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Approach to atypical Alzheimer’s disease and case studies of the major subtypes

Published online by Cambridge University Press:  15 February 2017

Bradford C. Dickerson*
Affiliation:
Frontotemporal Disorders Unit & Alzheimer’s Disease Research Center, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
Scott M. McGinnis
Affiliation:
Frontotemporal Disorders Unit & Alzheimer’s Disease Research Center, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
Chenjie Xia
Affiliation:
Frontotemporal Disorders Unit & Alzheimer’s Disease Research Center, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
Bruce H. Price
Affiliation:
Frontotemporal Disorders Unit & Alzheimer’s Disease Research Center, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
Alireza Atri
Affiliation:
California Pacific Medical Center, Ray Dolby Brain Health Center, San Francisco, California, USA
Melissa E. Murray
Affiliation:
Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA
Mario F. Mendez
Affiliation:
Department of Neurology, University of California–Los Angeles, Los Angeles, California, USA
David A. Wolk
Affiliation:
Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
*
*Address for correspondence: Brad Dickerson, MD, MGH Frontotemporal Disorders Unit & Alzheimer’s Disease Research Center, 149 13th St, Suite 2691, Charlestown, MA 02129, USA. (Email: brad.dickerson@mgh.harvard.edu)

Abstract

Alzheimer’s disease (AD) has long been recognized as a heterogeneous illness, with a common clinical presentation of progressive amnesia and less common “atypical” clinical presentations, including syndromes dominated by visual, aphasic, “frontal,” or apraxic symptoms. Our knowledge of atypical clinical phenotypes of AD comes from clinicopathologic studies, but with the growing use of in vivo molecular biomarkers of amyloid and tau pathology, we are beginning to recognize that these syndromes may not be as rare as once thought. When a clinician is evaluating a patient whose clinical phenotype is dominated by progressive aphasia, complex visual impairment, or other neuropsychiatric symptoms with relative sparing of memory, the differential diagnosis may be broader and a confident diagnosis of an atypical form of AD may require the use of molecular biomarkers. Despite the evolving sophistication in our diagnostic tools, and the acknowledgment of atypical AD syndromes in the 2011 revised diagnostic criteria for AD, the assessment of such patients still poses substantial challenges. We use a case-based approach to review the clinical and imaging phenotypes of a series of patients with typical and atypical AD, and discuss our current approach to their evaluation. One day, we hope that regardless of whether a patient exhibits typical or atypical symptoms of AD pathology, we will be able to identify the condition at a prodromal phase and institute a combination of symptomatic and disease-modifying therapies to support cognitive processes, function, and behavior, and slow or halt progression to dementia.

Type
Case-Based Review Article
Copyright
© Cambridge University Press 2017 

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Footnotes

This article is based in part on presentations from a platform session at the 26th American Neuropsychiatric Association meeting, March 26, 2015, Orlando, FL.

The authors thank the patients and their families for allowing their stories to be told, and our colleagues and staff for assistance in evaluating these patients. We also appreciate our funding sources, including R01 DC014296, R21 NS077059, R21 NS084156, P50 AG005134, Cure Foundation New Vision Award, and Gerstner Family Career Development Award.

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