Background: A decline in instrumental activities of daily living (IADL) correlates with the progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia and has been associated with frontal and parietal hypometabolism, lower cerebrospinal fluid amyloid β1-42, and inferior temporal cortical thinning. Identifying the underlying biomarkers of functional decline will allow for the early identification of individuals at risk of disease progression.
Objective: To investigate the association between IADL impairment and in vivo regional cerebral tau and cortical amyloid deposition across clinically normal (CN) elderly, MCI, and AD dementia.
Methods: Fifty-one CN elderly, 30 MCI, and 9 AD dementia participants of the Alzheimer's Disease Neuroimaging Initiative (ADNI) underwent assessment of regional tau deposition with flortaucipir (FTP) positron emission tomography (PET). An aggregate of cortical amyloid burden was assessed by florbetapir PET. IADL were assessed using the Functional Activities Questionnaire (FAQ). Tau regions with unadjusted correlations of p ≤ 0.006 (Bonferroni correction) with FAQ were used to evaluate the cross-sectional association between FAQ (dependent variable) and regional cerebral tau deposition, amyloid burden, and tau-amyloid interaction in separate general linear regression models with backward elimination. Covariates included age, American National Adult Reading Test (AMNART) intelligence quotient (IQ), and Rey Auditory Verbal Learning Test (RAVLT) total learning.
Results: Unadjusted correlations between FAQ and tau in the entorhinal cortex (EC) and inferior temporal cortex (IT) survived Bonferroni correction. FAQ was associated with the tau-amyloid interaction, such that in participants with greater amyloid burden, greater IADL impairment was associated with greater regional tau (EC tau × amyloid: partial r (pr) = 0.47, p < 0.001; IT tau × amyloid: pr = 0.54, p < 0.001). Significant associations were found when these regression models were repeated in symptomatic participants alone but not among CN participants.
Conclusions: Greater medial and inferior temporal tau and cortical amyloid burden were associated with greater IADL impairment in AD. Further elucidation of the biomarkers underlying the functional decline will allow for the early identification of individual at risk of disease progression.
Keywords: Alzheimer’s disease; Amyloid; Entorhinal cortex; Inferior temporal cortex; Instrumental activities of daily living; Mild cognitive impairment; Positron emission tomography; Tau.