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Dementia with features of Alzheimer's disease and HIV-associated dementia in an elderly man with AIDS (case study)
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"This is the first report of dementia with features characteristic of Alzheimer's disease in a patient with AIDS.....improvement in the cognitive features of HAD following addition of nevirapine....As HIV-infected individuals continue to age, it is imperative that HIV specialists become skilled at diagnosing and treating dementia."
AIDS:
15 May 2009 - Volume 23 - Issue 8 - p 1029-1031
doi: 10.1097/QAD.0b013e32832ac380
Correspondance
Brousseau, Kristin M; Filley, Christopher M; Kaye, Kathryn; Kiser, Jennifer J; Adler, Lawrence E; Connick, Elizabeth
aVISN 19 Mental Illness Research Education and Clinical Center (MIRECC), Denver Veterans Affairs Medical Center, USA
bUniversity of Colorado Denver School of Medicine, USA
cUniversity of Colorado Denver School of Pharmacy, USA
dColorado Center for AIDS Research, Aurora, Colorado, USA.
Improved survival of HIV-infected individuals increasingly poses new clinical challenges as they develop diseases associated with aging, such as dementia. Common risk factors (e.g. older age, lower education level, and apolipoprotein ϵ4 allele [1]) and pathophysiology including chronic immune activation [2,3] have been implicated in Alzheimer's disease and HIV-associated dementia. Although highly-active antiretroviral therapy has led to a decrease in HIV-associated dementia [3], it has been hypothesized that Alzheimer's disease will become epidemic among elderly HIV-infected individuals [4]. Alzheimer's disease in a HIV-infected individual has not been described previously.
Case report
We report a case of dementia in a 64-year-old male patient with features characteristic of both Alzheimer's disease and HIV-associated dementia (HAD). The patient's history was notable for a diagnosis of HIV infection in 1995, a distant history of intravenous drug use, a history of cytomegalovirus retinitis, and institution of Trizivir (abacavir, lamivudine, zidovudine; GlaxoSmithKline, London, UK) in 2000 with subsequent undetectable viral loads. In June 2006, the patient's son brought him for neuropsychiatric evaluation due to progressive cognitive problems and grief related to his wife's recent death.
Mental status examination revealed a poor informant with anosognosia, impaired judgment, apathy, and mild irritability. His thought process was circumstantial and tangential with repetitive themes about the past and his wife. Neurological examination revealed diffuse paratonia in the extremities, slowed coordination and gait, and positive glabellar and palmomental signs. Mini-Mental State Examination (MMSE) [5] score was 25/30 (1.8 SD below adjusted normative score), HIV Dementia Scale (HDS) [6] score was 10/16 (≤10 suggestive of HAD), and Frontal Assessment Battery [7] score was 12/18 (6.6 SD below adjusted normative score). Deficits were detected in memory, including encoding and recall; visual spatial skills; language, particularly word finding; psychomotor speed; and executive function. Remote memory was relatively preserved. Laboratory studies showed HIV RNA levels less than 20 copies/ml, 660 CD4+ T-cells/µl, B12 level of 154 pg/ml (normal 211-911 pg/ml), antibodies to hepatitis C virus (HCV), and undetectable HCV RNA. Serum chemistries, liver function tests, rapid plasma reagin test, urine toxicology, and thyroid stimulating hormone were normal. Brain magnetic resonance imaging (MRI) revealed nonspecific signal abnormalities in the subcortical gray and white matter on T-2 weighted images with atrophy in the cortex, particularly the medial temporal lobes, and the parietal and frontal lobes. Brain positron emission tomography (PET) demonstrated hypometabolism in the parietal and temporal cortices (Fig. 1). Neuropsychological testing revealed mild deficits in executive function and information processing speed and capacity, general impairment across memory domains, and word-finding difficulties on confrontational naming.
The initial impression was that the patient had dementia due to multiple causes including possible Alzheimer's disease, possible HAD, vitamin B12 deficiency, and possible substance-induced persisting dementia. The 'possible' modifiers were applied because the presence of multiple potential causes precluded selection of a single problem, and neuropathological examination is necessary to establish a 'definite' diagnosis [8]. Monthly injections restored vitamin B12 levels to normal. Grief was treated with supportive psychotherapy. For Alzheimer's disease, the cholinesterase inhibitor rivastigmine was prescribed. To treat HAD, nevirapine was initiated to optimize antiretroviral penetration into the central nervous system [9].
Two years later, the patient continued to live at home with assistance. His HDS score had improved to 12/16, but cognitive function and apathy had worsened. MMSE score was 20/30 (5.7 SD below adjusted normative score). Repeat neuropsychological testing demonstrated a decline in language and memory skills and information processing speed and capacity, and a mild improvement in immediate recall of information. Memantine, an N-methyl-D-aspartate receptor antagonist approved for the treatment of Alzheimer's disease, was initiated.
This is the first report of dementia with features characteristic of Alzheimer's disease in a patient with AIDS. The presence of Alzheimer's disease is supported by the pattern of cognitive decline, specifically memory-encoding deficits with relative preservation of remote memory; anosognosia; apathy; language difficulty; lack of motor deficits on neurological examination; and relatively preserved social behavior. Medial temporal lobe atrophy on MRI is suggestive of Alzheimer's disease, and bilateral parietal-temporal hypometabolism on PET has high specificity for Alzheimer's disease [10]. Concomitant HAD is suggested by the history of AIDS, executive dysfunction and psychomotor slowing, personality change, frontal release signs, slowed coordination and gait, subcortical white matter changes on MRI [11], and improvement in the cognitive features of HAD following addition of nevirapine. This case underscores the challenges of diagnosing dementia in older HIV-infected individuals in whom the presence of multiple predisposing conditions, as well as overlapping clinical syndromes, may lead to complex and ambiguous clinical presentations. As HIV-infected individuals continue to age, it is imperative that HIV specialists become skilled at diagnosing and treating dementia.
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