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- Gazzina, S, et al.
(author)
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Education modulates brain maintenance in presymptomatic frontotemporal dementia
- 2019
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In: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 90:10, s. 1124-1130
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Journal article (peer-reviewed)abstract
- Cognitively engaging lifestyles have been associated with reduced risk of conversion to dementia. Multiple mechanisms have been advocated, including increased brain volumes (ie, brain reserve) and reduced disease progression (ie, brain maintenance). In cross-sectional studies of presymptomatic frontotemporal dementia (FTD), higher education has been related to increased grey matter volume. Here, we examine the effect of education on grey matter loss over time.MethodsTwo-hundred twenty-nine subjects at-risk of carrying a pathogenic mutation leading to FTD underwent longitudinal cognitive assessment and T1-weighted MRI at baseline and at 1 year follow-up. The first principal component score of the graph-Laplacian Principal Component Analysis on 112 grey matter region-of-interest volumes was used to summarise the grey matter volume (GMV). The effects of education on cognitive performances and GMV at baseline and on the change between 1 year follow-up and baseline (slope) were tested by Structural Equation Modelling.ResultsHighly educated at-risk subjects had better cognition and higher grey matter volume at baseline; moreover, higher educational attainment was associated with slower loss of grey matter over time in mutation carriers.ConclusionsThis longitudinal study demonstrates that even in presence of ongoing pathological processes, education may facilitate both brain reserve and brain maintenance in the presymptomatic phase of genetic FTD.
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- Pilotto, A., et al.
(author)
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Steroid-Responsive Encephalitis in Coronavirus Disease 2019
- 2020
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In: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 88:2, s. 423-427
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Journal article (peer-reviewed)abstract
- Coronavirus disease 2019 (COVID-19) infection has the potential for targeting the central nervous system, and several neurological symptoms have been described in patients with severe respiratory distress. Here, we described the case of a 60-year-old patient with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection but only mild respiratory abnormalities who developed an akinetic mutism attributable to encephalitis. Magnetic resonance imaging was negative, whereas electroencephalography showed generalized theta slowing. Cerebrospinal fluid analyses during the acute stage were negative for SARS-CoV-2, positive for pleocytosis and hyperproteinorrachia, and showed increased interleukin-8 and tumor necrosis factor-alpha concentrations. Other infectious or autoimmune disorders were excluded. A progressive clinical improvement along with a reduction of cerebrospinal fluid parameters was observed after high-dose steroid treatment, thus arguing for an inflammatory-mediated brain involvement related to COVID-19. ANN NEUROL 2020
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- Assogna, M., et al.
(author)
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Association of Choroid Plexus Volume With Serum Biomarkers, Clinical Features, and Disease Severity in Patients With Frontotemporal Lobar Degeneration Spectrum
- 2023
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In: NEUROLOGY. - 0028-3878. ; 101:12
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Journal article (peer-reviewed)abstract
- Background and ObjectivesChoroid plexus (ChP) is emerging as a key brain structure in the pathophysiology of neurodegenerative disorders. In this observational study, we investigated ChP volume in a large cohort of patients with frontotemporal lobar degeneration (FTLD) spectrum to explore a possible link between ChP volume and other disease-specific biomarkers.MethodsParticipants included patients meeting clinical criteria for a probable syndrome in the FTLD spectrum. Structural brain MRI imaging, serum neurofilament light (NfL), serum phosphorylated-Tau181 (p-Tau181), and cognitive and behavioral data were collected. MRI ChP volumes were obtained from an ad-hoc segmentation model based on a Gaussian Mixture Models algorithm.ResultsThree-hundred and sixteen patients within FTLD spectrum were included in this study, specifically 135 patients diagnosed with behavioral variant frontotemporal dementia (bvFTD), 75 primary progressive aphasia, 46 progressive supranuclear palsy, and 60 corticobasal syndrome. In addition, 82 age-matched healthy participants were recruited as controls (HCs). ChP volume was significantly larger in patients with FTLD compared with HC, across the clinical subtype. Moreover, we found a significant difference in ChP volume between HC and patients stratified for disease-severity based on CDR plus NACC FTLD, including patients at very early stage of the disease. Interestingly, ChP volume correlated with serum NfL, cognitive/behavioral deficits, and with patterns of cortical atrophy. Finally, ChP volume seemed to discriminate HC from patients with FTLD better than other previously identified brain structure volumes.DiscussionConsidering the clinical, pathologic, and genetic heterogeneity of the disease, ChP could represent a potential biomarker across the FTLD spectrum, especially at the early stage of disease. Further longitudinal studies are needed to establish its role in disease onset and progression.Classification of EvidenceThis study provides Class III evidence that choroid plexus volume, as measured on MRI scan, can assist in differentiating patients with FTLD from healthy controls and in characterizing disease severity.
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- Benussi, A., et al.
(author)
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Differences and similarities between familial and sporadic frontotemporal dementia: An Italian single-center cohort study
- 2022
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In: Alzheimer's and Dementia: Translational Research and Clinical Interventions. - : Wiley. - 2352-8737. ; 8:1
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Journal article (peer-reviewed)abstract
- Introduction The possibility to generalize our understandings on treatments and assessments to both familial frontotemporal dementia (f-FTD) and sporadic FTD (s-FTD) is a fundamental perspective for the near future, considering the constant advancement in potential disease-modifying therapies that target particular genetic forms of FTD. We aimed to investigate differences in clinical features, cerebrospinal fluid (CSF), and blood-based biomarkers between f-FTD and s-FTD. Methods In this longitudinal cohort study, we evaluated a consecutive sample of symptomatic FTD patients, classified as f-FTD and s-FTD according to Goldman scores (GS). All patients underwent clinical, behavioral, and neuropsychiatric symptom assessment, CSF biomarkers and serum neurofilament light (NfL) analysis, and brain atrophy evaluation with magnetic resonance imaging. Results Of 570 patients with FTD, 123 were classified as f-FTD, and 447 as s-FTD. In the f-FTD group, 95 had a pathogenic FTD mutation while 28 were classified as GS = 1 or 2; of the s-FTD group, 133 were classified as GS = 3 and 314 with GS = 4. f-FTD and s-FTD cases showed comparable demographic features, except for younger age at disease onset, age at diagnosis, and higher years of education in the f-FTD group (all P < .05). f-FTD showed worse behavioral disturbances as measured with Frontal Behavioral Inventory (FBI) negative behaviors (14.0 +/- 7.6 vs. 11.6 +/- 7.4, P = .002), and positive behaviors (20.0 +/- 11.0 vs. 17.4 +/- 11.8, P = .031). Serum NfL concentrations were higher in patients with f-FTD (70.9 +/- 37.9 pg/mL) compared to s-FTD patients (37.3 +/- 24.2 pg/mL, P < .001), and f-FTD showed greater brain atrophy in the frontal and temporal regions and basal ganglia. Patients with f-FTD had significantly shorter survival than those with s-FTD (P = .004). Discussion f-FTD and s-FTD are very similar clinical entities, but with different biological mechanisms, and different rates of progression. The parallel characterization of both f-FTD and s-FTD will improve our understanding of the disease, and aid in designing future clinical trials for both genetic and sporadic forms of FTD. Highlights Do clinical features and biomarkers differ between patients with familial frontotemporal dementia (f-FTD) and sporadic FTD (s-FTD)? In this cohort study of 570 patients with FTD, f-FTD and s-FTD share similar demographic features, but with younger age at disease onset and diagnosis in the f-FTD group. f-FTD showed higher serum neurofilament light concentrations, greater brain damage, and shorter survival, compared to s-FTD. f-FTD and s-FTD are very similar clinical entities, but with different cognitive reserve mechanisms and different rates of progression.
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- Swift, Imogen J, et al.
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A systematic review of progranulin concentrations in biofluids in over 7,000 people-assessing the pathogenicity of GRN mutations and other influencing factors.
- 2024
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In: Alzheimer's Research & Therapy. - 1758-9193. ; 16:1
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Journal article (peer-reviewed)abstract
- Pathogenic heterozygous mutations in the progranulin gene (GRN) are a key cause of frontotemporal dementia (FTD), leading to significantly reduced biofluid concentrations of the progranulin protein (PGRN). This has led to a number of ongoing therapeutic trials aiming to treat this form of FTD by increasing PGRN levels in mutation carriers. However, we currently lack a complete understanding of factors that affect PGRN levels and potential variation in measurement methods. Here, we aimed to address this gap in knowledge by systematically reviewing published literature on biofluid PGRN concentrations.Published data including biofluid PGRN concentration, age, sex, diagnosis and GRN mutation were collected for 7071 individuals from 75 publications. The majority of analyses (72%) had focused on plasma PGRN concentrations, with many of these (56%) measured with a single assay type (Adipogen) and so the influence of mutation type, age at onset, sex, and diagnosis were investigated in this subset of the data.We established a plasma PGRN concentration cut-off between pathogenic mutation carriers and non-carriers of 74.8ng/mL using the Adipogen assay based on 3301 individuals, with a CSF concentration cut-off of 3.43ng/mL. Plasma PGRN concentration varied by GRN mutation type as well as by clinical diagnosis in those without a GRN mutation. Plasma PGRN concentration was significantly higher in women than men in GRN mutation carriers (p=0.007) with a trend in non-carriers (p=0.062), and there was a significant but weak positive correlation with age in both GRN mutation carriers and non-carriers. No significant association was seen with weight or with TMEM106B rs1990622 genotype. However, higher plasma PGRN levels were seen in those with the GRN rs5848 CC genotype in both GRN mutation carriers and non-carriers.These results further support the usefulness of PGRN concentration for the identification of the large majority of pathogenic mutations in the GRN gene. Furthermore, these results highlight the importance of considering additional factors, such as mutation type, sex and age when interpreting PGRN concentrations. This will be particularly important as we enter the era of trials for progranulin-associated FTD.
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