Abstract
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.
Highlights
The relationship between the biological modifications underlying Alzheimer’s disease (AD) and their phenotypic expression is highly complex
The primary goal of Alzheimer’s Disease Neuroimaging Initiative (ADNI) has been to test whether serial magnetic resonance imaging (MRI), positron emission tomography (PET), other biological markers, and clinical and neuropsychological assessment can be combined to measure the progression of MCI and early AD
To the best of our knowledge, this study constitutes the first attempt to test the hypothesis that frailty may act as a latent factor in the relationship between AD candidate biomarkers and the phenotypic expression of the neurodegenerative condition
Summary
The relationship between the biological modifications underlying Alzheimer’s disease (AD) and their phenotypic expression is highly complex. A relevant discordance between biomarker- and clinical-based definitions of AD has repeatedly been documented [2] The understanding of this relationship may be improved by the adoption of constructs and models that comprehensively reflect the biological complexity of the organism as well as the heterogeneity of health trajectories and outcomes within aging. Frailty is intended as a condition characterized by reduced homeostatic reserves and increased vulnerability to stressors exposing the individual to adverse outcomes [3, 4]. This construct has triggered growing attention in many medical areas [5] as it likely contributes
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