Academic Journal
Testing the 2018 NIA-AA research framework in a retrospective large cohort of patients with cognitive impairment: from biological biomarkers to clinical syndromes
| Title: | Testing the 2018 NIA-AA research framework in a retrospective large cohort of patients with cognitive impairment: from biological biomarkers to clinical syndromes |
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| Authors: | Tiziana Carandini, Andrea Arighi, Luca Sacchi, Giorgio G. Fumagalli, Anna M. Pietroboni, Laura Ghezzi, Annalisa Colombi, Marta Scarioni, Chiara Fenoglio, Milena A. De Riz, Giorgio Marotta, Elio Scarpini, Daniela Galimberti |
| Source: | Alzheimer’s Research & Therapy, Vol 11, Iss 1, Pp 1-11 (2019) |
| Publisher Information: | BMC, 2019. |
| Publication Year: | 2019 |
| Collection: | LCC:Neurosciences. Biological psychiatry. Neuropsychiatry LCC:Neurology. Diseases of the nervous system |
| Subject Terms: | Alzheimer’s disease, Dementia, CSF, Clinical neurology, Biomarkers, PET, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429 |
| More Details: | Abstract Background According to the 2018 NIA-AA research framework, Alzheimer’s disease (AD) is not defined by the clinical consequences of the disease, but by its underlying pathology, measured by biomarkers. Evidence of both amyloid-β (Aβ) and phosphorylated tau protein (p-tau) deposition—assessed interchangeably with amyloid-positron emission tomography (PET) and/or cerebrospinal fluid (CSF) analysis—is needed to diagnose AD in a living person. Our aim was to test the new NIA-AA research framework in a large cohort of cognitively impaired patients to evaluate correspondence between the clinical syndromes and the underlying pathologic process testified by biomarkers. Methods We retrospectively analysed 628 subjects referred to our centre in suspicion of dementia, who underwent CSF analysis, together with neuropsychological assessment and neuroimaging, and were diagnosed with different neurodegenerative dementias according to current criteria, or as cognitively unimpaired. Subjects were classified considering CSF biomarkers, and the prevalence of normal, AD-continuum and non-AD profiles in each clinical syndrome was calculated. The positivity threshold of each CSF biomarker was first assessed by receiver operating characteristic analysis, using Aβ-positive/negative status as determined by amyloid-PET visual reads. The agreement between CSF and amyloid-PET data was also evaluated. Results Among patients with a clinical diagnosis of AD, 94.1% were in the AD-continuum, whereas 5.5% were classified as non-AD and 0.4% were normal. The AD-continuum profile was found also in 26.2% of frontotemporal dementia, 48.6% of Lewy body dementia, 25% of atypical parkinsonism and 44.7% of vascular dementia. Biomarkers’ profile did not differ in amnestic and not amnestic mild cognitive impairment. CSF Aβ levels and amyloid-PET tracer binding negatively correlated, and the concordance between the two Aβ biomarkers was 89%. Conclusions The examination of the 2018 NIA-AA research framework in our clinical setting revealed a good, but incomplete, correspondence between the clinical syndromes and the underlying pathologic process measured by CSF biomarkers. The AD-continuum profile resulted to be a sensitive, but non-specific biomarker with regard to the clinical AD diagnosis. CSF and PET Aβ biomarkers were found to be not perfectly interchangeable to quantify the Aβ burden, possibly because they measure different aspects of AD pathology. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 1758-9193 15387534 |
| Relation: | http://link.springer.com/article/10.1186/s13195-019-0543-7; https://doaj.org/toc/1758-9193 |
| DOI: | 10.1186/s13195-019-0543-7 |
| Access URL: | https://doaj.org/article/bf7ba1538753468ba0f4569bac7606c9 |
| Accession Number: | edsdoj.bf7ba1538753468ba0f4569bac7606c9 |
| Database: | Directory of Open Access Journals |
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| ISSN: | 17589193 15387534 |
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| DOI: | 10.1186/s13195-019-0543-7 |
| Published in: | Alzheimer’s Research & Therapy |
| Language: | English |