Preclinical Alzheimer’s disease: Definition, natural history, and diagnostic criteria

By Bruno Dubois, Harald Hampel, Howard H. Feldman, Philip Scheltens, P. Aisen, S. Andrieu, H. Bakardjian, Habib Benali, Lars Bertram, Kaj Blennow and 25 more. Alzheimer's & Dementia, 2016

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During the past decade, a conceptual shift occurred in the field of Alzheimer's disease (AD) considering the disease as a continuum. Thanks to evolving biomarker research and substantial discoveries, it is now possible to identify the disease even at the preclinical stage before the occurrence of the first clinical symptoms. This preclinical stage of AD has become a major research focus as the field postulates that early intervention may offer the best chance of therapeutic success. To date, very little evidence is established on this “silent” stage of the disease. A clarification is needed about the definitions and lexicon, the limits, the natural history, the markers of progression, and the ethical consequence of detecting the disease at this asymptomatic stage. This article is aimed at addressing all the different issues by providing for each of them an updated review of the literature and evidence, with practical recommendations.

Subfields: Neurology, Physiology, Psychiatry and Mental health

View Paper: https://www.semanticscholar.org/paper/272d24317def219cbac05581a1c5b0c4281af480

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Citations in the corpus

NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease (2018, positive): “Preclinical AD in IWG 2016 [15] defines a CU individual with an abnormal Ab biomarker and normal tau (A1T2) as “at risk for AD, asymptomatic A1” and one with A2T1 as “at risk for AD, asymptomatic T1”.”
Transcranial magnetic stimulation of the precuneus enhances memory and neural activity in prodromal Alzheimer's disease (2018, methodology): “Patients' recruitment was performed according to current diagnostic criteria for prodromal AD (Dubois et al., 2016), referring to the early symptomatic phase of AD, characterized by episodic memory loss in the presence of AD pathology as supported by CSF or imaging biomarker evidence.”
Comprehensive Review on Alzheimer’s Disease: Causes and Treatment (2020, background): “This stage is characterized by mild memory loss and early pathological changes in cortex and hippocampus, with no functional impairment in the daily activities and absence of clinical signs and symptoms of AD [1,29,30].”
Diagnosis of Early Alzheimer's Disease: Clinical Practice in 2021 (2021, neutral): “…for diagnosing patients with preclinical AD, as there is no way to ascertain whether the hypometabolism is directly related to AD pathology (73); however, clinicians may refer patients with more established symptomatology for an FDG-PET scan to identify regions of glucose hypometabolism…”
Alzheimer’s disease prevention: from risk factors to early intervention (2017, background): “The criteria for AD diagnosis have been revised extensively, and experts agree that the hallmark pathological criteria include increased levels of amyloid-beta (Aβ) peptide, which is deposited extracellularly in diffuse and neuritic plaques, and hyperphosphorylated tau (p-tau), a microtubule assembl”