Journal article
Assessment of executive function declines in presymptomatic and mildly symptomatic familial frontotemporal dementia: NIH-EXAMINER as a potential clinical trial endpoint
Alzheimer's and Dementia, Vol.16(1), pp.11-21
2020
PMID: 31914230
Introduction: Identifying clinical measures that track disease in the earliest stages of frontotemporal lobar degeneration (FTLD) is important for clinical trials. Familial FTLD provides a unique paradigm to study early FTLD. Executive dysfunction is a clinically relevant hallmark of FTLD and may be a marker of disease progression. Methods: Ninety-three mutation carriers with no symptoms or minimal/questionable symptoms (MAPT, n = 31; GRN, n = 28; C9orf72, n = 34; Clinical Dementia Rating scale plus NACC FTLD Module < 1) and 78 noncarriers enrolled through Advancing Research and Treatment in Frontotemporal Lobar Degeneration/Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects studies completed the Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (NIH-EXAMINER) and the UDS neuropsychological battery. Linear mixed-effects models were used to identify group differences in cognition at baseline and longitudinally. We examined associations between cognition, clinical functioning, and magnetic resonance imaging volumes. Results: NIH-EXAMINER scores detected baseline and differences in slopes between carriers and noncarriers, even in carriers with a baseline Clinical Dementia Rating scale plus NACC FTLD Module = 0. NIH-EXAMINER declines were associated with worsening clinical symptoms and brain volume loss. Discussion: The NIH-EXAMINER is sensitive to cognitive changes in presymptomatic familial FTLD and is a promising surrogate endpoint. © 2019 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.
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- Title
- Assessment of executive function declines in presymptomatic and mildly symptomatic familial frontotemporal dementia: NIH-EXAMINER as a potential clinical trial endpoint
- Creators
- A.M. Staffaroni - University of California, San FranciscoL. Bajorek - University Memory and Aging CenterK.B. Casaletto - University Memory and Aging CenterY. Cobigo - University of California, San FranciscoS.-Y.M. GohA. Wolf - University Memory and Aging CenterH.W. Heuer - University of California, San FranciscoF.M. Elahi - University of California, San FranciscoP.A. Ljubenkov - University of California, San FranciscoR. Dever - University of California, San FranciscoJ. Kornak - University of California, San FranciscoB. Appleby - Case Western Reserve UniversityJ. Bove - University of PennsylvaniaY. Bordelon - University of California, Los AngelesP. Brannelly - Rainwater Charitable FoundationD. Brushaber - Mayo Clinic in FloridaC. Caso - University of WashingtonG. Coppola - University of California, Los AngelesC. Dheel - Mayo Clinic in ArizonaB.C. Dickerson - Massachusetts General HospitalS. Dickinson - Association for Frontotemporal DegenerationS. DominguezK. Domoto-Reilly - University of WashingtonK. Faber - Indiana University – Purdue University IndianapolisJ. Ferrall - University of North Carolina at Chapel HillJ.A. Fields - Mayo ClinicA. Fishman - Johns Hopkins UniversityJ. Fong - University of California, San FranciscoT. Foroud - Indiana University – Purdue University IndianapolisL.K. Forsberg - Mayo Clinic in ArizonaR. Gavrilova - Mayo Clinic in ArizonaD. Gearhart - Mayo Clinic in ArizonaB. Ghazanfari - University of TorontoN. Ghoshal - Washington University in St. LouisJ. Goldman - Columbia UniversityJ. Graff-Radford - Mayo Clinic in ArizonaN. Graff-Radford - Mayo Clinic in FloridaI. Grant - Northwestern UniversityM. Grossman - University of PennsylvaniaD. Haley - WinnMedG.-Y. HsiungE.D. Huey - Columbia UniversityD.J. Irwin - University of PennsylvaniaD.T. Jones - Mayo Clinic in ArizonaL. Jones - Washington University in St. LouisK. Kantarci - Mayo Clinic in ArizonaA. Karydas - University of California, San FranciscoD.I. Kaufer - University of North Carolina at Chapel HillD.R. Kerwin - The University of Texas Southwestern Medical CenterD.S. Knopman - Mayo Clinic in ArizonaR. Kraft - Mayo Clinic in ArizonaW.K. Kremers - Mayo Clinic in FloridaW.A. Kukull - University of WashingtonI. Litvan - University of California San DiegoD. Lucente - Massachusetts General HospitalC. Lungu - National Institute of Neurological Disorders and StrokeI.R. Mackenzie - University of British ColumbiaM. Maldonado - University of California, Los AngelesM. Manoochehri - Columbia UniversityS.M. McGinnis - Harvard UniversityE. McKinley - University of Alabama at BirminghamM.F. Mendez - University of California, Los AngelesB.L. Miller - University of California, San FranciscoN. Multani - University of TorontoC. Onyike - Johns Hopkins UniversityJ. Padmanabhan - Massachusetts General HospitalA. Pantelyat - Johns Hopkins UniversityR. Pearlman - Bluefield CollegeL. Petrucelli - Mayo Clinic in FloridaM. Potter - Indiana University – Purdue University IndianapolisR. Rademakers - Mayo Clinic in FloridaE.M. Ramos - University of California, Los AngelesK.P. Rankin - University of California, San FranciscoK. Rascovsky - University of PennsylvaniaE.D. Roberson - University of Alabama at BirminghamE. RogalskiP. Sengdy - University of British ColumbiaL.M. Shaw - University of PennsylvaniaJ. Syrjanen - Mayo Clinic in FloridaM.C. Tartaglia - Occupational Cancer Research CentreN. Tatton - Association for Frontotemporal DegenerationJ. Taylor - University of California, San FranciscoA. TogaJ.Q. Trojanowski - University of PennsylvaniaS. WeintraubP. Wang - University of California, San FranciscoB. Wong - Harvard UniversityZ. WszolekA.L. Boxer - University of California, San FranciscoB.F. Boeve - Mayo Clinic in ArizonaJ.H. Kramer - University of California, San FranciscoH.J. Rosen - University Memory and Aging Center
- Publication Details
- Alzheimer's and Dementia, Vol.16(1), pp.11-21
- Publisher
- John Wiley and Sons Inc; HOBOKEN
- Number of pages
- 11
- Grant note
- National Institutes of Health: AG045390 Larry L. Hillblom FoundationCDCBristol-Myers SquibbAssociation for Frontotemporal DementiaNew York State Department of Health: 1510130358 BiogenAbbViePiramalCanadian Institutes of Health ResearchAlzheimer Society of British ColumbiaBright Focus FoundationPenn Institute on AgingAlzheimer's Drug Discovery FoundationEisaiUniversity of Southern CaliforniaDODParkinson FoundationMichael J. Fox FoundationJanssen PharmaceuticalsNIANINDSAllerganAssociation for Frontotemporal DegenerationAlzheimer's AssociationGE HealthcareEli LillyPfizerWyethTau ConsortiumHDSAAvidRocheGenentechAstraZenecaMerckNational Institute of Mental Health: R01MH120794 National Institute on Aging: P01AG066597, K23AG061253, P30AG066509, P30AG062421, P01AG019724, K24AG045333, R01AG062268, T32AG023481, U24AG021886 National Institute on Aging; National Institute of Neurological Disorders and Stroke: U19AG063911
National Institutes of Health, Grant/Award Number: AG045390; Larry L. Hillblom Foundation; CDC; Bristol-Myers Squibb; Eli Lilly; Pfizer; Wyeth; Tau Consortium and Association for Frontotemporal Dementia; HDSA; New York State Department of Health, Grant/AwardNumber: 1510130358; Biogen; AbbVie; Avid, and Piramal; Canadian Institutes of Health Research; Alzheimer Society of British Columbia; Bright Focus Foundation; Penn Institute on Aging; Alzheimer's Drug Discovery Foundation; Roche; Genentech; Eisai; University of Southern California; AstraZeneca; DOD; Parkinson Foundation; Michael J. Fox Foundation; Janssen Pharmaceuticals; Merck; NIA; NINDS; Allergan; Association for Frontotemporal Degeneration; Alzheimer's Association; GE Healthcare
- Comment
- Export Date: 27 February 2026; Cited By: 41
- Academic Unit
- Level 02 - Executives; Executives; UMMG Department of Neurology
- Resource Type
- Journal article
- PMID
- 31914230
- Record Identifier
- 991032996201502976