Early Alzheimer’s Diagnosis: Key to Better Care

September is World Alzheimer’s Month, a global campaign led by Alzheimer’s Disease International with the support of pharmaceutical companies involved in Alzheimer’s research. The campaign aims to raise awareness of the disease, which afflicts an estimated 416 million people worldwide, and challenge the stigma that persists around all types of dementia.

Though there is no cure for the disease, people with Alzheimer’s can receive personalized, multimodal care and support to delay deterioration of their functional status and quality of life and alleviate the burden imposed on their care partners (Emblad, 2021; Bayly, 2021; Xiang, 2024). Timely and accurate diagnosis is critical to maximize the efficacy of available interventions – but for most individuals, the diagnostic journey remains long, complex and costly (Alzheimer’s Disease International, 2021; Chiari, 2022; Juganavar, 2023).

In this post, we will explore the challenges associated with early Alzheimer‘s diagnosis, and the opportunities for pharmaceutical companies to support those impacted by the disease.

What is Alzheimer’s disease?

Alzheimer’s disease is a burdensome, life-limiting and ultimately fatal neurodegenerative disease that progresses along a continuum from a preclinical asymptomatic stage to mild cognitive impairment (MCI) to clinically overt dementia (Gustavsson, 2022; Anon., 2024). The pathophysiology of Alzheimer’s is complex and involves multiple mechanisms, including extracellular deposition of amyloid-β (Aβ) plaques and intracellular formation of neurofibrillary tangles (NFT) of tau, causing progressive neuronal loss and atrophy (Counts, 2017).

It has been shown that Aβ deposition can begin more than 20 years before symptom onset (Gordon, 2018), and that accumulation of NFT starts during the preclinical stage (Counts, 2017), when cognitive function appears normal (Anon., 2024). Subtle cognitive symptoms typically appear at the MCI stage, but are frequently unrecognized (Anon., 2024). Approximately 43% of people with MCI develop dementia due to Alzheimer’s disease within 5 years (Roberts, 2014) (Figure 1). As dementia becomes more severe, people require greater care, and develop complications such as pressure ulcers, infections, dysphagia, malnutrition and aspiration pneumonia – a leading cause of death among people with Alzheimer’s (Anon., 2024).

Figure 1. Biomarker and clinical changes across the AD continuum

Modified from Counts et al, 2017 (10).
Abbreviations: AD, Alzheimer’s disease; MCI, mild cognitive impairment.

Early Alzheimer’s disease diagnosis: Why do we need it?

If there is no cure for Alzheimer’s, why is early diagnosis important? Firstly, to inform personalized care plans that may allow people living with Alzheimer’s to preserve their independence and quality of life for longer. This mitigates the burden imposed on their care partners (Bayly, 2021), who play a key role throughout the disease course. Personalized care relies on pharmacological and non-pharmacological interventions aimed at (temporarily) relieving cognitive and non-cognitive symptoms (Alzheimer’s Association, n.d.; Emblad, 2021; Xiang, 2024) and on disease-modifying therapies (DMTs) able to slow down Alzheimer’s progression. Currently, of the eight drugs approved by the U.S. Food and Drug Administration (FDA) for Alzheimer’s, six are symptomatic medications for use in people with mild to severe dementia due to the disease, and two are DMTs for MCI or mild dementia (Alzheimer’s Association, n.d.; U.S. Food and Drug Administration, 2023 and 2024).

Once a conclusive diagnosis is made, affected people and their care partners can start seeking practical and emotional support, as well as legal and financial assistance. People diagnosed with early Alzheimer’s may also be eligible for enrollment into clinical trials.

Current challenges associated with Alzheimer’s disease diagnosis

For people with Alzheimer’s and their care partners, the journey can be long and dotted with obstacles. Stigma and lack of awareness, both among the public and healthcare providers, remain major barriers to diagnosis (Alzheimer’s Disease International, 2021). Underdiagnosis, misdiagnosis, and slow diagnosis are common (Lang, 2017; Alzheimer’s Disease International, 2021; Chairi, 2022; Gjøra, 2024), and often lead to delayed care. Indeed, diagnosis typically occurs at later stages and relies on a combination of multi-disciplinary investigations, including clinical examination, medical history assessment, cognitive testing, and brain imaging techniques (Juganavar, 2023).

Recent advances in neuroimaging and biomarker analysis have the potential to facilitate earlier and more accurate diagnoses. However, current tools have limitations that challenge their broader clinical use (Table 1). For example, while amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF)-based tests reduce the rate of misdiagnosis compared with no prior PET or cognitive tests alone (Rabinovici, 2019; Esquivel, 2022), their use requires specialized centers and personnel and comes with significant costs (Juganavar, 2023). Blood tests and machine learning models based on neuroimaging and biomarker data represent a step forward in the search for optimal non-invasive diagnostic tools, offering faster, more affordable, and more accessible options than other diagnostic tests (Juganavar, 2023; Anon., 2024; Quanterix, 2024). However, such technologies require additional validation before they can be routinely implemented in clinical practice.

Table 1. Diagnostic tools used in Alzheimer’s disease

Pharmaceutical companies are well-placed to support those impacted by Alzheimer’s disease

While much progress has been made in recent decades, further efforts are required to break the remaining barriers to early and accurate diagnosis of Alzheimer’s and provide support to people affected by the disease. Pharmaceutical companies, with the knowledge and resources to impact healthcare provision at every level, from disease awareness to drug development, can contribute in several ways:

Educating healthcare professionals and the public. This will be key to overcoming the stigma associated with and lack of awareness of the disease. Effective communication materials, targeted to specific audiences, can help inform these stakeholders around the challenges and needs of people with Alzheimer’s experience during their diagnosis and care journey.
Funding research into non-invasive, low-cost, and fast biomarker-based tests. Such tests may shorten the time from physiological onset to diagnosis and provision of adequate care. In 2022, the U.S. FDA cleared the first CSF diagnostic test based on the detection of Aβ40/Aβ42 (U.S. Food and Drug Administration, n.d.), and in 2024, it granted Breakthrough Device designation to two novel tests measuring p-tau217 levels in the plasma or blood (Quanterix, 2024; Roche Diagnostics, 2024). Used with other diagnostic evaluations, these tests can increase the accuracy of diagnosis and facilitate prompt clinical decision-making.
Leveraging more timely and accurate diagnostic technologies. More efficient screening of potential clinical trial participants will boost trial sizes and ensure that subject characteristics better represent the real-world Alzheimer’s population, thus increasing the statistical power of studies and the generalizability of results.
Continued investment in drug development. Accelerating the availability of safe and effective therapeutic options to delay Alzheimer’s progression and potentially cure the disease is key. While the track record for clinical trials in Alzheimer’s over the past two decades is disappointing (Jain, 2022), failures have shed light on the mechanisms underlying pathophysiology, leading to the development of the first approved DMTs and supporting the development of future treatments.

Towards a better future for everyone affected by Alzheimer’s disease

Alzheimer’s disease develops silently, starting decades before clinical symptoms manifest. Early diagnosis is therefore critical to ensure affected people receive adequate care to preserve, for as long as possible, their neurological function and wellbeing as well as the wellbeing of their care partners. Recent advances in biomarker and imaging research have streamlined Alzheimer’s diagnosis and have the potential to address the demand in screening, monitoring and treatment that is expected to increase in the near future with increased access to DMTs (Alzheimer’s Disease International, 2021). More accurate and earlier diagnosis will allow expansion of access to personalized care, support and treatment, enabling more people with Alzheimer’s and their care partners to make plans.

Clarivate’s Value Communication team helps life science companies articulate the benefits of innovative medical technologies to market access stakeholders in clear, impactful ways. We specialize in the development of robust and compelling value communication materials, including payer value stories, global value dossiers, objection handlers and publications. We have extensive experience supporting clients across the product journey and addressing knowledge gaps relative to non-clinical aspects (e.g., identification of barriers to adequate diagnosis and treatment) of a range of diseases including AD. To learn more about our capabilities and how we can support you, please get in touch here.

References

Alzheimer’s Association, n.d. FDA-Approved Treatments for Alzheimer’s. [Online] Available at: http://www.alz.org/media/Documents/alzheimers-dementia-fda-approved-treatments-for-alzheimers-ts.pdf [Accessed 29 August 2024].
Alzheimer’s Disease International, 2021. World Alzheimer Report 2021. [Online] Available at: http://www.alzint.org/resource/world-alzheimer-report-2021/ [Accessed 29 August 2024].
Anon., 2024. 2024 Alzheimer’s disease facts and figures. Alzheimer’s & Dementia, 20(5), pp. 3708-3821.
Bayly, M., 2021. Does early-stage intervention improve caregiver well-being or their ability to provide care to persons with mild dementia or mild cognitive impairment? A systematic review and meta-analysis. Psychology and Aging, 36(7), pp. 834-854.
Chiari, A., 2022. How long does it take to diagnose young-onset dementia? A comparison with late-onset dementia. Neurological Sciences, 43(8), pp. 4729-4734.
Counts, S. E., 2017. Biomarkers for the Early Detection and Progression of Alzheimer’s Disease. Neurotherapeutics, 14(1), pp. 35-53.
Emblad, S. Y. M., 2021. Creative Art Therapy as a Non-Pharmacological Intervention for Dementia: A Systematic Review. Journal of Alzheimer’s Disease Reports, 5(1), pp. 353-364.
Esquivel, R. N., 2022. Reducing misdiagnosis of Alzheimer’s Disease pathology utilizing CSF and amyloid PET. Alzheimer’s & Dementia, 18(S5).
Gjøra, L., 2024. Prevalence and Determinants of Diagnosed Dementia: A Registry Linkage Study Linking Diagnosis of Dementia in the Population-Based HUNT Study to Registry Diagnosis of Dementia in Primary Care and Hospitals in Norway. Journal of Alzheimer’s Disease, 99(1), pp. 363-375.
Gordon, B. A., 2018. Spatial patterns of neuroimaging biomarker change in individuals from families with autosomal dominant Alzheimer’s disease: a longitudinal study. The Lancet Neurology, 17(3), pp. 241-250.
Gustavsson, A., 2022. Global estimates on the number of persons across the Alzheimer’s disease continuum. Alzheimer’s & Dementia, 19(2), pp. 658-670.
Jain, R., 2022. A review of therapeutic failures in late-stage clinical trials. Expert Opinion on Pharmacotherapy, 24(3), pp. 389-399.
Juganavar, A., 2023. Navigating Early Alzheimer’s Diagnosis: A Comprehensive Review of Diagnostic Innovations. Cureus, 15(9).
Lang, L., 2017. Prevalence and determinants of undetected dementia in the community: a systematic literature review and a meta-analysis. BMJ Open, 7(2).
Oostveen, W. M. v., 2021. International Journal of Molecular Sciences, 22(4).
Quanterix, 2024. Quanterix Granted Breakthrough Device Designation from U.S. FDA for Blood-Based p-Tau 217 Test for Alzheimer’s Disease. [Online] Available at: http://www.quanterix.com/press-releases/quanterix-granted-breakthrough-device-designation-from-u-s-fda-for-blood-based-p-tau-217-test-for-alzheimers-disease/ [Accessed 29 August 2024].
Rabinovici, G. D., 2019. Association of Amyloid Positron Emission Tomography with Subsequent Change in Clinical Management Among Medicare Beneficiaries with Mild Cognitive Impairment or Dementia. Journal of the American Medical Association, 321(3), pp. 1286-1294.
Roberts, R. O., 2014. Higher risk of progression to dementia in mild cognitive impairment cases who revert to normal. Neurology, 82(4), pp. 317-325.
Roche Diagnostics, 2024. Roche granted FDA Breakthrough Device Designation for pTau217 blood test to support earlier Alzheimer’s disease diagnosis. [Online] Available at: http://diagnostics.roche.com/us/en/news-listing/2024/roche-granted-fda-breakthrough-device-designation-ptau217-blood-test-support-earlier-alzheimers-disease-diagnosis.html [Accessed 29 August 2024].
Salvadó, G., 2024. Disease staging of Alzheimer’s disease using a CSF-based biomarker model. Nature Aging, 4(5), pp. 694-708.
U.S. Food and Drug Administration, 2023. FDA Converts Novel Alzheimer’s Disease Treatment to Traditional Approval. [Online] Available at: http://www.fda.gov/news-events/press-announcements/fda-converts-novel-alzheimers-disease-treatment-traditional-approval [Accessed 29 August 2024].
U.S. Food and Drug Administration, 2024. FDA approves treatment for adults with Alzheimer’s disease. [Online] Available at: http://www.fda.gov/drugs/news-events-human-drugs/fda-approves-treatment-adults-alzheimers-disease#:~:text=The%20U.S.%20Food%20and%20Drug,studied%20in%20the%20clinical%20trials [Accessed 29 August 2024].
U.S. Food and Drug Administration, n.d. EVALUATION OF AUTOMATIC CLASS Ill DESIGNATION FOR Lumipulse G 13-Amyloid Ratio (1-42/1-40) DECISION SUMMARY. [Online] Available at: http://www.accessdata.fda.gov/cdrh_docs/reviews/DEN200072.pdf [Accessed 29 August 2024].
Xiang, C., 2024. Comparison of Cognitive Intervention Strategies for Individuals with Alzheimer’s Disease: A Systematic Review and Network Meta-analysis. Neuropsychology Review, 34(2), pp. 402-416.