7. Final word

6.2. Disclosure of biomarker results

122 Alzheimer's Disease - The 21st Century Challenge

studies.

informed consent process.

the biomarkers are not validated.

6.3. Evidence-based disclosure practice

are also potential opportunities to further our understanding.

channelling of resources, and it also encourages healthy lifestyle change.

Disclosure of AD biomarker results is an important consideration in dementia trials. Study designs that reveal increased risk may facilitate willingness to participate [63]. People participate in studies because by knowing, they may potentially lower their risk, so they may give their time and effort [64]. Similarly investigators are more in favour of disclosing scan results to MCI than to healthy controls [65]. Communicating AD risk information has wideranging ethical, psychological, behavioural, and social implications. People have different views about whether or not they actually want to learn the results. Periodic assessments of mood and well-being, providing access to appropriate care if there are problems, and presence of a designate partner for support are important considerations for participation in

The practice in ADNI has been not to disclose biomarker results to participants. Yet being in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) study means that a participant is declaring that he has a positive amyloid PET scan. No disclosure would be needed in the A4 study if it was designed as a three-arm randomised control trial with normal controls. However this would require greater sample sizes escalating costs and complicating the

Although biomarker use had been limited to research, clinicians in tertiary care are often involved in biomarker research, and have an interest in the biomarker result to guide management of their patients. Before biomarkers were officially approved for routine clinical use, specialist clinicians were already applying biomarkers results informally in clinical practice with the informed consent of their patients [65]. It was openness for accumulating such experiences that drove thinking and enabled planning in biomarker validation studies. Clinicians are motivated to refer their patients for biomarker research studies, and patients are motivated to participate, when they can benefit from obtaining a copy of the results even if

The more opportunities there are to use biomarkers in the clinical setting, the more we are going to find cases of amyloid PET scans showing intermediate levels of amyloid in the brain, particularly as cases requiring biomarkers to improve the diagnostic work-up tend to present with some degree of diagnostic dilemma. While these cases are the hardest to diagnose, they

Both positive and negative biomarker results can benefit patients and families. A negative result brings relief, and unnecessary further clinical testing is avoided. A positive result when handled well enables early decision making when participants still have capacity, efficient

The problem with AD is not merely whether one has plaques in the brain or not, or whether people will want to know if they have the disease, but also how long do they have before they have to move into residential care, and if they do have the disease whether they can be eligible for costly drug treatment. One other consideration is what people will do once they get that Other than finding a cure, promoting healthy brain ageing is also important. This can be done by determining and promoting those factors that promote longevity and healthy brain ageing. Promotion involves staying mentally and physically active, staying socially engaged, and controlling cardiovascular risk factors like weight, blood pressure, cholesterol, and blood sugar, quitting smoking and having a balanced diet.

The need to be persistent, to innovate and to move forward is urgent despite numerous challenges. Whether we choose to address the conundrums or ignore them because of technical difficulties, the tsunami of the dementia epidemic will hit us in a few short years. Fortunately the dementia field has been very motivated. In spite of the numerous challenges in developing new models of understanding, diagnostic criteria, clinical markers, biomarkers, treatment, and improving diagnostic accuracy, the field is marching towards addressing, and intervening in, AD in its early stages.

Finally, attention to the nuances and caveats, and applying little tweaks in study designs can improve efficiency and study quality, reduce risk, and shed new insights.
