DOI: 10.1002/alz.078622 ISSN: 1552-5260

A systematic review of drug interventions to enhance cognition in patients with primary central nervous system infections

Syeda Taliya Rizvi, Jhankhana Shah, Sarah Shaaya, Tatyana Mollayeva
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Geriatrics and Gerontology
  • Neurology (clinical)
  • Developmental Neuroscience
  • Health Policy
  • Epidemiology



Although drug therapy is part of the clinical routine for individuals with central nervous system (CNS) infections, its efficacy with respect to cognitive impairments has not been systematically studied. We aimed to synthesize the evidence for optimal treatment decisions.


We searched for experimental studies published in English prior to October 2021 in MEDLINE, Embase and Cochrane databases. We selected non‐randomized studies (NRS) and randomized control trials (RCT) of a drug efficacy versus placebo, another drug, or a combination of drugs. The certainty of the evidence was rated according to GRADE guidelines.


We included eight RCTs and one NRS, involving a total of 805 patients (50.77% male patients; mean age 42.67±10.58; duration (in years) of primary CNS infections 4.69±3.16) with Lyme disease (LD), herpes simplex virus type 1 (HSV‐1), or Creutzfeldt–Jakob disease (CJD) studying the efficacy of antibiotics, antiviral, and non‐opioid analgesic drugs, respectively. The duration of the interventions varied, depending on the type of CNS infection and class of drug, with a range between four weeks in patients with LD treated with antibiotics and 18 weeks in patients with HSV‐1 treated with an antiviral drug. In patients with LD, antibiotics alone or in combination with other drugs enhanced certain cognitive domains relative to placebo. In patients with HSV‐1, the results were inconsistent. In patients with CJD, flupirtine maleate enhanced baseline cognitive scores. Of the available evidence, only one study had “low” risk of bias. An important limitation of the included studies was the lack of consistent reporting of adverse effects and safety parameters, which must be addressed in future work.


There is not enough existing evidence of sufficient quality to support the use of antimicrobials and non‐opioid analgesics in combatting cognitive deficits in patients with LD, HSV‐1, or CJD. Future clinical trials enrolling participants at earlier stages of primary CNS infections, at the time of greatest inflammation, and which address the elements of biases found in the existing clinical trials, are warranted.

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