The key's the hippocampus

Graham, a well-educated elderly gentleman, appears more forgetful than usual. Family and friends have noticed these changes and raised their concerns with professionals. Graham will likely be initially assessed using cognitive pen-and-paper tests, such as the Mini-Mental State Examination (MMSE) or Addenbrooke's Cognitive Examination III (ACE-III). Due to Graham's high intelligence, he is likely to be skilled at masking his decline. His mild cognitive impairment (MCI) may therefore go undetected with these measures.

Failing to detect this MCI means that Graham may go months, perhaps even years, until he or his family seek another consultation. By this time, his clinical symptoms would have progressed considerably due to the neurodegenerative nature of Alzheimer's Disease (AD), making detection now inevitable. This delayed detection means that any lifestyle changes which could have slowed Graham's decline will be less effective (Alzheimer's Association, 2019). His prognosis will not be a promising one.

Many readers may be familiar with this situation. AD has been identified as a global health priority by the World Health Organisation due to its prevalence, impacts, and lack of disease-modifying treatments (Lane et al., 2017). AD can change a person's behaviour and eat away at their memories, and seeing a family member slowly becoming unrecognisable can be brutal. Catching this decline early is crucial to enable lifestyle changes and pharmaceutical interventions as well as for Graham to be a more active member in planning his future.

For this to happen, there needs to be a change in the way we detect and diagnose AD. Here, I argue there is an over-reliance on flawed global cognition tests. With the advances in research into more specialised cognitive assessments, there is hope that this cognitive decline can be detected before considerable clinical symptoms present.

The current route, and an alternative

Small changes to a loved one's memory can initially be dismissed as someone being forgetful. These situations becoming more frequent and more worrying is often the prompt for seeking advice from professionals.

Initial triage tests such as the MMSE and ACE-III will likely be performed in a 10-minute surgery by GPs or at a person's bedside in a hospital. This is problematic in itself – the short time frame means significant amnestic decline could be missed if professionals rely too heavily on these tests. Systematic reviews have also found that tests such as the MMSE have very poor diagnostic utility for AD (Arevalo-Rodriguez et al., 2015), especially in the early stages of MCI, because their content relies heavily on general knowledge and verbosity.

A more promising diagnostic route would move away from these global tests of cognition and focus on the neurobiology underlying AD. Increased hippocampal atrophy characterises the early stages of AD, and significantly correlates with performance in memory tasks (Jahn., 2022). Thus, tests which assess a patient's hippocampal functioning – such as spatial and episodic memory tests (Maguire et al., 1996; Tulving, 1983) – should be able to detect this early damage.

One such test battery is the CANTAB (Égerházi et al., 2007) which assesses participants' cognitive functioning, including their spatial and episodic memory. AD participants performed significantly worse on all measures compared to both healthy participants and the MCI group. Another such test with considerable diagnostic utility is the 4 Mountains Test (4MT) (Hartley et al., 2007). By assessing allocentric spatial memory, the 4MT can significantly differentiate mild AD patients from healthy controls and predict the transition from MCI to AD with 93% accuracy (Bird et al., 2010; Wood et al., 2016).

Let's go back to Graham. How might his diagnostic experience differ if clinicians assessed his performance on hippocampal-dependent tests? By specifically targeting the function of his hippocampus, Graham will score low, unable to mask his cognitive decline. This earlier detection will enable Graham to make lifestyle changes that could slow the progression of his AD, such as increasing his level of social embeddedness and partaking in more physical exercise (Erickson et al., 2011; Ertel et al., 2008). These changes could preserve a greater degree of Graham's brain functioning and subsequently enable a greater quality of life for him. It will also allow his family to prepare better for the future and allow Graham to be a more active member in making decisions about his future care.

Barriers to change

Hippocampal-dependent memory tests do have their own limitations. For instance, many spatial memory tests (e.g., path-integration) rely on navigational tools such as virtual reality equipment, which are limited and not always available or standardised across facilities (Coughlan et al., 2018). With this new equipment, there is the need for further specialist training, which comes at an additional expense.

Also, for these tests to detect AD earlier, we need to test people before they present with considerable clinical symptoms. The NHS workforce does not have the capacity to implement such widescale diagnostic testing. As is the case with many proposed changes to healthcare, there is a need for increased funding, training, and accessibility of equipment.

Let's remember, though, that Alzheimer's is a debilitating neurodegenerative disease which causes loved ones to forget us and to become unrecognisable as the person they once were. Despite recent promising pharmaceutical advances, the majority of current treatment options fail to produce significant clinical improvements (Khoury & Grossberg, 2020; Imbimbo et al., 2020). In this context, there's a strong argument for healthcare providers to invest in the technology and training that will enable hippocampal-dependent memory tests to be included in their battery of tests. This may be the best way to detect more cases earlier, so that effective lifestyle changes can be made to reduce the devastating impact of this disease.

• Charlotte Ash is a Trainee Psychological Wellbeing Practitioner with a specific interest in older people's mental health.

References

Alzheimer's Association. (2019). 2019 Alzheimer's disease facts and figures. Alzheimer's & Dementia, 15(3), 321-387.

Arevalo‐Rodriguez, I., Smailagic, N., i Figuls, M. R., Ciapponi, A., Sanchez‐Perez, E., Giannakou, A., ... & Cullum, S. (2015). Mini‐Mental State Examination (MMSE) for the detection of Alzheimer's disease and other dementias in people with mild cognitive impairment (MCI). Cochrane Database of Systematic Reviews, (3).

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Ertel, K. A., Glymour, M. M., & Berkman, L. F. (2008). Effects of Social Integration on Preserving Memory Function in a Nationally Representative US Elderly Population. American Journal of Public Health, 98(7), 1215-1220.

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Tulving, E. (1983). Elements of Episodic Memory. Oxford University Press.

Wood, R. A., Moodley, K. K., Lever, C., Minati, L., & Chan, D. (2016). Allocentric Spatial Memory Testing Predicts Conversion from Mild Cognitive Impairment to Dementia: An Initial Proof-of-Concept Study. Frontiers in neurology, 7, 215.