Cognitive Impairment and Affective Symptoms: A systematic review

“…It has been shown that there is variability in awareness of cognitive impairment among individuals at similar AD stages (i.e., mild to moderate impairment; Leicht et al, 2010;Orfei et al, 2010;Ownsworth, Clare, & Morris, 2006). Among individuals with MCI, self-reports of cognitive problems may relate more to affective symptoms, whereas informant reports may more reliably indicate objective cognitive decline (Edmonds et al, 2014). In all likelihood, differences in awareness are represented among those with SCI as well, if in fact subtle cognitive change is present.…”