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Cognitive Screening After COVID-19 Tools Are Needed for the Assessment of Neurologic and Neuropsychologic Sequelae of Infection with the SARS-Cov-2 Virus

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Cognitive Screening After COVID-19 Tools Are Needed for the Assessment of Neurologic and Neuropsychologic Sequelae of Infection with the SARS-Cov-2 Virus SPECIAL REPORT Cognitive Screening After COVID-19 Tools are needed for the assessment of neurologic and neuropsychologic sequelae of infection with the SARS-CoV-2 virus. By Sarah H. Gulick, PsyD; Steven Mandel, MD; Edward A. Maitz, PhD, ABN; and Christopher R. Brigham, MD, MMS There is an emerging body of Cognitive Symptoms Reported After COVID-19 literature indicating that a sub‑ Many people report cognitive symptoms in the weeks set of people who experienced and months following diagnosis of COVID‑19 (Table).1‑11 As SARS‑CoV‑2 infection have many as 75% of people who were hospitalized with COVID‑19 neurocognitive symptoms for report persistent symptoms even 6 months later.2 The terms weeks or even months afterwards. post-acute sequelae of SARS-CoV-2 (PASC), COVID syndrome, Approximately a third of people long COVID, and long haulers have all been used to describe with COVID‑19 report neurologic people who report persistent cognitive, psychologic, and symptoms.1 Although cognitive somatic symptoms after COVID‑19.5 Brain fog is used to symptoms can occur secondary describe a sense that thinking is slowed, concentration is fuzzy, to systemic disease, and a small and mental abilities are not as sharp as they once were. There number of individuals have had may be other lingering symptoms, including fatigue, body meningoencephalitis and vascular events (eg, stroke) during aches, inability to exercise, headache, and difficulty sleeping. COVID‑19, some do not present with any known objective The underlying pathophysiology of long COVID is unclear. evidence of neurologic insult. Many who have cognitive com‑ Symptoms may be similar to myalgic encephalomyelitis or plaints have normal neurologic and physical examinations, chronic fatigue syndrome (ME/CFS) and autonomic dysfunc‑ lab results, and neuroimaging. This review addresses reported tion. Symptoms may be attributed to mitochondrial dysfunc‑ symptoms weeks or months after infection, how and when tion and metabolic changes; however, the pathophysiology neurologists and other physicians might be able to assess is often unknown.12,13 Chronic symptoms are also suggestive these, and whether cognitive screening will inform ability to of postural orthostatic tachycardia syndrome (POTS).14 A return to work and treatment recommendations. For individ‑ hypothesis regarding etiology of cognitive decline is that the uals who are experiencing persistent symptoms after infection, virus may enter the brain via nasal passages and the olfactory we must define current best practices, recognizing that our bulb to directly invade the hippocampus.15 Some preliminary understanding is evolving. A timeline for when maximal medi‑ research suggests risk factors for developing long COVID, and cal improvement can be expected remains to be determined. early research suggests that increased age, specific symptoms Although this research is being done, it is occurring primarily in the first week of infection, higher body mass index (BMI), in tertiary medical centers and teaching hospitals, and much and female sex carry a higher risk of persistent symptoms.16 of the information has not yet entered clinical practice. We A recent article explored self reports of cognitive symptoms, anticipate that physicians will have patients who present with including persistent memory loss (34%) and concentration brain fog, a not uncommon symptom in this population. deficits (28%), 110 days after people were discharged from a This article aims to provide a preliminary approach to hospital ward vs an intensive care unit (ICU), and no significant screening cognitive symptoms after COVID‑19. Physicians differences were found regarding reported cognitive symptoms may choose cognitive screening as an efficient way to evaluate between the 2 groups.4 Another study reported poor concen‑ those reporting cognitive issues, and these may inform both tration and attention, poor memory, executive functioning treatment recommendations and decisions of whether to refer deficits, and brain fog at least 28 days after COVID‑19.3 a patient for more comprehensive neuropsychologic testing. Preliminary research with neuropsychologic assessment There are several important limitations of cognitive screening shows that people with COVID‑19 exhibit deficits in several tests in this context that are discussed at the end of the article. cognitive domains. In a series of 2 cases, individuals recovering MAY 2021 PRACTICAL NEUROLOGY 19 SPECIAL REPORT TABLE. SUBJECTIVE AND OBJECTIVE COGNITIVE article, and future research is needed to continue examining IMPAIRMENT AFTER COVID-19 differences between those who had COVID‑19 and were or were not hospitalized, as well as between people with mild vs Domain Population Studied severe symptoms during COVID‑19. Subjective Concentration >28 days after symptom onset3 cognitive and attention and ≤110 days after hospital Cognitive Screening Tests impairment discharge3 Assessing cognitive complaints objectively during the short Memory >28 days after symptom onset3 time of a typical office visit can be challenging, but screening and ≤10 days after hospital tests can be done by a primary care physician or neurologist discharge4,5 to determine whether more comprehensive cognitive testing is indicated. Several cognitive screening tests have been devel‑ Executive >28 days after symptom onset3 oped and used in a variety of populations. It is important to functioning note, however, that literature directly comparing the 3 cogni‑ Slowed >28 days after symptom onset3 tive screening tests discussed in this article with each other is thinking or and ≤3 months after hospital somewhat limited. There is also no literature yet regarding use brain fog discharge6,7 of cognitive screening tests in a COVID‑19 population. Objective Concentration 2 people after acute phase8 cognitive and attention and severe COVID-19; inpatient Saint Louis University Mental Status (SLUMS) Examination impairment post-critical acute stage9 The SLUMS exam was created to detect mild cognitive impairment (MCI) in veterans,17 age 18 years and up; however, Memory 2 people after acute phase8 research regarding use in younger adults is limited. The SLUMS and severe COVID-19; inpatient exam takes approximately 7 minutes to administer and is avail‑ post-critical acute stage9 able in multiple languages. It is free to the public, with a brief 10 Executive 37 and 149 days after COVID-19; training video available on the developers’ webpage. functioning mixed participant group,11 severe COVID-19, inpatient MoCA 9 postcritical acute stage MoCA was developed as a rapid screening measure to detect Visual mixed participant group11 mild cognitive dysfunction18 and has been validated for use attention in individuals ages 55 to 85. MoCA has been used as a screen‑ Visuospatial severe COVID-19, inpatient ing tool in multiple populations, including people with a large functioning post-critical acute stage9 range of neuropsychiatric conditions from Alzheimer disease (AD) to HIV‑related dementia. Multiple versions are available from COVID‑19 (ages 33 and 56), who were not hospitalized, to allow for serial testing in approximately 100 languages. The had screening and neuropsychologic testing 37 and 149 days MoCA takes about 10 minutes to administer and is available after symptom onset. Cognitive screening with the Montreal digitally. The MoCA is available to the public, although the Cognitive Assessment (MoCA) and the Mini‑Mental State publishers require completion of brief (1 hour) training and Examination (MMSE) was unremarkable, but more comprehen‑ certification, which costs $125, before administering the MoCA. sive tests revealed deficits in executive functioning and work‑ ing memory.9 Neuropsychologic tests were administered to MMSE matched groups, age 30 to 64, who had recovered from vs not The MMSE was developed to screen for cognitive impair‑ had COVID‑19. Tests included the Trail Making Test (TMT), ment19 and is validated for use in ages 18 to 85 years. The Sign Coding Test (SCT), Continuous Performance Test (CPT), MMSE takes approximately 10 minutes to administer and is and Digital Span Test (DST). No differences were seen on the available in about 70 languages. Before 2001, the MMSE was TMT, SCT, or DST, but individuals who had recovered from free, but in 2001, the test was licensed to a commercial com‑ COVID‑19 scored lower on several aspects of the CPT, indicat‑ pany, PAR, through which MMSE must now be purchased. ing sustained attention deficits.8 Although cognition is an important factor for assessing Evidence for Use of Cognitive Screening Tests overall functioning and employment potential, other factors, Evidence for the MoCA such as medical and psychologic history, may also affect func‑ In a minireview of studies that used the MoCA to assess tioning. Fatigue, medication effects, possible dissimulation, people with traumatic brain injury (TBI),20 it was found to reli‑ and current psychologic functioning need to be considered. A ably detect cognitive impairment in people with mild TBI com‑ detailed discussion of these factors is outside the scope of this pared with normal controls. The MoCA is also said to differen‑ 20 PRACTICAL NEUROLOGY MAY 2021 SPECIAL REPORT tiate cognitive disturbances between mild and severe TBI. Still, SLUMS raw score change over a year did not correlate with more research is needed to determine if the the MoCA can any functional measures.29 In a population of veterans (mean differentiate functional cognitive differences in mild vs moder‑ age 75)
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