IC‐P‐134: Anteromedial temporal lobe diffusion tensor imaging and structural MRI changes in presymptomatic and symptomatic microtubule‐associated protein tau (MAPT) mutation carriers
Year: 2012
Type: article
Study design: Observational Study
Abstract: Frontotemporal dementia with parkinsonism linked to chromosome 17 is an autosomal dominant tauopathy that is linked to mutations in the gene encoding for the microtubule-associated protein tau (MAPT). Mutations in MAPT result in filamentous accumulation of hyperphosphorylated tau in neurons and glia leading to neurodegeneration and atrophy which predominantly involves the anteromedial temporal lobe. Our objective was to determine the volumetric changes in the anteromedial temporal lobe and DTI changes in white matter tracts that connect these cortical regions in MAPT mutation carriers. Patients with MAPT mutations from six families (n = 17) underwent MRI at 3T. Presymptomatic patients (n = 9) had median clinical dementia rating sum of boxes (CDR-SOB) score of zero and symptomatic patients (n = 8) had median CDR-SOB of 7. Age and sex matched controls (n = 17) were recruited. DTI was performed with 42 diffusion encoding steps and 2.7 mm. isotropic resolution. Automated tract-specific quantification of fractional anisotropy (FA) was performed using the FSL-JHU DTI atlas. Volumes of the anterior and medial temporal lobe structures were estimated with an automated segmentation algorithm on SPM5 using an in-house modified AAL atlas. Presymptomatic MAPT mutation carriers were characterized by decreased fornix FA (P = 0.02) and entorhinal cortex volume (P = 0.03). Symptomatic MAPT mutation carriers were characterized by decreased FA in the parahippocampal cingulum and fornix (p≤0.01) and decreased hippocampal, parahippocampal, entorhinal cortex, temporal pole gray matter volume (P<0.001). Decreased entorhinal cortex volume was associated with proximity to the expected age of symptom onset in presymptomatic MAPT mutation carriers. On the contrary, fornix FA was below the lower quartile of control values even in presymptomatic MAPT mutation carriers who had several decades to reach the expected age of symptom onset. Plots show the relationship between time to estimated age of disease onset and fornix FA (left), entorhinal cortex gray matter volume divided by % total intracranial volume (GM/%TIV) (right) in presymptomatic MAPT mutation carriers. Three families with different MAPT mutations are color-coded (red: N279K; blue: P301L; green: V337M). Orange line indicates the lower quartile in age and sex matched controls.
Source: Alzheimer s & Dementia
Institutions: Mayo Clinic, Mayo Clinic in Florida
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2032909284