The Missing Link of Episodic Memory Decline in Aging

Most people will experience that their memory deteriorates as they get older. This is especially the case for a specific form of memory often referred to as episodic memory. Episodic memories are typically personal memories, memories in which we are part of the memory. Three processes must all function for us to be able to form an episodic memory: encoding of the episode, storage, and retrieval. Unfortunately, aging research has focused almost exclusively on encoding and retrieval processes, largely ignoring the third critical process related to storage. For a memory to become resistant to forgetfulness, it must be consolidated in the brain. Consolidation was long seen as a process in which memories were made stable, made resistant to change. Now, we see consolidation as an active process, something that keeps memories 'restless and alive.' Recent research has indicated that true episodic memories are not passive reproductions of the past but rather dynamic and ever-changing. This view of consolidation as an active process that continuously works on our episodic memories also makes it more likely that aging plays a role in this process. The goal of this study is to develop a comprehensive model that explains why the ability to form new episodic memories declines with increasing age. The aim is to include both encoding, consolidation, and retrieval processes in the model. A large number of participants of different ages will undergo a series of memory experiments and brain imaging. An important point is that we are using a new strategy to construct memory tasks that are personal and naturalistic, as participants themselves will create associations related to the stimuli that will be used in the memory experiments. The research was delayed due to the COVID-19 situation, which imposed significant restrictions on participant testing, but we have still arrived at exciting results. For example, we have shown that changes in various structural features of the hippocampus are related to changes in memory function throughout life. Specifically, we observed that the volume and microstructure of different parts of the hippocampus could explain some of the age-related changes in the ability to recall previously learned information. We have also investigated this in relation to memory over longer time intervals than what is typically used in such studies and found that memory for things that happened 10 days earlier changes more with age than memory for what happened earlier the same day. Furthermore, we found that this is related to changes in how two different brain structures, namely the hippocampus and the striatum, communicate during learning in older participants. We have also shown that after learning, communication between the hippocampus and other brain areas, especially in the cortex, increases. This is probably due to early consolidation processes. Particularly interesting is that this upregulation of communication with the hippocampus does not seem to apply only to the brain areas that were involved in the original learning but involves most cortical areas and networks. Recently, we have also seen that successful retrieval of future enduring vs. transient memories was supported by increased activity in a right medial prefrontal and ventral parietal area. Individual differences in activation, as well as the subjective vivid feeling of memories during encoding, were positively related to individual differences in memory performance after 6 days. The results point to a unique aspect of brain activity supporting long-term memories, in that the activity during memory retrieval even after 12 hours of consolidation contains information about the potential for memories to endure over a long time.

Episodic memory function on average declines rather dramatically with higher age. While this age-decline in episodic memory can have multiple causes, research to date has focused almost entirely on two basic memory processes: encoding and retrieval. This had led to the third critical process - consolidation - largely being ignored. This is paradoxical, as there are theoretical and empirical reasons to expect that also changes in consolidation are important in aging. Thus, we lack knowledge about how consolidation of episodic memories decline in aging. The main objective of the current proposal is to provide this missing piece of the puzzle of age-related memory decline, through: (1) Develop an elaborate model of episodic memory deficits in aging by use of recent advances in memory consolidation theory. (2) Uncover how structural and functional brain changes affect episodic memory consolidation in general by using aging as a model for change. To achieve these, we propose to combine novel experimental cognitive paradigms with neuroimaging in a longitudinal large-scale attempt to directly test how age-related changes in consolidation processes in the brain impact episodic memory decline. This includes testing of more than 800 participants with structural and functional MRI on multiple occasions. A major R&D challenge is that consolidation of memories unfolds over time, and we propose to address this by studying consolidation-related brain activity over multiple time intervals, from seconds, to minutes, hours, weeks and months/ years. This has not previously been done. Equally important, we propose a new approach to study sleep-dependent memory consolidation by monitoring of spontaneously occurring memory reactivation as well as experimentally induced targeted memory reactivation. If successful, we believe this project has the potential to really advance theoretical and clinical models of memory decline in aging as well as the neuroscience of episodic memory per se.