EJNMMI Research (Apr 2024)

Mitochondrial complex I density is associated with IQ and cognition in cognitively healthy adults: an in vivo [18F]BCPP-EF PET study

  • Ekaterina Shatalina,
  • Thomas S. Whitehurst,
  • Ellis Chika Onwordi,
  • Barnabas J. Gilbert,
  • Gaia Rizzo,
  • Alex Whittington,
  • Ayla Mansur,
  • Hideo Tsukada,
  • Tiago Reis Marques,
  • Sridhar Natesan,
  • Eugenii A. Rabiner,
  • Matthew B. Wall,
  • Oliver D. Howes

DOI
https://doi.org/10.1186/s13550-024-01099-1
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 10

Abstract

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Abstract Background Mitochondrial function plays a key role in regulating neurotransmission and may contribute to general intelligence. Mitochondrial complex I (MC-I) is the largest enzyme of the respiratory chain. Recently, it has become possible to measure MC-I distribution in vivo, using a novel positron emission tomography tracer [18F]BCPP-EF, thus, we set out to investigate the association between MC-I distribution and measures of cognitive function in the living healthy brain. Results Analyses were performed in a voxel-wise manner and identified significant associations between [18F]BCPP-EF DVRCS−1 in the precentral gyrus and parietal lobes and WAIS-IV predicted IQ, WAIS-IV arithmetic and WAIS-IV symbol-digit substitution scores (voxel-wise Pearson’s correlation coefficients transformed to Z-scores, thresholded at Z = 2.3 family-wise cluster correction at p < 0.05, n = 16). Arithmetic scores were associated with middle frontal and post-central gyri tracer uptake, symbol-digit substitution scores were associated with precentral gyrus tracer uptake. RAVLT recognition scores were associated with [18F]BCPP-EF DVRCS−1 in the middle frontal gyrus, post-central gyrus, occipital and parietal regions (n = 20). Conclusions Taken together, our findings support the theory that mitochondrial function may contribute to general intelligence and indicate that interindividual differences in MC-I should be a key consideration for research into mitochondrial dysfunction in conditions with cognitive impairment.

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