PT - JOURNAL ARTICLE AU - Doering, Elena AU - Antonopoulos, Georgios AU - Hoenig, Merle AU - van Eimeren, Thilo AU - Daamen, Marcel AU - Boecker, Henning AU - Jessen, Frank AU - Düzel, Emrah AU - Eickhoff, Simon AU - Patil, Kaustubh AU - Drzezga, Alexander AU - for the Alzheimer’s Disease Neuroimaging Initiative and the DELCODE Study Group TI - MRI or <sup>18</sup>F-FDG PET for Brain Age Gap Estimation: Links to Cognition, Pathology, and Alzheimer Disease Progression AID - 10.2967/jnumed.123.265931 DP - 2024 Jan 01 TA - Journal of Nuclear Medicine PG - 147--155 VI - 65 IP - 1 4099 - http://jnm.snmjournals.org/content/65/1/147.short 4100 - http://jnm.snmjournals.org/content/65/1/147.full SO - J Nucl Med2024 Jan 01; 65 AB - Deviations of brain age from chronologic age, known as the brain age gap (BAG), have been linked to neurodegenerative diseases such as Alzheimer disease (AD). Here, we compare the associations of MRI-derived (atrophy) or 18F-FDG PET–derived (brain metabolism) BAG with cognitive performance, neuropathologic burden, and disease progression in cognitively normal individuals (CNs) and individuals with subjective cognitive decline (SCD) or mild cognitive impairment (MCI). Methods: Machine learning pipelines were trained to estimate brain age from 185 matched T1-weighted MRI or 18F-FDG PET scans of CN from the Alzheimer’s Disease Neuroimaging Initiative and validated in external test sets from the Open Access of Imaging and German Center for Neurodegenerative Diseases–Longitudinal Cognitive Impairment and Dementia studies. BAG was correlated with measures of cognitive performance and AD neuropathology in CNs, SCD subjects, and MCI subjects. Finally, BAG was compared between cognitively stable and declining individuals and subsequently used to predict disease progression. Results: MRI (mean absolute error, 2.49 y) and 18F-FDG PET (mean absolute error, 2.60 y) both estimated chronologic age well. At the SCD stage, MRI-based BAG correlated significantly with beta-amyloid1-42 (Aβ1-42) in cerebrospinal fluid, whereas 18F-FDG PET BAG correlated with memory performance. At the MCI stage, both BAGs were associated with memory and executive function performance and cerebrospinal fluid Aβ1-42, but only MRI-derived BAG correlated with phosphorylated-tau181/Aβ1-42. Lastly, MRI-estimated BAG predicted MCI-to-AD progression better than 18F-FDG PET–estimated BAG (areas under the curve, 0.73 and 0.60, respectively). Conclusion: Age was reliably estimated from MRI or 18F-FDG PET. MRI BAG reflected cognitive and pathologic markers of AD in SCD and MCI, whereas 18F-FDG PET BAG was sensitive mainly to early cognitive impairment, possibly constituting an independent biomarker of brain age-related changes.