Dataset Information

Lateral Temporal Lobe: An Early Imaging Marker of the Presymptomatic GRN Disease?

ABSTRACT: The preclinical stage of frontotemporal lobar degeneration (FTLD) is not well characterized. We conducted a brain metabolism (FDG-PET) and structural (cortical thickness) study to detect early changes in asymptomatic GRN mutation carriers (aGRN+) that were evaluated longitudinally over a 20-month period. At baseline, a left lateral temporal lobe hypometabolism was present in aGRN+ without any structural changes. Importantly, this is the first longitudinal study and, across time, the metabolism more rapidly decreased in aGRN+ in lateral temporal and frontal regions. The main structural change observed in the longitudinal study was a reduction of cortical thickness in the left lateral temporal lobe in carriers. A limit of this study is the relatively small sample (n?=?16); nevertheless, it provides important results. First, it evidences that the pathological processes develop a long time before clinical onset, and that early neuroimaging changes might be detected approximately 20 years before the clinical onset of disease. Second, it suggests that metabolic changes are detectable before structural modifications and cognitive deficits. Third, both the baseline and longitudinal studies provide converging results implicating lateral temporal lobe as early involved in GRN disease. Finally, our study demonstrates that structural and metabolic changes could represent possible biomarkers to monitor the progression of disease in the presymptomatic stage toward clinical onset.

SUBMITTER: Caroppo P

PROVIDER: S-EPMC4923734 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Lateral Temporal Lobe: An Early Imaging Marker of the Presymptomatic GRN Disease?

Caroppo Paola P Habert Marie-Odile MO Durrleman Stanley S Funkiewiez Aurélie A Perlbarg Vincent V Hahn Valérie V Bertin Hugo H Gaubert Malo M Routier Alexandre A Hannequin Didier D Deramecourt Vincent V Pasquier Florence F Rivaud-Pechoux Sophie S Vercelletto Martine M Edouart Geoffrey G Valabregue Romain R Lejeune Pascal P Didic Mira M Corvol Jean-Christophe JC Benali Habib H Lehericy Stephane S Dubois Bruno B Colliot Olivier O Brice Alexis A Le Ber Isabelle I

Journal of Alzheimer's disease : JAD 20150101 3

The preclinical stage of frontotemporal lobar degeneration (FTLD) is not well characterized. We conducted a brain metabolism (FDG-PET) and structural (cortical thickness) study to detect early changes in asymptomatic GRN mutation carriers (aGRN+) that were evaluated longitudinally over a 20-month period. At baseline, a left lateral temporal lobe hypometabolism was present in aGRN+ without any structural changes. Importantly, this is the first longitudinal study and, across time, the metabolism m ...[more]

PMID: 26401709

Similar Datasets

Project description:Human episodic memory critically depends on subregions of the medial temporal lobe, which are part of functional brain systems such as the anterior-temporal and the posterior-medial system. Here we analysed how Alzheimer's pathology affects functional connectivity within these systems. Data from 256 amyloid-β-negative cognitively unimpaired, 103 amyloid-β-positive cognitively unimpaired, and 83 amyloid-β-positive individuals with mild cognitive impairment were analysed. Amyloid-β and tau pathology were measured using the CSF amyloid-β42/40 ratio and phosphorylated tau, respectively. We found that amyloid-β-positive cognitively unimpaired individuals were mainly characterized by decreased functional connectivity between the medial temporal lobe and regions in the anterior-temporal system, most prominently between left perirhinal/entorhinal cortices and medial prefrontal cortex. Furthermore, correlation analysis in this group revealed decreasing functional connectivity between bilateral perirhinal/entorhinal cortices, anterior hippocampus and posterior-medial regions with increasing levels of phosphorylated tau. The amyloid-β-positive individuals with mild cognitive impairment mostly exhibited reduced connectivity between the medial temporal lobe and posterior-medial regions, predominantly between the anterior hippocampus and posterior cingulate cortex. In addition, they showed hyperconnectivity within the medial temporal lobe and its immediate proximity. Lower medial temporal-cortical functional connectivity networks resulting from the group comparisons of cognitively unimpaired individuals were associated with reduced memory performance and more rapid longitudinal memory decline as shown by linear mixed-effects regression analysis. Finally, we found that reduced medial temporal-cortical connectivity in mildly cognitively impaired individuals was related to reduced entorhinal thickness and white matter integrity of the parahippocampal cingulum and the fornix. No such relationships were found in cognitively unimpaired individuals. In conclusion, our findings show that the earliest changes in preclinical Alzheimer's disease might involve decreased connectivity within the anterior-temporal system, and early changes in connectivity might be related to memory impairment, but not to structural changes. With disease progression and increased tau pathology, medial temporal functional connectivity with posterior-medial regions seems to be increasingly impaired. In individuals with mild cognitive impairment, reduced functional connectivity is associated with structural brain changes as well as the emergence of locally increased connectivity patterns. Thus, functional connectivity between the medial temporal lobe and the anterior-temporal and posterior-medial system could serve as stage-specific functional markers in early Alzheimer's disease.

Project description:ObjectiveLateral temporal lobe epilepsy (LTLE) has been diagnosed in only a small number of patients; therefore, its surgical outcome is not as well-known as that of mesial temporal lobe epilepsy. We aimed to evaluate the long-term (5 years) and short-term (2 years) surgical outcomes and identify possible prognostic factors in patients with LTLE.MethodsThis retrospective cohort study was conducted between January 1995 and December 2018 among patients who underwent resective surgery in a university-affiliated hospital. Patients were classified as LTLE if ictal onset zone was in lateral temporal area. Surgical outcomes were evaluated at 2 and 5 years. We subdivided based on outcomes and compared clinical and neuroimaging data including cortical thickness between two groups.ResultsSixty-four patients were included in the study. The mean follow-up duration after the surgery was 8.4 years. Five years after surgery, 45 of the 63 (71.4%) patients achieved seizure freedom. Clinically and statistically significant prognostic factors for postsurgical outcomes were the duration of epilepsy before surgery and focal cortical dysplasia on postoperative histopathology at the 5-year follow-up. Optimal cut-off point for epilepsy duration was eight years after the seizure onset (odds ratio 4.375, p-value = 0.0214). Furthermore, we propose a model for predicting seizure outcomes 5 years after surgery using the receiver operating characteristic curve and nomogram (area under the curve = 0.733; 95% confidence interval, 0.588-0.879). Cortical thinning was observed in ipsilateral cingulate gyrus and contralateral parietal lobe in poor surgical group compared to good surgical group (p-value < 0.01, uncorrected).ConclusionsThe identified predictors of unfavorable surgical outcomes may help in selecting optimal candidates and identifying the optimal timing for surgery among patients with LTLE. Additionally, cortical thinning was more extensive in the poor surgical group.

Dataset Information

Lateral Temporal Lobe: An Early Imaging Marker of the Presymptomatic GRN Disease?

Publications

Lateral Temporal Lobe: An Early Imaging Marker of the Presymptomatic GRN Disease?

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets