Characterising encoding and retrieval contributions to age-related memory impairment

Lead Research Organisation: University of Cambridge
Department Name: Psychology

Abstract

Many older adults worry that forgetfulness, which may feel increasingly pervasive as the years go by, will eventually mean losing their ability to remember new experiences. Such memory failures can result from deficits in encoding experiences into memory effectively, or from impairments in retrieving information that has been stored. The proposed research aims to understand the factors underpinning these memory failures and, just as importantly, explore strategies designed to support and enhance older adults' memory abilities. The investigation will use novel cognitive tasks and advanced brain imaging methods to explore how variability in the structure and function of the brain influences the degree to which older adults can benefit from encoding and retrieval strategies designed to enhance recollection.

There are three main components to the project. The first component aims to identify the key cognitive processes and brain mechanisms governing effective encoding strategies that older adults can implement to enable the formation of rich and vivid memory representations. The second component will explore methods to promote the adoption by older adults of retrieval processes that can maximize successful recollection. The third component aims to assess the degree to which differences in specific brain regions and networks can predict how effectively individuals are able to benefit from the encoding and retrieval strategies tested.

The findings of the proposed research will advance understanding of how variations in brain structure and function can help to predict the usefulness of different memory strategies for older adults. These advances will feed into the development of rehabilitation approaches designed to enhance memory abilities in the elderly, with the potential for providing tangible improvements in quality of life and wellbeing.

Technical Summary

The proposed research aims to use novel behavioural manipulations and advanced structural and multivariate functional MRI analysis to explore how variability in the structure and function of the brain influences the degree to which older adults can benefit from encoding and retrieval strategies designed to enhance recollection.

There are three main components to the project, each with clearly defined objectives and measurable outcomes. The first component aims to identify the key cognitive and neural mechanisms governing effective encoding strategies that older adults can implement to enable the construction of rich and vivid memory representations. The second component will explore methods to promote the adoption by older adults of controlled retrieval processes that can maximize successful recollection, identify sources of deficits in these abilities, and reveal neural differences that determine the level of retrieval success observed. The third component will use structural MRI, diffusion tensor imaging, and resting state fMRI to assess the degree to which individual differences in structural and functional integrity of key brain regions and networks can predict the effectiveness with which individuals are able to benefit from the encoding and retrieval strategies targeted.

The findings of the proposed research will advance understanding of how individual differences in brain structure and function associated with controlled recollection processes can help to predict the efficacy of memory strategies for older adults. These advances will contribute to the development of rehabilitative interventions designed to enhance memory abilities in the elderly, with the potential for providing tangible improvements in quality of life and wellbeing.

Planned Impact

The most obvious beneficiaries of the proposed research will be older people. The effects of age on encoding and retrieval have rarely both been characterised in detail before within the same participants, either psychologically or neurocognitively, meaning that the proposed research will greatly advance our understanding of age-related changes in this important area of cognition. Forgetfulness is a pervasive worry amongst older adults, often associated with increasing anxiety about losing precious memories from the past and being unable to remember new experiences in the future. Understanding the factors underpinning these memory failures and, just as importantly, characterizing memory processes that are more resilient to the ageing process, may have considerable implications for older adults' functioning in everyday life. In this way the proposed research fits closely with the BBSRC's current strategic priority on Ageing/Lifelong Health and Wellbeing.

Improving our understanding of strategies that can be used to enhance remaining memory abilities in older adults could lead to important advances in preventative and rehabilitative tools designed to support older people who may be experiencing reduced social, intellectual and emotional stimulation as a result of their memory difficulties. If our hypothesis is correct that such deficits may be to some extent reversible, then effective strategies can be developed to combat the detrimental impact of these memory failures on everyday function. This has the potential to lead to policy recommendations about the importance of ensuring that older people in the community, and those who are in care settings, hospitals or other institutions, are given adequate opportunities and support to learn and practice strategies to enhance their encoding and retrieval of memories. See the accompanying "Pathways to Impact" statement for further details of the specific actions we will take in collaboration with clinicians, carers and other service-users to work towards translating our research findings into potential therapeutic interventions and policy recommendations to optimize health and wellbeing across the lifespan.

Publications

10 25 50
 
Description All the original objectives described in the grant proposal have been fulfilled, resulting in a number of pre-prints deposited in bioRxiv, publications in peer-reviewed journals and conference presentations, plus dissemination of the research more widely via public engagement activities.

We addressed the objectives relating to identifying different encoding and retrieval strategies that might influence memory acquisition in older adults. For example, we assessed the importance of self-referential and elaborative encoding strategies, pitting episodic autobiographical memory (AM) and semantic AM strategies against a general semantic knowledge strategy, as well as traditional binary self-referential and semantic encoding judgments. We found that both the AM and general semantic strategies at encoding resulted in substantial enhancements to recall and recognition memory of concrete nouns relative to binary encoding judgments across both age groups. Furthermore, older adults exhibited larger benefits from this additional elaboration than did younger adults, leading to elimination of age-related deficits in recognition memory. However, younger adults showed an additional boost to subsequent memory following episodic, relative to semantic, AM during free recall that was not exhibited by older adults. This may be due to greater demands on frontally mediated control processes and cognitive resources associated with the use of this strategy. Taken together, the results suggest that the mnemonic benefits associated with self-referential processing vary substantially depending on the specific nature of the encoding strategy, and suggest that, under certain conditions, semantic processing and self-referential processing are equally effective in mitigating age-related deficits in memory performance.

We also addressed the objectives relating to exploring the influence of representational quality and the use of controlled retrieval processes on memory performance in older adults. We sought to decouple these factors using an object recognition memory test with similar lures by comparing performance on a Yes/No (YN) test to that on a Forced Choice (FC) test, which minimizes demands on strategic retrieval processes, enabling a more direct measure of the availability of stimulus details. We found that older adults exhibited increased lure false recognition across test formats, suggesting a decline in the availability of object details contributes to deficits in performance. Manipulating interference by varying the number of objects studied selectively enhanced performance in the FC test, resulting in matched performance across groups, whereas age differences in YN performance persisted, indicating an additional contribution of impaired strategic retrieval. Consistent with differential sensitivity of test format to strategic retrieval and the quality of stimulus representations among older adults, variability in the quality of object representations, measured using a perceptual discrimination task, was selectively related to FC performance. In contrast, variability in memory control processes, as measured with tests of recall and executive function, was related to performance across test formats. These results suggest that both declines in the availability of object details and impaired retrieval of object details contribute to elevated rates of lure false recognition with age, and highlight the utility of test format for dissociating these factors in memory-impaired populations.

Finally, we address the objectives concerning the neural mechanisms underlying age differences in representational quality and strategic retrieval processes. We sought to identify neural evidence for age-related change in these factors by measuring neural differentiation during encoding of paired associates, and changes in regional BOLD activity, functional connectivity, and cortical reinstatement during retrieval conditions that placed low (intact pairs) and high (recombined pairs) demands on strategic retrieval processes. The results revealed age-related declines in the differentiation of stimulus representations during encoding and cortical reinstatement during retrieval, though a relationship between these metrics was observed only during conditions of low strategic demand (hits). Both older and younger adults preferentially engaged hippocampus and angular gyrus during hits, but only younger adults exhibited increased recruitment of, and hippocampal connectivity with, lateral prefrontal regions during correct rejections, consistent with greater age-related impairments in engaging the retrieval control mechanisms necessary to support goal-directed retrieval. Collectively, the data provide further insights into the neural mechanisms underlying age-related decline in episodic memory.
Exploitation Route The findings could be used by older adults, their families and carers, and other interested individuals, to better understand the changes in memory ability that occur with increasing age, and to implement mnemonic strategies that might help to support memory decline.
Sectors Communities and Social Services/Policy,Healthcare

 
Description As proposed in our Pathways to Impact document, we engaged with older adults and their families using questionnaires to gain insight about their primary memory concerns and to determine what areas they would most like research to address. Based on the responses received, we have run memory workshops for older adults aiming to provide general information regarding memory and ageing, information relevant to the specific difficulties reported within the questionnaires, as well as advice on strategies to support memory. Over the two sessions run so far, 51 older adults have attended. Based on feedback forms, and feedback received in person and via email, the response to the workshops was very positive. Attendees indicated that they found the workshops extremely informative and enjoyable. They particularly found it valuable to learn about the outcomes of their involvement and hoped further workshops would be run in the future. Some of the statements received from volunteers included: "Thank you for the opportunity to take part, I particularly appreciated the feedback session", "An interesting two hours", "A very good presentation and incredibly informative", "Thank you, it was very interesting and a guide to how we can help ourselves and others", "Excellent talk 10/10", "I just wanted to say how much I enjoyed the session, the presentations were really interesting and it was very good to hear the results of the studies".
First Year Of Impact 2016
Sector Education,Healthcare
Impact Types Societal

 
Title Executive function and high ambiguity perceptual discrimination contribute to individual differences in mnemonic discrimination in older adults 
Description n this study, we examined cognitive factors that underpin individual differences in mnemonic discrimination among healthy older adults. Mnemonic discrimination deficits, or impaired ability to discriminate between similar events in memory, is a hallmark of cognitive ageing, characterised by a stark age-related increase in false recognition. While individual differences in mnemonic discrimination have gained attention due to potential relevance for early detection of Alzheimer's disease (AD), our understanding of the component processes that contribute to variability in task performance across older adults remains limited. The present investigation explores the roles of representational quality, indexed by perceptual discrimination of objects and scenes with overlapping features, and strategic retrieval ability, indexed by standardized tests of executive function, to mnemonic discrimination in a large cohort of older adults (N=124). We took an individual differences approach and characterised the contributions of these factors to performance under Forced Choice (FC) and Yes/No (YN) recognition memory formats, which place different demands on strategic retrieval. Performance in both test formats declined with age. Accounting for age, individual differences in FC memory performance were best explained by perceptual discrimination score, whereas YN memory performance was best explained by executive functions. A dominance analysis confirmed the relatively greater importance of perceptual discrimination over executive functioning for FC performance, while the opposite was true for YN. These findings highlight parallels between perceptual and mnemonic discrimination in aging, the importance of considering demands on executive functions in the context of mnemonic discrimination, and the relevance of test format for modulating the impact of these factors on performance in older adults. 
Type Of Material Database/Collection of data 
Year Produced 2021 
Provided To Others? Yes  
Impact None 
URL https://osf.io/mcyh9/
 
Title Research data supporting "Healthy ageing reduces the precision of episodic memory retrieval" 
Description Microsoft excel spreadsheet containing anonymised behavioural data from three experiments reported in the manuscript "Healthy ageing reduces the precision of episodic memory retrieval". Sheet 1 contains data from Experiment 1, Sheet 2 data from Experiment 2, and Sheet 3 data from Experiment 3. Data were collected from healthy younger (aged 18 - 30) and older (aged 60 -82) individuals completing a computerized memory task. Two parameters of memory performance; the probability of successful memory retrieval (pT) and the precision of memory retrieval (?), were estimated for each participant and task condition with mixture modelling code available at https://www.paulbays.com/code/JV10/index.php. For Experiment 2, mean memory vividness is also reported for each participant. Variable names are defined in the "readme.txt" file. See the main manuscript for more details. 
Type Of Material Database/Collection of data 
Year Produced 2020 
Provided To Others? Yes  
Impact None 
URL https://www.repository.cam.ac.uk/handle/1810/299021
 
Description Interview for BBC World Service radio 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact BBC World Service programme, Crowd Science, featured interviews with several lab members and involved a segment in which the presenter participated in a brain scanning experiment comparing memory-related brain activity in older and younger adults.
Year(s) Of Engagement Activity 2017
URL http://www.bbc.co.uk/programmes/w3cswc8g
 
Description Keynote talk, Learning and Memory Processes Annual Meeting, Durham 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact Keynote talk, Learning and Memory Processes Annual Meeting, Durham
Year(s) Of Engagement Activity 2019
 
Description Memory Disorders Research Society 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Talk given to elected members of Memory Disorders Research Society on representational specificity and retrieval processes in ageing
Year(s) Of Engagement Activity 2015
 
Description Memory workshops 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Study participants or study members
Results and Impact As proposed in our Pathways to Impact document, we engaged with older adults and their families using questionnaires to gain insight about their primary memory concerns and to determine what areas they would most like research to address. Based on the responses received, we have run memory workshops for older adults aiming to provide general information regarding memory and ageing, information relevant to the specific difficulties reported within the questionnaires, as well as advice on strategies to support memory. Over the two sessions run so far, 51 older adults have attended.

Based on feedback forms, and feedback received in person and via email, the response to the workshops was very positive. Attendees indicated that they found the workshops extremely informative and enjoyable. They particularly found it valuable to learn about the outcomes of their involvement and hoped further workshops would be run in the future. Some of the statements received from volunteers included:
"Thank you for the opportunity to take part, I particularly appreciated the feedback session", "An interesting two hours", "A very good presentation and incredibly informative", "Thank you, it was very interesting and a guide to how we can help ourselves and others", "Excellent talk 10/10", "I just wanted to say how much I enjoyed the session, the presentations were really interesting and it was very good to hear the results of the studies".
Year(s) Of Engagement Activity 2016
 
Description Poster at Baycrest Rotman Research Institute Conference, Toronto, Canada 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Poster at Baycrest Rotman Research Institute Conference, Toronto, Canada
Year(s) Of Engagement Activity 2015
 
Description Poster at Cambridge Memory Meeting, Cambridge, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other audiences
Results and Impact Poster at Cambridge Memory Meeting, Cambridge, UK
Year(s) Of Engagement Activity 2014
 
Description Poster at Cognitive Neuroscience Society Annual Meeting, New York, NY. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Poster at Cognitive Neuroscience Society Annual Meeting, New York, NY.
Year(s) Of Engagement Activity 2016
 
Description Poster at Cognitive Neuroscience Society Annual Meeting, San Francisco, CA. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Poster at Cognitive Neuroscience Society Annual Meeting, San Francisco, CA.
Year(s) Of Engagement Activity 2015
 
Description Poster at International Conference on Memory Annual Meeting, Budapest, Hungary 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Poster at International Conference on Memory Annual Meeting, Budapest, Hungary
Year(s) Of Engagement Activity 2016
 
Description Symposium talk at Memory Disorders Research Society meeting (Toronto) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Symposium talk at Memory Disorders Research Society meeting (Toronto)
Year(s) Of Engagement Activity 2018
 
Description Talk at Cambridge Memory Meeting, University of Cambridge, Cambridge UK, 2015 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other audiences
Results and Impact Talk at Cambridge Memory Meeting, University of Cambridge, Cambridge UK, 2015
Year(s) Of Engagement Activity 2015
 
Description Talk at Experimental Psychology Society Aging Meeting, Pershore, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Talk at Experimental Psychology Society Aging Meeting, Pershore, UK
Year(s) Of Engagement Activity 2014