University of Waterloo: Mariam Malik and Her Insights #5

Hi everyone! I’m Mariam Malik and I am a recent graduate from the University of Waterloo, with Bachelor’s in Honours Health Sciences and Diploma in Gerontology. I am hoping to become a researcher either in health statistics or aging research. In my free time, I love reading and listening to audiobooks and I am always looking for recommendations!

Reviewed Article: Blood Biomarkers to Detect Alzheimer Disease in Primary Care and Secondary Care by Palmqvist et al.

Main Argument & Findings:

Alzheimer’s disease (AD) is one of the most common diagnosed disorders among older adults, with 1 in 5 women and 1 in 10 men diagnosed. Generally, when older adults first experience cognitive symptoms (confusion, memory issues, mood disturbances), they are seen by primary care providers (family doctors, general practitioners). If their symptoms warrant concern, older adults may be referred to secondary care providers to receive specialized care (hospitalists, specialist clinics). In both cases, AD has a misdiagnosis rate of 25-35%, signalling that current diagnostic tests for AD are clinically suboptimal. As a result, many older adults with AD experience continued disease progression due to delayed or missed diagnosis. The main diagnostic tests used for AD include positron emission tomography (PET) scans and cerebrospinal fluid (CSF) analysis. Primary care physicians lack the diagnostic tools needed to identify AD and must refer older adults to secondary care, which is itself constrained by limited resources.

A promising diagnostic tool that is less resource intensive and more cost effective is a blood test based on the ratio of plasma phosphorylated tau 217 (p-tau217) to non-p-tau217. A primary biomarker of AD is the presence of neurofibrillary tangles that accumulate in the brain, which form when naturally occurring tau protein becomes hyperphosphorylated. Among blood-based tau assays, phosphorylated tau at threonine 217 is more effective at distinguishing AD from other neurodegenerative disorders. Another primary biomarker of AD is the presence of amyloid beta plaques (Aβ). A blood test that measures the ratio of Aβ-42, a peptide strongly associated with AD pathology, to Aβ-40, a more abundant amyloid peptide. This ratio is used to derive the amyloid probability score 2 (APS2). This study aimed to determine whether p-tau217 and the combination of p-tau217 and APS2 were superior to current diagnostic tools for AD diagnosis in primary and secondary care settings.

In primary care, the diagnostic accuracy of the p-tau217 test and the combination of the p-tau217 test and the APS2 test was 88% and 92%, respectively. In secondary care, the diagnostic accuracy of the p-tau217 test and the combination of tests was both 88%. Overall, the p-tau217 test alone and the combination of APS2 and p-tau217 are highly accurate in detecting the abnormal brain pathology associated with AD. Although these tests show a high accuracy by themselves, how does it compare to a standard clinical evaluation that occurs in clinical settings?

In a standard clinical evaluation in primary care, AD was accurately diagnosed in only 58% of cases. However, when clinical evaluations were combined with APS2 and p-tau217 blood tests, diagnostic accuracy rose to 91%. In secondary care, a standard clinical evaluation accurately diagnoses AD in approximately 71% of cases. When combined with the blood tests, the diagnostic accuracy increases to 90%. These results demonstrate that the APS2 and p-tau217 blood tests are more accurate in diagnosing AD compared to current diagnostic tools used, including PET scans and CSF analysis.

The APS2 and p-tau217 blood tests are more time- and cost-effective, and more convenient for patients. These blood tests may replace more cumbersome diagnostic tools, although further research is needed to evaluate their use in other clinical care settings. Although blood tests exhibit high diagnostic accuracy, their results must be interpreted in a clinical context. AD can be asymptomatic for many years, and cognitive symptoms can be caused by an array of other neurodegenerative disorders. An incorrect interpretation of these results can lead to an under-diagnosis of common non-AD conditions. Ultimately, these blood tests show promise in accurately diagnosing patients with AD more conveniently, but further research needs to be conducted.

Importance for Youth:

Many older adults are misdiagnosed or diagnosed way too late because current tests are difficult to access, especially in primary care. This delay can be borne by families, including adult children or young caregivers balancing their own responsibilities. The p-tau217 test, the APS2, and many other diagnostic tools being trialled can facilitate faster and more accurate diagnosis. This can help reduce uncertainty and unnecessary stress. For youth, this research highlights how simple blood tests can replace delayed diagnostics and change how families experience AD.

What I Learned: 

What I learned is that blood-based tests for AD have potential for earlier diagnosis and prevention of AD. Once treatments are developed for AD, these tests can be used as a prevention strategy to eradicate AD. Tests such as p-tau217 and APS2 demonstrate that high diagnostic accuracy is achievable without invasive or resource-intensive procedures. This research shifted my thinking from diagnosis as a late-stage confirmation tool to a means of guiding more informed care decisions.

Citations: Palmqvist, S., Tideman, P., Mattsson-Carlgren, N., Schindler, S. E., Smith, R., Ossenkoppele, R., ... & Hansson, O. (2024). Blood biomarkers to detect Alzheimer disease in primary care and secondary care. JAMA, 332(15), 1245-1257. https://doi.org/10.1001/jama.2024.13855

LinkedIn: https://www.linkedin.com/in/mariammmalik/