aids dementia complex (powerpoint)
DESCRIPTION
"AIDS Dementia Complex" PowerPoint Presentation for Biology 300WTRANSCRIPT
AIDSAIDSDementia Dementia ComplexComplex
(ADC)(ADC)
SynonymsSynonyms
HIV-associated DementiaHIV-associated Dementia HIV DementiaHIV Dementia HIV (or AIDS) EncephalopathyHIV (or AIDS) Encephalopathy HIV-1 Cognitive/Motor ComplexHIV-1 Cognitive/Motor Complex AIDS Subacute EncephalitisAIDS Subacute Encephalitis
Intro Intro
HIVHIV
Retrovirus that kills T4 cells (cells Retrovirus that kills T4 cells (cells that fight off microorganisms)that fight off microorganisms)
Manufactures its DNA in host cellsManufactures its DNA in host cells
AIDSAIDS
Diagnosed when patient Diagnosed when patient
- has HIV- has HIV
- has an opportunistic infection or - has an opportunistic infection or Kaposi’s sarcomaKaposi’s sarcoma
- has a low ratio of T4 (CD4+) to T8 - has a low ratio of T4 (CD4+) to T8 (CD8+) cells (CD8+) cells
AIDS surfaced in the US in 1981AIDS surfaced in the US in 1981 By 1985, HIV was found to be in By 1985, HIV was found to be in
brain tissue of AIDS patients brain tissue of AIDS patients suffering from cognitive impairment suffering from cognitive impairment and dementiaand dementia
HIV-infected macrophages contribute HIV-infected macrophages contribute to cell death and will not fight to cell death and will not fight infection if signaled by T4 cellsinfection if signaled by T4 cells
HIV is the most common cause of HIV is the most common cause of dementia in adults 40 years old or dementia in adults 40 years old or lessless
If ADC is left untreated, it worsens in If ADC is left untreated, it worsens in monthsmonths
A decade ago, 40%-70% of AIDS A decade ago, 40%-70% of AIDS patients suffered from ADC; now it is patients suffered from ADC; now it is about 20%about 20%
Symptoms and Stages Symptoms and Stages
Stages of dementia range from mind Stages of dementia range from mind to severeto severe
Motor and cognitive skills decline Motor and cognitive skills decline progressivelyprogressively
Become mentally slow, weak Become mentally slow, weak physically, clumsy, and may develop physically, clumsy, and may develop tremorstremors
In end stages may become In end stages may become hallucinatory and unawarehallucinatory and unaware
Sometimes may develop mania in Sometimes may develop mania in late stageslate stages
Stage 0 (normal)Stage 0 (normal)
Normal motor and mental function Normal motor and mental function
Stage 0.5 Stage 0.5 (Equivocal/Subclinical)(Equivocal/Subclinical)
Minimal symptoms of motor and Minimal symptoms of motor and cognitive dysfunction (e.g., slow cognitive dysfunction (e.g., slow movement of extremities) movement of extremities)
No work and daily life activity No work and daily life activity impairmentsimpairments
Stage 1 (mild) Stage 1 (mild)
Clear motor or intellectual Clear motor or intellectual impairment present (through testing)impairment present (through testing)
Work and daily life activity Work and daily life activity impairments only in more demanding impairments only in more demanding aspectsaspects
Able to walk without helpAble to walk without help
Stage 2 (moderate)Stage 2 (moderate)
Some patients unable to walk at all; Some patients unable to walk at all; some able to walk with assistancesome able to walk with assistance
Can maintain basic self-care, but not Can maintain basic self-care, but not more demanding aspects of daily life more demanding aspects of daily life
Stage 3 (severe)Stage 3 (severe)
Severe motor or intellectual disabilitySevere motor or intellectual disability Cannot think through complex Cannot think through complex
dialog; cannot follow events or news, dialog; cannot follow events or news, etc.etc.
Slowness of limbs and cannot walk Slowness of limbs and cannot walk unassistedunassisted
Stage 4 (end stage) Stage 4 (end stage)
Almost vegetativeAlmost vegetative Social and intellectual capacities are Social and intellectual capacities are
nearly non-functionalnearly non-functional Little or no ability to speakLittle or no ability to speak Doubly incontinentDoubly incontinent Paraplegic or parapareticParaplegic or paraparetic
Tests and ImagingTests and Imaging
Most tests and imaging are not Most tests and imaging are not diagnostic, but characteristic diagnostic, but characteristic
ADC patients may have abnormal ADC patients may have abnormal cerebral atrophy, abnormal white cerebral atrophy, abnormal white matter, as well as abnormal basal matter, as well as abnormal basal ganglia or thalamusganglia or thalamus
Children with ADC may have Children with ADC may have calcification of the basal ganglia with calcification of the basal ganglia with brain atrophybrain atrophy
Cerebrospinal fluid (CSF) in ADC patients, Cerebrospinal fluid (CSF) in ADC patients, as compared with normal AIDS patients as compared with normal AIDS patients who do not have dementia, may have who do not have dementia, may have higher levels of quinolinic acid, Interleukin-higher levels of quinolinic acid, Interleukin-6, prostaglandins, tumor necrosis factor-α, 6, prostaglandins, tumor necrosis factor-α, and interleukin-1β neopterin, and β2-and interleukin-1β neopterin, and β2-microglobulinmicroglobulin
These chemicals have cytokinetic These chemicals have cytokinetic pathways involved, suggesting CNS effects pathways involved, suggesting CNS effects may be based on this type of reactionmay be based on this type of reaction
Epidemiology Epidemiology
ADC develops in severe ADC develops in severe immunosuppressionimmunosuppression
67% of AIDS patients with ADC in 67% of AIDS patients with ADC in stage 2, 3, or 4 died within six months stage 2, 3, or 4 died within six months
Low hemoglobin levels in patients with Low hemoglobin levels in patients with ADCADC
Older ADC patients may have high Older ADC patients may have high levels of neopterin and β2-levels of neopterin and β2-microglobulinmicroglobulin
Neuropathy Neuropathy
Multi-nucleated cell encephalitisMulti-nucleated cell encephalitis White matter is paleWhite matter is pale Excess astrocytesExcess astrocytes Vacuolar myelopathyVacuolar myelopathy
▪ ▪ Death in the:Death in the:
- Basal ganglia- Basal ganglia
- Hypothalamus- Hypothalamus
- Thalamus- Thalamus
- White matter- White matter
- Brainstem- Brainstem Cortex is not usually affectedCortex is not usually affected
Etiology and Pathogenesis Etiology and Pathogenesis
HIV affects neurons by way of an HIV affects neurons by way of an indirect mechanism that is not indirect mechanism that is not completely understoodcompletely understood
Toxic cytokines, viral gene products, Toxic cytokines, viral gene products, and neurotoxic pathways are involved and neurotoxic pathways are involved in these indirect mechanismsin these indirect mechanisms
High proviral DNA levelsHigh proviral DNA levels Viral DNA/RNA and viral antigens are Viral DNA/RNA and viral antigens are
present in brain tissuepresent in brain tissue
Macrophage maintains infection in Macrophage maintains infection in the brain and stimulates cytokine the brain and stimulates cytokine pathwayspathways
HIV causes macrophages and HIV causes macrophages and microglia to fuse, creating multi-microglia to fuse, creating multi-nucleated cellsnucleated cells
Virus infects astrocytes and Virus infects astrocytes and microglia, among other types of cellsmicroglia, among other types of cells
Treatment Treatment
Antiretroviral drugs can treat ADC Antiretroviral drugs can treat ADC Highly active antiretroviral therapy Highly active antiretroviral therapy
(HAART)(HAART)
Nucleoside Reverse Nucleoside Reverse Transcriptase InhibitorsTranscriptase Inhibitors
Drug Drug Clinical Clinical
Efficacy Efficacy CSF CSF
Efficacy Efficacy CSF:serumCSF:serum
ratioratio
Zidovudine Positive Positive 0.6
Didanosine Didanosine (dideoxyinosin(dideoxyinosine) e)
Conflicting Conflicting No DataNo Data
Available Available 0.2 0.2
Zalcitabine Zalcitabine Positive Positive No DataNo Data
Available Available 0.2 0.2
Lamivudine Lamivudine No DataNo Data
Available Available No DataNo Data
Available Available 0.1 0.1
Stavudine Stavudine No DataNo Data
Available Available No DataNo Data
Available Available 0.3-0.4 0.3-0.4
Abacavir Abacavir No DataNo Data
Available Available No DataNo Data
Available Available 0.2 0.2
Protease Inhibitors Protease Inhibitors
Drug Drug Clinical Clinical
Efficacy Efficacy CSF CSF
Efficacy Efficacy CSF:serumCSF:serum
ratio ratio
Indinavir Indinavir No DataNo Data
Available Available No DataNo Data
Available Available 0.18 0.18
Nelfinavir Nelfinavir No DataNo Data
Available Available No DataNo Data
Available Available No DataNo Data
Available Available
Saqinavir Saqinavir No DataNo Data
Available Available No DataNo Data
Available Available No DataNo Data
Available Available
Ritonavir Ritonavir No DataNo Data
Available Available No DataNo Data
Available Available No DataNo Data
Available Available
VX-478 VX-478 No DataNo Data
Available Available No DataNo Data
Available Available No DataNo Data
Available Available
Non-nucleoside reverse Non-nucleoside reverse transcriptase inhibitors transcriptase inhibitors
Drug Drug Clinical Clinical
Efficacy Efficacy CSF CSF
Efficacy Efficacy CSF:serumCSF:serum
ratio ratio
Delaviricine Delaviricine mesylate mesylate
No DataNo Data
Available Available No DataNo Data
Available Available No DataNo Data
Available Available
Loviride Loviride No DataNo Data
Available Available No DataNo Data
Available Available No DataNo Data
Available Available
Nevirapine Nevirapine No DataNo Data
Available Available No DataNo Data
Available Available 0.45 0.45
Agents that protect the neurons may Agents that protect the neurons may also be effective (neuroprotectants) also be effective (neuroprotectants)
Nimodipine (a CaNimodipine (a Ca2+2+ channel blocker) channel blocker) Memantine (NMDA-glutamate Memantine (NMDA-glutamate
antagonist)antagonist)
Conclusion Conclusion
Macrophages and migroglia live long, Macrophages and migroglia live long, enabling the virus to inhabit those enabling the virus to inhabit those cells and remain inactive for years in cells and remain inactive for years in the brainthe brain
Before immunodeficiency begins, Before immunodeficiency begins, replication may be more controlled; replication may be more controlled; but, when patient becomes severely but, when patient becomes severely immunodeficient, virus replication immunodeficient, virus replication may become out of controlmay become out of control
Before HAART was introduced, Before HAART was introduced, children with ADC were often left children with ADC were often left severely mentally disabledseverely mentally disabled
Up to 50% of AIDS patients had some Up to 50% of AIDS patients had some kind of cognitive impairment at kind of cognitive impairment at death (some sources say as many as death (some sources say as many as 70%)70%)