For good measure: Detecting and defining changes in everyday functioning in Alzheimer's disease and related disorders

In this thesis, we aimed to extend the knowledge about the measurement of changes in everyday functioning in the context of Alzheimer’s disease and related disorders. This may help clinicians and researchers identify when changes in everyday functioning occur and when they matter, as well as benefit the monitoring of disease progression and evaluation of potential treatment effects. We investigated differences between participants and their study partners in their report of difficulties in everyday functioning and found that depressive feelings and memory complaints, as well as greater tau burden, were associated with more discrepancy in the report of everyday functioning between participant and study partner. While participants from different countries endorsed activities differently, we found no evidence of systematic bias by country, nor by age, sex, or education. We also found that decline in everyday functioning starts early in the Alzheimer's disease trajectory and accelerates as the disease progresses. Because we observed a large heterogeneity in the change in everyday functioning over time, we then attempted to uncover groups of patients who showed a similar change over time. We found that more advanced disease stages, more neurodegeneration and worse cognitive performance were associated with a greater risk to be in a fast declining group. Finally, we defined the minimal important change in everyday functioning using the input from informal caregivers and clinicians, and found that patients were more likely to show a clinically meaningful decline if they had more neurodegeneration. By investigating how to measure everyday functioning, when changes in everyday functioning emerge, and what these changes mean for the patient and their caregiver, this thesis contributed important new insights that may help shape the clinical practice and research endeavors of the future.