The New Conceptualization of Alzheimer's Disease under the Microscope of Influential Definitions of Disease

Abstract

Background: According to its new conceptualization, Alzheimer's disease (AD) has preclinical and symptomatic phases, and biomarker abnormality justifies the diagnosis of the disease. Methods: The conceptual validity of AD is assessed on the basis of the disease definitions of T. Szasz, R.E. Kendell and J.G. Scadding, C. Boorse, K.W.M. Fulford and J.C. Wakefield, as well as of the DSM-5 classification system. Results: The new AD conceptualization could fit the Szaszian disease definition, provided that AD biomarkers reflected the pathological hallmarks of a singular disease, but it seems that they do not. Moreover, preclinical AD does not yield a biological disadvantage, being a central criterion for justifying the presence of a disease according to the disease definition of Scadding and Kendell. In addition, it remains unclear whether abnormality of biomarkers in elderly people embodies a statistical deviation from normal ageing and a pathological characteristic. Furthermore, not all stages of AD are related to experiences of failure of intentional doing, which is the criterion of the disease definition of Fulford, whilst the Wakefieldian harmful dysfunction and the DSM-5 mental disorder criteria are fulfilled only in the symptomatic phases of the disease course. Discussion: Our analytical endeavours unveiled weak sides and the fuzzy boundaries of the new conceptualization of AD. Future refinements of the criteria should address them so that the validity of the AD concept is increased.

Cerebrospinal Fluid BACE1 Activity and sAβPPβ as Biomarker Candidates of Alzheimer’s Disease

“…AD is currently undergoing a conceptual transformation from a clinicopathological to a clinicobiological entity [3]. Such an approach enables the identification of AD in its oligosymptomatic stage, which is commonly termed mild cognitive impairment due to AD (MCI-AD) [4-6], or even before the onset of symptoms (i.e., the pre clinical stage).…”

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

“…Although most authors acknowledged that biomarker information enhances diagnostic accuracy [14-24] and validity is strong in selected cohorts [17-21, 25, 26], the predictive value was debated [14-34]. 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].…”

“…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].…”

“…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].…”

A typology of clinical conditions

“…Indeed, Alexopoulous and Kurz think there is practical validity in defining preclinical states of AD, such as by its effect on protective behaviors across the lifespan. However, they propose using the term "advanced brain aging" instead of "preclinical AD" on the grounds that they think a biomarker-based conceptualization of AD is conceptually invalid (Alexopoulos & Kurz, 2015). Although they are correct that AD biomarkers should be sufficiently validated and accurately distinguish between AD dementia and normal aging, AD neuropathology has been shown in a substantial number of brains of people aged less than 30 years Braak, Thal, Ghebremedhin, & Del Tredici, 2011; although, to be fair, not all such people will necessarily go on to develop AD symptoms in their old age).…”