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

Bradford C. Dickerson, Scott M. McGinnis, Chenjie Xia, Bruce H. Price, Alireza Atri, Melissa E. Murray, Mario F. Mendez, David A. Wolk

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)439-449
Number of pages11
JournalCNS Spectrums
Issue number6
StatePublished - Dec 1 2017


  • Alzheimer's disease
  • biomarkers
  • corticobasal syndrome
  • mild cognitive impairment
  • posterior cortical atrophy
  • primary progressive aphasia

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health


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