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  • Writer's pictureEmine Topcu

Ageing and Memory - Part I

In the past half a century, the improvements in medicine caused a huge increase in life expectancy. With longer lives, we started to see illnesses that are mostly seen in late ages. Alzheimer’s disease is the first one that comes to mind because the memory impairments that come with it make it such a debilitating condition for both the patients and their families.

Image credit: Our World in Data

In the next couple of posts, I will not talk about illnesses but rather how memory is impacted in healthy people during the process of ageing. There are various terms used across the literature to define normal or better than normal ageing: “healthy,” “successful,” or “super” agers, to count a few (1–3). What happens to the brain during ageing that affects our memory? And what makes some of us healthy or super agers?

Ageing is generally used as synonymous with getting old; however, ageing starts the moment we are born. The brain changes begin before we are born and continue till we die. I recently read a very interesting article in Nature (4) about the development of the brain from pre-birth to till 100 years of age. According to this study, the gray matter volume (the region that mainly consists of cell bodies) in humans makes a peak around six years of age (4). This is not a typo! White matter (the region that mainly consists of the neurons’ axons), on the other hand, makes a peak around 29 years of age and starts a slight decrease afterwards. This decrease becomes more apparent around the age of 50. Our frontal lobe that is responsible for higher executive decisions does not complete its maturation until we are about 24-25 years old—vehicle insurance companies having a 24-age limit for certain discounts may not be random. But the general decline of brain volume starts even before the frontal lobe maturation is completed. This decline is not homogenous across all brain regions either. Hippocampus is an important region when it comes to episodic and spatial memory (5). The entorhinal cortex, which is the main cortical input to the hippocampus, reaches its peak volume at 23 years of age and starts decreasing afterwards. Is the change in brain volume the reason behind the memory decline?

There are multiple theories on what causes memory impairments. One of them is, in fact, the loss of brain volume (6). But memory is complicated. Different regions are responsible for various aspects of memory, and there are a lot of interactions necessary to learn and remember. For example, the hippocampus is an important region for both pattern separation and pattern completion (7). Pattern separation allows us to distinguish similar experiences (8). Pattern completion, on the other hand, enables us to remember things even with missing clues. A recent study found out that with ageing, an imbalance between pattern separation and completion causes confusion in the elderly (7). Impairment in associative memory with ageing is also shown by other studies (6), which is in line with declining pattern completion.

Another theory claims the decrease in processing speed is an important contributor to memory decline (6,9). The idea was brought decades ago and is still an active one today (9,10). In short, the speed of processing in the brain may not be fast enough for the cellular processes that need simultaneity or sequential processing to complete a memory task successfully (10). One of the reasons for slower processing speed can be due to deleted pathways, which causes less efficient alternative pathways to be used (6). The decrease in neurotransmitter release and their binding ability may also be a cause of the decrease in processing speed (Grady 2012). Moving away from the cellular level to the execution level, any memory test requiring speed in recall also shows a decrease with age (6).

The reserve hypothesis claims that the healthy agers start with healthier brains with higher reserves, to begin with (1). Some studies show differences in cross-sectional experimental designs (in which young and older adults of the same era are compared) and longitudinal designs (the same participants are studied for the duration of the study, sometimes spanning their lifetime) (1,4). These differences can be explained by higher reserves, but scientific support behind them is limited. Nevertheless, the regions of the brain that mature earlier being less vulnerable to functional decline later in life support this hypothesis (1).

Currently, it is widely accepted that all of these theories are valid, and they all contribute to memory impairments (6). Is this the end of the story? Is ageing a one-way street with a continuous decline in memory?

I will continue to talk about memory and ageing in my next post. Keep watching!


Blog by Emine Topcu


1. Bagarinao E, Watanabe H, Maesawa S, Kawabata K, Hara K, Ohdake R, et al. Reserve and Maintenance in the Aging Brain: A Longitudinal Study of Healthy Older Adults. eNeuro. 2022;9(1):1–10.

2. Nyberg L, Pudas S. Successful Memory Aging. Annu Rev Psychol. 2019;70:219–43.

3. Rowe JW, Kahn RL. Successful aging 2.0: Conceptual expansions for the 21st century. Journals Gerontol - Ser B Psychol Sci Soc Sci. 2015;70(4):593–6.

4. Bethlehem RAI, Seidlitz J, White SR, Vogel JW, Anderson KM, Adamson C, et al. Brain charts for the human lifespan. Nature. 2022;2022(February).

5. Li AWY, King J. Spatial memory and navigation in ageing: A systematic review of MRI and fMRI studies in healthy participants. Neurosci Biobehav Rev [Internet]. 2019;103(May):33–49. Available from:

6. Park DC, Festini SB. Theories of memory and aging: A look at the past and a glimpse of the future. Journals Gerontol - Ser B Psychol Sci Soc Sci. 2017;72(1):82–90.

7. Lee H, Wang Z, Tillekeratne A, Zeger S, Gallagher M, Knierim JJ, et al. Article Loss of functional heterogeneity along the CA3 transverse axis in aging Article Loss of functional heterogeneity along the CA3 transverse axis in aging. Curr Biol [Internet]. 2022;1–13. Available from:

8. Madar AD, Ewell LA, Jones M V. Pattern separation of spiketrains in hippocampal neurons. Sci Rep. 2019;9(1):1–20.

9. Shen Y, Zhou M, Cai D, Filho DA, Fernandes G, Cai Y, et al. CCR5 closes the temporal window for memory linking. bioRxiv [Internet]. 2021;606(March 2021):2021.10.07.463602. Available from:

10. Salthouse TA. The Procesing-Speed Theory of Adult Age Differences in Cognition. Psychol Rev. 1996;103(3):403–28.

11. Grady C. The cognitive neuroscience of ageing. Nat Rev Neurosci. 2012;13(7):491–505.


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