May 18, 2011

Doctors Misdiagnose Half Of Those With Early Alzheimer's Disease

People who develop early onset Alzheimer's disease often experience atypical symptoms rather than memory problems, which can make getting an accurate diagnosis difficult...

Alzheimer's Reading Room

Alzheimer's Reading Room

A research study suggests more than half of people who develop Alzheimer's disease before the age of 60 are initially misdiagnosed as having other kinds of brain disease when they do not have memory problems.

The research is published in the print issue of Neurology®, the medical journal of the American Academy of Neurology.

Subscribe to the Alzheimer's Reading Room

Study: Memory problems often not present in middle-aged people with Alzheimer's disease

For the study, researchers reviewed the cases of 40 people from the Neurological Tissue Bank-University of Barcelona-Hospital Clínic-IDIBAPS, Barcelona, Spain, whose brains showed that they had Alzheimer's disease in an autopsy. Researchers also reviewed information about the age at which the symptoms began and family history.

About 38 percent experienced initial symptoms other than memory problems.

The study found that one-third of people with confirmed early onset Alzheimer's disease showed symptoms other than memory problems, such as behavior, vision or language problems and a decline in executive function, or the ability to carry out tasks. In people with atypical symptoms and no memory problems, 53 percent were incorrectly diagnosed when first seen by a doctor, compared to four percent of those who had memory problems. They were mainly diagnosed with other types of dementia. Of those with unusual initial symptoms, 47 percent were still incorrectly diagnosed at the time of their death.
"People who develop early onset Alzheimer's disease often experience these atypical symptoms rather than memory problems, which can make getting an accurate diagnosis difficult," said study author Albert Lladó, MD, PhD, with the Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic of Barcelona and the Institute of Biomedical Investigation August Pi i Sunyer (IDIBAPS), in Barcelona, Spain. "Biomarkers of Alzheimer's disease and other disorders are needed for us to better recognize, diagnose and treat early onset Alzheimer's disease sooner to improve the quality of life of these patients."


Objectives: Early-onset Alzheimer disease (EOAD) diagnosis often represents a challenge because of the high frequency of atypical presentations. Our aim was to describe the clinical features, APOE genotype, and its pathologic correlations of neuropathologic confirmed EOAD.

Retrospective review of clinical data (age at onset, family history, clinical presentation, diagnostic delay, diagnosis) and APOE genotype of patients with neuropathologically confirmed EOAD (<60 years).


  • Forty cases were selected. 
  • Mean age at onset was 54.5 years (range 46–60). 
  • The mean disease duration was 11 years with a mean diagnostic delay of 3.1 years. 
  • A total of 37.5% had a nonmemory presentation. 
  • Behavioral/executive dysfunction was the most prevalent atypical presentation. 
  • Incorrect initial clinical diagnoses were common (53%) in patients with atypical presentations, but rare when anterograde amnesia was the presenting symptom (4%). 
  • The incorrect initial clinical diagnoses were 2 behavioral variant frontotemporal lobar degeneration, 2 normal pressure hydrocephalus, 1 semantic dementia, 1 primary progressive aphasia, 1 corticobasal degeneration, 1 pseudodementia with depression, and 1 unclassifiable dementia. 
  • APOE genotype was ϵ3/ϵ3 in 59%, with no significant differences between typical and atypical presentations. 
  • APOE ϵ4 was 3.3 times more frequent in subjects with family history of AD. 
  • A total of 97.5% of the cases presented advanced neurofibrillary pathology. 
  • A total of 45% of the patients had concomitant Lewy body pathology although localized in most cases and without a significant clinical correlate.

One third of patients with pathologic confirmed EOAD presented with atypical symptoms. Patients with EOAD with nonamnestic presentations often receive incorrect clinical diagnoses.

Related Content

The study was supported by a grant from the Hospital Clínic-Emili Letang.

The American Academy of Neurology, an association of more than 24,000 neurologists and neuroscience professionals, is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as epilepsy, dystonia, migraine, Huntington's disease, and dementia.

Original content Bob DeMarco, the Alzheimer's Reading Room