A 72-year-old man with a 15-year history of HIV comes to the office with his wife due to worsening forgetfulness. The patient has had mild difficulty with short-term memory for the past 5 years but had a more noticeable decline over the last 3. He often forgets recent conversations and names of familiar people. The patient also has had difficulty multitasking and learning new skills such as using a new cell phone. He performs most daily activities independently but requires some assistance, such as a reminder list for shopping or driving directions, even for known neighborhoods. He has had no behavioral changes, hallucinations, or delusions. The patient has been taking antiretroviral therapy since his HIV diagnosis and has had consistent CD4 counts >200/mm3; his viral load has remained undetectable. Vital signs are within normal limits. Mini-Mental State Examination score is 22/30. The patient recalls 0 of 3 words after brief distraction and has difficulty copying a geometric figure. There are no other focal neurologic deficits. MRI of the head shows generalized cerebral atrophy with no mass lesions or white matter changes. Which of the following is the most likely cause of this patient's memory impairment?
This patient's progressive memory loss and executive dysfunction are most likely due to Alzheimer disease (AD). He has a typical clinical presentation of the disease (ie, age of onset >65, early and relatively isolated memory loss, gradually progressive functional decline). The MRI findings of nonspecific, generalized atrophy are characteristic of AD. AD, the most common cause of dementia in the United States, typically occurs after age 65.
Although this patient has a history of HIV infection, his illness is well controlled on antiretroviral therapy (ART), and he has an undetectable viral load. HIV-associated dementia (HAD) occurs almost exclusively in untreated HIV-infected patients with advanced disease (eg, CD4 cell count is <200/mm3, AIDS) (Choice C). In contrast to the characteristic cortical dysfunction seen in AD (ie, amnestic symptoms), HAD is predominantly a subcortical dementia characterized by apathy, early impairments in attention, and subcortical motor symptoms. Because HIV-infected patients are living longer, common forms of dementias such as AD are a much more likely etiology for dementia in an ART-treated patient.
(Choice B) Frontotemporal dementia is characterized by early and prominent behavioral/personality change and only later by significant memory deficits. It manifests earlier than AD, typically around age 60.
(Choices D, E, and F) Although syphilis, primary CNS lymphoma, and progressive multifocal leukoencephalopathy (PML) are more common in immunosuppressed patients (eg, HIV-associated AIDS), this patient has no evidence of AIDS (ie, CD4 count consistently >200/mm3). Furthermore, the patient's presentation is not consistent with any of these conditions:
Late neurosyphilis is characterized by general paresis, dementia, and tabes dorsalis and typically develops 10-25 years after infection.
Primary CNS lymphoma in HIV-infected patients is strongly associated with Epstein-Barr virus and presents with focal neurologic findings with lesions evident on neuroimaging.
PML is associated with reactivation of the JC virus and presents with motor deficits, other neurologic signs, and demyelination evident on neuroimaging.
Educational objective:
Because HIV infection is being successfully managed with antiretroviral therapy and patients are living longer with lower morbidity, common forms of dementia such as Alzheimer disease have become much more common than HIV-associated dementia in these patients. HIV-associated dementia is a severe form of subcortical dementia found almost exclusively in untreated HIV-infected patients.