How Helpful Are the European AIDS Clinical Society Cognitive Screening Questions in Predicting Cognitive Impairment in an Aging, Well-Treated HIV-Positive Population?

M Metral; I Nadin; I Locatelli; PE Tarr; A Calmy; H Kovari; P Brugger; A Cusini; K Gutbrod; P Schmid; M Schwind; U Kunze; C Di Benedetto; R Pignatti; R Du Pasquier; KEA Darling; M Cavassini


HIV Medicine. 2020;21(5):342-348. 

In This Article

Abstract and Introduction


Objectives: Diagnosing neurocognitive impairment (NCI) in HIV infection requires time-consuming neuropsychological assessment. Screening tools are needed to identify when neuropsychological referral is indicated. We examined the positive and negative predictive values (PPVs and NPVs, respectively) of the three European AIDS Clinical Society (EACS) screening questions in identifying NCI.

Methods: The Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study recruited patients aged ≥45 years enrolled in the Swiss HIV Cohort Study between 1 May 2013 and 30 November 2016. NAMACO participants (1) answered EACS screening questions, (2) underwent standardized neuropsychological assessment and (3) completed self-report forms [Center for Epidemiologic Studies Depression Scale (CES-D)] rating mood. NCI categories were defined using Frascati criteria. PPVs and NPVs of the EACS screening questions in identifying NCI categories were calculated.

Results: Of 974 NAMACO participants with complete EACS screening question data, 244 (25.1%) expressed cognitive complaints in answer to at least one EACS screening question, of whom 51.3% had NCI (26.1% HIV-associated and 25.2% related to confounding factors). The PPV and NPV of the EACS screening questions in identifying HIV-associated NCI were 0.35 and 0.7, respectively. Restricting analysis to NCI with functional impairment or related to confounding factors, notably depression, the NPV was 0.90. Expressing cognitive complaints for all three EACS screening questions was significantly associated with depression (P < 0.001).

Conclusions: The EACS screening questions had an NPV of 0.7 for excluding patients with HIV-associated NCI as defined by Frascati criteria. The PPV and NPV may improve if NCI diagnoses are based on new criteria.


In the era of potent antiretroviral therapy (ART), HIV-associated neurocognitive impairment (NCI) remains a clinical problem, particularly in an aging population of people living with HIV (PLWH). NCI is also a diagnostic problem, as standardized neuropsychological testing of specific cognitive domains is time-consuming, costly and not available at all centres.[1]

Since NCI was first identified as an entity, ART has become more effective and patients now live well and for longer. With this, NCI categories were redefined in 2007, according to the Frascati criteria, into asymptomatic neurocognitive impairment (ANI; mild to moderate cognitive deficits without functional impairment), mild neurocognitive disorders (MND; mild to moderate cognitive deficits with functional impairment) and HIV-associated dementia (HAD; moderate to severe cognitive deficits with functional impairment).[2] Labelling NCI as 'HIV-associated' requires the exclusion of confounding factors, including organic brain pathology, substance misuse and psychiatric disorders, notably depression.[2,3]

The Frascati criteria are, to date, the only published criteria for categorizing NCI that have been arrived at by consensus. Whilst such criteria enable comparison of the results of cohort studies examining NCI in different patient populations, limitations have been described. Patients with mild cognitive deficits classified as ANI, for example, have been reclassified as cognitively normal when assessed using other criteria.[4] Equally, patients at the moderate end of the ANI spectrum may be classified as having ANI rather than MND as a consequence of the low sensitivity of testing methods for functional impairment. Using Frascati criteria alone, it is difficult to predict which individuals with ANI will deteriorate. This is important given the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study group observation that ANI diagnosis conferred a two- to six-fold increase in the risk of earlier development of symptomatic NCI.[5]

Potential NCI screening tools more rapid than neuropsychological testing (minutes rather than hours) have been examined.[6–10] However, as several studies were published prior to the 2007 Frascati criteria[6] or were conducted among younger patients or to identify more severe NCI stages[10] in advanced disease,[11] or without excluding patients with depression,[7] it is not possible to confidently apply these to aging populations of PLWH who have well-controlled infection on modern ART.

The European AIDS Clinical Society (EACS) recommends a simple tool to identify which patients merit formal neuropsychological testing, using three cognitive symptom questions which cover memory loss, mental slowing and attention difficulties.[12] The questions are taken from a paper by Simioni et al. which assessed patients with cognitive complaints for the presence of NCI[13] and are included in the EACS NCI assessment algorithm at the time of writing.[14] In Switzerland, PLWH enrolled in the Swiss HIV Cohort Study (SHCS)[15] are screened for NCI once a year using the EACS screening questions. Recruiting SHCS patients to the Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study has enabled a review of the value of the EACS screening question scores in identifying NCI in PLWH. The aim of this study was to determine the positive and negative predictive values (PPVs and NPVs, respectively) of these questions.