Prodromes and Preclinical Detection of Brain Diseases: Surveying the Ethical Landscape of Predicting Brain Health

Abstract

The future of medicine lies not primarily in cures but in disease modification and prevention. While the science of preclinical detection is young, it is moving rapidly. Preclinical interventions offer hope to decrease the severity of a disease or delay the development of a disorder. With such promise, the research and practice of detecting brain disorders at a preclinical stage present unique ethical challenges that must be addressed to ensure the benefit of these technologies. Direct brain interventions have the potential to impact not just what a patient has but who they are and who they could become. Further, receiving an assessment for a preclinical or prodromal state has potential to impact perceptions about capacity, autonomy and personhood and could become entangled with stigma and discrimination. Exploring ethical issues alongside and integrated into the experimental design and research of these technologies is critical. This review will highlight ethical issues attendant to the current and near future states of preclinical detection across the life span, specifically as it relates to autism spectrum disorder (ASD), schizophrenia, and Alzheimer’s disease.

Considerations regarding a diagnosis of Alzheimer’s Disease before dementia: a systematic review

“…Many discussed the difficulty to discern normal aging from latent AD [14-16, 18, 20, 22, 25, 26, 28-30, 32, 33, 35], as the majority of cognitively healthy elderly with abnormal biomarkers never develop dementia [14-16, 20-23, 25, 26, 28-30, 32, 33, 36], since AD is multi-factorial [16, 18, 25, 26, 30, 34]. It was argued that procedures are not without burden or risk [14, 16, 18, 20, 21, 23, 24, 33] and consequences of incorrectly labeling people as ‘patients in waiting’ [24, 33] could be severe [14, 16, 24-27, 30]. Most authors concluded that biomarker criteria require final demonstration of validity in populations without dementia [14-23, 25, 26, 29, 30, 32-34, 37].…”

“…Clinical utility was contested, mainly due to the absence of a disease-modifying therapy [14-16, 18, 20, 21, 23, 24, 26, 27, 30, 33, 34, 36, 38], and limited effectiveness of symptom suppressing medications, which has not been demonstrated in predementia stages of AD [21, 24]. On the other hand, several authors suggested lifestyle interventions could delay cognitive impairment [14, 16, 17, 21-31, 33], although evidence on their effectiveness remains inconclusive [14, 15, 21, 30], and according to some, such health improvements should be pursued regardless of one’s biomarker status [16, 23, 30].…”

“…On the other hand, several authors suggested lifestyle interventions could delay cognitive impairment [14, 16, 17, 21-31, 33], although evidence on their effectiveness remains inconclusive [14, 15, 21, 30], and according to some, such health improvements should be pursued regardless of one’s biomarker status [16, 23, 30]. Lastly, it was argued that early detection can improve patient care, e.g., by offering an explanation for concerns, anticipating medical needs, and facilitating access to support [14, 16, 18, 19, 22-24, 26, 27, 31, 34]. Nonetheless, others did not consider biomarker information medically meaningful [15, 16, 20-25, 28-31].…”

“…Many papers addressed the need for guidance regarding who to test, what findings signify, whether to disclose and how [17, 18, 20-22, 27, 30, 35-37]. Knowledge from the fields of oncology and genetic testing may offer a good starting point [14, 20, 23, 26, 27, 29, 35-37].…”

“…Many papers addressed the need for guidance regarding who to test, what findings signify, whether to disclose and how [17, 18, 20-22, 27, 30, 35-37]. Knowledge from the fields of oncology and genetic testing may offer a good starting point [14, 20, 23, 26, 27, 29, 35-37]. The literature referred to development of standardized processes and materials for disclosing biomarker levels in prevention trials [17, 29, 31, 35, 36], but reported ‘a complete lack of studies in a clinical setting’ [17].…”