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Cerebral microbleeds and CSF Alzheimer biomarkers in primary progressive aphasias
Aline Mendes1, Anne Bertrand1, Foudil Lamari1
1From the Department of Internal Medicine, Rehabilitation and Geriatrics (A.M.), Geneva University Hospitals and University of Geneva, Switzerland; Department of Neurology (A.M., S.E., B.D., M.T.), National Reference Center for PPA and Rare Dementias, Institute for Memory and Alzheimer's Disease, Pitié Salpêtrière Hospital, AP-HP, Paris; Sorbonne Universités (A.B., O.C., A.R., S.E., L.F., M.C., B.D., M.T.), UPMC University Paris 06, Inserm, CNRS, Institut du Cerveau et la Moelle, Paris; Inria Paris (A.B., O.C., A.R., S.E., T.K.), Aramis Project-Team, Paris; Departments of Neuroradiology (A.B.) and Metabolic Biochemistry (F.L.), Pitié Salpêtrière Hospital, AP-HP, Paris; Department of Neurology and Laboratory of Functional Neurosciences (EA 4559) (O.G.), University Hospital of Amiens; Department of Neurology (F.E.-B.), Memory Research and Resource Center for Alzheimer's Disease, University Hospital of Angers; Department of Psychiatry, Neurology and Rehabilitation (O. Moreaud), University Hospital of Grenoble, Memory Research and Resource Center for Alzheimer's Disease; Department of Neurology (F.P.), University Hospital of Lille; Department of Neurology (P.C.), University Hospital of Limoges; Department of Neurology (K.B.), Memory Research and Resource Center for Alzheimer's Disease, University Hospital of Montpellier; Department of Neurology (M.V.), University Hospital of Nantes; Department of Neurology (O. Martinaud), University Hospital of Rouen; Normandie University (O. Martinaud, S.B.), UNICAEN, EPHE, INSERM, U1077, Neuropsychologie et Imagerie de la Mémoire Humaine; Department of Neurology (B.L.), University Hospital of Saint-Etienne; Department of Neurology (J.P., M.P.), Pierre Paul Riquet Hospital, Toulouse; INSERM/UPS (J.P.), UMR 1214-ToNIC, Toulouse NeuroImaging Center, University of Toulouse III; and Department of Neurology (S.B.), Memory Research and Resource Center for Alzheimer's Disease, University Hospital Pontchaillou, Rennes, France.
Objective:
To reveal the prevalence and localization of cerebral microbleeds (CMBs) in the 3 main variants of primary progressive aphasia (PPA) (logopenic, semantic, and nonfluent/agrammatic), to identify the relationship with underlying Alzheimer pathology, and to explore whether CMBs contribute to language breakdown.
Methods:
We used a cross-sectional design in a multicenter cohort of 82 patients with PPA and 19 similarly aged healthy controls. MRI allowed for rating CMBs (2-dimensional gradient recalled echo T2*, susceptibility weighted imaging sequences) and white matter hyperintensities. CSF Alzheimer disease biomarker analyses available in 63 of the 82 patients provided the stratification of PPA into subgroups with patients who had or did not have probable underlying Alzheimer pathology.
Results:
The prevalence of CMBs was higher in patients with PPA (28%) than in controls (16%). They were more prevalent in logopenic PPA (50%) than in semantic PPA (18%) and nonfluent/agrammatic PPA (17%). The localization of CMBs was mainly lobar (81%) with no difference between the PPA variants. CMBs were more frequent in PPA patients with positive than with negative CSF Alzheimer disease biomarkers (67% vs 20%). Patients with and without lobar CMBs had similar volumes of white matter hyperintensities. Language and general cognitive impairment in PPA was unrelated to CMB rates.
Conclusions:
CMB prevalence in PPA is higher than in healthy controls. CMBs were most prevalent in the logopenic variant, were related to underlying Alzheimer pathology, and did not affect the language/cognitive impairment. Our findings also suggest that CMB detection with MRI contributes to PPA variant diagnosis, especially of logopenic PPA, and provides an estimator of the underlying neuropathology.
Insights
Cerebral microbleeds (CMBs) are more common in primary progressive aphasia (PPA) patients, especially logopenic PPA, and linked to Alzheimer's pathology. CMBs did not worsen language or cognitive decline in PPA.
Area of Science:
- Neurology
- Neuroimaging
- Neurodegenerative Diseases
Background:
- Primary progressive aphasia (PPA) encompasses three main variants: logopenic, semantic, and nonfluent/agrammatic.
- Cerebral microbleeds (CMBs) are small vascular lesions that can indicate underlying neuropathology.
- Understanding CMB prevalence and associations in PPA is crucial for diagnosis and prognosis.
Purpose of the Study:
- To determine the prevalence and location of CMBs across the three main PPA variants.
- To investigate the relationship between CMBs and Alzheimer's disease (AD) pathology in PPA.
- To explore the contribution of CMBs to language and cognitive impairment in PPA.
Main Methods:
- A multicenter, cross-sectional study involving 82 PPA patients and 19 healthy controls.
- Magnetic resonance imaging (MRI) was used to detect CMBs and white matter hyperintensities.
- Cerebrospinal fluid (CSF) Alzheimer's disease biomarkers were analyzed to stratify patients based on probable underlying AD pathology.
Main Results:
- CMB prevalence was higher in PPA patients (28%) than controls (16%), particularly in logopenic PPA (50%).
- CMBs were predominantly lobar and more frequent in PPA patients with positive AD biomarkers (67%) versus negative (20%).
- CMB rates did not correlate with white matter hyperintensity volumes or the severity of language/cognitive impairment.
Conclusions:
- CMB prevalence is elevated in PPA, most notably in the logopenic variant, and associated with Alzheimer's pathology.
- CMB detection via MRI aids in diagnosing PPA variants, especially logopenic PPA, and estimates underlying neuropathology.
- CMBs do not appear to directly influence the language or cognitive deficits observed in PPA.
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