Clinical diagnosis of Alzheimer's disease: recommendations of the International Working Group

Dubois, Bruno; Villain, Nicolas; Frisoni, Giovanni B.; Rabinovici, Gil D.; Sabbagh, Marwan; Cappa, Stefano F.; Bejanin, Alexandre; Bombois, Stéphanie; Epelbaum, Stéphane; Teichmann, Marc; Habert, Marie Odile; Nordberg, Agneta; Blennow, Kaj; Galasko, Douglas; Stern, Yaakov; Rowe, Christopher C.; Salloway, Stephen; Schneider, Lon S.; Cummings, Jeffrey L.; Feldman, Howard

doi:10.1016/s1474-4422(21)00066-1

Cited by 441 publications

(323 citation statements)

References 114 publications

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“…There is a clinical interest in assessing SM in the most accurate possible way. The latest clinical diagnostic guidelines for Alzheimer's disease discourage the use of available biomarkers as the sole diagnostic features at the pre-clinical stage (Dubois et al, 2021). It is thus of central importance to explore alternative methodological routes that can help identify subtle changes indicative of early stage neurodegeneration.…”

Section: Introductionmentioning

confidence: 99%

Serial Recall Order and Semantic Features of Category Fluency Words to Study Semantic Memory in Normal Ageing

Marco

Blackburn

Venneri

2021

Front. Aging Neurosci.

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Background: Category Fluency Test (CFT) is a common measure of semantic memory (SM). Test performance, however, is also influenced by other cognitive functions. We here propose a scoring procedure that quantifies the correlation between the serial recall order (SRO) of words retrieved during the CFT and a number of linguistic features, to obtain purer SM measures. To put this methodology to the test, we addressed a proof-of-concept hypothesis whereby, in alignment with the literature, older adults would show better SM.Methods: Ninety participants (45 aged 18–21 years; 45 aged 70–81 years) with normal neurological and cognitive functioning completed a 1-min CFT. SRO was scored as an ordinal variable incrementing by one unit for each valid entry. Each word was also scored for 16 additional linguistic features. Participant-specific normalised correlation coefficients were calculated between SRO and each feature and were analysed with group comparisons and graph theory.Results: Younger adults showed more negative correlations between SRO and “valence” (a feature of words pleasantness). This was driven by the first five words generated. When analysed with graph theory, SRO had significantly higher degree and lower betweenness centrality among older adults.Conclusion: In older adults, SM relies significantly less on pleasantness of entries typically retrieved without semantic control. Moreover, graph-theory metrics indicated better optimised links between SRO and linguistic features in this group. These findings are aligned with the principle whereby SM processes tend to solidify with ageing. Although additional work is needed in support of an SRO-based item-level scoring procedure of CFT performance, these initial findings suggest that this methodology could be of help in characterising SM in a purer form.

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Section: Introductionmentioning

confidence: 99%

Serial Recall Order and Semantic Features of Category Fluency Words to Study Semantic Memory in Normal Ageing

Marco

Blackburn

Venneri

2021

Front. Aging Neurosci.

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“…For instance, the predicted rise of patients suffering from Alzheimer’s disease (AD) during the upcoming decades demands a reliable, fast and non-invasive diagnostics method [ 110 ]. Although diagnosing AD becomes more and more based on specific biomarkers, clinical (neuropsychological) assessments combined with magnetic resonance imaging or positron emission tomography are often required for making actual reliable diagnoses [ 111 , 112 , 113 ]. The latter methods are time-consuming, invasive and are unreliable to detect early-stage AD.…”

Section: Application Examplesmentioning

confidence: 99%

Tackling Stereochemistry in Drug Molecules with Vibrational Optical Activity

et al. 2021

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Chirality plays a crucial role in drug discovery and development. As a result, a significant number of commercially available drugs are structurally dissymmetric and enantiomerically pure. The determination of the exact 3D structure of drug candidates is, consequently, of paramount importance for the pharmaceutical industry in different stages of the discovery pipeline. Traditionally the assignment of the absolute configuration of druggable molecules has been carried out by means of X-ray crystallography. Nevertheless, not all molecules are suitable for single-crystal growing. Additionally, valuable information about the conformational dynamics of drug candidates is lost in the solid state. As an alternative, vibrational optical activity (VOA) methods have emerged as powerful tools to assess the stereochemistry of drug molecules directly in solution. These methods include vibrational circular dichroism (VCD) and Raman optical activity (ROA). Despite their potential, VCD and ROA are still unheard of to many organic and medicinal chemists. Therefore, the present review aims at highlighting the recent use of VOA methods for the assignment of the absolute configuration of chiral small-molecule drugs, as well as for the structural analysis of biologics of pharmaceutical interest. A brief introduction on VCD and ROA theory and the best experimental practices for using these methods will be provided along with selected representative examples over the last five years. As VCD and ROA are commonly used in combination with quantum calculations, some guidelines will also be presented for the reliable simulation of chiroptical spectra. Special attention will be paid to the complementarity of VCD and ROA to unambiguously assess the stereochemical properties of pharmaceuticals.

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“…Additionally, the routine medical practice—based mostly on clinical and neuropsychological assessments in vivo—makes it possible to diagnose merely probable or possible AD [ 14 ]. Attempts have been made in the last few years to get to an in vivo neuropathological diagnosis of the disease, independent from the clinical symptoms [ 15 ]; however, the latest recommendation is to opt of a comprehensive approach, encompassing both the clinical assessment and in vivo neuropathological evaluation [ 16 ]. The goal is to diagnose AD as early as possible, in the prodromal phase (Mild Cognitive Impairment), when patients harbor pre-symptomatic pathological changes but maintain good brain functionality, in order to make use of treatments able to counteract or delay the appearance of symptoms [ 17 ].…”

Section: Alzheimer’s Disease and The Quest For Biomarkersmentioning

confidence: 99%

Blood-Based Biomarkers of Neuroinflammation in Alzheimer’s Disease: A Central Role for Periphery?

et al. 2021

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Neuroinflammation represents a central feature in the development of Alzheimer’s disease (AD). The resident innate immune cells of the brain are the principal players in neuroinflammation, and their activation leads to a defensive response aimed at promoting β-amyloid (Aβ) clearance. However, it is now widely accepted that the peripheral immune system—by virtue of a dysfunctional blood–brain barrier (BBB)—is involved in the pathogenesis and progression of AD; microglial and astrocytic activation leads to the release of chemokines able to recruit peripheral immune cells into the central nervous system (CNS); at the same time, cytokines released by peripheral cells are able to cross the BBB and act upon glial cells, modifying their phenotype. To successfully fight this neurodegenerative disorder, accurate and sensitive biomarkers are required to be used for implementing an early diagnosis, monitoring the disease progression and treatment effectiveness. Interestingly, as a result of the bidirectional communication between the brain and the periphery, the blood compartment ends up reflecting several pathological changes occurring in the AD brain and can represent an accessible source for such biomarkers. In this review, we provide an overview on some of the most promising peripheral biomarkers of neuroinflammation, discussing their pathogenic role in AD.

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Clinical diagnosis of Alzheimer's disease: recommendations of the International Working Group

Cited by 441 publications

References 114 publications

Serial Recall Order and Semantic Features of Category Fluency Words to Study Semantic Memory in Normal Ageing

Serial Recall Order and Semantic Features of Category Fluency Words to Study Semantic Memory in Normal Ageing

Tackling Stereochemistry in Drug Molecules with Vibrational Optical Activity

Blood-Based Biomarkers of Neuroinflammation in Alzheimer’s Disease: A Central Role for Periphery?

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