Age-related cognitive decline in baboons: modeling the prodromal phase of Alzheimer's disease and related dementias

Lizarraga, Stephanny; Daadi, Etienne W.; Roy-Choudhury, Gourav; Daadi, Marcel M.

doi:10.18632/aging.103272

Cited by 15 publications

(9 citation statements)

References 77 publications

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“…It is well-known that older rodents, NHPs, and humans have decreased motivation to earn rewards (Lanctôt et al, 2017; Lizarraga et al, 2020; Jackson et al, 2021). To evaluate the potential impact of age-related changes in motivation on DRST performance, we employed the well-established PRT to quantify motivation in our marmosets (Spinelli et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Age-related learning and working memory impairment in the common marmoset

Glavis-Bloom

Vanderlip

Reynolds

2022

Preprint

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Aging is the greatest risk factor for the development of neurodegenerative diseases, yet we still do not understand how the aging process leads to pathological vulnerability. The research community has relied heavily on mouse models, but the considerable anatomical, physiological, and cognitive differences between mice and humans limit their translational relevance. Ultimately, these barriers necessitate the development of novel aging models. As a non-human primate, the common marmoset (Callithrix jacchus) shares many features in common with humans and yet has a significantly shorter lifespan (10 years) than other primates, making it ideally suited to longitudinal studies of aging. Our objective was to evaluate the marmoset as a model of age-related cognitive impairment. To do this, we utilized the Delayed Recognition Span Task (DRST) to characterize age-related changes in working memory capacity in a cohort of sixteen marmosets varying in age from young adult to geriatric. These monkeys performed thousands of trials over periods of time ranging up to 50 percent of their adult lifespan. To our knowledge, this represents the most thorough cognitive profiling of any marmoset aging study conducted to-date. By analyzing individual learning curves, we found that aged animals exhibited delayed onset of learning, slowed learning rate after onset, and decreased asymptotic working memory performance. These findings are not accounted for by age-related impairments in motor speed and motivation. This work firmly establishes the marmoset as a model of age-related cognitive impairment.

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Section: Discussionmentioning

confidence: 99%

Age-related learning and working memory impairment in the common marmoset

Glavis-Bloom

Vanderlip

Reynolds

2022

Preprint

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“…A recent study reported that old baboons ( Papio anubis , 20 ± 3 years of age, n = 3) show a decline in attention, learning, and memory compared to young adults (13 ± 3 years of age, n = 3) (Lizarraga et al, 2020). Interestingly, age‐related pathology in baboons also appears around the age at which cognitive deficits are apparent.…”

Section: Cercopithecidsmentioning

confidence: 99%

Comparative neuropathology in aging primates: A perspective

Freire-Cobo

Edler

Varghese

et al. 2021

American J Primatol

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While humans exhibit a significant degree of neuropathological changes associated with deficits in cognitive and memory functions during aging, non-human primates (NHP) present with more variable expressions of pathological alterations among individuals and species. As such, NHP with long life expectancy in captivity offer an opportunity to study brain senescence in the absence of the typical cellular pathology caused by age-related neurodegenerative illnesses commonly seen in humans. Age-related changes at neuronal population, single cell, and synaptic levels have been well documented in macaques and marmosets, while age-related and Alzheimer's disease-like neuropathology has been characterized in additional species including lemurs as well as great apes. We present a comparative overview of existing neuropathologic observations across the primate order, including classic agerelated changes such as cell loss, amyloid deposition, amyloid angiopathy, and tau accumulation. We also review existing cellular and ultrastructural data on neuronal changes, such as dendritic attrition and spine alterations, synaptic loss and pathology, and axonal and myelin pathology, and discuss their repercussions on cellular and systems function and cognition.

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“…In a cross-sectional study of 19 baboons (aged 1-14), Bonté (2014) found that executive control (as measured by a transfer index task) declined with age. In another cross-sectional study of 6 baboons, older adults (20-23 years old) performed significantly worse on cognitive tasks (specifically, learning a novel task, precision, and simple discrimination) compared to younger adults (13-16 years old) (Lizarraga et al, 2020). These findings suggest that there are likely neurobiological changes occurring as baboons age.…”

Section: Introductionmentioning

confidence: 97%