Dementia Biomarkers are Changing Alzheimer’s Disease Clinical Practice

Alzheimer’s disease (AD) is a devastating, incurable, neurodegenerative condition experienced by more than 600,000 Canadians.1 More than 95% of cases are sporadic and occur late in life, with pathophysiological hallmarks of accumulated amyloid-β (Aβ) peptide and neurofibrillary tangles of tau protein in the brain.2 Preclinical disease may be present for decades before the onset of clinical signs and symptoms which, once overt, typically progress over 8 to 10 years, ultimately leading to death from complications.2

DIAGNOSIS COMPLEXITIES
AD symptoms usually emerge after the age of 60 although people with certain rare genetic mutations may develop the disease earlier.3 Currently and historically, AD diagnosis is confirmed post-mortem through brain autopsy, or based on clinical symptoms, including cognitive testing, with a significant number of patients diagnosed when their disease has already advanced. A diagnosis of AD based on cognitive measures alone is only correct in 70% to 80% of cases. Even with imaging studies such as computed tomography (CT) and magnetic resonance imaging (MRI), or positron emission tomography (PET) the diagnosis might not be conclusive.3 

In Canada, national guidelines for the diagnosis of AD suggest that most screening and clinical workup be completed by a primary care physician (PCP), and that more advanced diagnostics require referral to specialty clinics.4 However, studies suggest that less than half of those living with dementia receive a diagnosis, and many progress while they wait.5 While clinical criteria have been the primary basis for the diagnosis of AD dementia, biological definitions of AD, based on biomarkers of Aβ deposition, pathologic tau, and neurodegeneration, have been used in research settings.4 

NEW ERA OF DISEASE MODIFYING THERAPIES

Although historically, only symptomatic therapy is available and there have been no disease modifying treatment options for AD, a number of drugs aimed at modifying the disease in its earlier stages (i.e. mild cognitive impairment (MCI) due to AD and mild AD dementia) are currently under investigation. This indicates that the treatment approach for patients in early stages of the disease should be different from the approach for those in later stages.6,7,8 

As additional treatments are approved, there are more treatment options for managing this disease.  However, no national/provincial health-care system is ready to deliver these therapies to more than a fraction of patients who might be eligible as existing health system capacity constraints and the need for biomarker-driven diagnostics to confirm DMT eligibility are concerning.9

ROLE OF BIOMARKERS

Aβ-targeted therapies require detection of Aβ aggregation and here is where biomarkers are of enormous use in Alzheimer’s as they are objective measures, they are reproducible, and they are independent of the clinician’s judgment. Aβ aggregation evidence can be detected using cerebrospinal fluid (CSF) or positron emission tomography (PET) to determine treatment eligibility.12-16 A blood biomarker as evidence of Alzheimer’s pathology might also become available in the future.

These modalities have advantages and disadvantages in terms of cost, access, and acceptability. Upscaling access to CSF testing should be more cost-effective than PET and could provide evidence for both amyloid and tau pathology. CSF testing requires lumbar puncture capacity with trained nursing or medical staff, and laboratory staff and equipment for analysis and interpretation. Amyloid PET requires scanner and tracer availability, nuclear medicine physicians, and is expensive. 

Unfortunately, low numbers of dementia specialists and limited access to imaging lengthen wait times for such services in Canada.17 It was highlighted in the recent Canadian Conference of Dementia that, “expanding CSF biomarker access for Canadian patients while building stronger evidence for future blood-based biomarkers will lead to patients potentially eligible for DMTs receiving a diagnosis sooner”.18 

THE POWER OF KNOWING

Using a biomarker to provide timely diagnosis also brings other types of benefits for patients as shown in investigations done at University of British Columbia (UBC). Based on this research, many people who have Alzheimer’s disease want to know their diagnosis, and diagnostic clarity seems to be the major motivator in their decision to undergo diagnostic testing. Patients and care partners use biomarker results to their benefit in making positive lifestyle changes and planning for their futures. Learning biomarker results behind this diagnostic certainty produce positive feelings in patients and caregivers. Knowing can provide a sense of relief and allow patients and families to plan ahead, seek support, make practical decisions, learn how to adapt to the symptoms and maintain or even improve quality of life.19 Findings also demonstrated the value of early diagnosis in guiding medical care, even in the absence of disease-modifying therapeutics as substantial changes in clinical management were observed as a direct result of Alzheimer’s disease biomarker testing. Appropriate use of AD drug therapies increased for biomarker-positive patients, and decreased for biomarker-negative patients, and the use of biomarkers decreased the need for costly brain imaging diagnostics.20 

CONCLUSION

The key to transforming the life of people with Alzheimer’s disease is to diagnose as early as possible and to intervene with the right care plans. New diagnostics tests, like CSF biomarker testing, has the potential to streamline a patient’s journey, improving speed and access toward a confirmatory diagnosis, giving people with Alzheimer’s disease and their caregivers more time to plan and prepare for the future. By: Dr. Alonso Montoya | MSc, MD; Neuroscience Biomarkers Lead, Roche Diagnostics, Canada

By: Dr. Alonso Montoya | MSc, MD; Neuroscience Biomarkers Lead, Roche Diagnostics,

Canada [email protected]

Article References:

Roche Media Release (June 2023):

https://www.rochecanada.com/media/development-in-alzheimer

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19 Khushbu J, Yang D, Feldman HH., et al. What patients and caregivers do with knowledge of Alzheimer’s disease CSF test results: Findings from the IMPACT-AD BC study.

Alzheimer’s & Dementia, Volume18, IssueS5 Supplement: Biomarkers – Part 1, 20 December 2022 20 Yang D, Chambers C, Lee PE., et al. Drug therapy, imaging, and other aspects of clinical management change after Alzheimer’s biomarker testing in routine practice: Findings from the IMPACT-AD BC study.