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- subjective cognitive decline (SCD)
- 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.
Exclusion criteria included chronic major neurological …
Twitter @JenniferGatchel, @ytquiroz
Presented at Preliminary findings related to a subset of the data in the manuscript were presented at the 2017 Alzheimer’s Association International Conference.
Contributors The first (JRG) and senior (YTQ) authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study conception and design: JRG, GAM, FL, YTQ. Study supervision: JRG, GAM, FL, YTQ. Acquisition of data: FL, EGV, AA, DJN, AB, YTQ. Analysis and interpretation of data: JRG, GAM, FL, AB, DJN, EGV, JSS, FdOU, AS, PV, REA, DMR, PNT, EMR, KAJ, REA, YTQ. Statistical analysis: JRG, DJN, JSS, FdOU, YTQ. Drafting the manuscript: JRG, GAM, DJN, FL, PNT, EMR, YTQ. Preparation of figures and tables: JRG, JSS. Critical revision of the manuscript for important intellectual content: JRG, FL, DJN, AB, EGV, JSS, FdOU, AS, PV, AA, REA, DMR, PNT, EMR, KAJ, REA, GAM, YTQ.
Funding This work was supported by the NIH Office of the Director (DP5OD019833 to YTQ); NIH/NIA (R01AG054671 to YTQ); and the Massachusetts General Hospital ECOR (1200-228010 and 1200-228767 to YTQ). JRG is supported by NIH/NIA (K23 AG058805-01); the Alzheimer’s Association (AACF_16-440965); the BrightFocus Foundation (ADRF A2016434F); and the Massachusetts General Hospital Rappaport Fellowship.
Competing interests FL is supported by a grant to the Alzheimer’s Prevention Initiative (API) Colombia, funded by Genentech and Banner Alzheimer’s Institute in Arizona. PNT has received consulting fees from Acadia, Abbott Laboratories, AbbVie, AC Immune, Auspex, Boehringer Ingelheim, Chase Pharmaceuticals, Eisai, GliaCure, Insys Therapeutics and Pfizer. He has received consulting fees and research support from AstraZeneca, Avanir, Eli Lilly, Lundbeck, Merck & Co, Roche, and research support only from Amgen, Avid, Biogen, Elan, Functional Neuromodulation (f[nm]), GE Healthcare, Genentech, Novartis and Targacept. PNT has received other research support from the National Institute on Aging and Arizona Department of Health Services and holds stock options in ADAMAS. EMR has received research support from the National Institute on Aging, Novartis/Amgen, Banner Alzheimer's Foundation, Alzheimer's Association, GHR Foundation, F-Prime Biosciences Research Initiative and NOMIS Foundation. He also reports that he is a compensated scientific advisor with Alkahest, Alzheon, Axovant, Denali, Green Valley, United Neuroscience and Zinfandel Pharma. Banner Alzheimer's Institute has contracts with Genentech/Roche, Novartis/Amgen and Avid/Lilly. DMR has served as a consultant for Eli Lilly, Neurotrack and Lundbeck. KAJ has received salary support from Avid Radiopharmaceuticals, and served as a consultant for Eli Lilly, Novartis, Janssen, Roche, Piramal, GE Healthcare, Siemens, ISIS Pharma, AZTherapy and Biogen. RAS has received salary support from Eli Lilly and Janssen Alzheimer Immunotherapy and has served as a consultant for AbbVie, Biogen, Bracket, Genentech, Lundbeck, Merck, Pfizer, Roche and Sanofi. GAM received research salary support from Eisai, Eli Lilly, Janssen Alzheimer Immunotherapy, Novartis and Genentech. He also has served as a consultant for Eisai, Grifols Shared Services North America and Pfizer.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
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