Association of subjective cognitive decline with markers of brain pathology in preclinical autosomal dominant Alzheimer’s disease

Subjective cognitive decline (SCD) has been implicated as an early marker of subtle cognitive change in preclinical Alzheimer’s disease (AD).1 The relationship between SCD and molecular markers of disease progression in AD is poorly understood. Carriers of the presenilin ( PSEN1 E280A) mutation from the Colombian kindred2 are a compelling group in which to study SCD, as they will develop dementia with certainty, and have a well-characterised disease trajectory from presymptomatic to clinical stages.2 SCD has been associated with markers of AD pathology in older adults at risk for late-onset sporadic AD.3 We showed previously that self-reported subjective memory complaints (SMC), a proxy for SCD, were elevated in cognitively unimpaired PSEN1 mutation carriers, and that study-partner-reported SMCs were correlated with age and negatively correlated with hippocampal volume.4 In the present study, we explored the extent to which SCD relates to markers of brain pathology—in vivo amyloid and/or tau. We hypothesised that SCD would be related to neocortical amyloid and regional tau levels. Findings have the potential to inform whether SCD might be a sensitive marker of AD-related pathology and disease trajectory in the preclinical stage of AD. Participants were 21 PSEN1 E280A mutation carriers and 27 age, sex and education-matched non-carrier family members recruited from the Alzheimer’s Prevention Initiative Registry. All had at least one parent who bore the PSEN1 E280A mutation but were blind to their genetic status, in accordance with cultural norms and ethical regulations in this community. Clinical assessments, including neurological exam and psychiatric questionnaires probing depression and anxiety, were completed at the University of Antioquia. SCD was assessed using both the self-report and study-partner-based versions of the Memory Complaint Scale, Spanish version (online supplementary appendix 1). Positron-emission tomography (PET) imaging was done in Boston, Massachusetts, USA. ### Supplementary data [jnnp-2019-321205supp001.pdf] Exclusion criteria included chronic major neurological …