Earlier diagnosis is essential for better dementia care: conversations at AAIC 2022

By: Lennart Thurfjell, Chief Operating Officer (COO), and Greg Kingston, Chief Marketing Officer (CMO)
We recently attended the 2022 Alzheimer’s Association International Conference® (AAIC) and were excited to be back in person at this event, where we attended stimulating scientific sessions and had discussions with many researchers and neurologists trying to improve the care of patients with dementia. Across many of the presentations and exhibitor booths emerged a common theme: the importance of an earlier diagnosis for better patient outcomes, by being able to implement coordinated care plans, manage symptoms better, reduce costs, and postpone the need for long-term care in an assisted living facility.
The potential to realize these benefits is considered more likely with the development and introduction of disease-modifying drugs (DMDs), which can slow the disease trajectory. The earlier treatments such as DMDs can be administered, the more of a cumulative effect they can have, as described in the symposium sponsored by Eisai: “Defining meaningful benefits for patients with Alzheimer’s disease: timely diagnosis, the role of biomarkers, and interpreting treatment outcomes.”

Dementia screening for all

In the same Eisai-sponsored symposium, Dr. Malaz Boustani shared that 80% of people with moderate dementia and more than 95% of people with mild cognitive impairment (MCI) are not recognized within the current primary care system. Some of the key challenges to earlier detection include the delayed emergence of detectable symptoms and the perception by those affected that their symptoms are just due to older age or not troublesome enough to do something about. Then, by the time someone with cognitive or neuropsychological issues presents to their primary care physician (PCP) or neurologist, the underlying pathology, whether it’s amyloid or tau accumulation or structural changes in the brain, has been in progress for many years — sometimes as many as 10 to 20 years before symptoms become noticeable.
This understanding of how dementia manifests is not new. More than 10 years ago, Clifford Jack and colleagues presented a set of curves showing a model of the temporal relationship of pathophysiological processes underlying Alzheimer’s disease and the biomarkers that could be used to measure them. The dynamic processes start with the formation of β-amyloid (Aβ) plaques in the brain, while individuals are still cognitively normal. This is followed by neuronal dysfunction and neurodegeneration, indicated by increased cerebrospinal fluid (CSF) tau and cerebral atrophy on MRI. Next is impaired cognitive function, followed by decline in clinical function. Therefore, relying on noticeable symptoms of cognitive and functional impairment can delay dementia diagnoses.
Because the disease is already well underway by the time of symptoms, Dr. Boustani also advocated in his presentation for earlier screening across the general population. He suggested that easy-to-administer screening tools for everyone who is 65 years or older could identify patients who would benefit from further dementia diagnostic assessments such as imaging, neuropsychological testing, and a neurological exam. The idea of screening was supported by Dr. Alireza Atri in the symposium sponsored by Biogen: “Clinical Issues in Alzheimer’s Disease: Debates and Discussions About Diagnosis, New Therapies, and Healthcare Delivery.” In fact, he suggested that, in addition to cognitive testing, MRI should become part of standard of care, as “neither necessary nor sufficient but supportive” of a dementia diagnosis. Then, selective use of additional tests such as FDG-PET, amyloid-PET, and CSF could further refine the diagnosis.

Patient-focused collection of information

The concept of “neither necessary nor sufficient” applies to many of the tools used for dementia detection and diagnosis: cognitive tests, blood-based biomarkers, or imaging. Dementia is multifactorial, presentations are heterogeneous, and a single test is likely inadequate for an accurate diagnosis. Therefore, collection of all the information relevant to the patient’s situation is required to balance the strengths and limitations of each test, while at the same time, trying to minimize patient burden. This ties into the iterative approach to screening and further testing, allowing the outcomes at each step to inform the next.
Another key consideration to earlier dementia diagnosis presented at the conference is approaching each patient as an individual, within the context of established population-level evidence. Patient-centered care was at the core of many of the presentations, with considerable discussion around needing to acquire a multidimensional view of the patient’s situation and the outcomes that matter most to them: cognitive status, global or functional status, patient-reported and caregiver-reported outcomes, neuropsychiatric and behavioral outcomes, and socioeconomic outcomes. In addition, when presented with treatment options, patients and caregivers are asking for predictions of the potential benefits.
Meeting patient and caregiver expectations is becoming increasingly important with the approval and pending approval of new DMDs. Dr. Sharon Cohen presented evidence that patients want DMDs to help them preserve everyday functioning, maintain relationships and social connections, enjoy life, preserve a sense of identity, and alleviate symptoms. However, we currently lack good tools to measure most of these outcomes, and many are highly subjective. It was interesting to hear all clinicians presenting in the Biogen-sponsored symposium emphasize the importance of careful management of expectations when prescribing Aduhulem™, given the potentially small positive effect, increased burden of additional testing and imaging, and risk of side effects.

Are DMDs here to stay?

At the scientific session/panel discussion titled “Relationship between beta-amyloid (Ab) plaque reduction and clinical benefit: the rationale for aducanumab approval,” Dr. Yaning Wang, the Director of the Division of Pharmacometrics in the Office of Clinical Pharmacology at the US FDA and lead FDA reviewer for aducanumab (Aduhelm), was among the speakers. He presented a strong argument around the association between reduction in amyloid plaques and clinical benefit and also advocated for earlier treatment with DMDs such as Aduhelm to provide patients with the maximum benefit.
His conclusion: “We would approve aducanumab again if we had to redo it!”
The general feeling we perceived from the conference was that pharma and clinicians alike believe that anti-amyloid treatment is a viable option and other drugs in the pipeline, such as donanemab and lecanemab, will also be approved in the near future.
Being patient-focused also requires a balance between collecting additional information for a more confident diagnosis and increasing the patient and caregiver burden and stress. A possible solution presented by the speakers is to develop, validate, and use digital tools for early symptom detection and long-term monitoring of progression. At the same time, the industry needs to work toward establishing definitions for clinically meaningful changes in outcome measures that reflect the patients’ priorities.

Advancing the clinical care pathway

Bringing all of these concepts together, from early screening and detection and deciding which tests to pursue, to communicating with other clinicians and patients, is the idea of a new clinical care pathway that was presented in the Eisai-sponsored symposium.
Adapted from the presentation in the Eisai-sponsored symposium: “Defining meaningful benefits for patients with Alzheimer’s disease: timely diagnosis, the role of biomarkers, and interpreting treatment outcomes”

As more patient information is collected along this pathway, being able to collate it all in one location and make sense of it all is the next challenge. Software tools, such as our cDSI™ application, provide clinicians with a single source of information as well as AI-driven insights from that information. This will become more important with new developments, such as collecting and incorporating data from gait analyses and other apps to support a dementia analysis, that we heard about from some conference attendees. Given that one of the barriers to a timely and accurate Alzheimer’s diagnosis presented in the Lilly-sponsored symposium is a lack of physician confidence in differentiating between dementias and issuing a diagnosis, tools that support an accurate diagnosis are important.

Collaboration and communication between PCPs, radiologists, neurologists, other clinicians, and the patients are also essential for the proposed clinical care pathway, which was discussed during the Lilly-sponsored symposium “How Do We Optimize the Information Relay? A Team-Based Approach to Timely and Accurate Diagnosis of Alzheimer’s Disease.” Similar to reducing the burden on patients by making it easier to complete assessments online, digital tools offer opportunities for clinicians to enhance their communication. That is the approach we’ve taken with our new clinically focused cMRI™ and Dementia Differential Analysis reports as well as the Dementia for Patients report, which was designed to facilitate a discussion of the findings between the treating physician and their patients.
Dr. Linda Davis, in the Lilly-sponsored symposium “How Do We Optimize the Information Relay? A Team-Based Approach to Timely and Accurate Diagnosis of Alzheimer’s Disease,” admitted that primary care physicians might be reluctant to diagnose dementias early because of the limited treatment options and uncertainty around the next step in the patient’s care pathway.
Preparing healthcare systems for early diagnosis and a more collaborative approach to patient care
Moving from conference discussions to clinical care settings is the next step in facilitating earlier diagnoses. We view parallel paths to making this happen:
Dr. Boustani summarized it well in his presentation:
Since Combinostics was founded, we’ve focused on providing tools that enable earlier detection and diagnosis of dementias. It was encouraging to see the same focus at AAIC 2022, especially in the sessions sponsored by pharmaceutical companies. Earlier diagnosis leads to more appropriate care and, ultimately, better patient outcomes. For our part, we’re planning on using the feedback from booth visitors and insights from the symposia to continue developing and refining our applications to better support clinicians.
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