Longitudinal associations between energy utilization and brain volumes in cognitively normal middle aged and older adults

Peak energy capacity of the whole person is associated with neurodegeneration. However, change in ability to utilize energy manifests as combination of declining peak energy capacity and rising energetic costs of mobility in mid-to-late life. We examined longitudinal associations between change in energy utilization and brain volumes. Cognitively normal participants from the Baltimore Longitudinal Study of Aging (N = 703, age = 70.4 ± 12.1 years, 54.1% women, 30% black) had concurrent data on brain volumes and energy utilization (defined as ratio of energetic cost of walking to peak energy capacity (“cost-to-capacity ratio”) at ≥ 1 visit between 2008 and 2018. We performed linear mixed-effect models, adjusting for demographics, medical history and walking engagement. Average baseline cost-to-capacity ratio was 0.55 ± 0.16, with average annual increase of 0.04 ± 0.13 over 3.9 follow-up years. A 10% higher baseline cost-to-capacity ratio was associated with 2.00 cm 3 (SE = 0.44) larger baseline ventricular volume (p < 0.001), and 0.10 cm 3 (SE = 0.03) greater annual increase in ventricular volume (p = 0.004) after adjustment. Longitudinal change in cost-to-capacity ratio was not associated with brain volumes. These findings highlight, among cognitive-normal adults, poorer baseline energy utilization is associated with subsequent ventricular enlargement, an indirect measure of central brain atrophy. Future studies should explore whether early detection of worsening energy utilization may act as a marker of underlying brain atrophy.