AIDS

Dementia
Complex
(ADC)
 Synonyms

 HIV-associated Dementia
 HIV Dementia
 HIV (or AIDS) Encephalopathy
 HIV-1 Cognitive/Motor Complex
 AIDS Subacute Encephalitis
Intro
 HIV

 Retrovirus that kills T4 cells (cells

that fight off microorganisms)
 Manufactures its DNA in host cells
 AIDS
 Diagnosed when patient
- has HIV
- has an opportunistic infection or
Kaposi’s sarcoma
- has a low ratio of T4 (CD4+) to T8
(CD8+) cells
 AIDS surfaced in the US in 1981
 By 1985, HIV was found to be in
brain tissue of AIDS patients
suffering from cognitive impairment
and dementia
 HIV-infected macrophages contribute
to cell death and will not fight
infection if signaled by T4 cells
 HIV is the most common cause of
dementia in adults 40 years old or
less
 If ADC is left untreated, it worsens in
months
 A decade ago, 40%-70% of AIDS
patients suffered from ADC; now it is
about 20%
Symptoms and Stages
 Stages of dementia range from mind
to severe
 Motor and cognitive skills decline
progressively
 Become mentally slow, weak
physically, clumsy, and may develop
tremors
 In end stages may become
hallucinatory and unaware
 Sometimes may develop mania in
late stages
 Stage 0 (normal)

 Normal motor and mental function

 Stage 0.5
(Equivocal/Subclinical)

 Minimal symptoms of motor and

cognitive dysfunction (e.g., slow
movement of extremities)
 No work and daily life activity
impairments
 Stage 1 (mild)
 Clear motor or intellectual
impairment present (through testing)
 Work and daily life activity
impairments only in more demanding
aspects
 Able to walk without help
 Stage 2 (moderate)
 Some patients unable to walk at all;
some able to walk with assistance
 Can maintain basic self-care, but not
more demanding aspects of daily life
 Stage 3 (severe)
 Severe motor or intellectual disability
 Cannot think through complex
dialog; cannot follow events or news,
etc.
 Slowness of limbs and cannot walk
unassisted
 Stage 4 (end stage)
 Almost vegetative
 Social and intellectual capacities are
nearly non-functional
 Little or no ability to speak
 Doubly incontinent
 Paraplegic or paraparetic
Tests and Imaging
 Most tests and imaging are not
diagnostic, but characteristic
 ADC patients may have abnormal
cerebral atrophy, abnormal white
matter, as well as abnormal basal
ganglia or thalamus
 Children with ADC may have
calcification of the basal ganglia with
brain atrophy
 Cerebrospinal fluid (CSF) in ADC patients,
as compared with normal AIDS patients
who do not have dementia, may have
higher levels of quinolinic acid, Interleukin-
6, prostaglandins, tumor necrosis factor-α,
and interleukin-1β neopterin, and β2-
microglobulin
 These chemicals have cytokinetic
pathways involved, suggesting CNS effects
may be based on this type of reaction
Epidemiology
 ADC develops in severe
immunosuppression
 67% of AIDS patients with ADC in
stage 2, 3, or 4 died within six
months
 Low hemoglobin levels in patients
with ADC
 Older ADC patients may have high
levels of neopterin and β2-
microglobulin
Neuropathy
 Multi-nucleated cell encephalitis
 White matter is pale
 Excess astrocytes
 Vacuolar myelopathy
▪ Death in the:
- Basal ganglia
- Hypothalamus
- Thalamus
- White matter
- Brainstem
 Cortex is not usually affected
Etiology and Pathogenesis
 HIV affects neurons by way of an
indirect mechanism that is not
completely understood
 Toxic cytokines, viral gene products,
and neurotoxic pathways are
involved in these indirect
mechanisms
 High proviral DNA levels
 Viral DNA/RNA and viral antigens are
present in brain tissue
 Macrophage maintains infection in
the brain and stimulates cytokine
pathways
 HIV causes macrophages and
microglia to fuse, creating multi-
nucleated cells
 Virus infects astrocytes and
microglia, among other types of cells
 Treatment

 Antiretroviraldrugs can treat ADC

 Highly active antiretroviral therapy
(HAART)
 Nucleoside Reverse
Transcriptase Inhibitors
Drug Clinical CSF CSF:serum
Efficacy Efficacy ratio
Zidovudine Positive Positive 0.6

Didanosine Conflicting No Data 0.2

(dideoxyinosin Available
e)
Zalcitabine Positive No Data 0.2
Available
Lamivudine No Data No Data 0.1
Available Available
Stavudine No Data No Data 0.3-0.4
Available Available
Abacavir No Data No Data 0.2
Available Available
 Protease Inhibitors
Drug Clinical CSF CSF:serum
Efficacy Efficacy ratio
Indinavir No Data No Data 0.18
Available Available
Nelfinavir No Data No Data No Data
Available Available Available
Saqinavir No Data No Data No Data
Available Available Available
Ritonavir No Data No Data No Data
Available Available Available
VX-478 No Data No Data No Data
Available Available Available
 Non-nucleoside reverse
transcriptase inhibitors
Drug Clinical CSF CSF:serum
Efficacy Efficacy ratio

Delaviricine No Data No Data No Data

mesylate Available Available Available

Loviride No Data No Data No Data

Available Available Available

Nevirapine No Data No Data 0.45

Available Available
 Agents that protect the neurons may
also be effective (neuroprotectants)
 Nimodipine (a Ca2+ channel blocker)
 Memantine (NMDA-glutamate
antagonist)
Conclusion
 Macrophages and migroglia live long,
enabling the virus to inhabit those
cells and remain inactive for years in
the brain
 Before immunodeficiency begins,
replication may be more controlled;
but, when patient becomes severely
immunodeficient, virus replication
may become out of control
 Before HAART was introduced,
children with ADC were often left
severely mentally disabled
 Up to 50% of AIDS patients had some
kind of cognitive impairment at
death (some sources say as many as
70%)