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- Chetelat, G., et al.
(author)
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Amyloid-PET and 18-F-FDG-PET in the diagnostic investigation of Alzheimer's disease and other dementias
- 2020
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In: Lancet Neurology. - 1474-4422 .- 1474-4465. ; 19:11, s. 951-962
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Research review (peer-reviewed)abstract
- Various biomarkers are available to support the diagnosis of neurodegenerative diseases in clinical and research settings. Among the molecular imaging biomarkers, amyloid-PET, which assesses brain amyloid deposition, and F-18-fluorodeoxyglucose (F-18-FDG) PET, which assesses glucose metabolism, provide valuable and complementary information. However, uncertainty remains regarding the optimal timepoint, combination, and an order in which these PET biomarkers should be used in diagnostic evaluations because conclusive evidence is missing. Following an expert panel discussion, we reached an agreement on the specific use of the individual biomarkers, based on available evidence and clinical expertise. We propose a diagnostic algorithm with optimal timepoints for these PET biomarkers, also taking into account evidence from other biomarkers, for early and differential diagnosis of neurodegenerative diseases that can lead to dementia. We propose three main diagnostic pathways with distinct biomarker sequences, in which amyloid-PET and F-18-FDG-PET are placed at different positions in the order of diagnostic evaluations, depending on clinical presentation. We hope that this algorithm can support diagnostic decision making in specialist clinical settings with access to these biomarkers and might stimulate further research towards optimal diagnostic strategies.
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- van Rheenen, W, et al.
(author)
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Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology
- 2021
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 53:12, s. 1636-
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Journal article (peer-reviewed)abstract
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.
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- Vera, Jaime H, et al.
(author)
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CLINICAL UTILITY OF β-AMYLOID PET IMAGING IN PEOPLE LIVING WITH HIV WITH COGNITIVE SYMPTOMS.
- 2021
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In: Journal of acquired immune deficiency syndromes (1999). - 1944-7884. ; 87:2, s. 826-833
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Journal article (peer-reviewed)abstract
- Imaging with β-amyloid (Aβ) PET has the potential to aid the diagnosis of the cause of cognitive impairment affecting people living with HIV (PLWH) when neurodegenerative disorders are considered. We evaluated the clinical utility of [18F]Florbetaben (FBB) in PLWH with cognitive symptoms.Imaging with FBB PET was performed in 20 patients with cognitive concerns about dementia. Neuropsychological testing, plasma neurofilament light protein, plasma Aβ40, Aβ42 and CSF Aβ42, tau, and HIV RNA were obtained. FBB PET images were assessed visually by three readers blinded to the clinical diagnosis, and quantitatively by obtaining a composite cortical to cerebellar cortex standardized uptake value ratio (SUVR). FBB SUVR from 10 age-matched healthy controls were compared to SUVR of PLWH.Most participants were male (90%) of white ethnicity (90%) with a median age (IQR) of 59 (43-79) years. Median CD4 count was 682 (74-1056). All patients were on cART with plasma and CSF HIV RNA< 40 copies/mL. Fourteen patients had objective cognitive impairment including two who met clinical criteria for a diagnosis of dementia. No significant differences in composite SUVRs between PLWH and controls [mean (SD): 1.18 (0.03) vs 1.16 (0.09); p=0.37] were observed. Four patients were FBB+ with the highest SUVR in the posterior cingulate, superior temporal and frontal superior lobe. Amyloid PET results contributed to a change in diagnosis and treatment for 10 patients.[18F]Florbetaben PET has potential as an adjunctive tool in the diagnosis of PLWH with cognitive impairment, increasing diagnostic certainty and optimizing management.
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