Patterns of cognitive decline in aged rhesus monkeys

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

doi:10.1016/s0166-4328(96)02256-5

Cited by 257 publications

(222 citation statements)

References 24 publications

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“…Nevertheless, a host of studies confirm that rhesus monkeys show age-related cognitive impairments in multiple domains including working memory, recognition memory, and executive function (e.g., Bartus et al 1978;Rapp and Amaral 1989;Moss et al 1988;Herndon et al 1997;Moore et al 2006). Thus a critical question is to determine what brain changes occur and whether they are diffusely distributed or localized to particular anatomical substrates or loci.…”

Section: The Non-human Primate As a Model Of Normative Agingmentioning

confidence: 99%

Age-related changes in human and non-human primate white matter: from myelination disturbances to cognitive decline

Kohama

Rosene

Sherman

2011

AGE

107

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The cognitive decline associated with normal aging was long believed to be due primarily to decreased synaptic density and neuron loss. Recent studies in both humans and non-human primates have challenged this idea, pointing instead to disturbances in white matter (WM) including myelin damage. Here, we review both cross-sectional and longitudinal studies in humans and non-human primates that collectively support the hypothesis that WM disturbances increase with age starting at middle age in humans, that these disturbances contribute to age-related cognitive decline, and that age-related WM changes may occur as a result of free radical damage, degenerative changes in cells in the oligodendrocyte lineage, and changes in microenvironments within WM.

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Section: The Non-human Primate As a Model Of Normative Agingmentioning

confidence: 99%

Age-related changes in human and non-human primate white matter: from myelination disturbances to cognitive decline

Kohama

Rosene

Sherman

2011

AGE

107

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“…The behavioral tests used to assess the cognitive status of these monkeys have been described in previous publications (e.g. Herndon et al, 1997;Moss et al, 1999Moss et al, , 2007Peters et al, , 2000Killiany et al, 2000). The assessment is made on the basis of the scores obtained by the monkeys on three visual recognition tasks.…”

Section: Behavioral Testingmentioning

confidence: 99%

“…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.…”

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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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“…Retention scores in some versions of the radial maze are notably better in rats at 3 months than at 14 months of age (Granger et al, 1996). Middle-aged monkeys are similarly impaired relative to young adults (Herndon et al, 1997;Sloane et al, 1997). Memory loss is thus an early manifestation of brain aging across the mammals.…”

Section: Loss Of Synaptic Plasticity In Early Middle Agementioning

confidence: 99%

Synaptic plasticity in early aging

Lynch

Rex

Gall

2006

Ageing Research Reviews

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Studies of how aging affects brain plasticity have largely focused on old animals. However, deterioration of memory begins well in advance of old age in animals, including humans; the present review is concerned with the possibility that changes in synaptic plasticity, as found in the long-term potentiation (LTP) effect, are responsible for this. Recent results indicate that impairments to LTP are in fact present by early middle age in rats but only in certain dendritic domains. The search for the origins of these early aging effects necessarily involves ongoing analyses of how LTP is induced, expressed, and stabilized. Such work points to the conclusion that cellular mechanisms responsible for LTP are redundant and modulated both positively and negatively by factors released during induction of potentiation. Tests for causes of the localized failure of LTP during early aging suggest that the problem lies in excessive activity of a negative modulator. The view of LTP as having redundant and modulated substrates also suggests a number of approaches for reversing age-related losses. Particular attention will be given to the idea that induction of brain-derived neurotrophic factor, an extremely potent positive modulator, can be used to provide long periods of normal plasticity with very brief pharmacological interventions. The review concludes with a consideration of how the selective, regional deficits in LTP found in early middle age might be related to the global phenomenon of brain aging. #

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Patterns of cognitive decline in aged rhesus monkeys

Cited by 257 publications

References 24 publications

Age-related changes in human and non-human primate white matter: from myelination disturbances to cognitive decline

Age-related changes in human and non-human primate white matter: from myelination disturbances to cognitive decline

Synapses are lost during aging in the primate prefrontal cortex

Synaptic plasticity in early aging

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