MAPT and Brain atrophy: This finding is in accordance with our a priori hypothesis because older patients are more likely to exhibit brain atrophy independent of tau burden (eg, owing to cerebrovascular disease, synaptic loss, or comorbid proteinopathies, such as transactive response DNA binding protein 43 kDa [TDP-43] or α-synuclein).42,43 Furthermore, neuronal repair mechanisms may become less efficient with age,44 which potentially increases the susceptibility to downstream effects of tau aggregates in older participants.