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

Abstract

Background The NIA-AA research framework proposes a purely biological definition of Alzheimer’s disease (AD). This implies that AD can be diagnosed based on biomarker abnormalities, irrespective of clinical manifestation. While this brings opportunities, it also raises challenges. We aimed to provide an overview of considerations regarding the disclosure of AD pathology before the onset of dementia. Methods A systematic literature review was conducted and reported according to PRISMA guidelines. We searched PubMed, Embase, APA PsycINFO, and Web of Science Core Collection (on 10 December 2020) for references on conveying AD biomarker results to individuals without dementia. Our query combined variations on the terms Alzheimer’s disease, disclosure, or diagnosis, preclinical or prodromal, and biomarkers. Two reviewers independently screened the resulting 6860 titles and abstracts for eligibility and examined 162 full-text records for relevance. We included theoretical articles in English, on communicating amyloid and/or tau results to individuals with mild cognitive impairment, subjective cognitive decline, or normal cognition. MAXQDA-software was used for inductive data analysis. Results We included 27 publications. From these, we extracted 26 unique considerations, which we grouped according to their primary relevance to a clinical, personal, or societal context. Clinical considerations included (lack of) validity, utility, and disclosure protocols. Personal considerations covered psychological and behavioral implications, as well as the right to (not) know. Finally, societal considerations comprised the risk of misconception, stigmatization, and discrimination. Overall, views were heterogeneous and often contradictory, with emphasis on harmful effects. Conclusions We found 26 diverse and opposing considerations, related to a clinical, personal, or societal context, which are relevant to diagnosing AD before dementia. The theoretical literature tended to focus on adverse impact and rely on common morality, while the motivation for and implications of biomarker testing are deeply personal. Our findings provide a starting point for clinicians to discuss biomarker-based diagnosis with their patients, which will become even more relevant in light of the conditional approval of a first disease-modifying drug for AD.

Blood-Based Biomarkers for Alzheimer’s Disease Diagnosis and Progression: An Overview

“…This is not only a limitation of our extensive review, which should gather as many novelties in the field as possible, but it represents a weakness of the AD research worldwide, overinflated with the enormous crowding of biomolecular data, yet showing scant ability in using this data as an orchestrated methodology to narrow the time between earliest symptoms or signs and diagnosis. A recent systematic review by van der Schaar et al proposed that a starting point for clinicians is to deepen the discussion about biomarkers, more than personal views or thoughts from societal contexts, particularly to diagnose AD before dementia [ 398 ]. This should make this review particularly important to accurately know what is currently discussed in the neurobiology of AD diagnosis.…”

Common Fatal Neurodegenerative Diseases Revisited: Beyond Age, Comorbidities, and Devastating Terminal Neuropathology There Is Hope With Prevention

“…It is absolutely no doubt that we should have a clear understanding of how to protect our populations before disclosure of aberrant protein pathology as discussed by van der Schaar et al ( 52 ).…”

Identifying interactions in omics data for clinical biomarker discovery using symbolic regression

“…Despite many decades of research, neurodegenerative diseases remain a major threat to human health and are a substantial cause of mortality. Alzheimer’s disease (AD) is the most common type of dementia, and currently no therapeutics can halt or significantly slow its fatal progression ( van der Schaar et al , 2021 ). Furthermore, short of an autopsy, there is no definitive way to diagnose AD, and it is in general impossible to predict who will develop the disease.…”