Building a robust diagnostic pathway for Alzheimer’s Disease
To help tackle the rising burden of Alzheimer’s disease (AD), dementia services should be structured to keep people in better health for as long as possible. Lilly is calling on clinicians, payers and policymakers to place greater emphasis on practices and programs that can increase awareness and understanding of AD, support timely action when cognitive changes are first noticed and recognize the importance of an accurate diagnosis in early symptomatic AD.
We know that the hallmarks of AD can begin appearing in the brain about 20 years before the onset of clinical symptoms, and therefore hope lies in detecting and treating AD in its earliest stages, when it may be possible to slow disease progression. Research has shown that the use of biomarker testing combined with assessment of clinical symptoms is key to ensure the timely and accurate diagnosis of AD in those exhibiting initial symptoms of the disease.
Unfortunately, securing a formal diagnosis of AD can be a long and complicated process, and less than half of all AD patients will ever receive a diagnosis of their condition.
By improving understanding of the AD diagnostic pathway, we hope to empower key decision makers to recognize the value of innovation of AD diagnostics and ultimately support policy changes that can deliver more effective diagnostic strategies, improve patient outcomes, and foster a healthcare environment that is better equipped to address the complexities of AD.
GLOSSARY
Continuum: AD can be viewed as a continuum, which is often divided into three stages: 3,4
Preclinical AD
Prodromal AD (characterized by mild cognitive impairment)
Dementia due to AD (characterized by functional impairment)
Preclinical AD: The “silent” stage of AD, before the occurrence of clinical symptoms. 3
Mild cognitive impairment: Mild cognitive impairment is when a person starts to have problems with their memory or thinking. It can be a sign of a disease that will eventually cause dementia, but MCI does not necessarily lead to dementia because it can be caused by other conditions. 7
Amyloid plaques: The beta-amyloid protein involved in AD is formed from the breakdown of a larger protein called the amyloid precursor. In the Alzheimer’s brain, abnormal levels of this protein clump together to form amyloid plaques that disrupt cell function. 9
Tau neurofibrillary tangles: Tau is a protein that helps to stabilize the nerve cells in the brain. Abnormal forms of tau protein cling with other tau proteins inside the neuron and form ‘tangles’. 9,10
Cognitive changes: The earliest clinical signs of AD appear to be the subjective experience of memory decline, followed by subtle changes in higher-order cognitive functioning. The effects of cognitive decline in daily life can be captured in the performance of cognitively complex activities such as cooking, managing personal and financial paperwork, and keeping appointments. 11
Cognitive screening tools: Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) are the most commonly used methods in cognitive impairment detection. 13 MMSE is a brief 10-minute assessment of cognitive performance, and MoCA takes up to 15 minutes but has a slightly higher sensitivity to MCI. sup]13[/sup] These tests can assess a number of mental abilities including: memory, concentration and attention span, language and communication skills, orientation and visuospatial abilities. 14
Blood test: Blood tests are often arranged by GPs during the initial diagnostic assessment to exclude other causes of symptoms. 15
Functional assessments: Progressive loss in the ability to perform activities of daily living is a primary characteristic for diagnosing dementia. Functional tests assess basic daily functional abilities such as personal hygiene, feeding and instrumental daily abilities such as meal preparation, domestic chores, financial management. 16
A biological marker, or biomarker, is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes or pharmacological responses to a therapeutic intervention. 17 Biomarkers can identify amyloid plaques and tau fibrillary tangles to confirm the diagnosis of AD. 18
Lumbar puncture (or spinal tap): The collection of cerebrospinal fluid (CSF) via a thin needle inserted into the lower back to measure the levels of amyloid and tau proteins. CSF is considered a good source for biomarker development as it can mirror biochemical changes occurring in the brain. 20,21
Blood based biomarkers*: This diagnostic test requires the collection of blood, which is less invasive, likely less costly, and more feasible at the primary care levels where most individuals will present with cognitive symptoms. 22 Using both cognitive screening tests and blood-based biomarkers has the potential to improve the efficiency of AD diagnostic process and access to treatment, lead to better outcomes for individuals while reducing costs, as well as the need for more expensive (PET scans) or perceived invasive (CSF) specialist evaluations. 12,23,24
Magnetic resonance imaging (MRI) is a medical imaging procedure that utilizes a strong magnetic field and radio waves to produce three dimensional detailed anatomical images. It can effectively show shrinkage in specific area of the brain associated with AD pathology. 15,25
Computerized Tomography (CT) is an imaging technique that uses several X-rays to create detailed cross-sectional images of brain structure to support the identification of abnormalities. 26
Tau/Amyloid PET imaging: Both amyloid and tau PET scans may support a timely and accurate diagnosis of AD as they enable the detection of brain amyloid deposition and aggregated tau protein respectively. 27,28
REFERENCES
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13. Li X, Dai J, Zhao S, Liu W, Li H. Comparison of the value of Mini-Cog and MMSE screening in the rapid identification of Chinese outpatients with mild cognitive impairment. Medicine. 2018;97(22):10966.
14. NHS UK: Alzheimer’s disease diagnosis; 2021. Available at: https://www.nhs.uk/conditions/alzheimers-disease/diagnosis/. Last accessed: May 2024.
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17. Puntmann VO. How-to guide on biomarkers: biomarker definitions, validation and applications with examples from cardiovascular disease. Postgraduate medical journal. 2009;85(1008):538–45.
18. Humpel C. Identifying and validating biomarkers for Alzheimer’s disease. Trends Biotechnol. 2011;29(1):26-32. doi: 10.1016/j.tibtech.2010.09.007.
19. Paczynski, et al. Alzheimer Disease Biomarkers in Clinical Practice: A Blood-Based Diagnostic Revolution. Journal of Primary Care & Community Health. 2022; 13(1-7).
20. Alzheimer’s Research UK. Why is a lumbar puncture used in Dementia? Available at: https://www.alzheimersresearchuk.org/news/why-is-a-lumbar-puncture-used-in-dementia/#:~:text=In%20recent%20years%2C%20research%20has,can%20be%20 measured%20in%20CSF. Last accessed: May 2024.
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28. Hampel H, et al. Designing the next-generation clinical care pathway for Alzheimer’s disease. Nat Aging. 2022;2(8):692-703
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