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May 14, 2019; 92 (20) Article

Network-targeted stimulation engages neurobehavioral hallmarks of age-related memory decline

Aneesha S. Nilakantan, M.-Marsel Mesulam, Sandra Weintraub, Erica L. Karp, Stephen VanHaerents, Joel L. Voss
First published April 17, 2019, DOI: https://doi.org/10.1212/WNL.0000000000007502
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Article Information

vol. 92 no. 20 e2349-e2354
DOI: 
https://doi.org/10.1212/WNL.0000000000007502
PubMed: 
30996057
Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Print ISSN: 
0028-3878
Online ISSN: 
1526-632X
History: 
  • Received September 12, 2018
  • Accepted in final form January 17, 2019
  • First Published April 17, 2019.

Article Versions

Copyright & Usage: 
© 2019 American Academy of Neurology

Author Disclosures

    1. Aneesha S. Nilakantan, PhD,
    2. M.-Marsel Mesulam, MD,
    3. Sandra Weintraub, PhD,
    4. Erica L. Karp, MEd,
    5. Stephen VanHaerents, MD and
    6. Joel L. Voss, PhD
  1. Aneesha S. Nilakantan, PhD,
    2. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  2. M.-Marsel Mesulam, MD,
    3. Scientific Advisory Boards:

    1. Cure Alzheimer Fund; Association on Frontotemporal Dementia

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. Brain, Annals of Neurology, Human Brain Mapping, Journal of Cognitive Neuroscience- Member of Editorial Board

    Patents:

    1. NONE

    Publishing Royalties:

    1. Principles of Behavioral and Cognitive Neurology, Oxford University Press

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NIH- AG13854 1996-now PI NIH- DC008552 2005-now PI

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  3. Sandra Weintraub, PhD,
    4. Scientific Advisory Boards:

    1. Non profit: Dominantly Inherited Alzheimer's Network- neuropsychological assessment

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. 2005- Editorial Board, Alzheimer?s and Dementia: Journal of the Alzheimer?s Association 2005- International Advisory Board, Turkish Journal of Neurology 2006- Editorial Board, Dementia & Neuropsychologia, Journal of the Brazilian Academy of Neurology

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. 1) Commerical entity: Global Bracket: consultant

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. P30 AG013854 (Mesulam) 07/15/97 ? 06/30/21 NIH/NIA Alzheimer's Disease Core Center The Northwestern Alzheimer?s Disease Core Center was renewed in 2016, supporting an additional five years of research, and marking 25 years of continuous grant support. Role: Core B Leader, Co-investigator R01 DC008552 (Mesulam) 05/05/07 ? 04/30/22 NIH/NICDC Language in Primary Progressive Aphasia The major goal of this project is to investigate the language disorder and treatment modalities in PPA. Role: Co-Investigator R01 AG056258 (Rogalski) 05/01/17 ? 02/28/18 Determinants of neurodegenerative decline in the aphasic variant of Alzheimer?s disease The goal of this project is understanding of the neuropathology of PPA by bridging clinico-anatomical features and markers of underlying AD pathology, with the goal of informing therapeutic strategies. Role: Co-Investigator U01 AG052943 (Grossman) 06/01/16 ? 05/31/20 NIA via University of Pennsylvania Connectomic Imaging in Familial and Sporadic Frontotemporal Degeneration The purpose of this study is to assess advanced imaging in individuals with frontotemporal degeneration associated with FTLD-tau or FTLD-TDP pathology Role: Co-Investigator R01 AG045571 (Rogalski, Geula, Mesulam) 09/30/14 ? 04/30/19 NIH/NIA Exceptional Cognitive Aging: Neuropsychologic, Anatomic and Pathologic Correlates The proposed research will characterize, in a comprehensive, interdisciplinary and longitudinal manner, a cohort of octo- and nonagenarians who display an unusually successful cognitive aging trajectory. Identification of neurobiologic features that contribute to exceptionally successful cognitive aging may make it possible to help elderly avoid disease and disability, improve quality of life and alleviate a looming public health crisis. Role: Co-Investigator R01 NS085002 (Sorond) 06/01/14 ? 04/30/18 NIH/NINDS Cerebral small vessels in motor and cognitive decline The goal of this study is to identify vascular measures of cerebral small vessels which precede the onset of cognitive and motor decline and are predictive of clinical radiographic outcomes in small vessel disease. Role: Co-Investigator R01 NR014182 (Wang) 09/26/12 ? 08/31/17 NIH/NINR HippoPCI Hippocampal Predictors of Cognitive Impairment in Breast Cancer Patients This project will use longitudinal magnetic resonance imaging (MRI) to identify predictors and mechanisms of cognitive impairment in breast cancer patients receiving hormonal treatment. Role: Co-investigator U01 AG016976 (Kukull) 07/15/09 ? 06/30/19 NIA via University of Washington National Alzheimer?s Coordinating Center (NACC) Combine resources from four NIH-funded Alzheimer Disease Centers Northwestern, Washington Univ., Rush Univ., and UT Southwestern) to refine and standardize a common protocol for unbiased clinical and neuropathologic classification of frontotemporal dementias (FTDs) in a large pooled sample. Role: Co-Investigator U54 NS092089 (Boxer) 09/30/14 ? 07/31/17 NINDS via University of California, San Francisco The Frontotemporal Lobar Degeneration Clinical Research Consortium (ARTFL) Research Project 1 will collect cross-sectional data in sporadic FTLD patients using a new FTLD assessment battery, as well as screening all individuals for known FTLD- causing mutations and evidence of systemic inflammation, to prepare for trials of anti-tau and anti- inflammatory agents. Research Project 2 will collect longitudinal clinical and MRI data on familial FTLD (f-FTLD) individuals who carry mutations in MAPT, GRN and C90RF72 and their asymptomatic family members to enable disease prevention clinical trials. Role: Subsite PI U19 AG010483 (Aisen) 12/01/15 ? 08/31/17 NIA via University of California, San Diego The Anti-Amyloid Treatment in Asymptomatic Alzheimer?s Disease (A4 Study) Multi-center phase III clinical trial looking at efficacy of solanezumab to affect progression of disease in subjects with elevated brain amyloid but no cognitive symptoms. Role: Subsite PI Agreement (Aisen) 12/11/15 ? 12/10/17 Eli Lilly and Company via UCSD The Anti-Amyloid Treatment in Asymptomatic Alzheimer?s Disease (A4 Study) Multi-center phase III clinical trial looking at efficacy of solanezumab to affect progression of disease in subjects with elevated brain amyloid but no cognitive symptoms. Role: Subsite PI LEARN-15-338730 (Aisen) 11/01/15 ? 10/31/17 Alzheimer?s Association via UCSC Longitudinal Evaluation of Amyloid Risk and Neurodegeneration ? the LEARN Study. A companion study to A4 Trial A companion observational study to the A4 trial Role: Subsite PI Completed Research Support R01 AG030611 (Wolf) 03/01/11 ? 02/28/17 NIH/NIA LITCOG II: Health Literacy and Cognitive Function among Older Adults The proposed longitudinal study will provide an in-depth investigation of older adults? health literacy and ability to manage health, and whether these skills are affected by cognitive decline and the aging process. Role: Co-Investigator R01 NS075075 (Rogalski) 03/15/12 ? 02/28/17 NIH/NINDS Determinants of Neurodegenerative Decline in Primary Progressive Aphasia This project represents the first multidimensional study of longitudinal course using the new antemortem amyloid biomarker [18F]-AV-45 in PPA. Role: Co-Investigator

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  4. Erica L. Karp, MEd,
    5. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  5. Stephen VanHaerents, MD and
    6. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. SAGE Pharmaceuticals Neuropace

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  6. Joel L. Voss, PhD
    7. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. Hippocampus, Editorial Board Member, 2018-present

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  1. From the Departments of Medical Social Sciences (A.S.N., E.L.K., J.L.V.), Ken and Ruth Davee Department of Neurology (M.-M.M., S.V., J.L.V.), and Psychiatry and Behavioral Sciences (S.W., J.L.V.), Cognitive Neurology and Alzheimer's Disease Center (A.S.N., M.-M.M., S.W.), Feinberg School of Medicine, Northwestern University, Chicago, IL.
  1. Correspondence
    Dr. Voss joel-voss{at}northwestern.edu
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