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Practical recommendations for timely,accurate diagnosis of symptomatic Alzheimer’s disease (MCI and dementia) in primary care: a review and synthesis
Authors:J L Liss  S Seleri Assunção  J Cummings  A Atri  D S Geldmacher  S F Candela  D P Devanand  H M Fillit  J Susman  J Mintzer  T Bittner  S A Brunton  D R Kerwin  W C Jackson  G W Small  G T Grossberg  C K Clevenger  V Cotter  R Stefanacci  A Wise-Brown  M N Sabbagh
Institution:1. The Columbus Memory Center, Columbus, GA, USA

Contribution: Conceptualization (lead), Project administration (supporting), Supervision (supporting), Visualization (lead), Writing - original draft (lead), Writing - review & editing (equal);2. US Medical Affairs – Neuroscience, Genentech, A Member of the Roche Group, South San Francisco, CA, USA

Contribution: Conceptualization (lead), Project administration (lead), Supervision (supporting), Visualization (lead), Writing - original draft (lead), Writing - review & editing (equal);3. Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, NV, USA

Lou Ruvo Center for Brain Health – Cleveland Clinic Nevada, Las Vegas, NV, USA

Contribution: Conceptualization (supporting), Visualization (supporting), Writing - original draft (supporting), Writing - review & editing (equal);4. Banner Sun Health Research Institute, Sun City, AZ, USA

Center for Brain/Mind Medicine, Department of Neurology, Brigham and Women’s Hospital, Boston, MA, USA

Harvard Medical School, Boston, MA, USA

Contribution: Conceptualization (supporting), Visualization (supporting), Writing - original draft (supporting), Writing - review & editing (equal);5. Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA

Contribution: Conceptualization (supporting), Writing - original draft (supporting), Writing - review & editing (equal);6. Health & Wellness Partners, LLC, Upper Saddle River, NJ, USA

Contribution: Conceptualization (lead), Project administration (supporting), Visualization (lead), Writing - original draft (lead), Writing - review & editing (equal);7. Division of Geriatric Psychiatry, New York State Psychiatric Institute and Columbia University Irving Medical Center, New York, NY, USA

Contribution: Conceptualization (supporting), Visualization (supporting), Writing - original draft (supporting), Writing - review & editing (equal);8. Departments of Geriatric Medicine, Medicine, and Neuroscience, Icahn School of Medicine and Mt. Sinai, New York, NY, USA

Alzheimer’s Drug Discovery Foundation, New York, NY, USA

Contribution: Conceptualization (supporting), Writing - original draft (supporting), Writing - review & editing (equal);9. Department of Family and Community Medicine, Northeast Ohio Medical University, Rootstown, OH, USA

Contribution: Conceptualization (supporting), Writing - original draft (supporting), Writing - review & editing (equal);10. Roper St Francis Healthcare, Charleston, SC, USA

Ralph H. Johnson VA Medical Center, Charleston, SC, USA

Contribution: Conceptualization (supporting), Writing - original draft (supporting), Writing - review & editing (equal);11. F.Hoffmann-LaRoche, Basel, Switzerland

Contribution: Conceptualization (supporting), Writing - original draft (supporting), Writing - review & editing (equal);12. Department of Family Medicine, Touro University, Vallejo, CA, USA

Contribution: Conceptualization (supporting), Writing - original draft (supporting), Writing - review & editing (equal);13. Kerwin Medical Center, Dallas, TX, USA

Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA

Contribution: Conceptualization (supporting), Writing - original draft (supporting), Writing - review & editing (equal);14. Departments of Family Medicine and Psychiatry, University of Tennessee College of Medicine, Memphis, TN, USA

Contribution: Conceptualization (supporting), Writing - original draft (supporting), Writing - review & editing (equal);15. Division of Geriatric Psychiatry, UCLA Longevity Center, Semel Institute for Neuroscience & Human Behavior, University of California – Los Angeles, Los Angeles, CA, USA

Contribution: Conceptualization (supporting), Writing - original draft (supporting), Writing - review & editing (equal);16. Division of Geriatric Psychiatry, St Louis University School of Medicine, St Louis, MO, USA

Contribution: Conceptualization (supporting), Writing - original draft (supporting), Writing - review & editing (equal);17. Department of Neurology, Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA, USA

Contribution: Conceptualization (supporting), Writing - original draft (supporting), Writing - review & editing (equal);18. Johns Hopkins School of Nursing, Baltimore, MD, USA

Contribution: Conceptualization (supporting), Writing - original draft (supporting), Writing - review & editing (equal);19. Jefferson College of Population Health, Thomas Jefferson University, Philadelphia, PA, USA

Contribution: Conceptualization (supporting), Writing - original draft (supporting), Writing - review & editing (equal);20. US Medical Affairs – Neuroscience, Genentech, A Member of the Roche Group, South San Francisco, CA, USA

Contribution: Conceptualization (supporting), Writing - original draft (supporting), Writing - review & editing (equal);21. Lou Ruvo Center for Brain Health – Cleveland Clinic Nevada, Las Vegas, NV, USA

Abstract:The critical role of primary care clinicians (PCCs) in Alzheimer’s disease (AD) prevention, diagnosis and management must evolve as new treatment paradigms and disease-modifying therapies (DMTs) emerge. Our understanding of AD has grown substantially: no longer conceptualized as a late-in-life syndrome of cognitive and functional impairments, we now recognize that AD pathology builds silently for decades before cognitive impairment is detectable. Clinically, AD first manifests subtly as mild cognitive impairment (MCI) due to AD before progressing to dementia. Emerging optimism for improved outcomes in AD stems from a focus on preventive interventions in midlife and timely, biomarker-confirmed diagnosis at early signs of cognitive deficits (i.e. MCI due to AD and mild AD dementia). A timely AD diagnosis is particularly important for optimizing patient care and enabling the appropriate use of anticipated DMTs. An accelerating challenge for PCCs and AD specialists will be to respond to innovations in diagnostics and therapy for AD in a system that is not currently well positioned to do so. To overcome these challenges, PCCs and AD specialists must collaborate closely to navigate and optimize dynamically evolving AD care in the face of new opportunities. In the spirit of this collaboration, we summarize here some prominent and influential models that inform our current understanding of AD. We also advocate for timely and accurate (i.e. biomarker-defined) diagnosis of early AD. In doing so, we consider evolving issues related to prevention, detecting emerging cognitive impairment and the role of biomarkers in the clinic.
Keywords:Alzheimer disease  biomarkers  dementia  disease-modifying therapies  mild cognitive impairment  primary health care
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