TY - JOUR
T1 - Mitochondrial complex I density is associated with IQ and cognition in cognitively healthy adults
T2 - an in vivo [18F]BCPP-EF PET study
AU - Shatalina, Ekaterina
AU - Whitehurst, Thomas S.
AU - Onwordi, Ellis Chika
AU - Gilbert, Barnabas J.
AU - Rizzo, Gaia
AU - Whittington, Alex
AU - Mansur, Ayla
AU - Tsukada, Hideo
AU - Marques, Tiago Reis
AU - Natesan, Sridhar
AU - Rabiner, Eugenii A.
AU - Wall, Matthew B.
AU - Howes, Oliver D.
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - 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.
AB - 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.
KW - Auditory verbal learning
KW - General intelligence
KW - IQ
KW - Mitochondrial complex I (MC-I)
KW - [F]BCPP-EF
UR - http://www.scopus.com/inward/record.url?scp=85190703378&partnerID=8YFLogxK
U2 - 10.1186/s13550-024-01099-1
DO - 10.1186/s13550-024-01099-1
M3 - Article
AN - SCOPUS:85190703378
SN - 2191-219X
VL - 14
JO - EJNMMI Research
JF - EJNMMI Research
IS - 1
M1 - 41
ER -