The uniqueness of human vulnerability to brain aging in great ape evolution

Abstract

Aging is associated with progressive gray matter loss in the brain. This spatially specific, morphological change over the life span in humans is also found in chimpanzees, and the comparison between these great ape species provides a unique evolutionary perspective on human brain aging. Here, we present a data-driven, comparative framework to explore the relationship between gray matter atrophy with age and recent cerebral expansion in the phylogeny of chimpanzees and humans. In humans, we show a positive relationship between cerebral aging and cortical expansion, whereas no such relationship was found in chimpanzees. This human-specific association between strong aging effects and large relative cortical expansion is particularly present in higher-order cognitive regions of the ventral prefrontal cortex and supports the "last-in-first-out" hypothesis for brain maturation in recent evolutionary development of human faculties.

Fig. 1.. Sample, workflow, and phylogeny.

(A) Age, sex, and scanner field strength distribution of the chimpanzee (N = 189) and human (N = 480) samples. (B) Workflow outlining our comparative approach by using OPNMF and creating cross-species expansion maps. (C) Diagram showing the phylogenetic relationship of humans to the other three primate species investigated in this study.

Fig. 2.. The 17-cluster OPNMF solution for cross-species comparison.

(A) OPNMF granularity selection using ARI to assess cross-species similarity and relevant change in reconstruction error over a granularity range of 2 to 40 clusters and bootstrapped (k = 100) to ensure stability. The 1 SD from the change in MRE over 100 bootstraps is represented as a shadow; the gray dashed line represents the selected number of 17 clusters. (B) Cross-species single parcel ARI in human template space. (C) Human selected 17-cluster OPNMF solution with macroanatomical labels: 1, occipital lobe; 2, temporal pole; 3, putamen, caudate nucleus, amygdala, and hippocampus; 4, prefrontal and orbito-frontal cortex; 5, lingual and fusiform gyrus; 6, superior and middle frontal gyrus; 7, insula; 8, precentral gyrus and premotor area; 9, temporal parietal junction; 10, anterior and middle cingulate cortex; 11, posterior middle and inferior temporal gyri; 12, supramarginal gyrus, inferior postcentral gyrus, and inferior precentral sulcus; 13, precuneus; 14, superior parietal lobe; 15, angular and fusiform gyrus; 16, superior parietal sulcus and parahippocampal cortex; 17, thalamus. (D) Selected 17-cluster OPNMF solution for chimpanzees with macroanatomical labels: 1, occipital lobe, primary motor cortex, and thalamus; 2, temporal pole; 3, caudate nucleus; 4, prefrontal and orbito-frontal cortex; 5, putamen; 6, middle frontal gyrus; 7, superior temporal gyrus and anterior insula; 8, posterior superior frontal gyrus; 9, temporal parietal junction and supramarginal gyrus; 10, anterior and middle cingulate cortex; 11, posterior cingulate, precuneus, and peristriate cortex; 12, supplementary and premotor areas; 13, cuneus and medial occipital-parietal sulcus; 14, superior and inferior parietal lobe and inferior temporal gyrus; 15, lateral parietal-occipital sulcus; 16, superior parietal sulcus and posterior insula; 17, amygdala and hippocampus.

Fig. 3.. Age-related GM decline.

(A) Maximum chimpanzee-matched age human sample (n = 304) significant (FWE P ≤ 0.05) age-mediated GM changes presented as absolute t-statistic from cluster-wise regression model. (B) Scatterplot representing percentage GM of TIV against age in maximum age-matched human sample. (C) Chimpanzee significant (FWE P ≤ 0.05) age-mediated GM changes presented as absolute t-statistic from cluster-wise regression model. (D) Chimpanzee scatterplot showing percentage GM of TIV against age. (E) Human 1:1 matched sample based on age, sex, and scanner field strength (n = 189) percentage GM of TIV age regression (left) and violin plots showing age and sex distributions in 1:1 chimpanzee human-matched samples (right). (F) Violin plots presenting age and sex distribution of chimpanzee and maximum age-matched human samples.

Fig. 4.. Species-specific OPNMF 17-cluster of cerebral expansion.

Average relative cross-species template expansion for each OPNMF 17-cluster is shown for (A) human expansion from chimpanzee, (B) chimpanzee from baboon, and (C) chimpanzee from macaque expansion.

Fig. 5.. GM aging and cerebral expansion.

Each dot represents an OPNMF brain parcel, and a selection of parcels for human and chimpanzee is shown above the scatterplots of (A) and (B), respectively. (A) Chimpanzee to human expansion and human age-related GM decline in maximum age-matched sample. (B) Baboon to chimpanzee expansion and (D) baboon to chimpanzee expansion correlated with chimpanzee age-related GM decline. (C) Chimpanzee to human expansion and human age-related changes relationship presented in eNKI whole life-span external replication dataset. Significance (P) of Person’s correlation (r) for cross-species expansion and age-related GM decline relationship is determined by permutation testing (k = 100,000).