Impairment in complex activities of daily living is related to neurodegeneration in Alzheimer's disease–specific regions

Impairment in instrumental activities of daily living (IADL) is an early clinical feature of Alzheimer's disease (AD). The neurobiology underlying IADL disruptions is still unclear. We aimed to investigate the relationship between IADL functioning and cortical atrophy across the AD spectrum. We selected 162 memory-clinic subjects with subjective cognitive decline (n = 49), mild cognitive impairment (n = 26) or AD dementia (n = 87), and an available structural MRI acquired at 3.0 Tesla and Amsterdam IADL Questionnaire (A-IADL-Q) assessment. We used linear regression correcting for age, sex, education, vascular injuries, and total intracranial volume to investigate the association between gray matter volume and A-IADL-Q score, and voxel-based morphometry to investigate whether any associations were specific for distinct regions. Less gray matter volume was associated with lower A-IADL-Q scores (β = 0.346, 95% CI = [0.185-0.507], p < 0.001), specifically in cortical regions covering the medial temporal lobes, cingulate cortex, and precuneus (all p(familywise error–corrected) < 0.05). Results were similar when repeating the analyses in amyloid-positive subjects (n = 78). Our findings illustrate that the A-IADL-Q detects functional impairment related to AD-specific neurodegeneration.