Impairment in abstraction and set shifting in aged Rhesus monkeys

Moore, Tara; Killiany, Ronald J.; Herndon, James G.; Rosene, Douglas L.; Moss, Mark B.

doi:10.1016/s0197-4580(02)00054-4

Cited by 115 publications

(111 citation statements)

References 82 publications

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“…Studies involving the rhesus monkey as an animal model for normal aging have focused on behavioral [2,3,16,24,25,27,[31][32][33]36,37,[45][46][47] and anatomical [1,28] endpoints, but few have examined both [40][41][42]. The rhesus monkey model provides the opportunity to study agerelated brain structural changes using MRI with the assurance that Alzheimer's disease pathology will not confound the interpretation of results.…”

Section: Introductionmentioning

confidence: 99%

“…The rhesus monkey model of normal aging also provides the opportunity to study cognitive decline [2,3,16,24,27,[31][32][33]36,37,[40][41][42][45][46][47] using behavioral tasks that are similar to clinical tests [4,8,25,44]. Similar to anatomical studies, the advantage of using the rhesus monkey as an animal model for cognitive decline in normal aging is the absence of Alzheimer's Disease-associated cognitive impairment.…”

Section: Introductionmentioning

confidence: 99%

“…The goal of this investigation was to utilize MRI methods to determine if there are age-related changes in the major components of the forebrain in behaviorally characterized monkeys participating in ongoing investigations of normal aging [16,24,32,33,36,37,[40][41][42]. To accomplish this efficiently we applied the automated MRI segmentation technique Template Driven Segmentation (TDS) to legacy rhesus monkey MRI data.…”

Section: Introductionmentioning

confidence: 99%

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An MRI study of age-related white and gray matter volume changes in the rhesus monkey

Wisco

Killiany

Guttmann

et al. 2008

Neurobiology of Aging

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We applied the automated MRI segmentation technique Template Driven Segmentation (TDS) to dual-echo spin echo (DE SE) images of eight young (5-12 years), six middle-aged (16-19 years) and eight old (24-30 years) rhesus monkeys. We analyzed standardized mean volumes for 18 anatomically defined regions of interest (ROI's) and found an overall decrease from young to old age in the total forebrain (5.01%), forebrain parenchyma (5.24%), forebrain white matter (11.53%) forebrain gray matter (2.08%), caudate nucleus (11.79%) and globus pallidus (18.26%). Corresponding behavioral data for five of the young, five of the middle-aged and seven of the old subjects on the Delayed Non-matching to Sample (DNMS) task, the Delayed-Recognition Span Task (DRST) and the Cognitive Impairment Index (CII) were also analyzed. We found that none of the cognitive measures were related to ROI volume changes in our sample size of monkeys.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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An MRI study of age-related white and gray matter volume changes in the rhesus monkey

Wisco

Killiany

Guttmann

et al. 2008

Neurobiology of Aging

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“…Gallagher and Rapp, 1997;Herndon et al, 1997;Moss et al, 1999;Moore et al, 2003) and the question arises as to what is the underlying cause of this cognitive decline. On the basis of early morphological studies it was assumed that the cognitive decline in normal aging is due to neuronal loss, but more recent studies have shown there is not a significant loss of neurons from the neocortex during normal aging (e.g.…”

mentioning

confidence: 99%

“…We have chosen to examine the effects of age on the numerical density of synapses in the neuropil of area 46 of the rhesus monkey cortex since prefrontal cortex is considered, in part at least, to subserve spatial and reversal learning tasks, as well as recognition memory tasks, and as monkeys age they become impaired on these tasks (Kojima and Goldman-Rakic, 1982;Lai et al, 1995;Fuster 1997;Moss et al, 1997Moss et al, , 2007Moore et al, 2003). These behavioral changes occur even though there is no change in the volume of prefrontal cortex with age (O'Donnell et al, 1999) and no loss of neurons (Peters et al, 1994;Peters and Sethares, 2002a).…”

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confidence: 99%

Synapses are lost during aging in the primate prefrontal cortex

2008

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Abstract-An electron microscopic analysis has been carried out on the effects of age on the numerical density of both excitatory (asymmetric) and inhibitory (symmetric) synapses in the neuropil of layers 2/3 and of layer 5 in area 46 from the frontal cortex of behaviorally tested rhesus monkeys. There is no change in the lengths of synaptic junctions with age or in the percentage distribution of synapses relative to the postsynaptic spines and dendritic shafts. However, in layers 2/3 there is an overall loss of about 30% of synapses from 5 to 30 years of age, and both asymmetric and symmetric synapses are lost at the same rate. In layer 5 the situation is different; the overall loss of synapses is only 20% and this is almost entirely due to a loss of asymmetric synapses, since there is no significant loss of symmetric synapses from this layer with age. When the synapse data are correlated with the overall cognitive impairment shown by the monkeys, it is found that there is a strong correlation between the numerical density of asymmetric synapses in layers 2/3 and cognitive impairment, with a weaker correlation between symmetric synapse loss and cognitive impairment. In layer 5 on the other hand there is no correlation between synapse loss and cognitive impairment. However synapse loss is not the only factor causing cognitive impairment, since in previous studies of area 46 we have found that age-related alteration in myelin in this frontal area also significantly contributes to cognitive decline. The synapse loss is also considered in light of earlier studies, which show that the frequency of spontaneous excitatory synaptic responses is reduced with age in layers 2/3 neurons.

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Why primate models matter

Phillips

Bales

Capitanio

et al. 2014

American J Primatol

473

366

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Research involving nonhuman primates (NHPs) has played a vital role in many of the medical and scientific advances of the past century. NHPs are used because of their similarity to humans in physiology, neuroanatomy, reproduction, development, cognition, and social complexity—yet it is these very similarities that make the use of NHPs in biomedical research a considered decision. As primate researchers, we feel an obligation and responsibility to present the facts concerning why primates are used in various areas of biomedical research. Recent decisions in the United States, including the phasing out of chimpanzees in research by the National Institutes of Health and the pending closure of the New England Primate Research Center, illustrate to us the critical importance of conveying why continued research with primates is needed. Here, we review key areas in biomedicine where primate models have been, and continue to be, essential for advancing fundamental knowledge in biomedical and biological research. Am. J. Primatol. 76:801–827, 2014. © 2014 Wiley Periodicals, Inc.

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Impairment in abstraction and set shifting in aged Rhesus monkeys

Cited by 115 publications

References 82 publications

An MRI study of age-related white and gray matter volume changes in the rhesus monkey

An MRI study of age-related white and gray matter volume changes in the rhesus monkey

Synapses are lost during aging in the primate prefrontal cortex

Why primate models matter

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