The present study aimed at investigating if the main
biomarkers of
Alzheimer's disease (AD) neuropathology and their association with cognitive disturbances and
dementia are modified by the individual's
frailty status. We performed a cross-sectional analysis of data from participants with normal cognition,
mild cognitive impairment (MCI), and AD
dementia enrolled in the
Alzheimer's Disease Neuroimaging Initiative 2 (ADNI2) study.
Frailty was operationalized by computing a 40-item
Frailty Index (FI). The following AD
biomarkers were considered and analyzed according to the participants'
frailty status: CSF Aβ1-42, 181P-tau, and T-tau; MRI-based hippocampus volume; cortical
glucose metabolism at the FDG PET imaging;
amyloid deposition at the
18F-AV-45 PET imaging. Logistic regression models, adjusted for age, sex, and education, were performed to explore the association of
biomarkers with cognitive status at different FI levels. Subjects with higher FI scores had lower CSF levels of Aβ1-42, hippocampus volumes at the MRI, and
glucose metabolism at the FDG PET imaging, and a higher
amyloid deposition at the
18F-AV-45 PET. No significant differences were observed among the two
frailty groups concerning
ApoE genotype, CSF T-tau, and P-tau. Increasing
frailty levels were associated with a weakened relationship between
dementia and
18F-AV-45 uptake and hippocampus volume and with a stronger relationship of
dementia with FDG PET.
Frailty contributes to the discrepancies between AD pathology and clinical manifestations and influences the association of AD pathological modifications with cognitive changes. AD and
dementia should increasingly be conceived as "complex diseases of aging," determined by multiple, simultaneous, and interacting pathophysiological processes.