Age-related Changes In Memory Research Articles

Contribution of the D-Serine-dependent pathway to the cellular mechanisms underlying cognitive aging

An association between age-related memory impairments and changes in functional plasticity in the aging brain has been under intense study within the last decade. In this article, we show that an impaired activation of the strychnine-insensitive glycine site of N-methyl-d-aspartate receptors (NMDA-R) by its agonist d-serine contributes to deficits of synaptic plasticity in the hippocampus of memory-impaired aged rats. Supplementation with exogenous d-serine prevents the age-related deficits of isolated NMDA-R-dependent synaptic potentials as well as those of theta-burst-induced long-term potentiation and synaptic depotentiation. Endogenous levels of d-serine are reduced in the hippocampus with aging, that correlates with a weaker expression of serine racemase synthesizing the amino acid. On the contrary, the affinity of d-serine binding to NMDA-R is not affected by aging. These results point to a critical role for the d-serine-dependent pathway in the functional alterations of the brain underlying memory impairment and provide key information in the search for new therapeutic strategies for the treatment of memory deficits in the elderly.

Deficits in Aversive but not in Safe Taste Memory in the APPswe/PS1dE9 mice

Age-related changes in taste memory were evaluated in APPswe/PS1dE9 transgenic (Tg) mice and age-matched wild type littermate controls (Wt). These Tg mice produce increasing amounts of amyloid-beta in the brain with age, develop significant amounts of plaques by 9 months of age, and provide an opportunity to study the effects of Alzheimer's disease-like amyloidosis on different aspects of taste memory. In groups of mice ranging from 15-16 months of age, the neophobic response and its attenuation were similar in Tg and Wt mice. However, conditioned taste aversion (CTA), which resulted from the association between a new taste and an artificially induced gastric malaise, was significantly reduced in the 15-16 month old Tg mice compared to the Wt mice, but not in the 3-4 or 7-8 month old mice. The extinction of CTA was normal in 3-4 month old Tg mice, but occurred more rapidly in the 7-8 and 15-16 months old Tg mice than in the age-matched controls. These results provide evidence of differences in the neuronal systems involved in the attenuation of neophobia and CTA and suggest that the progressive amyloidosis that takes place in APPswe/PS1dE9 mice selectively affects the aversion component of taste memory.

Age-related Changes in Memory and Fluid Reasoning in a Sample of Healthy Old People

ABSTRACT Participants in the Healthy Old People in Edinburgh (HOPE) study (N = 398) were assessed on Raven's Progressive Matrices and Logical Memory on up to three occasions. Covariates included education, social class, disease and medication status, blood pressure and study outcome. Raven's score declined linearly with age, whereas decline in Logical Memory was accelerating. There was significant variation in individuals' rates of decline for Ravens but not Logical Memory. Slope–intercept covariances were not significant. Those who later developed dementia already exhibited lower scores, more so for Logical Memory than Raven's. Death and study attrition were related to performance, again greater for Logical Memory. Conclusions: The HOPE approach of progressive screening is a feasible and practical method for studying healthy cognitive ageing. As predicted for an initially healthy sample, rates of decline were relatively homogeneous. The hypothesis of differential decline was not supported, nor was a strict interpretation of the hypothesis that cognitive ageing is entirely pathology driven.

Age-related changes in associative learning for olfactory and visual stimuli in rodents.

Memory for olfactory stimuli may be particularly affected by age-related brain changes in humans and may be an early indicator of cognitive impairment and Alzheimer's disease. Studies involving rats have offered insights into impaired cognition in aged animals, but few have examined odor memory. Therefore, it is unclear whether aged rats are a good model for possible age-related changes in odor memory in humans. Young (6-month-old) and old (24-month-old) rats were tested on associative learning tasks involving visual and olfactory stimuli. The first task examined age-related differences in discrimination and reversal learning for olfactory and visual stimuli; the second task utilized an associative contextual learning task involving olfactory and visual cues. Although old rats were able to perform the olfactory and visual discrimination tasks as well as young rats, old rats displayed significant age-related impairment on the reversal learning and contextual learning tasks. The results suggest that aging may have a similar deleterious effect on odor memory in rats and in humans. The findings may have important implications for the selection of memory paradigms for future research studies on aging. In addition, the use of an animal model to investigate the effects of aging on odor memory will allow researchers the ability to investigate how age-related neuroanatomical and neurochemical changes may result in impaired odor memory.

Age-related memory impairments due to reduced blood glucose responses to epinephrine

Increases in blood glucose levels are an important component of the mechanisms by which epinephrine enhances memory formation. The present experiments addressed the hypothesis that a dysfunction in the blood glucose response to circulating epinephrine contributes to age-related memory impairments. Doses of epinephrine and glucagon that significantly increased blood glucose levels in young adult rats were far less effective at doing so in 2-year-old rats. In young rats, epinephrine and glucose were about equally effective in enhancing memory and in prolonging post-training release of acetylcholine in the hippocampus. However, glucose was more effective than epinephrine in enhancing both memory and acetylcholine release in aged rats. These results suggest that an uncoupling between circulating epinephrine and glucose levels in old rats may lead to an age-related reduction in the provision of glucose to the brain during training. This in turn may contribute to age-related changes in memory and neural plasticity.

The effects of TNF deficiency on age-related cognitive performance

Growing evidence suggests that 'pro-inflammatory' cytokines such as TNF play a role in cognitive processes and in aging. To test the effects of TNF on cognitive function throughout aging, we used transgenic mice which were TNF deficient. We then tested these mice along with wild-type mice, at 3, 6 and 12 months of age, using the Barnes maze. Wild-type controls showed better memory than TNF knock-out mice at 3 months of age, but not at 6 and 12 months of age. Results of our experiment show that endogenous TNF plays an important role in cognitive processes throughout aging processes. The implications of these findings are far-reaching and include a possible role for cytokines in the molecular and cellular mechanisms subserving age-related changes in learning, memory and cognition.

Guest Editor's Page

It ain't what we don't know that gets us into trouble. It's what we know for sure that ain't so. --Mark Twain The year 2008 represents a new world for visual impairment in the United States and Canada. The demographics of vision loss have changed radically in the last several decades. Today, the greatest number of people with visual impairments are not children or young adults; rather they are seniors with age-related macular degeneration (AMD), who outnumber younger visually impaired adults and children by wide margins. According to the National Eye Institute, people 80 years of age and older currently make up 8 percent of the population, but account for 69 percent of those with visual impairment and blindness, largely from AMD. Indeed, macular degeneration is the cause of the majority of all visual impairment and blindness in Americans. This matters because much of what we know for sure about visual impairment and vision rehabilitation just ain't with macular degeneration. Why? Two key reasons. DIFFERENT LIFE EXPERIENCE Seniors are a population distinct from all others, including younger and middle-aged adults. Just as children have their own medical specialty--pediatrics--so seniors have theirs--geriatrics. Just as kids are not little adults, seniors are not wrinkled adults. They are unique physiologically, medically, and psychosocially. They require different rehabilitation strategies and approaches, different visual and functional devices, and different teaching approaches and methods for effective rehabilitation. Age-related physiological changes in hearing, balance, agility, recovery time, learning patterns and memory make part of the difference. Seniors often rely on their vision to compensate for these other age-related losses, so that when vision is lost too, they are particularly vulnerable to age-specific functional declines and dangerous falls. This situation does not preclude them from being successful in vision rehabilitation, but it does mean that rehabilitation professionals must understand how to address these conditions and assume the responsibility for doing so, or else partner closely with other health care professionals who can address them. When working with seniors, successful vision rehabilitation professionals may need to modulate the pitch and pacing of their voices, adapt their teaching practices to maximize learning, and take the physiological differences of seniors into account. Clients with low vision may need support canes, rather than long canes, to maintain safe balance when walking. They may need contrasting shower bars, contrasting color mats, and adaptive lighting in order to remain safe in the bathroom. With seniors, these considerations are not side issues but are an integral part of vision rehabilitation practice. Seniors also present with a range of medical conditions that shape vision rehabilitation practice, possibly including a history of minor strokes, diabetes, early-onset Parkinson's, arthritis, hypertension, heart disease, osteoporosis, chronic joint or back problems, reduced range of motion, under- or overdosing on medications, and clinical depression as a result of vision loss. Vision rehabilitation professionals must recognize the symptoms of these conditions, understand their interplay with vision loss in compromising function, and address them as an intrinsic part of vision rehabilitation. Seniors are also at a different life stage, with different skills and resources from younger and middle-aged adults, often with other profound losses in their lives--the loss of a spouses, siblings, jobs, or even homes as they move to retirement or assisted living facilities distant from their familiar neighborhoods. Successful vision rehabilitation requires understanding and incorporating these physical, psychological, and cultural differences that sculpt seniors' experiences of vision loss and influence their approach to rehabilitation. …

Memory Changes in Normal and Pathological Aging

Declining memory abilities are reported by virtually all older adults and give rise to the greatest number of complaints about aging in older people. The important questions that arise clinically concern the differences between the so-called benign memory losses of healthy aging and the pathological losses associated with Alzheimer disease and other dementias. Also arising are questions such as to what extent can memory loss be used as a diagnostic tool, and (crucially) can anything be done about it? The 2 In Review articles survey what is known about age-related memory changes: first from the point of view of cognitive psychologists Dr Lin Luo and myself,1 and second from the perspective of a clinical neuropsychologist Dr Lars Backman.2 When does memory decline begin? A rather general answer could be that most people report some problems from their early sixties; however, a study by Park et al3 showed that some memory functions decline as early as the thirties. Two important points in this connection are first that memory is not one monolithic entity, and second that (paradoxically perhaps) memory is also intimately related to other cognitive functions. On the first point, the article by Dr Luo and myself1 describes ideas and evidence from cognitive psychology suggesting that there are at least 5 major memory systems, and that these systems show very different rates of decline in the course of aging. Episodic memory (for specific events) and working memory (for information held and manipulated in conscious awareness) typically fall off relatively rapidly, whereas memory for perceptual information, for highly practiced habits and procedures, and for general knowledge (semantic memory) hold up relatively well. The reasons behind these differential patterns of age-related losses are still under active debate; however, 2 suggestions at the cognitive level of analysis are that age-related problems are found especially in situations requiring large amounts of self-initiated processing and where access to highly specific information is required. The notion of self-initiated processing4 describes cognitive operations that are neither habitual nor well supported by the environmental context; rather, they must be initiated and performed in a conscious, effortful manner, often using new processing operations directed at the specific task. Such operations are typically considered to be frontal lobe functions, and the frontal lobes are known to decline in efficiency in the course of aging.5 Older people are also penalized when the information sought from memory is highly specific in nature-proper names are an obvious example, but specific episodes from the individual's autobiographical past are another. Older people are relatively unimpaired when retrieving general information about a topic, but do less well when specifics are required. One suggestion here is that knowledge is represented and organized hierarchically, with general commonalities easily accessible at the top, and increasingly specific pieces of information that are less easy to access at the bottom of the hierarchy.6 The point that memory is related to other cognitive functions is in line with Dr Backman's2 observation that other cognitive abilities such as attention, executive control, learning, and problem-solving also decline in the course of both normal and pathological aging. To some extent this general cognitive decline may reflect the growing inefficiency of general neurophysiological systems-blood supply, neural connectivity, dopamine depletion, poor glucose metabolism, and so forth-but it is also the case that memory integrity both affects and is affected by other cognitive abilities. Brief examples include: attention-paying attention, especially to the meaning and implication of perceived events, is an obvious prerequisite for subsequent memory performance; memory operations involving elaboration and organization are also crucial for good long-term learning; finally, good working memory abilities reflect good executive control functions (frontal lobes again) and affect such higher-level cognitive activities as problem-solving and planning. …

Age, Memory Changes, and the Varying Utility of Recognition as a Media Effects Pathway

Numerous media campaign evaluations use self-reported exposure measures in assessing media effects, and many of these measures rely on participant recognition of campaign material. Rather than accepting the utility of such measures at face value, however, we should probe their limits. We can predict at least one theoretically important limit on the basis of what we know about age-related memory changes. Specifically, the utility of a recognition item as an indicator of past exposure should decline as audiences age, especially for the most elderly. Analysis of data from a science communication project evaluation offers support for these ideas, demonstrating that age predicts recognition error and that the relationship between experimentally assigned physical exposure and subsequent self-reported recognition wanes among adults 70 and older. We also examine the possibility that media content might nonetheless affect older adults in ways often overlooked by reliance on recognition items.

Placing Neuroanatomical Models of Executive Function in a Developmental Context

Children show gradual and protracted improvement in an array of behaviors involved in the conscious control of thought and emotion. Behavioral research has shown that these abilities, collectively referred to as executive functions (EF), can be dissociated into separable processes, such as inhibition and working memory. Furthermore, noninvasive neuroimaging shows that these component processes often rely on separable neural circuits involving areas of the frontal cortex and nuclei of the basal ganglia. As additional noninvasive methodologies become available, it is increasingly possible to continue to dissect and dissociate components of EF and also test predictions made by a number of theoretical neuroanatomical models. One method of late is genetics, which is noninvasive and readily used in concert with neuroimaging. The biological data obtained with neuroimaging and genetics is particularly able to inform neuroanatomical models that link specific brain systems with higher more abstract process models derived from purely behavioral work. As much progress in this area continues to occur, we seek to evaluate the age dependency and manner in which certain aspects of EF and certain anatomical circuits show changes and interactions as children develop. Some examples are taken from research on children with the developmental disability attention deficit hyperactivity disorder. A review of selected developmental research shows that current cognitive and neuroanatomical models of EF offer a great many system- and synaptic-level hypotheses that can be tested using imaging and imaging genetics in longitudinal and cross-sectional study designs. Here, we focus on age-related changes in inhibition and working memory.

The response-signal method reveals age-related changes in object working memory.

Sixteen healthy young adults (ages 18-32) and 16 healthy older adults (ages 67-81) completed a delayed response task in which they saw the following visual sequence: memory stimuli (2 abstract shapes; 3,000 ms), a blank delay (5,000 ms), a probe stimulus of variable duration (one abstract shape; 125, 250, 500, 1,000, or 2,000 ms), and a mask (500 ms). Subjects decided whether the probe stimulus matched either of the memory stimuli; they were instructed to respond during the mask, placing greater emphasis on speed than accuracy. The authors used D. L. Hintzman & T. Curran's (1994) 3-parameter compound bounded exponential model of speed-accuracy tradeoff to describe changes in discriminability associated with total processing time. Group-level analysis revealed a higher rate parameter and a higher asymptote parameter for the young adult group, but no difference across groups in x-intercept. Proxy measures of cognitive reserve (Y. Stern et al., 2005) predicted the rate parameter value, particularly in older adults. Results suggest that in working memory, aging impairs both the maximum capacity for discriminability and the rate of information accumulation, but not the temporal threshold for discriminability.

Age-related changes in memory and in acetylcholine functions in the hippocampus in the Ts65Dn mouse, a model of Down syndrome

Spatial working memory and the ability of a cholinesterase inhibitor to enhance memory were assessed at 4, 10, and 16 months of ages in control and Ts65Dn mice, a partial trisomy model of Down syndrome, with possibly significant relationships to Alzheimer’s disease as well. In addition, ACh release during memory testing was measured in samples collected from the hippocampus using in vivo microdialysis at 4, 10, and 22–25 months of age. When tested on a four-arm spontaneous alternation task, the Ts65Dn mice exhibited impaired memory scores at both 4 and 10 months. At 16 months, control performance had declined toward that of the Ts65Dn mice and the difference in scores across genotypes was not significant. Physostigmine (50 μg/kg) fully reversed memory deficits in the Ts65Dn mice in the 4-month-old group but not in older mice. Ts65Dn and control mice exhibited comparable baseline levels of ACh release at all ages tested; these levels did not decline significantly across age in either genotype. ACh release increased significantly during alternation testing only in the young Ts65Dn and control mice. However, the increase in ACh release during alternation testing was significantly greater in control than Ts65Dn mice at this age. The controls exhibited a significant age-related decline in the testing-related increase in ACh release. With only a small increase during testing in young Ts65Dn mice, the age-related decline in responsiveness of ACh release to testing was not significant in these mice. Overall, these results suggest that diminished responsiveness of ACh release in the hippocampus to behavioral testing may contribute memory impairments in Ts65Dn mice.

Social recognition memory: Influence of age, sex, and ovarian hormonal status

Social recognition memory underlies many forms of rodent interaction and can be easily tested in the laboratory. Sex differences in aspects of this memory have been reported among young adults, and some studies indicate an age-related decline among male rats. In contrast, neither the impact of natural fluctuations in ovarian hormones nor the performance of aged female rats on social recognition memory has been previously evaluated. In experiments 1 and 2, the social recognition memory of young adult female Long–Evans rats (age 3–5 months) was compared during proestrus and estrus, and performance was found to be stable across estrous cycle phases. In experiment 3, the social recognition memory of young adults as compared to aged (16.5–19.5 months) rats was tested using the social discrimination procedure, following delays of 15, 45, 90 or 120 min. The estropausal status of aged female rats was tracked during the experiment but was not found to influence memory ability. Males of both ages investigated juveniles (both novel and familiar) more than did females, although despite this difference, both sexes demonstrated robust memory. Interestingly, only young adult females were capable of demonstrating memory following the longest delay. Collectively, our findings indicate that the pattern of age-related changes in social recognition memory is subtle and that aging does not greatly alter the behavioral sex differences observed among young adults.

Rapid forgetting of social transmission of food preferences in aged rats: Relationship to hippocampal CREB activation

A major characteristic of age-related changes in memory in rodents is an increase in the rate of forgetting of new information, even when tests given soon after training reveal intact memory. Interference with CREB functions similarly results in rapid decay of memory. Using quantitative immunocytochemistry, the present experiment examined the number of CREB- and pCREB-immunoreactive neurons in three regions of the dorsal and ventral hippocampus (dentate gyrus, CA3, and CA1) as a function of age and training. Rats were trained in a social transmission of food preference task. Using different food pairings, memory was tested in each rat immediately and 1, 2, 3, and 7 d later. Both young and old rats had intact and comparable memory scores at the immediate and 24-h tests, but old rats exhibited more rapid forgetting thereafter relative to that of young rats. The main findings were that training resulted in large increases in the number of pCREB-immunoreactive cells throughout the hippocampus in both young and aged rats. However, particularly in the ventral hippocampus, the training-elicited increase in pCREB-positive neurons was significantly lower in old than in young rats. Based on Western blot analyses in a separate set of rats, CREB levels were not responsive to training but were lower in the ventral hippocampus of old rats than of young rats. The present findings suggest that lower activation of CREB after training may contribute to the rapid forgetting seen in aged rats.

Ageing and autobiographical memory for emotional and neutral events

We investigated age-related effects in recall of emotional and neutral autobiographical memories. Protocols were scored according to episodic and non-episodic detail categories using the Autobiographical Interview. Young adults recalled a greater number of episodic details compared to older adults, whereas older adults recalled more semantic details, replicating previous findings. Both young and older adults’ emotional memories contained more overall detail than neutral ones, with the enhancement from emotion-specific to episodic details, but this did not alter the effect of age group on the pattern of episodic and semantic details. However, the age effect on episodic details was attenuated for neutral autobiographical memories. The findings suggest that age differences for emotional autobiographical recollection might reflect a more general pattern of age-related changes in memory, with impaired recall of episodic components and relative sparing of semantic aspects of autobiographical memory in older adults when compared to young adults.

Effects of global atrophy, white matter lesions, and cerebral blood flow on age-related changes in speed, memory, intelligence, vocabulary, and frontal function.

Brain images were obtained from 133 healthy people of ages 61-85 years who completed 20 tests of information processing speed, intelligence, frontal and executive function, memory, and vocabulary. Structural equation models examined relationships between cognitive test scores, ages and measurements of global age-associated atrophy, white matter lesions, and cerebral blood flow. These neurophysiological measures jointly account for all age-related variance in information processing speed. Speed entirely mediated relationships between neurophysiological measures and memory and partly mediated relationships between neurophysiological measures and intelligence and frontal function. Neurophysiological measures, but not calendar age, accounted for vocabulary scores. Cognitive slowing was responsible for some, but not all, age-related declines in mental function. Age-related declines in intelligence, frontal function, and speed were due to changes in different functional systems.

Episodic Encoding in Normal Aging: Attentional Resources Hypothesis Extended to Musical Material

ABSTRACT The goal of the present study was to examine age-related changes in musical episodic memory for novel tunes. This was conducted by manipulating the encoding condition in a recognition paradigm. After receiving memory instructions (intentional condition), older and younger participants obtained equivalent hits. In contrast, when intentional encoding was accompanied by a dancing judgment (dancing + intentional condition), the recognition performance of the older persons was severely impaired. Impaired recognition was also found when participants only judged the excerpts without being instructed to memorize them (dancing judgment condition). Although older participants demonstrated a preserved ability to perform the dancing judgment on its own, this ability was not optimal and likely precluded the initiation of more elaborate encoding strategies. These results suggest that asking older persons to divide their attention in the study phase reduces the quality of their musical encoding. Given this extension to musical material, we discuss the notion that the age-related attentional resource decline appears to be domain-general rather than specific to verbal material.

The multiple-choice formats (forms F and G) of the Benton Visual Retention Test as a tool to detect age-related memory changes in population-based studies and clinical settings

The Benton Visual Retention Test (BVRT) is a widely used test for the evaluation of visuospatial memory. Alternate forms and various types of administration are available. Whereas most of the formats are visuoconstructional tasks, the forms F and G involve visual recognition. There are several reasons to use multiple-choice formats when studying age-related memory changes. Its procedure involving immediate recognition of geometric designs allows assessment of visuospatial working memory--a memory system particularly vulnerable to aging. The administration is rapid--it can be completed in 5 min--and is easily standardized. The multiple-choice format, relative to the drawing-response formats, also has the advantage of eliminating the influence of visuomotor and manual dexterity problems common in the elderly. Another advantage is the possibility of referring to recent geriatric norms, which can help clinicians or researchers identify individuals with low scores and potentially at risk for dementia.

Age-related changes in visual acuity, learning and memory in C57BL/6J and DBA/2J mice

The DBA/2J mouse is a model of age-related pigmentary glaucoma in humans. Visual detection, pattern discrimination and visual acuity were evaluated in DBA/2J, C57BL/6J, B6. mpc1d (a C57 congenic strain) and D2. mpc1b (a D2 congenic strain) mice at 6, 12, 18 and 24 months of age. Mice were also tested in the Morris Water Maze and olfactory discrimination learning task. At 6 months, DBA/2J and D2. mpc1b mice outperformed C57BL/6J and B6. mpc1d mice in the visual detection task and there were no strain differences in performance on the water maze. At 12, 18 and 24 months, C57BL/6J and B6. mpc1d mice outperformed DBA/2J and D2. mpc1b mice in the vision tasks and in the water maze. Strains did not differ in the olfactory learning task. Therefore, loss of visual function occurs between 6 and 12 months of age in DBA/2J mice. Strain differences in visual task performance accounted for a significant proportion of the variance in measures of learning and memory in the water maze at 12, 18 and 24 months of age.

Processing Speed, Attentional Capacity, and Age-Related Memory Change

This study compared the relative importance (i.e., proportion of shared variance) of attentional capacity and processing speed accounts of cognitive aging to predict age differences in episodic and working memory performance. Right-handed adults (n = 100), 18 to 88 years of age, completed measures of attentional capacity (divided attention), processing speed, and episodic and working memory. The results provide little support for the predictive utility of the attentional capacity construct, independent of processing speed ability in accounting for age-specific episodic memory relations. The results are, however, consistent with the notion that attentional capacity mediates aspects of age-related working memory change.