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  • Oxford University Press (OUP)  (16)
  • Levin, Johannes  (16)
  • 2020-2024  (16)
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  • Oxford University Press (OUP)  (16)
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Years
  • 2020-2024  (16)
Year
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Subjects(RVK)
  • 1
    Online Resource
    Online Resource
    Single-subject grey matter network trajectories over the disease course of autosomal dominant Alzheimer’s disease
    Oxford University Press (OUP) ; 2020
    In:  Brain Communications Vol. 2, No. 2 ( 2020-07-01)
    Details
    In: Brain Communications, Oxford University Press (OUP), Vol. 2, No. 2 ( 2020-07-01)
    Abstract: Structural grey matter covariance networks provide an individual quantification of morphological patterns in the brain. The network integrity is disrupted in sporadic Alzheimer’s disease, and network properties show associations with the level of amyloid pathology and cognitive decline. Therefore, these network properties might be disease progression markers. However, it remains unclear when and how grey matter network integrity changes with disease progression. We investigated these questions in autosomal dominant Alzheimer’s disease mutation carriers, whose conserved age at dementia onset allows individual staging based upon their estimated years to symptom onset. From the Dominantly Inherited Alzheimer Network observational cohort, we selected T1-weighted MRI scans from 269 mutation carriers and 170 non-carriers (mean age 38 ± 15 years, mean estimated years to symptom onset −9 ± 11), of whom 237 had longitudinal scans with a mean follow-up of 3.0 years. Single-subject grey matter networks were extracted, and we calculated for each individual the network properties which describe the network topology, including the size, clustering, path length and small worldness. We determined at which time point mutation carriers and non-carriers diverged for global and regional grey matter network metrics, both cross-sectionally and for rate of change over time. Based on cross-sectional data, the earliest difference was observed in normalized path length, which was decreased for mutation carriers in the precuneus area at 13 years and on a global level 12 years before estimated symptom onset. Based on longitudinal data, we found the earliest difference between groups on a global level 6 years before symptom onset, with a greater rate of decline of network size for mutation carriers. We further compared grey matter network small worldness with established biomarkers for Alzheimer disease (i.e. amyloid accumulation, cortical thickness, brain metabolism and cognitive function). We found that greater amyloid accumulation at baseline was associated with faster decline of small worldness over time, and decline in grey matter network measures over time was accompanied by decline in brain metabolism, cortical thinning and cognitive decline. In summary, network measures decline in autosomal dominant Alzheimer’s disease, which is alike sporadic Alzheimer’s disease, and the properties show decline over time prior to estimated symptom onset. These data suggest that single-subject networks properties obtained from structural MRI scans form an additional non-invasive tool for understanding the substrate of cognitive decline and measuring progression from preclinical to severe clinical stages of Alzheimer’s disease.
    Type of Medium: Online Resource
    ISSN: 2632-1297
    URL: Article
    DOI: 10.1093/braincomms/fcaa102
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 3020013-1
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  • 2
    Online Resource
    Online Resource
    Brain network decoupling with increased serum neurofilament and reduced cognitive function in Alzheimer’s disease
    Oxford University Press (OUP) ; 2023
    In:  Brain Vol. 146, No. 7 ( 2023-07-03), p. 2928-2943
    Details
    In: Brain, Oxford University Press (OUP), Vol. 146, No. 7 ( 2023-07-03), p. 2928-2943
    Abstract: Neurofilament light chain, a putative measure of neuronal damage, is measurable in blood and CSF and is predictive of cognitive function in individuals with Alzheimer’s disease. There has been limited prior work linking neurofilament light and functional connectivity, and no prior work has investigated neurofilament light associations with functional connectivity in autosomal dominant Alzheimer’s disease. Here, we assessed relationships between blood neurofilament light, cognition, and functional connectivity in a cross-sectional sample of 106 autosomal dominant Alzheimer’s disease mutation carriers and 76 non-carriers. We employed an innovative network-level enrichment analysis approach to assess connectome-wide associations with neurofilament light. Neurofilament light was positively correlated with deterioration of functional connectivity within the default mode network and negatively correlated with connectivity between default mode network and executive control networks, including the cingulo-opercular, salience, and dorsal attention networks. Further, reduced connectivity within the default mode network and between the default mode network and executive control networks was associated with reduced cognitive function. Hierarchical regression analysis revealed that neurofilament levels and functional connectivity within the default mode network and between the default mode network and the dorsal attention network explained significant variance in cognitive composite scores when controlling for age, sex, and education. A mediation analysis demonstrated that functional connectivity within the default mode network and between the default mode network and dorsal attention network partially mediated the relationship between blood neurofilament light levels and cognitive function. Our novel results indicate that blood estimates of neurofilament levels correspond to direct measurements of brain dysfunction, shedding new light on the underlying biological processes of Alzheimer’s disease. Further, we demonstrate how variation within key brain systems can partially mediate the negative effects of heightened total serum neurofilament levels, suggesting potential regions for targeted interventions. Finally, our results lend further evidence that low-cost and minimally invasive blood measurements of neurofilament may be a useful marker of brain functional connectivity and cognitive decline in Alzheimer’s disease.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    URL: Article
    DOI: 10.1093/brain/awac498
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1474117-9
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    Subcortical tau is linked to hypoperfusion in connected cortical regions in 4-repeat tauopathies
    Oxford University Press (OUP) ; 2024
    In:  Brain ( 2024-06-06)
    Details
    In: Brain, Oxford University Press (OUP), ( 2024-06-06)
    Abstract: 4-repeat (4R) tauopathies are neurodegenerative diseases characterized by cerebral accumulation of 4R tau pathology. The most prominent 4R-tauopathies are progressive-supranuclear-palsy (PSP) and corticobasal-degeneration (CBD) characterized by subcortical tau accumulation and cortical neuronal dysfunction, as shown by PET-assessed hypoperfusion and glucose hypometabolism. Yet, there is a spatial mismatch between subcortical tau deposition patterns and cortical neuronal dysfunction, and it is unclear how these two pathological brain changes are interrelated. Here, we hypothesized that subcortical tau pathology induces remote neuronal dysfunction in functionally connected cortical regions to test a pathophysiological model that mechanistically links subcortical tau accumulation to cortical neuronal dysfunction in 4R tauopathies. We included 51 Aβ-negative patients with clinically diagnosed PSP variants (n=26) or Corticobasal Syndrome (CBS; n=25) who underwent structural MRI and 18F-PI-2620 tau-PET. 18F-PI-2620 tau-PET was recorded using a dynamic one-stop-shop acquisition protocol, to determine an early 0.5-2.5 min post-tracer-injection perfusion window for assessing cortical neuronal dysfunction, as well as a 20-40 min post-tracer-injection window to determine 4R-tau load. Perfusion-PET (i.e. early-window) was assessed in 200 cortical regions, and tau-PET was assessed in 32 subcortical regions of established functional brain atlasses. We determined tau epicenters as subcortical regions with highest 18F-PI-2620 tau-PET signal and assessed the connectivity of tau epicenters to cortical ROIs using a resting-state fMRI-based functional connectivity template derived from 69 healthy elderly controls from the ADNI cohort. Using linear regression, we assessed whether i) higher subcortical tau-PET was associated with reduced cortical perfusion and ii) whether cortical perfusion reductions were observed preferentially in regions closely connected to subcortical tau epicenters. As hypothesized, higher subcortical tau-PET was associated with overall lower cortical perfusion, which remained consistent when controlling for cortical tau-PET. Using group-average and subject-level PET data, we found that the seed-based connectivity pattern of subcortical tau epicenters aligned with cortical perfusion patterns, where cortical regions that were more closely connected to the tau epicenter showed lower perfusion. Together, subcortical tau-accumulation is associated with remote perfusion reductions indicative of neuronal dysfunction in functionally connected cortical regions in 4R-tauopathies. This suggests that subcortical tau pathology may induce cortical dysfunction, which may contribute to clinical disease manifestation and clinical heterogeneity.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    URL: Article
    DOI: 10.1093/brain/awae174
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
    detail.hit.zdb_id: 1474117-9
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    Neurodevelopmental effects of genetic frontotemporal dementia in young adult mutation carriers
    Oxford University Press (OUP) ; 2023
    In:  Brain Vol. 146, No. 5 ( 2023-05-02), p. 2120-2131
    Details
    In: Brain, Oxford University Press (OUP), Vol. 146, No. 5 ( 2023-05-02), p. 2120-2131
    Abstract: While frontotemporal dementia has been considered a neurodegenerative disease that starts in mid-life or later, it is now clearly established that cortical and subcortical volume loss is observed more than a decade prior to symptom onset and progresses with ageing. To test the hypothesis that genetic mutations causing frontotemporal dementia have neurodevelopmental consequences, we examined the youngest adults in the GENFI cohort of pre-symptomatic frontotemporal dementia mutation carriers who are between 19 and 30 years of age. Structural brain differences and improved performance on some cognitive tests were found for MAPT and GRN mutation carriers relative to familial non-carriers, while smaller volumes were observed in C9orf72 repeat expansion carriers at a mean age of 26 years. The detection of such early differences supports potential advantageous neurodevelopmental consequences of some frontotemporal dementia-causing genetic mutations. These results have implications for the design of therapeutic interventions for frontotemporal dementia. Future studies at younger ages are needed to identify specific early pathophysiologic or compensatory processes that occur during the neurodevelopmental period.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    URL: Article
    DOI: 10.1093/brain/awac446
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1474117-9
    SSG: 12
    Location Call Number Limitation Availability
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  • 5
    Online Resource
    Online Resource
    Anti-amyloid antibody therapies in Alzheimer’s disease
    Oxford University Press (OUP) ; 2023
    In:  Brain Vol. 146, No. 3 ( 2023-03-01), p. 842-849
    Details
    In: Brain, Oxford University Press (OUP), Vol. 146, No. 3 ( 2023-03-01), p. 842-849
    Abstract: After years of failed attempts to develop a disease-modifying therapy for Alzheimer’s disease, consistent evidence in support of clinical efficacy was finally presented for a monoclonal antibody targeting the amyloid-β protofibrils. In addition to meeting the primary outcome of slowing clinical disease progression over 18 months, secondary clinical outcomes and amyloid-β lowering on PET also underpin the positive results of the trial. In this opinion piece, we highlight the key characteristics of the previous unsuccessful trials and analyse the potential reasons why those attempts to develop a treatment for early Alzheimer’s disease failed. We compare the safety profiles of the different antibodies and highlight cautionary measures for their routine clinical use. Last, we discuss the role of blood-based biomarkers in transforming the clinical care pathway to facilitate the uptake of antibody treatments, proposing an integrated case-finding and treatment model crossing the different healthcare sectors. Taken together, a real breakthrough may have been achieved by proving that amyloid-β reduction results in clinical benefits, rather than just biomarker changes. At the same time, routine use of the new generation of drugs will show if statistical efficacy translates into clinically meaningful change. This may just be the beginning of a new era of Alzheimer’s disease drug development.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    URL: Article
    DOI: 10.1093/brain/awad005
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1474117-9
    SSG: 12
    Location Call Number Limitation Availability
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  • 6
    Online Resource
    Online Resource
    Structural MRI predicts clinical progression in presymptomatic genetic frontotemporal dementia: findings from the GENetic Frontotemporal dementia Initiative cohort
    Oxford University Press (OUP) ; 2023
    In:  Brain Communications Vol. 5, No. 2 ( 2023-03-02)
    Details
    In: Brain Communications, Oxford University Press (OUP), Vol. 5, No. 2 ( 2023-03-02)
    Abstract: Biomarkers that can predict disease progression in individuals with genetic frontotemporal dementia are urgently needed. We aimed to identify whether baseline MRI-based grey and white matter abnormalities are associated with different clinical progression profiles in presymptomatic mutation carriers in the GENetic Frontotemporal dementia Initiative. Three hundred eighty-seven mutation carriers were included (160 GRN, 160 C9orf72, 67 MAPT), together with 240 non-carrier cognitively normal controls. Cortical and subcortical grey matter volumes were generated using automated parcellation methods on volumetric 3T T1-weighted MRI scans, while white matter characteristics were estimated using diffusion tensor imaging. Mutation carriers were divided into two disease stages based on their global CDR®+NACC-FTLD score: presymptomatic (0 or 0.5) and fully symptomatic (1 or greater). The w-scores in each grey matter volumes and white matter diffusion measures were computed to quantify the degree of abnormality compared to controls for each presymptomatic carrier, adjusting for their age, sex, total intracranial volume, and scanner type. Presymptomatic carriers were classified as ‘normal’ or ‘abnormal’ based on whether their grey matter volume and white matter diffusion measure w-scores were above or below the cut point corresponding to the 10th percentile of the controls. We then compared the change in disease severity between baseline and one year later in both the ‘normal’ and ‘abnormal’ groups within each genetic subtype, as measured by the CDR®+NACC-FTLD sum-of-boxes score and revised Cambridge Behavioural Inventory total score. Overall, presymptomatic carriers with normal regional w-scores at baseline did not progress clinically as much as those with abnormal regional w-scores. Having abnormal grey or white matter measures at baseline was associated with a statistically significant increase in the CDR®+NACC-FTLD of up to 4 points in C9orf72 expansion carriers, and 5 points in the GRN group as well as a statistically significant increase in the revised Cambridge Behavioural Inventory of up to 11 points in MAPT, 10 points in GRN, and 8 points in C9orf72 mutation carriers. Baseline regional brain abnormalities on MRI in presymptomatic mutation carriers are associated with different profiles of clinical progression over time. These results may be helpful to inform stratification of participants in future trials.
    Type of Medium: Online Resource
    ISSN: 2632-1297
    URL: Article
    DOI: 10.1093/braincomms/fcad061
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 3020013-1
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  • 7
    Online Resource
    Online Resource
    Hierarchical spectral clustering reveals brain size and shape changes in asymptomatic carriers of C9orf72
    Oxford University Press (OUP) ; 2022
    In:  Brain Communications Vol. 4, No. 4 ( 2022-07-04)
    Details
    In: Brain Communications, Oxford University Press (OUP), Vol. 4, No. 4 ( 2022-07-04)
    Abstract: Traditional methods for detecting asymptomatic brain changes in neurodegenerative diseases such as Alzheimer’s disease or frontotemporal degeneration typically evaluate changes in volume at a predefined level of granularity, e.g. voxel-wise or in a priori defined cortical volumes of interest. Here, we apply a method based on hierarchical spectral clustering, a graph-based partitioning technique. Our method uses multiple levels of segmentation for detecting changes in a data-driven, unbiased, comprehensive manner within a standard statistical framework. Furthermore, spectral clustering allows for detection of changes in shape along with changes in size. We performed tensor-based morphometry to detect changes in the Genetic Frontotemporal dementia Initiative asymptomatic and symptomatic frontotemporal degeneration mutation carriers using hierarchical spectral clustering and compared the outcome to that obtained with a more conventional voxel-wise tensor- and voxel-based morphometric analysis. In the symptomatic groups, the hierarchical spectral clustering-based method yielded results that were largely in line with those obtained with the voxel-wise approach. In asymptomatic C9orf72 expansion carriers, spectral clustering detected changes in size in medial temporal cortex that voxel-wise methods could only detect in the symptomatic phase. Furthermore, in the asymptomatic and the symptomatic phases, the spectral clustering approach detected changes in shape in the premotor cortex in C9orf72. In summary, the present study shows the merit of hierarchical spectral clustering for data-driven segmentation and detection of structural changes in the symptomatic and asymptomatic stages of monogenic frontotemporal degeneration.
    Type of Medium: Online Resource
    ISSN: 2632-1297
    URL: Article
    DOI: 10.1093/braincomms/fcac182
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 3020013-1
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  • 8
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    Molecular neuroimaging in dominantly inherited versus sporadic early-onset Alzheimer’s disease
    Oxford University Press (OUP) ; 2024
    In:  Brain Communications
    Details
    In: Brain Communications, Oxford University Press (OUP)
    Abstract: Approximately 5% of Alzheimer’s Disease patients develop symptoms before age 65 (EOAD), with either sporadic (sEOAD) or dominantly inherited (DIAD) presentations. Both sEOAD and DIAD are characterized by brain amyloid-beta accumulation, tau tangles, hypometabolism and neurodegeneration, but differences in topography and magnitude of these pathological changes are not fully elucidated. In this study, we directly compared patterns of amyloid-beta plaque deposition and glucose hypometabolism in sEOAD and DIAD individuals. Our analysis included 134 symptomatic sEOAD Amyloid-PET positive cases from the University of California, San Francisco, Alzheimer’s Disease Research Center (mean ± standard deviation age 59.7 ± 5.6 years), 89 symptomatic DIAD cases (age 45.8 ± 9.3 years) and 102 cognitively unimpaired non-mutation carriers from the Dominantly Inherited Alzheimer Network study (age 44.9 ± 9.2). Each group underwent clinical and cognitive examinations, 11C-labeled Pittsburgh compound B-PET (PIB-PET) and structural Magnetic Resonance Imaging. 18F-fluorodeoxyglucose-PET (FDG-PET) was also available for most participants. PET scans from both studies were uniformly processed to obtain Standardized Uptake Value Ratio (SUVR, PIB50-70 cerebellar gray reference, FDG30-60 pons reference) images. Statistical analyses included pairwise global and voxelwise group comparisons and group-independent component analyses. Analyses were performed also adjusting for covariates including age, sex, Mini-Mental State Examination, Apolipoprotein-ε4 status, and average composite cortical of Standardized Uptake Value Ratio. Compared to DIAD, sEOAD participants were older at age of onset (mean ± standard deviation, 54.8 ± 8.2 vs. 41.9 ± 8.2, Cohen’s d = 1.91), with more years of education (16.4 ± 2.8 vs. 13.5 ± 3.2, d = 1) and more likely to be Apolipoprotein-ε4 carriers (54.6% ε4 vs. 28.1%, Cramer’s V = 0.26), but similar Mini-Mental State Examination (20.6 ± 6.1 vs. 21.2 ± 7.4, d = 0.08). sEOAD had higher global cortical PIB-PET binding (mean ± standard deviation SUVR, 1.92 ± 0.29 vs. 1.58 ± 0.44, d = 0.96) and greater global cortical FDG-PET hypometabolism (mean ± standard deviation SUVR, 1.32 ± 0.1 vs. 1.39 ± 0.19, d = 0.48) compared to DIAD. Fully adjusted comparisons demonstrated relatively higher PIB-PET SUVR in the medial occipital, thalami, basal ganglia and medial/dorsal frontal regions in DIAD vs. sEOAD. sEOAD showed relatively greater FDG-PET hypometabolism in Alzheimer’s Disease signature temporoparietal regions and caudate nuclei, whereas DIAD showed relatively greater hypometabolism in frontal white matter and pericentral regions. Independent component analyses largely replicated these findings by highlighting common and unique PIB-PET and FDG-PET binding patterns. In summary, our findings suggest both common and distinct patterns of amyloid and glucose hypometabolismin in sporadic and dominantly inherited EOAD.
    Type of Medium: Online Resource
    ISSN: 2632-1297
    URL: Article
    DOI: 10.1093/braincomms/fcae159
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
    detail.hit.zdb_id: 3020013-1
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  • 9
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    Segregation of functional networks is associated with cognitive resilience in Alzheimer’s disease
    Oxford University Press (OUP) ; 2021
    In:  Brain Vol. 144, No. 7 ( 2021-08-17), p. 2176-2185
    Details
    In: Brain, Oxford University Press (OUP), Vol. 144, No. 7 ( 2021-08-17), p. 2176-2185
    Abstract: Cognitive resilience is an important modulating factor of cognitive decline in Alzheimer’s disease, but the functional brain mechanisms that support cognitive resilience remain elusive. Given previous findings in normal ageing, we tested the hypothesis that higher segregation of the brain’s connectome into distinct functional networks represents a functional mechanism underlying cognitive resilience in Alzheimer’s disease. Using resting-state functional MRI, we assessed both resting-state functional MRI global system segregation, i.e. the balance of between-network to within-network connectivity, and the alternate index of modularity Q as predictors of cognitive resilience. We performed all analyses in two independent samples for validation: (i) 108 individuals with autosomal dominantly inherited Alzheimer’s disease and 71 non-carrier controls; and (ii) 156 amyloid-PET-positive subjects across the spectrum of sporadic Alzheimer’s disease and 184 amyloid-negative controls. In the autosomal dominant Alzheimer’s disease sample, disease severity was assessed by estimated years from symptom onset. In the sporadic Alzheimer’s sample, disease stage was assessed by temporal lobe tau-PET (i.e. composite across Braak stage I and III regions). In both samples, we tested whether the effect of disease severity on cognition was attenuated at higher levels of functional network segregation. For autosomal dominant Alzheimer’s disease, we found higher functional MRI-assessed system segregation to be associated with an attenuated effect of estimated years from symptom onset on global cognition (P = 0.007). Similarly, for patients with sporadic Alzheimer’s disease, higher functional MRI-assessed system segregation was associated with less decrement in global cognition (P = 0.001) and episodic memory (P = 0.004) per unit increase of temporal lobe tau-PET. Confirmatory analyses using the alternate index of modularity Q revealed consistent results. In conclusion, higher segregation of functional connections into distinct large-scale networks supports cognitive resilience in Alzheimer’s disease.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    URL: Article
    DOI: 10.1093/brain/awab112
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1474117-9
    SSG: 12
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  • 10
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    Genetic forms of primary progressive aphasia within the GENetic Frontotemporal dementia Initiative (GENFI) cohort: comparison with sporadic primary progressive aphasia
    Oxford University Press (OUP) ; 2023
    In:  Brain Communications Vol. 5, No. 2 ( 2023-03-02)
    Details
    In: Brain Communications, Oxford University Press (OUP), Vol. 5, No. 2 ( 2023-03-02)
    Abstract: Primary progressive aphasia is most commonly a sporadic disorder, but in some cases, it can be genetic. This study aimed to understand the clinical, cognitive and imaging phenotype of the genetic forms of primary progressive aphasia in comparison to the canonical nonfluent, semantic and logopenic subtypes seen in sporadic disease. Participants with genetic primary progressive aphasia were recruited from the international multicentre GENetic Frontotemporal dementia Initiative study and compared with healthy controls as well as a cohort of people with sporadic primary progressive aphasia. Symptoms were assessed using the GENetic Frontotemporal dementia Initiative language, behavioural, neuropsychiatric and motor scales. Participants also underwent a cognitive assessment and 3 T volumetric T1-weighted MRI. One C9orf72 (2%), 1 MAPT (6%) and 17 GRN (44%) symptomatic mutation carriers had a diagnosis of primary progressive aphasia. In the GRN cohort, 47% had a diagnosis of nonfluent variant primary progressive aphasia, and 53% had a primary progressive aphasia syndrome that did not fit diagnostic criteria for any of the three subtypes, called primary progressive aphasia-not otherwise specified here. The phenotype of the genetic nonfluent variant primary progressive aphasia group largely overlapped with that of sporadic nonfluent variant primary progressive aphasia, although the presence of an associated atypical parkinsonian syndrome was characteristic of sporadic and not genetic disease. The primary progressive aphasia -not otherwise specified group however was distinct from the sporadic subtypes with impaired grammar/syntax in the presence of relatively intact articulation, alongside other linguistic deficits. The pattern of atrophy seen on MRI in the genetic nonfluent variant primary progressive aphasia group overlapped with that of the sporadic nonfluent variant primary progressive aphasia cohort, although with more posterior cortical involvement, whilst the primary progressive aphasia-not otherwise specified group was strikingly asymmetrical with involvement particularly of the insula and dorsolateral prefrontal cortex but also atrophy of the orbitofrontal cortex and the medial temporal lobes. Whilst there are overlapping symptoms between genetic and sporadic primary progressive aphasia syndromes, there are also distinct features. Future iterations of the primary progressive aphasia consensus criteria should encompass such information with further research needed to understand the earliest features of these disorders, particularly during the prodromal period of genetic disease.
    Type of Medium: Online Resource
    ISSN: 2632-1297
    URL: Article
    DOI: 10.1093/braincomms/fcad036
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 3020013-1
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