Diagnostic Tools

Patient screening

Signs of mild-to-moderate neurocognitive impairment are often subtle and require questioning to determine if they are present.


The European AIDS Clinical Society (EACS) recommend1 that all HIV-infected people without any highly confounding conditions (severe psychiatric conditions, use of psychotropic drugs, alcohol abuse, sequelae from previous opportunistic infections of the CNS or a current CNS infection) should be screened using three questions on comprehension, clarity and speed every 2 years.

  • Do you experience frequent memory loss (e.g. do you forget the occurrence of special events even the more recent ones, appointments, etc.)?
  • Do you feel that you are slower when reasoning, planning activities, or solving problems?
  • Do you have difficulties paying attention (e.g. to a conversation, a book, or a movie)?

Figure 1. Neurocognitive impairment: diagnosis and management

 

ANI=Asymptomatic Neurocognitive Impairment
CSF=Cerebrospinal Fluid
GDR=genotypic drug resistance test
HAD=HIV-Associated Dementia
HAND=HIV-Associated Neurocognitive Disorder
IADL=Instrumental Activities of Daily Living
MND=Mild Neurocognitive Disorders
MRI=Brain Magnetic Resonance Imaging
NP=Neuropsychological

i Highly confounding conditions 1. Severe psychiatric conditions; 2. Abuse of psychotropic drugs; 3. Alcohol abuse; 4. Sequelae from previous CNS-OIs or other neurological diseases; 5. Current CNS-OIs or other neurological diseases. 
ii 3 questions (ref. Simioni et al., AIDS 2009). 1. Do you experience frequent memory loss (e.g. do you forget the occurrence of special events even the more recent ones, appointments, etc.)? 2. Do you feel that you are slower when reasoning, planning activities, or solving problems? 3. Do you have difficulties paying attention (e.g. to a conversation, a book, or a movie)? For each question, patients can answer: a) never, b) hardly ever, or c) yes, definitely. Patients are considered to have an “abnormal” result when answering “yes, definitely” on at least one question. 
iii NP examination will have to include tests exploring the following cognitive domains: fluency, executive functions, speed of information processing, attention/working memory, verbal and visual learning, verbal and visual memory, motor skills (ref. Antinori et al., Neurology 2007).
 iv Brain MRI and CSF examination. These are required to further exclude other pathologies and to further characterize HAND, by including assessment of CSF HIV-RNA level and, where appropriate, evidence for genotypic drug resistance (GDR) in a paired CSF and plasma sample.
 v HAD and MND definitions (ref. Antinori et al., Neurology 2007). HAD is defined in the presence of 1) marked acquired impairment in cognitive functioning involving at least 2 cognitive domains, as documented by performance of at least 2 SD below the mean for age-education appropriate norms on NP tests; 2) marked interference in daily functioning; 3) no evidence of another pre-existing cause for the dementia. MND is defined in the presence of 1) acquired impairment in cognitive functioning involving at least 2 cognitive domains, as documented by performance of at least 1 SD below the mean for age-education appropriate norms on NP tests; 2) mild interference in daily functioning; 3) no evidence of another preexisting cause for the MND. 
vi If GDR in CSF and/or plasma not available, store aliquots for possible future use
. vii Definition of ‘potentially CNS-active’ drugs: ARV drugs with either demonstrated clear CSF penetration when studied in healthy HIV-infected populations (concentration above the IC90 in > 90 % examined patients) or with proven short-term (3-6 months) efficacy on cognitive function or CSF viral load decay when evaluated as single agents or in controlled studies in peer reviewed papers:
- Agents with demonstrated clear CSF penetration:
- NRTIs: ZDV, ABC
- NNRTIs: EFV, NVP
- Boosted PIs: IND/r, LPV/r, DRV/r
- Other classes: MAR
- Drugs with proven “efficacy”:
- NRTIs: ZDV, d4T, ABC
- Boosted PIs: LPV/r

Reproduced with permission from the European AIDS Clinical Society Guidelines Version 6.0. 


Download the diagnostic flowchart.

Screening tools 

The International HIV Dementia Scale2 as a screening tool for neurocognitive impairment:

  • The International HIV Dementia Scale2 comprises three tests: one of motor speed (timed finger tapping), one of psychomotor speed (timed alternating hand sequence test) and one of memory (recall of four items at two minutes).

The recently developed Cysique algorithm3,4 has shown some success as a screening tool for HAND, with good prediction accuracy and specificity:

  • • it is recommended for use in HIV-infected Caucasian men with advanced disease
     

Mental health screening: A quick reference guide for HIV primary care clinicians contains questions to identify mental health disorders associated with HIV infection, including cognitive impairment.5



Find out more about neuropsychological assessment tools and tests, or refer to the signs and symptoms section for information on the misdiagnosis of HIV-associated dementia (HAD). 
 


Please see below for other neuropsychological assessment tools and tests:


  • Trail Making Tests (Parts A and B) ask the participant to connect a series of numbers and/or letters as quickly as possible.
  • Wechsler Adult Intelligence Scale Revised (WAIS-R) Digit Symbol Subtest is a test of memory and speed. The participant is asked to learn a code in which each digit is represented by a symbol and then substitute the correct symbols for a series of digits as quickly and accurately as possible.
  • CogState tools supply computerised tests that provide a quantitative, validated, rapid and accurate measure of cognitive function.
  • The HIV Dementia Motor Scale is a 20-point scale that measures neurological function in five domains – strength, tone, reflexes, co-ordination and gait.6 However; this may not be sensitive enough to detect mild HAND.
  • Grooved Pegboard is a dexterity test that requires complex visual–motor coordination.7
  • Action (Verb) Fluency is a verbal fluency task that requires rapid generation of as many verbs as possible within one minute.8

References

  1. European AIDS Clinical Society (EACS). Guidelines Version 6.0. Accessed 4 July 2012.
  2. Sacktor NC, Wong M, Nakasujja N, et al. The International HIV Dementia Scale: a new rapid screening test for HIV dementia. AIDS. 2005;19:1367–1374.
  3. Cysique LA, Murray JM, Dunbar M, et al. A screening algorithm for HIV-associated neurocognitive disorders. HIV Medicine. 2010;11:642–649. 
  4. Dunbar M, Murray JM, Cysique LA, et al. Simultaneous classification and feature selection via convex quadratic programming with application to HIV-associated neurocognitive disorder assessment. Eur J Oper Res. 2010;206:470–478. 
  5. Office of the Medical Director, New York State Department of Health AIDS Institute in collaboration with the Johns Hopkins University Division of Infectious Diseases. Clinical Guidelines: Cognitive Disorders and HIV/AIDS. Accessed 3 March 2011.
  6. Power C, Selnes OA, Grim JA, McArthur JC. HIV Dementia Scale: a rapid screening test. J Acquir Immune Defic Syndr Hum Retrovirol. 1995;8:273–278.
  7. Ellis R, Evans SR, Clifford DB, et al. Clinical validation of the NeuroScreen. J Neurovirol. 2005;11:503–511.
  8. Woods S, Carey CL, Tröster AI, et al. Action (verb) generation in HIV-1 infection. Neuropsychologia. 2005;43:1144–1151.