Age-related Working Memory Deficits Research Articles

Parallel patterns of cognitive aging in marmosets and macaques.

As humans age, some experience cognitive impairment while others do not. When impairment does occur, it is not expressed uniformly across cognitive domains and varies in severity across individuals. Translationally relevant model systems are critical for understanding the neurobiological drivers of this variability, which is essential to uncovering the mechanisms underlying the brain's susceptibility to the effects of aging. As such, non-human primates are particularly important due to shared behavioral, neuroanatomical, and age-related neuropathological features with humans. For many decades, macaque monkeys have served as the primary non-human primate model for studying the neurobiology of cognitive aging. More recently, the common marmoset has emerged as an advantageous model for this work due to its short lifespan that facilitates longitudinal studies. Despite their growing popularity as a model, whether marmosets exhibit patterns of age-related cognitive impairment comparable to those observed in macaques and humans remains unexplored. To address this major limitation for the development and evaluation of the marmoset as a model of cognitive aging, we directly compared working memory ability as a function of age in macaques and marmosets on the identical working memory task. Our results demonstrate that marmosets and macaques exhibit remarkably similar age-related working memory deficits, highlighting the value of the marmoset as a model for cognitive aging research within the neuroscience community.

Reversal of Age-Related Neuronal Atrophy by α5-GABAA Receptor Positive Allosteric Modulation.

Aging is associated with reduced brain volume, altered neural activity, and neuronal atrophy in cortical-like structures, comprising the frontal cortex and hippocampus, together contributing to cognitive impairments. Therapeutic efforts aimed at reversing these deficits have focused on excitatory or neurotrophic mechanisms, although recent findings show that reduced dendritic inhibition mediated by α5-subunit containing GABA-A receptors (α5-GABAA-Rs) occurs during aging and contributes to cognitive impairment. Here, we aimed to confirm the beneficial effect on working memory of augmenting α5-GABAA-R activity in old mice and tested its potential at reversing age-related neuronal atrophy. We show that GL-II-73, a novel ligand with positive allosteric modulatory activity at α5-GABAA-R (α5-PAM), increases dendritic branching complexity and spine numbers of cortical neurons in vitro. Using old mice, we confirm that α5-PAM reverses age-related working memory deficits and show that chronic treatment (3months) significantly reverses age-related dendritic shrinkage and spine loss in frontal cortex and hippocampus. A subsequent 1-week treatment cessation (separate cohort) resulted in loss of efficacy on working memory but maintained morphological neurotrophic effects. Together, the results demonstrate the beneficial effect on working memory and neurotrophic efficacy of augmenting α5-GABAA-R function in old mice, suggesting symptomatic and disease-modifying potential in age-related brain disorders.

Memory load, distracter interference, and dynamic adjustments in cognitive control influence working memory performance across the lifespan.

Capacity-limited working memory (WM) systems have been known to degrade in older age. In line with inhibition-deficit theories of aging, WM deficits in older individuals have been attributed to failures in the ability to suppress the processing of task irrelevant, distracting information. Yet, other cognitive mechanisms underlying age-related WM deficits have been observed, including failures in WM with increasing memory load. Moreover, both distracting information and high memory load have been shown to trigger adjustments in cognitive control leading to subsequent performance benefits on later trials. However, no studies have characterized these dynamic adjustments across the life span or examined their contribution to WM deficits in older adults. We investigated the contribution of distracter interference, memory load, and dynamic adjustments in cognitive control on WM performance in 505 individuals with ages ranging from adolescence to older adulthood. Distracter interference and memory load were parametrically manipulated (high vs. low) in a delayed-recognition WM task, and accuracy was examined as a function of current (N) and previous (N-1) trial demands. Curvilinear models revealed that performance differs over the life span depending on specific WM task demands. Specifically, the ability to suppress task irrelevant distracters was greater in adulthood compared with adolescence, but worse in later life. In contrast, memory load resulted in performance deficits with increasing age, which were exacerbated when high load and interference demands combined. Dynamic adjustments in cognitive control was spared, in part, with memory-load triggered sequential trial effects maintained across the life span, but interference-triggered benefits observable up to middle age. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Do Temporal Regularities during Maintenance Benefit Short-term Memory in the Elderly? Inhibition Capacities Matter

ABSTRACT Background/Study context Recent research has shown a benefit of temporally regular structure presented during the maintenance period in short-term memory for young adults. Because maintenance is impaired in aging, we investigated whether older adults can also benefit from the temporal regularities for maintenance and how their cognitive capacities might affect this potential benefit. Methods Healthy older adults (range: 63–90 years old) had to memorize visually presented letters and maintain them in short-term memory for 6 s until recall. The six-second retention interval was either filled with an isochronous rhythmic sound sequence that provided a temporally regular structure or silent. Results The effect of the isochronous rhythm on recall performance was modulated by inhibition capacities of older adults: as compared to silence, improved recall performance thanks to the rhythm emerged with increased inhibitory capacity of the participants. Conclusion Even though maintenance of older adults benefits less from the presence of temporal regularities than does the maintenance of younger ones, our findings provide evidence for improved maintenance in short-term memory for older adults in the presence of a temporally regular structure, probably due to enhanced attentional refreshing. It further provides perspectives for training and rehabilitation of age-related working memory deficits.

Social housing protects against age-related working memory decline independently of physical enrichment in rats

Longitudinal human studies suggest that as we age, sociality provides protective benefits against cognitive decline. However, little is known about the underlying neural mechanisms. Rodent studies, which are ideal for studying cognition, fail to examine the independent effects of social housing while controlling for physical enrichment in all groups. In this study, rats were socially housed or nonsocially housed throughout their lifespan and tested in the radial arm maze to measure working memory (WM) and reference memory longitudinally at 3 ages. In old age, exclusively, socially housed rats made significantly less WM errors than nonsocially housed rats, while reference memory errors did not differ between groups at any age. Anxiety, as assessed behaviorally and physiologically, could not account for the observed differences in WM. These data provide the first evidence that social enrichment alone can prevent age-related WM deficits in spite of the effects of practice seen in longitudinal designs. Importantly, our model will facilitate future investigations into the mechanisms underlying the neuroprotective benefits of sociability in old age.

Saying it with a natural child's voice! When affective auditory manipulations increase working memory in aging

Objectives: Working memory functions and their relations with affective auditory factors, have not been extensively investigated in aging yet. Method: In this study, younger and older participants completed a classical working memory test (a running working memory task) pronounced by three different voices. In particular, in Experiment 1 the natural voices of a 3-year-old child, a 26-year-old young adult and an 86-year-old older adult were used for task presentation. In Experiment 2 stimuli were morphed in order to better control for sound properties across the three voices. Results: Results showed that working memory increased for older adults compared to younger adults when the task was presented with natural voices and especially so when the task was presented in a child's voice. However, the child-voice effect disappeared with morphed voices. Conclusion: Data confirm the importance of studying the relationship between auditory features and emotional variations as a possible practical means of reducing typical age-related working memory deficits.

Age-related working memory impairment is correlated with increases in the L-type calcium channel protein α 1D (Ca v1.3) in area CA1 of the hippocampus and both are ameliorated by chronic nimodipine treatment

The hippocampus is critical for spatial memory formation in rodents. Calcium currents through L-type voltage-sensitive calcium channels (L-VSCCs) are increased in CA1 neurons of the hippocampus of aged rats. We have recently shown that expression of the calcium conducting L-VSCC subunit α 1D (Ca v1.3) is selectively increased in area CA1 of aged rats. We and others have speculated that excessive Ca 2+ influx through L-VSCC may be detrimental to memory formation. Therefore, we investigated the relationship between age-related working memory decline and α 1D protein expression in the hippocampus. In addition, we studied the effects of chronic treatment with the L-VSCC antagonist nimodipine (NIM) on age-related working memory deficits and α 1D expression in the hippocampus. Here we report that age-related increases in α 1D expression in area CA1 correlate with working memory impairment in Fischer 344 rats. Furthermore, we demonstrate that chronic NIM treatment ameliorates age-related working memory deficits and reduces expression of α 1D protein in the hippocampus. The present results suggest that L-VSCCs participate in processes underlying memory formation and that increases in L-VSCC protein and currents observed with aging may play a role in age-related memory decline. Furthermore, the amelioration in age-related memory decline produced by NIM treatment may be mediated, at least in part, by reductions in the abnormally high levels of α 1D protein in the aged hippocampus. These findings may have implications for patients with Alzheimer’s disease, who show increased L-VSCC protein expression in the hippocampus, and for patients receiving chronic treatment with L-VSCC antagonists.

ADULT AGE DIFFERENCES IN VOCABULARY ACQUISITION

Both working memory (WM) and existing vocabulary knowledge are used when the meaning of a new word is deciphered in context. Age-related WM deficits and vocabulary strengths suggest that younger and older adults rely on these factors differently. Participants gave definitions for rare, novel words that appeared in short passages. Three measures of each individual difference factor (WM and vocabulary) were administered. Older adults gave more complete definitions for the novel words, had higher vocabulary knowledge test scores, but reduced WM scores compared to younger adults. As predicted, existing vocabulary knowledge contributed more to extracting word meaning from context than did WM for the older adults only.

Age-related working memory deficits in the allocentric place discrimination task: possible involvement in cholinergic dysfunction

It is well known that learning and memory ability declines with aging. Age-related long-term changes in learning and memory ability in rats were investigated with the place navigation task and the allocentric place discrimination task (APDT) in a water maze using the same animals for each task. In a working memory place navigation task, aged animals could learn the location of the platform as well as when they were young, although strategy shifts were observed. In contrast, accuracy in the APDT significantly declined from 90% to 65% with aging. This impairment was ameliorated by an acetylcholine esterase inhibitor physostigmine at 22–23 months old. No amelioration was, however, detected in the same animals tested when they further aged to 26–27 months old. These results suggest that the APDT performance is sensitive to age-related memory deficits and that this may be due to the cholinergic dysfunction.