In a recent study published in the journal Nature Aging, researchers highlighted the need to shift focus toward pre-dementia stages of Alzheimer’s disease (AD) to move towards a future where personalized medicine for AD will become available.
Perspective: Towards a future where Alzheimer’s disease pathology is stopped before the onset of dementia. Image Credit: Orawan Pattarawimonchai / Shutterstock
Background
AD is the most common cause of dementia and, subsequently, one of the major healthcare challenges of the 21st century, for which, at present, there is no curative treatment available.
Advancements in biomarkers for AD pathology have enabled estimating the number of people in pre-dementia stages of AD. Per some preliminary estimates, 69 million (M) patients suffer from mild cognitive impairment (MCI), and over 300M have preclinical AD.
The former is a prodromal stage of AD where cognitive deficits manifest but remain inadequate for a dementia diagnosis. In preclinical AD, patients do not experience any signs or symptoms of dementia. Nonetheless, there is an apparent need to delineate the concepts of AD from dementia because late diagnosis substantially compromises the quality of life of a patient and burdens the healthcare infrastructure and healthcare professionals (HCPs).
Therapeutic strategies that could even slightly delay the onset of dementia and the progression of AD in a timely fashion could considerably reduce the socioeconomic burden of the disease by empowering patients and their families to self-manage the disease.
Most importantly, such therapies could help rescue the brain, which usually becomes unfeasible when AD manifests as dementia. Fortunately, the window of opportunity to take preventive action is enormous because research has shown that AD takes 20 to 30 years to develop.
About the study
In the present study, researchers outlined the importance of AD-modulating drugs, lifestyle interventions, molecular diagnosis of AD via blood-based biomarkers, and digital and genetic tools. Additionally, they highlighted the need to invest in personalizing the risk profiles of patients to gather prognostic information on all relevant patient outcomes.
Furthermore, they recommended adopting an inclusionary approach where patients at high risk of developing AD remain engaged in their health and disease management journey, with easy and affordable access to healthcare facilities.
Overall, they described a futuristic approach in which patient-orchestrated AD care would help achieve a timely and precise diagnosis for preventing dementia among AD patients.
From AD prevention to diagnosis, prediction, and personalized care
Complementing pharmacological and non-pharmacological strategies, which are not mutually exclusive, are available for the treatment of AD. The former slows down the progression of symptoms effectively, but only when administered in the pre-dementia stages. For instance, aducanumab and lecanemab are two drugs with AD-modulating properties; however, several challenges hinder their integration into clinical care.
The broad portfolio of therapeutic targets for AD found in preclinical AD studies increasingly focuses on AD risk genes, including apolipoprotein E (ApoE). Studies have also identified 12 modifiable risk factors responsible for 40% of dementia risk, which have become attractive targets for lifestyle interventions.
In the future, with personalized medicine for AD, disease modulation will be associated with a specific type of pathology, and molecular diagnosis will be crucial. However, currently, standard diagnostic workup encompasses neuropsychological investigations of day-to-day activities.
Cognitive screening tests are available at memory clinics; for instance, Montreal Cognitive Assessment (MoCA) indicates cognitive functioning. In addition, data on the genetic determinants of AD is quickly increasing, suggesting that diagnostic workup of the future will incorporate genomics.
Computer-adapted, digital versions of paper-and-pencil tests will allow the extraction of more data points, save costs, shorten the administration time, and make the patient journey more patient-friendly. Also, tailored prognostic information and individualized risk predictions will be available to help identify patients who will benefit most from a specific preventive strategy.
However, the authors emphasized that all these endeavors would require the active involvement of patients from an early stage. They may begin dementia risk assessment at home; later, HCPs could accurately predict the disease stage and make a molecular diagnosis. Also, they could identify individuals who would benefit from personalized prevention strategies.
However, throughout the patient journey, educating HCPs to optimally navigate their patients and support a process of shared decision-making is a necessary pre-requisite. Another pre-requisite for patient-orchestrated personalized care is providing information to patients and their families about what to expect from diagnostic tests and the disease and disease trajectory.
Conclusions
In conclusion, the current study provides an outlook on a future with personalized medicine for AD where patients and HCPs would be actively involved in disease management through tailored combinations of lifestyle interventions and disease-modulating therapies. It would help timely target AD pathology that would delay or prevent the onset of dementia altogether.
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