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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 ( N  = 25) and two ( N  = 25) and four ( N  = 16) years later. During the follow-up, the rate constant for brain extraction of glucose (K glc ) declined by 6%–12% mainly in the temporo-parietal lobes and cingulate gyri ( p  ≤ 0.05), whereas brain acetoacetate extraction (Kacac) and utilization remained unchanged in all brain regions ( p  ≥ 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 glc  in the caudate was directly related to performance on several cognitive tests ( r  = +0.41 to +0.43,  all   p  ≤ 0.04). Peripheral insulin resistance assessed by the homeostasis model assessment of insulin resistance (HOMA-IR) was significantly inversely related to K glc  in the thalamus ( r  = −0.44,  p  = 0.04) and in the caudate ( r  = −0.43,  p  = 0.05), and also inversely related to executive function, attention and processing speed ( r  = −0.45 to −0.53, all  p  ≤ 0.03). We confirm in a longitudinal setting that the age-related decline in K glc  is directly associated with declining performance on some tests of cognition but does not significantly affect Kacac.

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