Outcome measures of cognitive gain in clinical trials of patients with primary central nervous system infections: A systematic review

Abstract

AbstractBackgroundPrimary central nervous system (CNS) infections are often accompanied with cognitive deficits. Cognitive deficits are assessed by a wide range of outcome measures to determine the severity of deficits and their response to intervention. The aim of this review was to provide description of outcome measures used to assess cognitive function in patients with primary CNS infections enrolled in clinical trials.MethodWe searched MEDLINE, Embase, and CENTRAL from inception to October 2022 to identify clinical trials that enrolled patients with cognitive deficits due to primary CNS infections. All outcome measures evaluating cognitive function in these clinical trials were considered. Outcome measure was defined as any standardized measure evaluating one or more of the six cognitive domains: complex attention, executive functioning, learning and memory, language, perceptual‐motor ability, and social cognition.ResultEight randomized controlled trials (RCTs) and one pre‐post intervention study enrolled patients with Lyme disease (infectious agent bacterium borrelia burgdorferi), herpes simplex virus type 1 (infectious agent herpes simples virus), and Creutzfeldt–Jakob disease (infectious agent prion). Within these clinical trials, 29 outcome measures were utilized to evaluate change in cognitive function in response to treatment with antibiotics (five studies), antiviral (three studies), or non‐opioid analgesic (one study). Out of all outcome measures, only two assessed all six cognitive domains: Penn computerized neurocognitive battery and Wechsler Adult Intelligence Scale; the remaining evaluated one or several cognitive domains using a variety of measures. The three most frequently evaluated cognitive domains were complex attention (19 distinct outcome measures within nine studies), executive functioning (19 distinct outcome measures within eight studies) and perceptual‐motor ability (16 distinct outcome measures within eight studies). The least evaluated cognitive domain was social cognition (four distinct outcome measures within four studies).ConclusionClinical trials included in this review were designed to improve cognitive function in patients with primary CNS infection. Selection of outcome measures that have been previously used is desirable as it would allow between‐study comparisons. Assessment of social cognition is important to consider. Evaluations using multiple outcome measures might be tiring and intrusive to patients, and therefore implications of practical constraints should be tested.