Links Between Metabolic and Structural Changes in the Brain of Cognitively Normal Older Adults: A 4-Year Longitudinal Follow-Up

We aimed to longitudinally assess the relationship between changing brain energy metabolism (glucose and acetoacetate) and cognition during healthy aging. Participants aged 71 ± 5 year underwent cognitive evaluation and quantitative positron emission tomography (PET) and magnetic resonance imaging (MRI) scans at baseline ( = 25) and two ( = 25) and four ( = 16) years later. During the follow-up, the rate constant for brain extraction of glucose (K ) declined by 6%-12% mainly in the temporo-parietal lobes and cingulate gyri ( ≤ 0.05), whereas brain acetoacetate extraction (Kacac) and utilization remained unchanged in all brain regions ( ≥ 0.06). Over the 4 years, cognitive results remained within the normal age range but an age-related decline was observed in processing speed. K in the caudate was directly related to performance on several cognitive tests ( = +0.41 to +0.43, ≤ 0.04). Peripheral insulin resistance assessed by the homeostasis model assessment of insulin resistance (HOMA-IR) was significantly inversely related to K in the thalamus ( = -0.44, = 0.04) and in the caudate ( = -0.43, = 0.05), and also inversely related to executive function, attention and processing speed ( = -0.45 to -0.53, all ≤ 0.03). We confirm in a longitudinal setting that the age-related decline in K is directly associated with declining performance on some tests of cognition but does not significantly affect Kacac.