4 results on '"Lesnick, Timothy G."'
Number of results to display per page
Search Results
2. Tracking white matter degeneration in asymptomatic and symptomatic MAPT mutation carriers
- Author
-
Chen, Qin, Boeve, Bradley F, Schwarz, Christopher G, Reid, Robert, Tosakulwong, Nirubol, Lesnick, Timothy G, Bove, Jessica, Brannelly, Patrick, Brushaber, Danielle, Coppola, Giovanni, Dheel, Christina, Dickerson, Bradford C, Dickinson, Susan, Faber, Kelley, Fields, Julie, Fong, Jamie, Foroud, Tatiana, Forsberg, Leah, Gavrilova, Ralitza H, Gearhart, Debra, Ghoshal, Nupur, Goldman, Jill, Graff-Radford, Jonathan, Graff-Radford, Neill R, Grossman, Murray, Haley, Dana, Heuer, Hilary W, Hsiung, Ging-Yuek R, Huey, Edward, Irwin, David J, Jack, Clifford R, Jones, David T, Jones, Lynne, Karydas, Anna M, Knopman, David S, Kornak, John, Kramer, Joel, Kremers, Walter, Kukull, Walter A, Lapid, Maria, Lucente, Diane, Lungu, Codrin, Mackenzie, Ian RA, Manoochehri, Masood, McGinnis, Scott, Miller, Bruce L, Pearlman, Rodney, Petrucelli, Leonard, Potter, Madeline, Rademakers, Rosa, Ramos, Eliana M, Rankin, Katherine P, Rascovsky, Katya, Sengdy, Pheth, Shaw, Leslie, Syrjanen, Jeremy, Tatton, Nadine, Taylor, Joanne, Toga, Arthur W, Trojanowski, John, Weintraub, Sandra, Wong, Bonnie, Boxer, Adam L, Rosen, Howie, Wszolek, Zbigniew, Kantarci, Kejal, and LEFFTDS Consortium
- Subjects
Adult ,Male ,Heterozygote ,Aging ,Clinical Sciences ,tau Proteins ,Neuropsychological Tests ,Neurodegenerative ,LEFFTDS Consortium ,Clinical Research ,MAPT ,Acquired Cognitive Impairment ,Genetics ,Humans ,2.1 Biological and endogenous factors ,Genetic Testing ,Gray Matter ,Aetiology ,Aged ,Diffusion tensor image ,Neurology & Neurosurgery ,Neurosciences ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Neurodegenerative Diseases ,Middle Aged ,White Matter ,Asymptomatic ,Brain Disorders ,Diffusion Magnetic Resonance Imaging ,Diffusion Tensor Imaging ,Frontotemporal Dementia ,Mutation ,Disease Progression ,Longitudinal ,Female ,Dementia - Abstract
Our aim was to investigate the patterns and trajectories of white matter (WM) diffusion abnormalities in microtubule-associated protein tau (MAPT) mutations carriers. We studied 22 MAPT mutation carriers (12 asymptomatic, 10 symptomatic) and 20 noncarriers from 8 families, who underwent diffusion tensor imaging (DTI) and a subset (10 asymptomatic, 6 symptomatic MAPT mutation carriers, and 10 noncarriers) were followed annually (median= 4years). Cross-sectional and longitudinal changes in mean diffusivity (MD) and fractional anisotropy were analyzed. Asymptomatic MAPT mutation carriers had higher MD in entorhinal WM, which propagated to the limbic tracts and frontotemporal projections in the symptomatic stage compared with noncarriers. Reduced fractional anisotropy and increased MD in the entorhinal WM were associated with the proximity to estimated and actual age of symptom onset. The annualized change of entorhinal MD on serial DTI was accelerated in MAPT mutation carriers compared with noncarriers. Entorhinal WM diffusion abnormalities precede the symptom onset and track with disease progression in MAPT mutation carriers. Our cross-sectional and longitudinal data showed a potential clinical utility for DTI to track neurodegenerative disease progression for MAPT mutation carriers in clinical trials.
- Published
- 2019
3. Rates of lobar atrophy in asymptomatic MAPT mutation carriers
- Author
-
Chen, Qin, Boeve, Bradley F, Senjem, Matthew, Tosakulwong, Nirubol, Lesnick, Timothy G, Brushaber, Danielle, Dheel, Christina, Fields, Julie, Forsberg, Leah, Gavrilova, Ralitza, Gearhart, Debra, Graff-Radford, Jonathan, Graff-Radford, Neill R, Jack, Clifford R, Jones, David T, Knopman, David S, Kremers, Walter K, Lapid, Maria, Rademakers, Rosa, Syrjanen, Jeremy, Boxer, Adam L, Rosen, Howie, Wszolek, Zbigniew K, Kantarci, Kejal, and LEFFTDS Consortium
- Subjects
LEFFTDS Consortium ,Magnetic resonance image ,Rare Diseases ,Prevention ,Longitudinal ,MAPT ,Neurosciences ,Acquired Cognitive Impairment ,Dementia ,Neurodegenerative ,Frontotemporal dementia ,Asymptomatic ,Brain Disorders - Abstract
IntroductionThe aim of this study was to investigate the rates of lobar atrophy in the asymptomatic microtubule-associated protein tau (MAPT) mutation carriers.MethodsMAPT mutation carriers (n=14; 10 asymptomatic, 4 converters from asymptomatic to symptomatic) and noncarriers (n=13) underwent structural magnetic resonance imaging and were followed annually with a median of 9.2years. Longitudinal changes in lobar atrophy were analyzed using the tensor-based morphometry with symmetric normalization algorithm.ResultsThe rate of temporal lobe atrophy in asymptomatic MAPT mutation carriers was faster than that in noncarriers. Although the greatest rate of atrophy was observed in the temporal lobe in converters, they also had increased atrophy rates in the frontal and parietal lobes compared to noncarriers.DiscussionAccelerated decline in temporal lobe volume occurs in asymptomatic MAPT mutation carriers followed by the frontal and parietal lobe in those who have become symptomatic. The findings have implications for monitoring the progression of neurodegeneration during clinical trials in asymptomatic MAPT mutation carriers.
- Published
- 2019
4. Large-scale replication and heterogeneity in Parkinson disease genetic loci
- Author
-
Sharma, Manu, Ioannidis, John P A, Facheris, Maurizio, Klein, Christine, Djarmati, Ana, Hagenah, Johann, Lohmann, Katja, Auburger, Georg, Hilker, Rüdiger, van de Loo, Simone, Dardiotis, Efthimios, Tsimourtou, Vaia, Ralli, Styliani, Farrer, Matthew, Kountra, Persa, Patramani, Gianna, Vogiatzi, Cristina, Hattori, Nobutaka, Tomiyama, Hiroyuki, Funayama, Manabu, Yoshino, Hiroyo, Li, Yuanzhe, Imamichi, Yoko, Toda, Tatsushi, Garraux, Gaetan, Satake, Wataru, Lynch, Tim, Gibson, J Mark, Valente, Enza Maria, Ferraris, Alessandro, Dallapiccola, Bruno, Ialongo, Tamara, Brighina, Laura, Corradi, Barbara, Piolti, Roberto, Gispert, Suzana, Tarantino, Patrizia, Annesi, Ferdinanda, Jeon, Beom S, Park, Sung-Sup, Aasly, J., Opala, Grzegorz, Jasinska-Myga, Barbara, Klodowska-Duda, Gabriela, Boczarska-Jedynak, Magdalena, Tan, Eng King, Belin, Andrea Carmine, Olson, Lars, Galter, Dagmar, Westerlund, Marie, Sydow, Olof, Nilsson, Christer, Puschmann, Andreas, Lin, J. J., Maraganore, Demetrius M, Ahlskog, J Eric, Vilariño-Güell, Carles, de Andrade, Mariza, Lesnick, Timothy G, Rocca, Walter A, Checkoway, Harvey, Ross, Owen A, Wszolek, Zbigniew K, Uitti, Ryan J, Hadjigeorgiou, Georgios M, Hicks, Andrew A, Jeon, Beom, Aasly, Jan O, Lesage, Suzanne, Lill, Christina M, Lin, Juei-Jueng, Lynch, Timothy, Lichtner, Peter, Lang, Anthony E, Mok, Vincent, Mellick, George D, Morrison, Karen E, Annesi, Grazia, Pramstaller, Peter P, Pichler, Irene, Park, Sung Sup, Quattrone, Aldo, Rogaeva, Ekaterina, Stefanis, Leonidas, Stockton, Joanne D, Brice, Alexis, Silburn, Peter A, Theuns, Jessie, Tan, Eng-King, Wirdefeldt, Karin, Wszolek, Zbigniew, Xiromerisiou, Georgia, Yueh, Kuo-Chu, Van Broeckhoven, Christine, Zhao, Yi, Gasser, Thomas, Maraganore, Demetrius, Krüger, Rejko, Consortium, GEO-PD, Boyle, R. S., Sellbach, A., O'Sullivan, J. D., Sutherland, G. T., Siebert, G. A., Bertram, Lars, Dissanayaka, N. N. W., Crosiers, David, Pickut, Barbara, Engelborghs, Sebastiaan, Meeus, Bram, De Deyn, Peter P, Cras, Patrick, Bozi, Maria, Agid, Y., Anheim, M., Bonnet, A-M, Borg, M., Brice, A., Broussolle, E., Corvol, J. C., Damier, P., Destée, A., Dürr, A., Durif, F., Lesage, S., Lohmann, E., Pollak, P., Rascol, O., Tison, F., Tranchant, C., Viallet, F., Vidailhet, M., Clarke, Carl, Tzourio, Christophe, Amouyel, Philippe, Loriot, Marie-Anne, Mutez, Eugénie, Duflot, Aurélie, Legendre, Jean-Philippe, Waucquier, Nawal, Riess, Olaf, Berg, Daniela, Schulte, Claudia, Pathologic Biochemistry and Physiology, Pollak, Pierre, De Deyn, Peter Paul, and GEO-PD Consortium
- Subjects
Male ,Genotype ,Single-nucleotide polymorphism ,Genome-wide association study ,Case-control studies ,Biology ,Polymorphism, Single Nucleotide ,Gene Frequency ,genetics [Parkinson Disease] ,Humans ,Genetic Predisposition to Disease ,ddc:610 ,Allele ,Parkinson Disease/genetics ,Allele frequency ,Alleles ,Genetic association ,Aged ,Genetics ,Medicine(all) ,Case-control study ,Parkinson Disease ,Odds ratio ,Middle Aged ,ddc:616.8 ,Genetic epidemiology ,Genetic Loci ,Case-Control Studies ,Female ,Neurology (clinical) ,Human medicine ,Genome-Wide Association Study - Abstract
Objective: Eleven genetic loci have reached genome-wide significance in a recent meta-analysis of genome-wide association studies in Parkinson disease (PD) based on populations of Caucasian descent. The extent to which these genetic effects are consistent across different populations is unknown. Methods: Investigators from the Genetic Epidemiology of Parkinson9s Disease Consortium were invited to participate in the study. A total of 11 SNPs were genotyped in 8,750 cases and 8,955 controls. Fixed as well as random effects models were used to provide the summary risk estimates for these variants. We evaluated between-study heterogeneity and heterogeneity between populations of different ancestry. Results: In the overall analysis, single nucleotide polymorphisms (SNPs) in 9 loci showed significant associations with protective per-allele odds ratios of 0.78–0.87 ( LAMP3 , BST1 , and MAPT ) and susceptibility per-allele odds ratios of 1.14–1.43 ( STK39 , GAK , SNCA , LRRK2 , SYT11 , and HIP1R ). For 5 of the 9 replicated SNPs there was nominally significant between-site heterogeneity in the effect sizes ( I 2 estimates ranged from 39% to 48%). Subgroup analysis by ethnicity showed significantly stronger effects for the BST1 (rs11724635) in Asian vs Caucasian populations and similar effects for SNCA , LRRK2 , LAMP3 , HIP1R , and STK39 in Asian and Caucasian populations, while MAPT rs2942168 and SYT11 rs34372695 were monomorphic in the Asian population, highlighting the role of population-specific heterogeneity in PD. Conclusion: Our study allows insight to understand the distribution of newly identified genetic factors contributing to PD and shows that large-scale evaluation in diverse populations is important to understand the role of population-specific heterogeneity. Neurology ® 2012;79:659–667
- Full Text
- View/download PDF
Catalog
Books, media, physical & digital resources
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.