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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number41
JournalEJNMMI Research
Volume14
Issue number1
DOIs
Publication statusPublished - Dec 2024

Keywords

  • Auditory verbal learning
  • General intelligence
  • IQ
  • Mitochondrial complex I (MC-I)
  • [F]BCPP-EF

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