# Diagnostic Criteria of Postoperative Cognitive Dysfunction: A Focused Systematic Review

Authors: Kim van Sinderen; Lothar A. Schwarte; Patrick Schober
Journal: Anesthesiology Research and Practice
 (2020)

---

## Abstract

Postoperative Cognitive Dysfunction (POCD) is characterized by a deterioration in cognitive performance after surgery and is increasingly addressed in research studies. However, a uniform definition of POCD seems to be lacking, which is a major threat to clinical research in this area. We performed a focused systematic review to determine the current degree of heterogeneity in how POCD is defined across studies and to identify those diagnostic criteria that are used most commonly. The search identified 173 records, of which 30 were included. Neurocognitive testing was most commonly performed shortly before surgery and at 7 days postoperatively. A variety of neurocognitive tests were used to test a range of cognitive domains, including complex attention, language, executive functioning, perceptual-motor function, and learning and memory. The tests that were used most commonly were the Mini-Mental State Examination, the digit span test, the trail making test part A, and the digit symbol substitution test, but consensus on which test result would be considered “positive” for POCD was sparse. The results of this systematic review suggest the lack of a consistent approach towards defining POCD. However, commonalities were identified which may serve as a common denominator for deriving consensus-based diagnostic guidelines for POCD.


---

## Body

## 1. Introduction

Postoperative Cognitive Dysfunction (POCD) is characterized by a deterioration in cognitive performance after surgery and is particularly prevalent in elderly patients [1]. The cognitive decline is usually transient, but can be a substantial threat to the quality of life as it occasionally persists for months to years after surgery. The pathophysiology and risk factors are incompletely understood, and effective strategies for prevention and treatment yet need to be established. Thus, POCD is the target of an increasing amount of research studies and reviews published in leading anesthesia journals [2–4].Despite the clinical relevance and the need for standardized research, a uniform definition of POCD seems to be lacking. A systematic review in 2010 revealed a major inconsistency in diagnostic criteria, neurocognitive tests, and timing of the assessment of POCD across studies in cardiac surgery [5]. The need for uniform terminology and diagnostic criteria in POCD research has in the meantime been widely recognized, and recommendations on uniform nomenclature for perioperative neurocognitive disorders have been published [6]. Yet, it is unclear whether POCD research has recently adopted a more uniform approach to defining POCD and which criteria and tests are currently most commonly used to define POCD.We thus performed a focused systematic review, limited to literature published in the last two years, to determine the current degree of heterogeneity in how POCD is defined and diagnosed across research studies. The results of this review may identify those tests and criteria that are currently used most often and can serve as a common denominator to derive a broader consensus on which tests and criteria should actually be used to diagnose POCD.


## 2. Methods

PubMed was searched for original research studies on POCD in adult patients published between January 1, 2018 and January 14, 2020, using the following search strategy: (“Postoperative Cognitive Complications” [Mesh] OR “Postoperative Period” [Mesh] OR Postoperative [tiab] OR Post-operative [tiab]) AND (“Cognitive Dysfunction” [Mesh] OR (cognitive dysfunction [tiab] OR cognitive dysfunctioning [tiab] OR cognitive dysfunctions [tiab]) OR cognitive decline [tiab]) AND ((“2018/01/01” [PDAT]: “2020/01/14” [PDAT]) AND “adult” [MeSH Terms]). Titles and abstracts were screened by 2 authors, and the full text of potentially relevant articles was retrieved. Original research studies on human subjects, published in English language, that explicitly reported which diagnostic criteria had been used to define POCD, were eligible for inclusion. Data on study and patient characteristics, POCD criteria, and tests used to assess POCD, as well as the time points at which the tests were performed, were extracted using a standardized data extraction form.Because the research question does not lend itself to quantitative pooling of data across studies, and due to substantial heterogeneity across studies, a meta-analysis of the collected data was not performed, and all results are presented descriptively.


## 3. Results

The PubMed search identified 173 records, and 61 full-text articles were assessed for eligibility (Figure1). Of these, 30 studies reporting POCD criteria were included in this systematic review [7–36]. Seven studies report data of a randomized controlled trial, while the rest were observational study designs (cohort, case-control, and longitudinal studies). The study characteristics, POCD criteria, and POCD assessment tests and time points are summarized in Table 1.Figure 1
Flow diagram of studies included in the systematic review.Table 1
Characteristics of studies reporting diagnostic criteria to define POCD.
Author (year)Study type/topicStudy population(s)Type of surgeryPOCD criteriaPOCD assessmentTimepoint of assessmentClaes et al., 2018 [7]Prospective cohort studyIncidence POCD cochlear implantation26 (16 male, 10 female)≥55 yearsPOCD incidence 7 days post-op: 11.5%Cochlear implantationAz-score of change in MoCA scores ≥1.96.(i) MoCA(i) Baseline:(ii) Day of surgery(iii) Post-op:(iv) 7 daysDuan et al., 2018 [8]Prospective observational studyGlial cell line derived neurotropic factor as predictor for POCD80 (36 male/44 female)20 healthy controls>50 yearsPOCD incidence 7 days post-op: 47.5%Elective heart valve replacementAt least 2z scores >1.96.Compared to 20 healthy controls matched by gender, age, and education.(i) MMSE(ii) Digit span test(iii) Trail making test A(iv) Digit symbol  (v) Modalitiesclock drawing test(i) Baseline:(ii) 1 day before surgery(iii) Post-op:(iv) 7 daysGong et al., 2018 [9]Cohort studyIncidence of POCD laparoscopic vs. open surgery70 (41 male/29 female)32–85 yearsPOCD incidence 7 days post-op:Open: 18.7%Laparoscopic: 12.5%Abdominal surgeryPatients with an MMSE score reduction of two.(i) MMSE(i) Baseline:(ii) 1 day before(iii) Post-op:(iv) 1 and 7 daysHayashi et al., 2018 [10]Secondary analysis6-minute walk distance and POCD181 (121 male/60 female)≥ 60 yearsPOCD incidence 14 days post-op: 28%Cardiac surgerySignificant decline in cognitive function based on a decrease of 2 or more in the MMSE score.(i) MMSE(i) Baseline:(ii) Admission(iii) Post-op:(iv) 14 daysHou et al., 2018 [11]RCTDeep versus light anesthesia and POCD60 (26 male/34 female)≥60 yearsPOCD incidence 1 day post-op:Low doses: 20%High doses: 3%Total knee replacementA z-score of >1.96 using cross‐reference.(i) MoCA(i) Baseline:(ii) Day of surgery(iii) Post-op:(iv) 1, 3, and 7 daysKonishi et al., 2018 [12]Secondary analysis of prospective observational study (ACE study)Incidence of POCD sevoflurane vs. propofol121 sevoflurane (77 male/44 female), 171 propofol (114 male/57 female)≥60 yearsPOCD incidence 7 days post-op:Sevoflurane: 20.2%Propofol: 15%Total hip replacement≥2 tests were at least 1.96 SD lower than the mean score of the matched control group after adjusting for expected change over time using controls or the combinedz-score was less than −1.96.(i) Auditory verbal learning test(ii) Trail making test (parts A and B)(iii) Digit symbol substitution test(iv) Controlled oral word association test(v) CERAD semantic fluency test (animals)(vi) Grooved pegboard test (both hands)(i) Baseline:(ii) The week before surgery(iii) Post-op:(iv) 7 days3, 12 monthsKumpaitiene et al., 2018 [13]Prospective observational studyPOCD and decreased cerebral oxygen saturation59 (32 male/24 female)≥60 yearsPOCD incidence 7–10 days post-op: 37%Coronary artery bypass graft surgeryThe sum of allz-scores was >2 or at least two z-scores for separate tests were >2.(i) MMSE(ii) Rey auditory verbal learning test(iii) Digit symbol substitution test and Schulte table(iv) Digit span test(v) Trail making test (parts A and B)(i) Baseline:(ii) Day before surgery(iii) Post-op:(iv) 7–10 daysŞahan et al., 2018 [14]Pilot studyCerebral oxygen changes40 (34 male/6 female)≥60 yearsPOCD incidence 7 days post-op:45% in target group41% in control groupCoronary surgeryA drop of 1 standard deviation from baseline on two or more neuropsychological tests.(i) Logical memory subtest(ii) Clock drawing testVisuospatial skill test(iii) Word list generation test(iv) Digit span subtest(i) Baseline:(ii) 2-3 days before surgery(iii) Post-op:7 days(iv) 3 monthsZhang et al., 2018 [15]Case control studyGoal-directed fluid therapy60 (40 male/20 female)≥60POCD incidence 21.67%Spinal stenosis surgeryIf one standard deviation of MoCA score was decreased one or more after surgery.(i) MoCA(i) Baseline:(ii) 1 day before surgery(iii) Post-op:(iv) 1, 3, and 7 daysZhang et al., 2018 [16]Cohort studyPropofol versus sevoflurane and cognitive function379 (263 male/116 female)≥ 65 and <90 yearsPOCD incidence 7 days post-op:Sevoflurane: 23.2%propofol: 19.0%Major cancer surgery (≥2 hours)Twoz scores in individual tests or the combined z score ≤1.96.(i) Mental control(ii) Paired associate verbal learning(iii) Grooved pegboard (both hands)(iv) Visual retention(v) Digit symbol(vi) Trail making (part A)(vii) Digit span (forward and backward)(i) Baseline:(ii) Before surgery(iii) Post-op:(iv) 7 daysZhang et al., 2018 [17]Predefined exploratory subanalysisVitamin D deficiency and POCD123 (81 male/42 female)≥65 yearsPOCD incidence 7 days post-op: 24.4%Major cancer surgeryTwo or morez-scores in individual tests or the combined z-score ≤−1.96.(i) MMSEMental control and digit span (forward and backward)(ii) Visual retention and paired associate verbal learning(iii) Digit symbol subtest(iv) Halstead–Reitan trail making test (part A)(v) Grooved pegboard test(i) Baseline:(ii) Day before surgery(iii) Post-op:(iv) 7 days(v) Telephone:(vi) 30 days post-opCheng et al., 2019 [18]Cohort studyDexmedetomidine versus saline placebo and POCD535 (392 male/143 female)100 patients with chronic gastroenteritis (reference normal values)≥65 yearsPOCD incidence 7 days post-op:Saline: 18%Dexmedetomidine: 12%Abdominal surgeryRCI ≤−1.96 or az-score ≤−1.96 in at least two tests.(i) Trail making test (parts A and B)(ii) Digit symbol test(iii) Brief visuospatial memory test-revised(iv) Immediate recall and delayed recall(v) Hopkins verbal learning test-revised(vi) Forward and backward digit span test(i) Baseline:(ii) Day before surgery(iii) Post-op:(iv) Days 3 and 7 (iv) Telephone:(v) After 1, 3, and 6 monthsDaiello et al., 2019 [19]Secondary analysis of an observational studyAssociation between POCD and postoperative delirium551 (231 male/320 female)>65 yearsIncidence POCD 1-month post-op: 47%Major noncardiac surgeryA compositez-score of at least 1.96 across all tests, or z-scores for ≥2 tests scores at least 1.96.(i) Rey visual verbal learning test(ii) Concept shifting test(iii) Stroop color-word test(iv) Letter digit substitution(i) Baseline:(ii) Within 2 weeks before surgery(iii) Post-op:(iv) 1, 2, and 6 monthsGao et al., 2019 [20]Prospective studyRisk factors of POCD257 (male 108/149 female)≥65 yearsPOCD incidence 7 days post-op: 21.4%Elective total joint arthroplastyAz score >1.96 at least 2 times.(i) MMSE(ii) Word recognition, memory tests(iii) Digit span test(iv) Verbal fluency test(v) Trail making test (part A)(vi) Symbol digit test(i) Baseline:(ii) 1 day before surgery(iii) Post-op:(iv) 7 daysHan et al., 2019 [21]Cohort studyCortisol ratio in saliva as predictor for POCD94 (65 male/29 female)>60 yearsPOCD incidence 7 days post-op: 17%Major cardiac surgeryAz-score of ≤−1.96 on at least 2 different tests(i) The short story module of the Randt memory(ii) Grooved pegboard test (dominant and nondominant)(iii) Digit symbol subtest(iv) Trail making test (part A)(v) The verbal fluency test(vi) Digit span (forward and backward)(vii) Finger tapping(viii) Block subtest(i) Baseline:(ii) 1 day before surgery(iii) Post-op:(iv) 7 daysHolmgaard et al., 2019 [22]Secondary analysis of a randomized trialCerebral oximetry and POCD153 (138 male/15 female)≥55 yearsPOCD incidence: 29% at discharge, 8% after 3 monthsCardiac surgery (heart valve surgery, coronary artery bypass grafting, or both)Two out of sevenz-scores for individual tests or the composite z-score >1.96.(i) MMSE (≤24 excluded)(ii) Visual verbal learning test(iii) Concept shifting test(iv) Stroop color word interference (SCWI) test(v) Letter digit coding (LCD) test(i) Baseline:(ii) Before surgery(iii) Post-op:(iv) Day before discharge/after 8 days(v) 2–4 monthsHongyu et al., 2019 [23]Cohort studyEffect of penehyclidine hydrochloride on POCD90 (47 male/43 female)>60 yearsPOCD incidence 7 days post-op:A 53.3% (penehyclidine hydrochloride)B 26.7% (atropine)C 13.3% (saline)Thoracoscopic surgery for lung cancerUneducated <17 points, primary education <20 points, and >6 years education <24 points.(i) MMSE(i) Baseline:(ii) 1 day before surgery(iii) Post-op:(iv) 1, 4, and 7 daysKristek et al., 2019 [24]Prospective RCTIncidence of POCD effect levobupivacaine versus morphine70 (4 male/66 female)≥65 yearsPOCD incidence day 1–discharge:levobupivacaine: 9%Morphine: 31%Femoral fracture fixationA decline in the MMSE score below 17 or a reduction in the MMSE score for ≥3 compared with the baseline on at least one measurement.(i) MMSE(i) Baseline:(ii) Before surgery(iii) Post-op:(iv) Days 1–5(v) Day of dischargeLachmann et al., 2019 [25]Prospective, observational studyAssociation between cerebral microbleeds and POCD65 (30 male/35 female)>65 yearsIncidence POCD 7 days post-op: 20%Major elective surgery (>60 minutes)RCI by Rasmussen et al., 2001.(i) Paired associates learning(ii) Verbal recognition memory(iii) Spatial span time(iv) Simple reaction time(v) Grooved pegboard(vi) Trail making tests(i) Baseline:(ii) Performed but not mentioned when.(iii) Post-op:(iv) 7 days(v) 3 monthsLanger et al., 2019 [26]RCT pilotHypotension and POCD101 patients (53 male/48 female)33 age-matched controls≥75 yearsPOCD incidence 3 months post-op: 9%Elective noncardiac surgeryRCI was usedA z-score below −1.96 on at least 2 neuropsychological tests and/or the combined z-score below −1.96.(i) MMSE(ii) Stroop test(iii) Symbol digit modalities test(iv) Trail making test (parts A and B)(v) Immediate and delayed recall(vi) Free and cued selective reminding test (FCSRT)(vii) Verbal phonemic fluency test(viii) Denomination test(i) Baseline:(ii) Before surgery(iii) Post-op:(iv) After 3 monthsLi et al., 2019 [27]Prospective, observational studyAssociation between serum levels S100A12 and POCD186 patients (male 78/female 108)186 controls (for serum)≥65 yearsPOCD incidence 7 days post-op: 35%Femoral neck fracture or intertrochanteric fractureTwo or morez-scores in individual tests or the combined z-score ≤−1.96.(i) Visual verbal learning test(ii) Concept shifting test(iii) Stroop color word interference test(iv) Paper and pencil memory scanning test(v) Letter digit coding(vi) Four boxes test(i) Baseline:(ii) 1 day before surgery(iii) Post-op:(iv) 7 daysLi et al., 2019 [28]Prospective RCT preliminary trialSedation by dexmedetomidine, midazolam, or propofol and POCD205 (72 male/133 female)≥65 yearsPOCD incidence 7 days post-op: 36.6%Hip or knee arthroplastyRCI score less than −1.96 on ≥2 tests and/or combinedz-score less than −1.96.(i) Montreal cognitive assessment (MoCA)(ii) Stroop color-word test (SCWT)(iii) Associative learning and memory test (iv) Digit symbol test(v) Digit span test(i) Baseline:(ii) Before surgery(iii) Post-op:(iv) 7 days(v) Telephone:(vi) 1 year using 5-minute MoCA protocolQuan et al., 2019 [29]RCTLight vs. deep anesthesia and POCD120 (66 male/54 female)≥60 yearsPOCD incidence 7 days post-op:Deep: 19.2%Light: 39.6%Abdominal surgeryDeterioration in postoperative performance by 1 or more standard deviations on 2 or more tests.(i) Mental control(ii) Digit span (backward and forward)(iii) Paired associate verbal learning(iv) Digit symbol subtest(v) Visual retention-Halstead–Reitan trail making test (part A)-grooved pegboard test(i) Baseline:(ii) Before surgery(iii) Post-op:(iv) 7 days(v) 3 monthsSánchez et al., 2019 [30]Longitudinal studyOptimization of delirium assessment1500≥70 years POCD incidence:Elective surgeryThoracic, cardiac, vascular, proximal big joints and spine, gastrointestinal, genitourinary, and general elective surgeryA test value ≤0.5 standard deviations, normalized for age, gender, and education, in one of these tests.(i) Montreal cognitive assessment (MoCA)(ii) Digit span backwards(iii) Trail making test A and B(i) Baseline:(ii) Preadmission(iii) Before surgery(iv) Post-op:(v) 2, 6, and 12 monthsWang et al., 2019 [31]Prospective cohort studyGlucocorticoid receptor, FKBP51, and POCD in elderly111 (49 male/62 female)≥65 yearsPOCD incidence 7 days post-op: 28.3%Hip fracture surgeryA decline of 1 or more standard deviations (SDs) in 2 or more tests.(i) MMSE(ii) Verbal learning(iii) Mental control(iv) Digit span (forward and backward)(v) Visual retention(vi) Grooved pegboard test (both hands)(vii) Digit symbol test(viii) Trail making test (part A)(i) Baseline:(ii) 1 day before surgery(iii) Post-op:(iv) 7 daysWang et al., 2019 [32]Cohort studycircRNA_089763 as biomarker for POCD35 (30 male/5 female)40–90 yearsPOCD incidence 7 days post-op: 34%Coronary artery bypass graftingReduction in postoperative test score compared with the preoperative test score ≥20% in ≥2 tests.(i) Stroop color and word test(ii) Trail making test(iii) Digit symbol substitution test(iv) Verbal learning test(v) The symbol digits modalities test(i) Baseline:(ii) 1 day before surgery(iii) Post-op:(iv) 7 daysWang et al., 2019 [33]Prospective observational cohort studySmoking history and risk for POCD382 (189 male/193 female)≥60 yearsPOCD incidence 5 days post-op: 50.4%Noncardiac surgeryAz-score of ≥1.96.(i) MMSE(ii) Concept shifting test(iii) Stroop color-word interference test(i) Baseline:(ii) 1 day before surgery(iii) Post-op:(iv) 5 and 7 daysWang et al., 2019 [34]RCTRopivacaine intercostal nerve block and POCD100 (50 male/50 female)Age: 43–46 yearsPOCD incidence:With block: 21%Without block: 39%Thoracotomy for esophageal cancerScore less than or equal to 25 points, or if more than 2 points reduction on the MMSE score after surgery compared with the score before surgery.(i) MMSE(i) Baseline:(ii) 1 hour before surgery(iii) Post-op:(iv) 2, 12, and 24 hoursZhang et al., 2019 [35]Cohort studyEffects of fentanyl versus sufentanil on POCD96 (47 male/49 female)≥65 yearsPOCD incidence 7 days post-op:Fentanyl: 11.9%Sufentanil: 6.2%Open surgeryA drop of 1 standard deviation from baseline on two or more items.(i) MoCA(i) Baseline:(ii) 1 day before surgery(iii) Post-op:(iv) 1, 7 daysZhang et al., 2019 [36]Cohort studyRisk factors for POCD77 (42 male/35 female)≥65 yearsPOCD 7 days post-op: 24.7%Colorectal surgeryz-score was greater than 1.96 or the combined z- score was ≥1.96.(i) MMSE(ii) Visual verbal learning test(iii) Digit span test(iv) Digit symbol substitution test(i) Baseline:(ii) 1 day before surgery(iii) Post-op:(iv) 7 daysIn the majority of studies (n = 25), baseline neurocognitive performance was measured either on the day of surgery or on the day before surgery, while the other studies used varying preoperative time intervals. The most frequently used follow-up time was 7 days after surgery (n = 23). Ten out of the 30 studies followed patients up over a longer period of time, up to one year after surgery.A variety of different neurocognitive tests (Table2) were used to test a range of cognitive domains, including complex attention, language, executive functioning, perceptual-motor function, and learning and memory. We refer to Sachdev et al. [37] for a detailed description of the different cognitive domains and to Evered and Silbert [3] for an overview over which domains are being tested by which neurocognitive test. Nine studies included in our systematic review relied on only one test, either the Mini-Mental State Examination (MMSE, n = 5) or the Montreal Cognitive Assessment (MoCA, n = 4), both of which actually test several neurocognitive domains. The other studies used a battery of different tests for different domains, and some of these studies also additionally included the MMSE (n = 9) or MoCA (n = 2) tests. Besides the MMSE, the most commonly used tests were the digit span test (forward test n = 13, backward test n = 14), which measures short-term memory, the trail making test part A (n = 13), which tests processing speed and mental flexibility by connecting numbered dots in sequence, and the digit symbol substitution test (n = 11), which measures visuoperceptual functions and motor speed.Table 2
Neurocognitive tests used in the included studies to define POCD.
Neurocognitive testNumber of studies, in which the test was usedAssociative learning and memory test1Auditory verbal learning testBlock subtest21Clock drawing test2Concept shifting test4Controlled oral word association test1Denomination test1Digit symbol substitution test11Digit span testForwardBackwardFinger tapping test13141Four boxes test1Free and cued selective reminding test1Grooved pegboard test7Hopkins verbal learning test1Immediate recall and delayed recall2Letter digit coding testLetter digit substitution test21Logical memory test1Mental control4MMSE14MoCA6Paired association verbal learning test5Paper pencil memory scanning test1Stroop color interference testShort story module of the Randt memorySimple reaction timeSpatial span timeSymbol digits modalities test71111Trail making testPart APart B136Verbal fluency test3Verbal learning test4Visuospatial memory test (brief)1Visuospatial skill test1Visual retention4Visual verbal learning test (here: with capital letters)4Word list generation test1Word recognition memory test1Not only the used tests and timing of testing differed considerably between studies, but also the criteria to define a “positive” test result. While some authors use a deterioration compared to baseline testing in terms of the absolute test score (e.g., >2-point deterioration in the MMSE), other authors define a positive test result in terms of the deterioration of ≥1 standard deviation from the baseline measurement. Other authors usez-scores, in which the difference in the observed change from baseline between surgical patients and control patients is scaled by the standard deviation of control patients [38]. The “reliable change index” (RCI)—a measure of change from baseline in units of the standard error of the change [39]—has occasionally been used in addition to, or instead of, z-scores.


## 4. Discussion

Symptoms of cognitive dysfunction are estimated to occur postoperatively in about 12% of patients without apparent preoperative cognitive dysfunction undergoing noncardiac surgery [4], and the incidence may be as high as 50–70% after cardiac surgery [40]. While these symptoms are often transient, cognitive impairment has been observed in up to 10% of elderly patients at 3 months after surgery [4], and it has been estimated that about one-half of elderly patients with POCD suffer permanent dysfunction [41]. POCD is thus evidently a major threat after an operation in particular to elderly patients, and every effort is needed to prevent, diagnose, and treat POCD in this vulnerable patient population.Unfortunately, the pathophysiology and risk factors are still poorly understood, and evidence-based treatment options are scarce. It is thus not surprising that POCD is a target of an increasing amount of research papers in anesthesiologic, surgical, and neurologic literature. Using the search term “postoperative cognitive dysfunction” in PubMed yields almost 4,000 results at the time of the writing of this manuscript, with a steady increase over the years: while there were 50 publications in the year 2000, this has increased to 168 in 2010 and to 426 in 2019. The literature, however, has in the past been very heterogenous in how POCD was defined, and this is a major threat to clinical research in this area: when the condition being studied is not well characterized and well defined, study results may not be readily comparable and applicable to clinical practice. Moreover, there are several types of cognitive impairments that can be observed after an operation, including delirium, POCD, and dementia. These terms are sometimes used interchangeably or with a broad overlap in the literature, and a clear distinction is often lacking. In 2010, Rudolph and colleagues have demonstrated a substantial inconsistency in diagnostic criteria, neurocognitive tests, and timing of the assessment of POCD across studies in cardiac surgery [5]. Since then, multiple authors have emphasized the need for uniform terminology and diagnostic criteria in POCD research. However, while it is clear that a uniform approach to defining POCD was previously lacking, it is unclear whether this issue has been successfully improved or even resolved in recent years.In this focused systematic review, we therefore aimed to study how POCD is defined and measured in the recent literature. The results suggest that even in the most recent POCD literature, a consistent approach towards defining and measuring POCD is still lacking. As previously noted by other authors [4, 42, 43], uniform diagnostic criteria are needed, and this is clearly reinforced by our data.While our systematic review identified the lack of a consistent approach towards defining POCD, the data, however, provide more than a mere description of heterogeneity across recent studies. We observed some patterns that may serve as a common denominator in the process of reaching standardized diagnostic criteria: with respect to timing, a follow-up measurement at 7 days postoperatively seems to be broadly accepted. With respect to the tests being used, the MMSE, digit span test, trail making test part A, and the digit symbol substitution test were used most commonly, suggesting a broad consensus that these tests are particularly useful for the diagnosis of postoperative neurocognitive disorders. However, it is still unclear which test result would be considered “positive” for POCD. Moreover, it should be noted that these tests have not been developed for POCD testing and have also not been rigorously validated for this purpose. For example, the MMSE has been shown to be less sensitive than the MoCA for a variety of neurocognitive disorders [44], and this could also be true for POCD. This implies that more research not only on the pathophysiology, prevention, and treatment of POCD is required, but also on the diagnostic accuracy [45] of the tests themselves that are commonly used to diagnose POCD.Our data suggest that strong efforts are necessary to define precise and applicable diagnostic criteria for POCD, involving key-opinion leaders and researchers in the field. This would, in our opinion, be a strong and necessary step towards a precise characterization of the disease, its underlying pathophysiology, risk factors, and treatment options. Notably, however, perhaps the term POCD itself is too broad and vague and actually represents several distinct neuropathologic conditions, rather than one underlying common pathophysiology. If so, this may have important implications for the identification of risk factors as well as prevention and treatment strategies and may explain the heterogeneity in findings across the literature. In this context, Evered et al. have previously suggested that the overarching term POCD should be changed to “delayed neurocognitive recovery” for symptoms expected to have been resolved before 30 days and “postoperative mild neurocognitive disorder” or “postoperative major neurocognitive disorder” for an expected recovery between 30 days and 12 months, depending on the severity of symptoms [6]. Therefore, future efforts should perhaps not so much focus on defining diagnostic criteria for the overarching concept of “POCD” itself, but rather more specifically, for distinct postoperative neurocognitive disorders comprised within this umbrella term. Moreover, it is also well possible that some cognitive domains may be more vulnerable after surgery and anesthesia than others, or that a cognitive decline in some domains may affect patients more severely than a decline in other domains. We believe that identification of those domains that are particularly relevant in the context of POCD is an important topic for future research because broad testing for a decline in all cognitive domains may neither be necessary nor ideal. Focusing on those domains which are most vulnerable and/or most severely affect the patients’ wellbeing would reduce the patients’ burden to undergo a whole battery of neurocognitive tests, facilitate clinical testing, and allow for a more efficient allocation of clinical and research resources.The results of this systematic review must be viewed in the context of its limitations. First, this was a focused review, deliberately limited to the literature published in the last two years, and it thus does not claim to be an exhaustive review of all published literature on the topic. However, we specifically attempted to assess how POCD is currently diagnosed, and older literature would merely have been of historic interest. We only searched one database, however, one with comprehensive coverage of reputable medical literature. It was neither our intention to identify gray literature on the topic, nor to identify literature published in predatory or otherwise untrustworthy literature. We are also aware that the mere fact that a majority of studies used a certain definition to diagnose POCD does not necessarily mean that this is the optimal way to diagnose POCD. It does, however, suggest that there is a rather broad consensus among researchers that certain tests at certain time points may play a useful role and can serve as a starting point towards a more uniform definition and assessment of POCD in clinical practice and in research settings.In conclusion, this systematic review identified the lack of a consistent approach towards defining POCD. Commonalities were identified which may serve as a common denominator for deriving consensus based diagnostic guidelines for POCD. However, more research is necessary to characterize the diagnostic accuracy of the tests used to identify a postoperative cognitive decline and on what would constitute a “positive” test result. Finally, future efforts should perhaps not so much focus on finding a uniform definition of POCD itself, but rather on characterizing and defining distinct postoperative neurocognitive disorders comprised within this overarching term.



---

*Source: 7384394-2020-11-17.xml*