Alzheimer's disease neuropathology and longitudinal change in subjective cognitive complaints.

Introduction: Subjective cognitive complaints often precede declines in objective measures of cognitive performance. Associations of incipient Alzheimer's disease (AD) neuropathology with subjective cognitive complaints may be detectable earlier than associations with neuropsychological testing among cognitively normal individuals.

Methods: We examined the independent associations of positron emission tomography measures of amyloid beta and tau pathologies with longitudinal subjective complaints and memory among 91 cognitively normal Baltimore Longitudinal Study of Aging participants using linear mixed effects models. Subjective complaints and memory performance were assessed with the Cognitive Failures Questionnaire and the California Verbal Learning Test, respectively.

Results: Greater parahippocampal tau, independent of amyloid, was associated with higher subjective complaints (estimate = 0.25, standard error [SE] = 0.1, P = $0.015$ ), while greater entorhinal tau corresponded to an attenuated increase in complaints over time (estimate = -0.06, SE = 0.03, P = $0.047$ ). Hippocampal tau was associated with steeper memory decline (estimate = -0.03, SE = 0.01, P = $0.040$ ).

Conclusion: Subjective cognitive complaints may be a reflection of early cerebral tau pathology in cognitively normal individuals.

Highlights: Greater parahippocampal tau was linked with higher subjective cognitive complaints.Entorhinal tau was associated with slower increases in cognitive complaints over time.Subjective complaints may reflect early amyloid and tau in cognitively normal adults.