The Ambivalence of Early Diagnosis – Returning Results in Current Alzheimer Research

Abstract

In the case of non-symptomatic volunteers, the result of the risk-benefit-assessment seems to be less distinctive. Given that disclosing results can, at least initially, cause severe distress and harm and taking into account that research examinations have a significantly increased risk of producing false-positive findings, we suggest to make use of a research-ethical "princple of caution" that supports a restrictive disclosure policy for the second group of potential study participants. This differentiated view on the benefits of disclosed findings in AD research is reflected in recommendations for the set-up of return of result processes.

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

“…Although most authors acknowledged that biomarker information enhances diagnostic accuracy [ 14 – 25 ] and validity is strong in selected cohorts [ 17 – 21 , 26 , 27 ], the predictive value was debated [ 14 – 36 ]. About half of the articles covered the difficulty to discern normal aging from latent AD [ 14 – 16 , 18 , 20 , 22 , 26 , 27 , 29 – 31 , 33 , 34 , 37 ], as the majority of cognitively healthy older persons with abnormal biomarkers never develop dementia [ 14 – 16 , 20 – 23 , 26 , 27 , 29 – 31 , 33 , 34 , 38 ], since AD is multi-factorial [ 16 , 18 , 26 , 27 , 31 , 35 ].…”

“…About half of the articles covered the difficulty to discern normal aging from latent AD [ 14 – 16 , 18 , 20 , 22 , 26 , 27 , 29 – 31 , 33 , 34 , 37 ], as the majority of cognitively healthy older persons with abnormal biomarkers never develop dementia [ 14 – 16 , 20 – 23 , 26 , 27 , 29 – 31 , 33 , 34 , 38 ], since AD is multi-factorial [ 16 , 18 , 26 , 27 , 31 , 35 ]. It was argued that procedures are not without burden or risk [ 14 , 16 , 18 , 20 , 21 , 23 , 24 , 34 ] and consequences of incorrectly labeling people as “patients in waiting” [ 34 ] could be severe for the individuals and relatives concerned [ 14 , 16 , 24 – 28 , 31 , 36 ]. Most authors concluded that biomarker criteria require final demonstration of validity in populations without dementia [ 14 – 23 , 26 , 27 , 30 , 31 , 33 – 36 , 39 ].…”

“…It was argued that procedures are not without burden or risk [ 14 , 16 , 18 , 20 , 21 , 23 , 24 , 34 ] and consequences of incorrectly labeling people as “patients in waiting” [ 34 ] could be severe for the individuals and relatives concerned [ 14 , 16 , 24 – 28 , 31 , 36 ]. Most authors concluded that biomarker criteria require final demonstration of validity in populations without dementia [ 14 – 23 , 26 , 27 , 30 , 31 , 33 – 36 , 39 ].…”

“…Clinical utility was contested, mainly due to the absence of a disease-modifying therapy [ 14 – 16 , 18 , 20 , 21 , 23 – 25 , 27 , 28 , 31 , 34 – 36 , 38 , 40 ], and limited effectiveness of symptom suppressing medications, which has not been demonstrated in predementia stages of AD [ 21 , 24 , 40 ]. However, several authors suggested lifestyle interventions could delay cognitive impairment [ 14 , 16 , 17 , 21 – 32 , 34 , 36 ], although evidence on their effectiveness remains inconclusive [ 14 , 15 , 21 , 31 , 36 ], and according to some, such health improvements should be pursued regardless of one’s biomarker status [ 16 , 23 , 31 ]. 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 – 25 , 27 , 28 , 32 , 35 ].…”

Identifying Patterns in Signs and Symptoms Preceding the Clinical Diagnosis of Alzheimer’s Disease: Retrospective Medical Record Review Study and a Nested Case-control Design

“…Given the rise in morbidity and mortality of AD and the devastating effect of worsening cognitive impairment, providing GPs with a predictive model for earlier detection and timely intervention is essential. This would minimise the occurrence of misdiagnosis, which is often emphasised by the critics of early diagnosis (20), who call for "research principle of caution" that supports a restrictive disclosure, as the benefit of early assessment outweighs the potential adverse effect. The model will also support the current diagnostic criteria.…”