MAPT and Cognitive impairment: In Alzheimer’s disease (AD), patients with higher cognitive reserve (CR) can tolerate greater brain pathological damage at a particular degree of cognitive impairment than those with lower CR, such as coping with decreased cerebral 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) metabolism [4–8], cortical thinning, or gray matter volume (GMV) atrophy [4, 6, 9–11]; having more severe white matter damage [12, 13]; and also primary AD pathologies such as greater amyloid-beta (Aβ) accumulation and increased tau deposition [14–16].