Five‐year change in brain metabolism across the spectrum of cognitive impairment in older adults: a quantitative MRI study

INTRODUCTION It is desirable to measure brain metabolism without needing ionizing radiation and elucidate its time trajectory. This study employed a positron emission tomography ‐validated, non‐invasive magnetic resonance imaging (MRI) technique to characterize longitudinal changes in cerebral metabolic rate of oxygen (CMRO 2 ) in both cognitively normal and impaired older adults. METHODS Participants received serial MRI‐based CMRO 2 scans between 2015 and 2025. Levels of AD pathology were measured in cerebrospinal fluid and plasma at the initial MRI. RESULTS At the initial visit, participants with MCI/dementia had lower CMRO 2 than normal participants. In the longitudinal analyses, CMRO 2 decreased over time in those who were cognitively impaired but remained unchanged in normals. Among normal participants, higher initial levels of total tau and phosphorylated tau at threonine 181 were associated with an increase in CMRO 2 during follow‐up, especially in amyloid‐positive individuals. DISCUSSION Aside from the well‐known metabolic slowdown in the later phases of AD, the brain exhibits tau‐dependent hypermetabolism during the preclinical stage.