Elsevier

NeuroImage

Volume 101, 1 November 2014, Pages 59-67
NeuroImage

Age-related effects in the neocortical organization of chimpanzees: Gray and white matter volume, cortical thickness, and gyrification

https://doi.org/10.1016/j.neuroimage.2014.06.053Get rights and content

Highlights

  • Tested for potential age-related decline in cortical organization in chimpanzees

  • Used BrainVisa to measure organization and folding in the cerebral cortex

  • This is the single largest study examining age-related changes in chimpanzees.

  • Chimpanzees exhibit few age-related changes in global cortical organization.

Abstract

Among primates, humans exhibit the most profound degree of age-related brain volumetric decline in particular regions, such as the hippocampus and the frontal lobe. Recent studies have shown that our closest living relatives, the chimpanzees, experience little to no volumetric decline in gray and white matter over the adult lifespan. However, these previous studies were limited with a small sample of chimpanzees of the most advanced ages. In the present study, we sought to further test for potential age-related decline in cortical organization in chimpanzees by expanding the sample size of aged chimpanzees. We used the BrainVisa software to measure total brain volume, gray and white matter volumes, gray matter thickness, and gyrification index in a cross-sectional sample of 219 captive chimpanzees (8–53 years old), with 38 subjects being 40 or more years of age. Mean depth and cortical fold opening of 11 major sulci of the chimpanzee brains were also measured. We found that chimpanzees showed increased gyrification with age and a cubic relationship between age and white matter volume. For the association between age and sulcus depth and width, the results were mostly non-significant with the exception of one negative correlation between age and the fronto-orbital sulcus. In short, results showed that chimpanzees exhibit few age-related changes in global cortical organization, sulcus folding and sulcus width. These findings support previous studies and the theory that the age-related changes in the human brain is due to an extended lifespan.

Introduction

Normal aging in humans is a complex process that brings about many structural changes in the brain. Research shows that normal brain aging in humans is characterized by particularly severe volume loss in regions involved in memory and executive functions, such as the hippocampus and frontal lobe (Abe et al., 2008, Peters, 2006, Raz et al., 1997, Rosen et al., 2002, Tisserand et al., 2004). The volumetric decline is associated with shrinkage of gray matter (GM) and white matter (WM) volumes and enlargement of the cerebrospinal fluid (CSF) spaces, resulting in an increase of the opening of cortical sulci (Ge et al., 2002, Lemaitre et al., 2012, Matsumae et al., 1996, Pfefferbaum et al., 1994, Sherwood et al., 2011, Sullivan et al., 1995). Evidence suggests that cerebral gray matter volume decreases at a linear rate with age in adulthood, whereas hippocampal volume is relatively stable until middle age, after which there is an accelerated rate of shrinkage (Ge et al., 2002, Good et al., 2001, Raz et al., 2005, Sherwood et al., 2011, Taki et al., 2011, Walhovd et al., 2005). White matter volume shows a quadratic change over the lifespan, in which it increases until the middle age period and then decreases with increasing age (Ge et al., 2002, Giorgio et al., 2010, Sowell et al., 2003, Walhovd et al., 2005, Westlye et al., 2010).

From a comparative perspective, previous studies have examined age-related changes in the brains of other mammals, and specifically primates. Nonhuman primates are of particular interest for studying the neurobiological correlates of aging because of their close phylogenetic relationship with humans (Finch and Austad, 2012). Nonhuman primates are often used as models to understand the effects of aging independent of the cellular changes that cause age-related neurodegenerative disorders commonly seen in humans such as Alzheimer's disease (Gearing et al., 1996, Kimura et al., 2003, Koo et al., 2012, Lemaitre et al., 2012, Sherwood et al., 2011, Squire et al., 1988). Characteristics of neurodegenerative diseases, such as diffuse plaques and vascular lesions, have been observed in the hippocampus and frontal lobes of aged macaque monkeys, chimpanzees, gorillas and orangutans (Gearing et al., 1997, Kimura, 2001, Poduri et al., 1994). At the present time there are only two reports of the existence of neurofibrillary tangles in great apes including one in a 41 year old chimpanzee (Rosen et al., 2008), and more recently in a sample of lowland gorillas (Perez et al., 2013). Finally, there is also evidence that apes and monkeys show age-related volumetric decline in the striatum and modest reductions in total brain volume (Alexander et al., 2008, Herndon et al., 1999, Matochik et al., 2000, Rapp and Amaral, 1992).

In terms of behavior and cognition, age-related decline in motor and cognitive functions have been described extensively in monkeys (Herndon et al., 1997, Lacreuse et al., 2005, Moss et al., 1988, Rapp and Amaral, 1989). In humans, the age-related volumetric reductions of the frontal lobe and the hippocampus are associated with decline in cognitive processes, including fluid reasoning, mental processing speed, episodic memory, and spatial ability (Park et al., 2001, Salthouse, 1996, Verhaeghen and Salthouse, 1997, Whalley et al., 2004). In aged nonhuman primates, there are impairments in delayed response tasks, delayed matching-to-sample tasks, delayed recognition span tasks, reversal learning tasks, and conceptual set-shifting task (Bartus et al., 1978, Hara et al., 2012, Moss et al., 1988). Far fewer data are available from great apes, including chimpanzees; however, a recent study by Lacreuse et al. (2014) reported a moderate but statistically significant decline in spatial memory in a sample of 4 chimpanzees over the age of 50 years old.

It has been hypothesized that a possible factor explaining the more pronounced pathological and cognitive changes found in humans compared to nonhuman primates is increased longevity (Hawkes, 2003, Herndon, 2009). Compared to other primates, humans have evolved an extended lifespan, particularly post reproductively, which has been proposed to increase the risk for the development of cognitive impairments and associated brain changes in later life (Herndon, 2009). The “grandmother hypothesis” suggests that human longevity resulted from selection for longer post-menopausal survival in women, who could contribute to the cooperative care of dependent offspring in their families (Finch and Sapolsky, 1999, Hawkes, 2003). According to Herndon (2009), chimpanzees' shorter post-menopausal lifespan might allow them to avoid cognitive impairments or neurodegenerative disorders that occur during the very latest stages of life in humans, such as Parkinson's or Alzheimer's disease.

To date, there are two studies on age-related changes in cortical organization in chimpanzee brains based on post-mortem or in vivo magnetic resonance imaging. Sherwood et al. (2011) examined age-related changes in cortical organization in chimpanzees compared to humans. They measured the volumes of brain regions in 69 chimpanzees and found that there was little evidence of marked age-related change. Specifically, chimpanzees did not show statistically significant volumetric age-related decline in gray and white matter volume for either the entire brain or frontal lobe or hippocampus. More recently, Chen et al. (2013) found that chimpanzees do show age-related declines in both gray and white matter, but the declines were much smaller than typically occur in older humans. One limitation of this prior research was the minimal number of very old or “aged” subjects, defined as those chimpanzees greater than 40 years of age. For instance, there were only 7 subjects over the age of 40 in the previous study by Sherwood et al., with only one being a male. Similarly, Chen et al. (2013) had only a small portion of chimpanzees over the age of 40 and the sample consisted entirely of females. Thus, both Chen et al. (2013) and Sherwood et al. (2011) may not have had enough statistical power to detect more robust age-related changes in cortical organization among the most geriatric chimpanzees, and particularly older males.

The aim of the current research was to further test for potential age-related decline in cortical organization in chimpanzees. This study differs from previous reports on age-related changes in the chimpanzee brain in two important ways. First, this study had a larger sample of male and female chimpanzees that included substantially more individuals representing the upper end of their lifespan. Second, we employed a different methodology and approach to the measurement of different dimensions of cortical organization. Here, we used the BrainVisa (BV) software to measure the organization and folding in the cerebral cortex. This software has been previously employed to assess age-related changes in human and baboon brains (Kochunov et al., 2005). Using the BV software, we measured the total brain volume, gray and white matter volumes, gray matter thickness, and gyrification index of 219 captive chimpanzees, with 38 subjects being 40 or more years of age, therefore considerably expanding the sample size in the oldest cohort of individuals. Furthermore, we measured the mean depth and cortical fold opening of 11 major sulci of the chimpanzee brains. We hypothesized that if age-related changes in the chimpanzee brain are reduced compared to humans, then age would account for a small proportion of variance in cortical organization, sulcus depth and fold opening in our sample.

Section snippets

Subjects

There were 219 captive chimpanzees (134 females, 85 males) in this study including 84 chimpanzees housed at the Yerkes National Primate Research Center (YNPRC) and 135 chimpanzees housed at The University of Texas M. D. Anderson Cancer Center (UTMDACC). Ages at the time of their magnetic resonance image scans ranged from 8 to 53 years (Mean = 27.04, SD = 6.74). In addition to analyzing the neuroanatomical variables against chronological age, we also classified the chimpanzees into 4 age groups

Global cortical measures

Prior to conducting the sex and age effect analyses, we performed a Pearson Product Moment correlation between age and body weight and found that older subjects had lower body weights (r =  .223, p = .001). Because age was associated with body weight and body weight can correlate with brain size within and between different primate species, we subsequently used body weight as a covariate in the analyses examining sex and age effects on the global measures of cortical organization.

In the initial

Discussion

Brain aging in nonhuman primates displays both similarities and differences from humans (Koo et al., 2012, Nagahara et al., 2010, Poduri et al., 1994). Studies have shown that there is little to no changes in cortical organization in the chimpanzee brain (Chen et al., 2013, Sherwood et al., 2011), yet these studies had a small number of chimpanzees over the age of 40. This study is the single largest study ever examining age-related changes in cortical organization in nonhuman primates and

Acknowledgment

This research was supported by NIH grants MH-92923, NS-42867, NS-73134, HD-60563 to WDH, NIA P01AG-026423 to JGH Cooperative Agreement RR-15090 to M.D. Anderson Cancer Center, and National Center for Research Resources P51RR000165 to YNPRC, which is currently supported by the Office of Research Infrastructure Programs/OD P51OD11132. We would like to thank Yerkes National Primate Research Center and the University of Texas MD Anderson Cancer Center and their respective veterinary and care staffs

References (84)

  • S. Groeschel et al.

    Developmental changes in cerebral grey and white matter volume from infancy to adulthood

    Int. J. Dev. Neurosci.

    (2010)
  • J.G. Herndon et al.

    Patterns of cognitive decline in aged rhesus monkeys

    Behav. Brain Res.

    (1997)
  • N. Kimura et al.

    Age-related changes in Alzheimer's disease-associated proteins in cynomolgus monkey brains

    Biochem. Biophys. Res. Commun.

    (2003)
  • A. Lacreuse et al.

    Sex differences in age-related motor slowing in the rhesus monkey: behavioral and neuroimaging data

    Neurobiol. Aging

    (2005)
  • A. Lacreuse et al.

    Cognitive and motor aging in female chimpanzees

    Neurobiol. Aging

    (2014)
  • J.A. Matochik et al.

    Age-related decline in striatal volume in monkeys as measured by magnetic resonance imaging

    Neurobiol. Aging

    (2000)
  • K. Milton

    Nutritional characteristics of wild primate foods: do the diets of our closest living relatives have lessons for us?

    Nutrition

    (1999)
  • M.B. Moss et al.

    Effects of aging on visual recognition memory in the rhesus monkey

    Neurobiol. Aging

    (1988)
  • A.H. Nagahara et al.

    Age-related cognitive deficits in rhesus monkeys mirror human deficits on an automated test battery

    Neurobiol. Aging

    (2010)
  • K.A. Phillips et al.

    Cortical development in brown capuchin monkeys: a structural MRI study

    NeuroImage

    (2008)
  • P.J. Pierre et al.

    Age-related neuroanatomical differences from the juvenile period to adulthood in mother-reared macaques (Macaca radiata)

    Brain Res.

    (2008)
  • P.R. Rapp et al.

    Individual differences in the cognitive and neurobiological consequences of normal aging

    Trends Neurosci.

    (1992)
  • J.K. Rilling et al.

    The primate neocortex in comparative perspective using magnetic resonance imaging

    J. Hum. Evol.

    (1999)
  • J. Rogers et al.

    On the genetic architecture of cortical folding and brain volume in primates

    NeuroImage

    (2010)
  • L.R. Squire et al.

    Memory: brain systems and behavior

    Trends Neurosci.

    (1988)
  • E.V. Sullivan et al.

    Age related decline in MRI volumes of temporal gray matter but not hippocampus

    Neurobiol. Aging

    (1995)
  • K.B. Walhovd et al.

    Effects of age on volumes of cortex, white matter and subcortical structures

    Neurobiol. Aging

    (2005)
  • S.C. Alberts et al.

    Reproductive aging patterns in primates reveal that humans are distinct

    Proc. Natl. Acad. Sci.

    (2013)
  • G.E. Alexander et al.

    Age-related regional network of magnetic resonance imaging gray matter in the rhesus macaque

    J. Neurosci.

    (2008)
  • E. Armstrong et al.

    Cortical folding and the evolution of the human brain

    J. Hum. Evol.

    (1993)
  • S. Atsalis et al.

    Reproductive aging in captive and wild common chimpanzees: factors influencing the rate of follicular depletion

    Am. J. Primatol.

    (2009)
  • P. Bailey et al.

    The Isocortex of the Chimpanzee

    (1950)
  • R.T. Bartus et al.

    Aging in the rhesus monkey: debilitating effects on short-term memory

    J. Gerontol.

    (1978)
  • P. Elwood et al.

    Healthy lifestyles reduce the incidence of chronic diseases and dementia: evidence from the Caerphilly Cohort Study

    PLoS One

    (2013)
  • C.E. Finch et al.

    Primate aging in the mammalian scheme: the puzzle of extreme variation in brain aging

    Age

    (2012)
  • Y. Ge et al.

    Age-related total gray matter and white matter changes in normal adult brain. Part I: volumetric MR imaging analysis

    Am. J. Neuroradiol.

    (2002)
  • R.C. Gur et al.

    Sex differences in temporo-limbic and frontal brain volumes of healthy adults

    Cereb. Cortex

    (2002)
  • Y. Hara et al.

    Neuronal and morphological bases of cognitive decline in aged rhesus monkeys

    Age

    (2012)
  • K. Hawkes

    Grandmothers and the evolution of human longevity

    Am. J. Hum. Genet.

    (2003)
  • J.G. Herndon

    The grandmother effect: implications for studies on aging and cognition

    Gerontology

    (2009)
  • J.G. Herndon et al.

    “Reproductive aging in captive and wild common chimpanzees: Factors influencing the rate of follicular depletion,” by S. Atsalis and E. Videan

    Am. J. Primatol.

    (2009)
  • J.G. Herndon et al.

    Brain weight throughout the life span of the chimpanzee

    J. Comp. Neurol.

    (1999)
  • Cited by (35)

    • The nervous system of the non-human primate

      2023, Spontaneous Pathology of the Laboratory Non-human Primate
    • In-vivo diffusion MRI protocol optimization for the chimpanzee brain and examination of aging effects on the primate optic nerve at 3T

      2021, Magnetic Resonance Imaging
      Citation Excerpt :

      Interestingly, some neurodegenerative diseases, such as Alzheimer disease, that occur in humans are not known to occur in our closest biological relatives, the NHPs [19,42]. Previous MRI studies demonstrated that there are few aging-related volumetric changes in chimpanzee brains compared to human and suggested the age-related changes in the human brain may be due to the extended lifespan [39,43]. Also, age-related white matter degeneration has been seen in previous studies of human [44–46] and other mammalian brains, including rhesus monkeys [47,48] and mice [49,50].

    • Nonhuman primates as models for aging and Alzheimer’s disease

      2021, Assessments, Treatments and Modeling in Aging and Neurological Disease: The Neuroscience of Aging
    View all citing articles on Scopus
    View full text