1. To determine, in the Quillen College of Medicine HIV+ outpatient clinic, the prevalence of

   • NC (normal cognition )
   • ANI (asymptomatic neurocognitive impairment )
   • MCD (mild cognitive disorder )
   • HAD (HIV-associated dementia )

2. To determine whether the following variables affect the three categories of HAND

   • Time since first diagnosis of HIV infection
   • Anti-viral medications used
   • Age
   • Gender

As life expectancy increases, dementia becomes more common, and the need for its correct diagnosis and treatment becomes more urgent. Alzheimer's disease (AD) is the leading cause of dementia, but its diagnosis is by exclusion of all other causes. Successful treatment of HIV/AIDS has resulted in more patients living long enough to develop HIV-Associated Neurocognitive Disorders (HAND), including dementia.

The National Institute of Mental Health, and the National Institute of Neurological Diseases and Stroke, updated standards for diagnosing HAND. The new criteria created an additional category, HIV-associated asymptomatic neurocognitive impairment (ANI), and modified the name and criteria for what was called MCMD (minor cognitive/motor disorder) to mild cognitive disorder (MCD). HIV-associated dementia (HAD) remained unchanged. Their definition of HAND includes: Cognitive impairment must be attributable to HIV and no other etiology (Dementia, Delirium, Depression, CNS neoplasm, CNS infection other than HIV/AIDS. Cerebrovascular disease, Substance abuse). Their criteria state that cognitive impairment should be validated by neuropsychological testing.

The three categories of HAND are:

1. HIV-associated asymptomatic neurocognitive impairment (ANI)

   Impairment involves at least two cognitive domains, and results in neuropsychological testing performance at least 1 Standard Deviation (SD) below the appropriate mean age/education norm for:

   • Information processing speed
   • Sensory/motor skills
   • Short-term and long-term memory
   • Ability to learn new skills and solve problems
   • Attention, concentration, and distractibility
   • Logical and abstract reasoning functions
   • Ability to understand and express language
   • Visual-spatial organization Visual-motor coordination
   • Planning, synthesizing and organizing abilities

2. Mild Cognitive Disorder (MCD) Same as ANI but patient or caregivers report that cognitive deficit interferes with mental acuity, work efficiency, home making or social activity

3. HIV-associated dementia (HAD)

   Impairment involves at least two cognitive domains and results in neuropsychological testing at least 2 SD below the appropriate mean age/education norm for:

   • Information processing speed
   • Short-term and long-term memory
   • Ability to learn new skills and solve problems
   • Attention, concentration, and distractibility
   • Logical and abstract reasoning functions
   • Ability to understand and express language
   • Visual-spatial organization Visual-motor coordination
   • Planning, synthesizing and organizing abilities Cognitive impairment significantly interferes with work, home life, social activities or ADL's.

4. Non-HIV healthy Controls

Our P300 COGNISION apparatus, provided by Neuronetrix, has been used only in subjects over the age of 60, whereas our participants in the HAND study will all be younger than 60. So, we cannot use COGNISION normative data base for comparison. We will add 10 HIV- healthy controls to our planned 40 HIV+ subjects. These HIV- participants will be age- and gender-matched to the HIV- Asymptomatic Neurocognitive Impairment (ANI) patients, and will undergo all the same assessments

Our IRB-approved study of HAND is limited to neuropsychological assessment. The study could be improved by adding a biological marker assessment, which could help validate the HAND categories. Such a marker is the P300 event-related potential (ERP), known to be related to cognitive processes, such as attention and working memory and abnormal in most neurologic and mental disorders. It could also possibly detect vulnerability to later cognitive impairment in those determined to be of normal cognition by neuropsychological testing. For example, Olichney et al (2011) concluded that ERP studies of individuals at risk for AD may reveal neurophysiological changes prior to clinical deficits, which could advance the early detection and diagnosis of "pre-symptomatic AD". Another example of the association of the P300 and cognition was the study of Onofri et al (2003). In this study donepezil resulted in improved cognition, as measured by a significant increase in MMSE scores. This was accompanied by a reduction of P3 latency. Logistic analysis showed that P3 latency predicted the beneficial effect of donepezil.

Inclusion Criteria:

• All participants will have been diagnosed as HIV+.
• Health controls with be age (+/- 5 years) and gender matched to the HIV+ participants.

Exclusion Criteria:

• Alzheimer's DIsease
• Vascular Dementia
• Delirium
• Severe Depression
• CNS Neoplasm
• CNS Infection Other Than HIV/AIDS
• Cerebrovascular Disease
• Alcohol Or Drug Intoxication Or Dependence
• Parkinson's
• Thyroid Disease
• Pernicious Anemia
• Subdural Hematoma
• Occult Hydrocephalus
• Huntington's
• Creutzfeldt-Jakob
• Electroconvulsive Therapy
• Seizure Disorder
• Medical/Psychiatric Disease
• Medication Influencing Cognition

HIV+ individuals and Healthy controls (HIV-, age and gender matched)