A 51-Year-Old Who Lost Her Job Due to Cognitive Decline

Lisa C. Silbert, MD; Deniz Erten-Lyons, MD


April 19, 2021


Early-onset Alzheimer disease was diagnosed on the basis of the patient's history of progressive short-term memory loss, impairment in multiple areas of cognition, and loss of function in activities that she used to be able to do before the onset of symptoms. The diagnosis of dementia requires the presence of the following cognitive symptoms:[4]

  • Symptoms that interfere with the ability to function at work or at usual activities

  • Symptoms that represent a decline from previous levels of functioning and performing

  • Symptoms that are not explained by delirium or major psychiatric disorder

Cognitive impairment is detected and diagnosed through a combination of both history-taking from the patient and a reliable informant and objective cognitive assessment. Cognitive impairment involves at least two of the following domains:

  • Memory (ability to acquire and remember new information)

  • Executive function (eg, reasoning and handling of complex tasks, judgment)

  • Visual-spatial abilities

  • Language function

  • Personality or behavior

This patient meets the criteria for dementia because she has had a subjective decline in cognition that has begun to interfere with her activities of daily living—notably working, managing the finances, and driving. In addition, she shows objective evidence of cognitive deficits in the areas of memory and visual-spatial skills.

The patient performed well on the memory portion of the brief 30-point mental status screening but had notable difficulties in this area when a somewhat harder test was given. In this case, the patient's history of progressive short-term memory decline, along with early deficits in the areas of orientation, memory, and visual-spatial skills, is typical of Alzheimer dementia. However, her age at onset (49 years) is younger than that seen in typical Alzheimer disease, which usually begins after age 65 years. Because of this, additional tests were required to rule out other causes of dementia in the young.

In this case, the differential diagnosis of early-onset dementia included HIV encephalopathy, Hashimoto encephalopathy, paraneoplastic encephalitis, and a central nervous system (CNS) inflammatory or infectious process. These were subsequently excluded as potential diagnoses with serum and CSF testing.

Frontotemporal lobar degeneration should also be considered in cases of younger-onset dementia. However, this patient did not present with symptoms consistent with a frontotemporal lobar degeneration diagnosis, which include prominent personality or language changes. In addition, no evidence of focal frontal atrophy was noted on neuroimaging.

This patient's MRI scan revealed focal atrophy in the bilateral hippocampi, which has been shown to be significantly associated with underlying Alzheimer disease pathology.[5] Because of the patient's young age at onset of her symptoms, additional CSF studies were performed to examine amyloid beta and tau. The CSF amyloid beta (1-42) tau index represents a normalized amyloid/tau ratio that optimally differentiates Alzheimer disease from normal aging and other dementia syndromes. An amyloid beta (1-42) tau index of less than 1 is typical of individuals with Alzheimer disease.

In addition, the CSF phosphor-tau level is elevated in Alzheimer disease to > 61 pg/mL. This patient's CSF amyloid beta (1-42) tau index of 0.28 and phospho-tau level of 117 pg/mL were both consistent with a diagnosis of Alzheimer disease.


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