Supplementary Material for: Measuring Global Brain Atrophy with the Brain Volume/Cerebrospinal Fluid Index: Normative Values, Cut-Offs and Clinical Associations

<b><i>Background:</i></b> Global brain atrophy is present in normal aging and different neurodegenerative disorders such as Alzheimer's disease (AD) and is becoming widely used to monitor disease progression. <b><i>Summary:</i></b> The brain volume/cerebrospinal fluid index (BV/CSF index) is validated in this study as a measurement of global brain atrophy. We tested the ability of the BV/CSF index to detect global brain atrophy, investigated the influence of confounders, provided normative values and cut-offs for mild, moderate and severe brain atrophy, and studied associations with different outcome variables. A total of 1,009 individuals were included [324 healthy controls, 408 patients with mild cognitive impairment (MCI) and 277 patients with AD]. Magnetic resonance images were segmented using FreeSurfer, and the BV/CSF index was calculated and studied both cross-sectionally and longitudinally (1-year follow-up). Both AD patients and MCI patients who progressed to AD showed greater global brain atrophy compared to stable MCI patients and controls. Atrophy was associated with older age, larger intracranial volume, less education and presence of the ApoE ε4 allele. Significant correlations were found with clinical variables, CSF biomarkers and several cognitive tests. <b><i>Key Messages:</i></b> The BV/CSF index may be useful for staging individuals according to the degree of global brain atrophy, and for monitoring disease progression. It also shows potential for predicting clinical changes and for being used in the clinical routine.