Browsing by Author "Finger, Elizabeth"

Now showing 1 - 4 of 4
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    A DAT1 gene and APOE ε4 interaction is associated with apathy and structural brain changes in Alzheimer’s Disease
    (Wiley, 2025-01-09) Malik, Rubina; Beaton, Derek; Saykin, Andrew J.; Nho, Kwangsik; Finger, Elizabeth; Radiology and Imaging Sciences, School of Medicine
    Background: Apathy in patients with Alzheimer’s disease (AD) is associated with significant morbidity. We examined whether interactions between genetic variants related to neurotransmitter systems and regional brain atrophy are associated with apathy in patients with mild cognitive impairment (MCI) and AD. Method: For 1162 participants in the Alzheimer’s Disease Neuroimaging Initiative, including those with AD, MCI and cognitively normal individuals, a partial least squares correspondence analysis (PLS‐CA) modeled interactions between single nucleotide polymorphisms (SNPs), structural whole‐brain imaging variables, and apathy. Result: An interaction between apathy, the possession of an APOE (apolipoprotein E) ε4 allele combined with minor homozygosity for the DAT1 (dopamine transporter 1) gene, and brain atrophy. Conclusion: The results point to an association of a dopaminergic genetic marker and apathy in AD and may inform future design of clinical trials of apathy, as well as new treatment targets.
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    Plasma Neurofilament Light for Prediction of Disease Progression in Familial Frontotemporal Lobar Degeneration
    (American Academy of Neurology, 2021-05-04) Rojas, Julio C.; Wang, Ping; Staffaroni, Adam M.; Heller, Carolin; Cobigo, Yann; Wolf, Amy; Goh, Sheng-Yang M.; Ljubenkov, Peter A.; Heuer, Hilary W.; Fong, Jamie C.; Taylor, Joanne B.; Veras, Eliseo; Song, Linan; Jeromin, Andreas; Hanlon, David; Yu, Lili; Khinikar, Arvind; Sivasankaran, Rajeev; Kieloch, Agnieszka; Valentin, Marie-Anne; Karydas, Anna M.; Mitic, Laura L.; Pearlman, Rodney; Kornak, John; Kramer, Joel H.; Miller, Bruce L.; Kantarci, Kejal; Knopman, David S.; Graff-Radford, Neill; Petrucelli, Leonard; Rademakers, Rosa; Irwin, David J.; Grossman, Murray; Ramos, Eliana Marisa; Coppola, Giovanni; Mendez, Mario F.; Bordelon, Yvette; Dickerson, Bradford C.; Ghoshal, Nupur; Huey, Edward D.; Mackenzie, Ian R.; Appleby, Brian S.; Domoto-Reilly, Kimiko; Hsiung, Ging-Yuek R.; Toga, Arthur W.; Weintraub, Sandra; Kaufer, Daniel I.; Kerwin, Diana; Litvan, Irene; Onyike, Chiadikaobi U.; Pantelyat, Alexander; Roberson, Erik D.; Tartaglia, Maria C.; Foroud, Tatiana; Chen, Weiping; Czerkowicz, Julie; Graham, Danielle L.; van Swieten, John C.; Borroni, Barbara; Sanchez-Valle, Raquel; Moreno, Fermin; Laforce, Robert; Graff, Caroline; Synofzik, Matthis; Galimberti, Daniela; Rowe, James B.; James B., Mario; Finger, Elizabeth; Vandenberghe, Rik; de Mendonça, Alexandre; Tagliavini, Fabrizio; Santana, Isabel; Ducharme, Simon; Butler, Chris R.; Gerhard, Alexander; Levin, Johannes; Danek, Adrian; Otto, Markus; Sorbi, Sandro; Cash, David M.; Convery, Rhian S.; Bocchetta, Martina; Foiani, Martha; Greaves, Caroline V.; Peakman, Georgia; Russell, Lucy; Swift, Imogen; Todd, Emily; Rohrer, Jonathan D.; Boeve, Bradley F.; Rosen, Howard J.; Boxer, Adam L.; Neurology, School of Medicine
    Objective: We tested the hypothesis that plasma neurofilament light chain (NfL) identifies asymptomatic carriers of familial frontotemporal lobar degeneration (FTLD)-causing mutations at risk of disease progression. Methods: Baseline plasma NfL concentrations were measured with single-molecule array in original (n = 277) and validation (n = 297) cohorts. C9orf72, GRN, and MAPT mutation carriers and noncarriers from the same families were classified by disease severity (asymptomatic, prodromal, and full phenotype) using the CDR Dementia Staging Instrument plus behavior and language domains from the National Alzheimer's Disease Coordinating Center FTLD module (CDR+NACC-FTLD). Linear mixed-effect models related NfL to clinical variables. Results: In both cohorts, baseline NfL was higher in asymptomatic mutation carriers who showed phenoconversion or disease progression compared to nonprogressors (original: 11.4 ± 7 pg/mL vs 6.7 ± 5 pg/mL, p = 0.002; validation: 14.1 ± 12 pg/mL vs 8.7 ± 6 pg/mL, p = 0.035). Plasma NfL discriminated symptomatic from asymptomatic mutation carriers or those with prodromal disease (original cutoff: 13.6 pg/mL, 87.5% sensitivity, 82.7% specificity; validation cutoff: 19.8 pg/mL, 87.4% sensitivity, 84.3% specificity). Higher baseline NfL correlated with worse longitudinal CDR+NACC-FTLD sum of boxes scores, neuropsychological function, and atrophy, regardless of genotype or disease severity, including asymptomatic mutation carriers. Conclusions: Plasma NfL identifies asymptomatic carriers of FTLD-causing mutations at short-term risk of disease progression and is a potential tool to select participants for prevention clinical trials. Trial registration information: ClinicalTrials.gov Identifier: NCT02372773 and NCT02365922. Classification of evidence: This study provides Class I evidence that in carriers of FTLD-causing mutations, elevation of plasma NfL predicts short-term risk of clinical progression.
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    Sex differences in clinical phenotypes of behavioral variant frontotemporal dementia
    (Wiley, 2025) Liu, Xulin; de Boer, Sterre C. M.; Cortez, Kasey; Poos, Jackie M.; Illán-Gala, Ignacio; Heuer, Hilary; Forsberg, Leah K.; Casaletto, Kaitlin; Memel, Molly; Appleby, Brian S.; Barmada, Sami; Bozoki, Andrea; Clark, David; Cobigo, Yann; Darby, Ryan; Dickerson, Bradford C.; Domoto-Reilly, Kimiko; Galasko, Douglas R.; Geschwind, Daniel H.; Ghoshal, Nupur; Graff-Radford, Neill R.; Grant, Ian M.; Hsiung, Ging-Yuek Robin; Honig, Lawrence S.; Huey, Edward D.; Irwin, David; Kantarci, Kejal; Léger, Gabriel C.; Litvan, Irene; Mackenzie, Ian R.; Masdeu, Joseph C.; Mendez, Mario F.; Onyike, Chiadi U.; Pascual, Belen; Pressman, Peter; Bayram, Ece; Ramos, Eliana Marisa; Roberson, Erik D.; Rogalski, Emily; Bouzigues, Arabella; Russell, Lucy L.; Foster, Phoebe H.; Ferry-Bolder, Eve; Masellis, Mario; van Swieten, John; Jiskoot, Lize; Seelaar, Harro; Sanchez-Valle, Raquel; Laforce, Robert; Graff, Caroline; Galimberti, Daniela; Vandenberghe, Rik; de Mendonça, Alexandre; Tiraboschi, Pietro; Santana, Isabel; Gerhard, Alexander; Levin, Johannes; Sorbi, Sandro; Otto, Markus; Pasquier, Florence; Ducharme, Simon; Butler, Chris R.; Le Ber, Isabelle; Finger, Elizabeth; Rowe, James B.; Synofzik, Matthis; Moreno, Fermin; Borroni, Barbara; Boeve, Brad F.; Boxer, Adam L.; Rosen, Howie J.; Pijnenburg, Yolande A. L.; Rohrer, Jonathan D.; Tartaglia, Maria Carmela; ALLFTD Consortium; GENFI Consortium; Medicine, School of Medicine
    Introduction: Higher male prevalence in sporadic behavioral variant frontotemporal dementia (bvFTD) has been reported. We hypothesized differences in phenotypes between genetic and sporadic bvFTD females resulting in underdiagnosis of sporadic bvFTD females. Methods: We included genetic and sporadic bvFTD patients from two multicenter cohorts. We compared behavioral and cognitive symptoms, and gray matter volumes, between genetic and sporadic cases in each sex. Results: Females with sporadic bvFTD showed worse compulsive behavior (p = 0.026) and language impairments (p = 0.024) compared to females with genetic bvFTD (n = 152). Genetic bvFTD females had smaller gray matter volumes than sporadic bvFTD females, particularly in the parietal lobe. Discussion: Females with sporadic bvFTD exhibit a distinct clinical phenotype compared to females with genetic bvFTD. This difference may explain the discrepancy in prevalence between genetic and sporadic cases, as some females without genetic mutations may be misdiagnosed due to atypical bvFTD symptom presentation. Highlights: Sex ratio is equal in genetic behavioral variant of frontotemporal dementia (bvFTD), whereas more males are present in sporadic bvFTD. Distinct neuropsychiatric phenotypes exist between sporadic and genetic bvFTD in females. Phenotype might explain the sex ratio difference between sporadic and genetic cases.
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    Temporal order of clinical and biomarker changes in familial frontotemporal dementia
    (Springer Nature, 2022) Staffaroni, Adam M.; Quintana, Melanie; Wendelberger, Barbara; Heuer, Hilary W.; Russell, Lucy L.; Cobigo, Yann; Wolf, Amy; Goh, Sheng-Yang Matt; Petrucelli, Leonard; Gendron, Tania F.; Heller, Carolin; Clark, Annie L.; Taylor, Jack Carson; Wise, Amy; Ong, Elise; Forsberg, Leah; Brushaber, Danielle; Rojas, Julio C.; VandeVrede, Lawren; Ljubenkov, Peter; Kramer, Joel; Casaletto, Kaitlin B.; Appleby, Brian; Bordelon, Yvette; Botha, Hugo; Dickerson, Bradford C.; Domoto-Reilly, Kimiko; Fields, Julie A.; Foroud, Tatiana; Gavrilova, Ralitza; Geschwind, Daniel; Ghoshal, Nupur; Goldman, Jill; Graff-Radford, Jonathon; Graff-Radford, Neill; Grossman, Murray; Hall, Matthew G. H.; Hsiung, Ging-Yuek; Huey, Edward D.; Irwin, David; Jones, David T.; Kantarci, Kejal; Kaufer, Daniel; Knopman, David; Kremers, Walter; Lago, Argentina Lario; Lapid, Maria I.; Litvan, Irene; Lucente, Diane; Mackenzie, Ian R.; Mendez, Mario F.; Mester, Carly; Miller, Bruce L.; Onyike, Chiadi U.; Rademakers, Rosa; Ramanan, Vijay K.; Ramos, Eliana Marisa; Rao, Meghana; Rascovsky, Katya; Rankin, Katherine P.; Roberson, Erik D.; Savica, Rodolfo; Tartaglia, M. Carmela; Weintraub, Sandra; Wong, Bonnie; Cash, David M.; Bouzigues, Arabella; Swift, Imogen J.; Peakman, Georgia; Bocchetta, Martina; Todd, Emily G.; Convery, Rhian S.; Rowe, James B.; Borroni, Barbara; Galimberti, Daniela; Tiraboschi, Pietro; Masellis, Mario; Finger, Elizabeth; van Swieten, John C.; Seelaar, Harro; Jiskoot, Lize C.; Sorbi, Sandro; Butler, Chris R.; Graff, Caroline; Gerhard, Alexander; Langheinrich, Tobias; Laforce, Robert; Sanchez-Valle, Raquel; de Mendonça, Alexandre; Moreno, Fermin; Synofzik, Matthis; Vandenberghe, Rik; Ducharme, Simon; Le Ber, Isabelle; Levin, Johannes; Danek, Adrian; Otto, Markus; Pasquier, Florence; Santana, Isabel; Kornak, John; Boeve, Bradley F.; Rosen, Howard J.; Rohrer, Jonathan D.; Boxer, Adam L.; Frontotemporal Dementia Prevention Initiative (FPI) Investigators; Medicine, School of Medicine
    Unlike familial Alzheimer’s disease, we have been unable to accurately predict symptom onset in presymptomatic familial frontotemporal dementia (f-FTD) mutation carriers, which is a major hurdle to designing disease prevention trials. We developed multimodal models for f-FTD disease progression and estimated clinical trial sample sizes in C9orf72, GRN, and MAPT mutation carriers. Models included longitudinal clinical and neuropsychological scores, regional brain volumes, and plasma neurofilament light chain (NfL) in 796 carriers and 412 non-carrier controls. We found that the temporal ordering of clinical and biomarker progression differed by genotype. In prevention-trial simulations employing model-based patient selection, atrophy and NfL were the best endpoints, whereas clinical measures were potential endpoints in early symptomatic trials. F-FTD prevention trials are feasible but will likely require global recruitment efforts. These disease progression models will facilitate the planning of f-FTD clinical trials, including the selection of optimal endpoints and enrollment criteria to maximize power to detect treatment effects.