HAI Book 2025 - Flipbook - Page 99
Dubbelman, Mark
1
Decline in everyday functioning over time relates to amyloid and tau in
cognitively unimpaired older adults
Mark Dubbelman1,2, Andy Liu3, Michael Donohue3, Oliver Langford3, Rema Raman3, Dorene
Rentz1,2, Rebecca Amariglio1,2, Reisa Sperling1,2, Paul Aisen3, Gad Marshall1,2
Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women’s Hospital, Harvard
Medical School, Boston, MA, US
2
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, US
3
Alzheimer Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego,
CA, US
1
Introduction: Everyday functioning declines gradually over time in Alzheimer9s disease, with the earliest changes
occurring at the preclinical stage. We aimed to investigate how changes in everyday functioning relate to amyloid
and tau in a large sample of cognitively unimpaired older adults who participated in the A4 and LEARN clinical
trials.
Methods: We included 1,707 participants (71.5±4.7 years, 60% female, mean education 16 years) from the A4 Study
(n=1,147, 67%) in which participants had elevated cortical amyloid at baseline and the LEARN Study (n=560, 33%) in
which participants had low amyloid at baseline. All underwent amyloid positron emission tomography (PET) scans,
and a subset of n=434 underwent tau PET scans. Participants and their study partners completed the Alzheimer9s
Disease Cooperative Study Activities of Daily Living Prevention Instrument (ADCS ADL-PI) multiple times over a
six-year follow-up period. Using generalized least squares models, we analyzed how changes in everyday
functioning related to a cortical aggregate of amyloid and neocortical and mediotemporal aggregates of tau. We
also correlated changes in amyloid and tau PET and changes in everyday functioning.
Results: In the whole sample, everyday functioning declined marginally over time. Among individuals with
elevated amyloid, those with the highest levels of neocortical and mediotemporal tau at baseline showed the
largest decline in everyday functioning, as reported by the participants and their study partners (see Figure).
Increases in neocortical and mediotemporal tau correlated moderately (correlation coefficient ranging from -0.2
to -0.5) with a decline in everyday functioning over time.
Conclusion: In this study, higher tau levels were associated with the fastest decline in everyday functioning in the
presence of elevated amyloid, and those accumulating more tau showed a faster decline in daily functioning. This
demonstrates the utility of including sensitive measures of everyday functioning in clinical trials at the stage of
preclinical Alzheimer9s disease.
HAI2025 - 99
