A Mutual Self- and Informant-Report of Cognitive Complaint Correlates with Neuropathological Outcomes in Mild Cognitive Impairment

This study examines whether different sources of cognitive complaint (i.e., self and informant) predict Alzheimer's disease (AD) neuropathology in elders with mild cognitive impairment (MCI). Data were drawn from the National Alzheimer's Coordinating Center Uniform and Neuropathology Datasets (observational studies) for participants with a clinical diagnosis of MCI and postmortem examination (n = 1843, 74±8 years, 52% female). Cognitive complaint (0.9±0.5 years prior to autopsy) was classified into four mutually exclusive groups: no complaint, self-only, informant-only, or mutual (both self and informant) complaint. Postmortem neuropathological outcomes included amyloid plaques and neurofibrillary tangles. Proportional odds regression related complaint to neuropathology, adjusting for age, sex, race, education, depressed mood, cognition, APOE4 status, and last clinical visit to death interval. Mutual complaint related to increased likelihood of meeting NIA/Reagan Institute (OR = 6.58, p = 0.004) and Consortium to Establish a Registry for Alzheimer's Disease criteria (OR = 5.82, p = 0.03), and increased neurofibrillary tangles (OR = 3.70, p = 0.03), neuritic plaques (OR = 3.52, p = 0.03), and diffuse plaques (OR = 4.35, p = 0.02). Informant-only and self-only complaint was not associated with any neuropathological outcome (all p-values>0.12). In MCI, mutual cognitive complaint relates to AD pathology whereas self-only or informant-only complaint shows no relation to pathology. Findings support cognitive complaint as a marker of unhealthy brain aging and highlight the importance of obtaining informant corroboration to increase confidence of underlying pathological processes.