Acta Neurol Scand 2014: 129: 209–218 DOI: 10.1111/ane.12211

© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd ACTA NEUROLOGICA SCANDINAVICA

Review Article

Information processing speed in obstructive sleep apnea syndrome: a review Kilpinen R, Saunamäki T, Jehkonen M. Information processing speed in obstructive sleep apnea syndrome: a review. Acta Neurol Scand 2014: 129: 209–218. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. To provide a comprehensive review of studies on information processing speed in patients with obstructive sleep apnea syndrome (OSAS) as compared to healthy controls and normative data, and to determine whether continuous positive airway pressure (CPAP) treatment improves information processing speed. A systematic review was performed on studies drawn from Medline and PsycINFO (January 1990–December 2011) and identified from lists of references in these studies. After inclusion criteria, 159 articles were left for abstract review, and after exclusion criteria 44 articles were fully reviewed. The number of patients in the studies reviewed ranged from 10 to 157 and the study samples consisted mainly of men. Half of the studies reported that patients with OSAS showed reduced information processing speed when compared to healthy controls. Reduced information processing speed was seen more often (75%) when compared to norm-referenced data. Psychomotor speed seemed to be particularly liable to change. CPAP treatment improved processing speed, but the improvement was marginal when compared to placebo or conservative treatment. Patients with OSAS are affected by reduced information processing speed, which may persist despite CPAP treatment. Information processing is usually assessed as part of other cognitive functioning, not as a cognitive domain per se. However, it is important to take account of information processing speed when assessing other aspects of cognitive functioning. This will make it possible to determine whether cognitive decline in patients with OSAS is based on lower-level or higher-level cognitive processes or both.

Introduction

Obstructive sleep apnea syndrome (OSAS) is the most common cause of sleep apnea. It is characterized by repetitive episodes of upper airway obstruction during sleep (1). Peppard et al. (2) have currently estimated that approximately 13% of men and 6% of women among adults 30–70 years of age have moderate to severe sleepdisordered breathing. In addition, the prevalence is even higher in some professional groups (3). The most common daytime symptoms of OSAS are excessive daytime sleepiness, reduced quality of life, mood changes, and cognitive changes

R. Kilpinen1,2, T. Saunam€aki1, M. Jehkonen2 1 Department of Neurology and Rehabilitation, Tampere University Hospital, Tampere, Finland; 2Department of Psychology, School of Social Sciences and Humanities, University of Tampere, Tampere, Finland

Key words: obstructive sleep apnea syndrome; information processing speed; continuous positive airway pressure R. Kilpinen, Department of Neurology and Rehabilitation, Tampere University Hospital, PO Box 2000, FI-33521 Tampere, Finland Tel.: +358 3 31169942 Fax: +358 3 31164367 e-mail: [email protected] Accepted for publication November 18, 2013

especially in attention, executive functioning, memory, and visuoconstructive abilities (4–7). Continuous positive airway pressure (CPAP) treatment is the most common form of treatment in moderate and severe OSAS. CPAP provides a constant pressure to offset airway collapse, thereby maintaining airway patency. With properly titrated pressure, it minimizes sleepdisordered breathing events (8). CPAP treatment generally improves cognitive performance, but some deficits may persist (6, 9). Cognitive decline in executive and visuoconstructive functioning is reported mainly to persist (6, 10). Attention and vigilance generally improves, while the effects of 209

Kilpinen et al. CPAP on memory are inconsistent (6, 11). It has been suggested that longer treatment times may be required for specific cognitive changes to take effect (12). Although executive function is thought to be among the most vulnerable cognitive domains in OSAS (10), it has been suggested that executive function may also be impacted by lower-level cognitive deficits. Verstraeten et al. (7, 13) have pointed out that higher-level executive dysfunction in OSAS may be caused by impaired lower-level attentional processes, such as slowed information processing and decreased short-term memory span. It follows that instead of sleep disruption, hypoxemia and hypercapnia induced frontally related executive dysfunction (10), basal slowing due to sleepiness may be the most vulnerable cognitive deficit in OSAS (7, 13). Bearing in mind that fronto-subcortical circuits of the brain are very dense, it is possible that both of these theories are correct, and OSAS may impact both higher-level executive functions and lower-level processing speed and attentional skills. For example, OSAS patients’ working memory performance has been shown to be affected by both executive and attentional deficits (14, 15). Information processing is not a separate cognitive process, but it involves many cognitive functions and is closely related to the assessment of attention. Attention can be seen as a quality of information processing: the perception, processing, and storing of information are optimal when the attentional system is properly directed and when the required level of intensity is present (16). On this basis, it has been argued that attention and information processing speed can only be measured indirectly through other cognitive processes, such as the efficiency of visual search or the speed of visuomotor responses. The slowing of mental activity is manifested in delayed reaction times and longer psychomotor performance times. It should be noted that a single neuropsychological test method requires always overlapping cognitive skills, and no generally approved consensus what cognitive functions are assessed by different test methods exists (4). For example, a time score obtained in a visual search task may reflect both the speed of processing of visual information, and higher-order aspects of attention such as strategy and flexibility (16). Thus, impairment in one test method can be interpreted differently between studies even using same neuropsychological test. In addition, when different test methods are used, the making of comparisons between studies is even harder. The use of a theoretical background may be one solution to handle this problem. 210

According to Spikman and van Zomeren (16), the assessment of attention can be divided into three levels depending on the structure of the task and time pressure during performance: (i) operational, (ii) tactical, and (iii) strategic. It is thought that performance at the operational level provides a measure of the basic speed of information processing; tasks are relatively simple and highly structured, but there is always an element of time pressure. Attention can be here tested at the basic level and time is the essential dependent variable. Performance in these tasks is called stimulus driven, and the working memory load is minimal. One of the methods used to assess basic mental speed is through recordings of reaction time. Examples of clinical tools designed to assess this level of cognitive performance include Trails A of the Trail Making Test (17), word reading and colour naming in the Stroop Colour Word Test (18) and the Digit Symbol of the Wechsler Adult Intelligence Scale (WAIS-R) (19). The assessment of information processing speed requires finely graded norms that take into account of the decline in processing speed with advancing age (16, 20). At the tactical level, subjects are still expected to work as quickly as possible, but the tasks are more complicated and challenging than at the operational level, requiring both speed and planning. Performance on this level is called memory driven. It is partially structured since instructions and rules must remain activated in the working memory throughout the performance. Among the clinical tools that can be used to assess this tactical level of attention and information processing are Trails B of the Trail Making Test (17), the Continuous Performance Test (21), the Stroop Interference Task of the Stroop Colour Word Test (18), and the Paced Auditory Serial Addition Task (22). At the strategic level, time pressure is minimal, and the tests offer less structure. These tasks require the application of autonomous strategy, and therefore, performance is called strategy driven. This level of information processing involves more executive demands, and it can be assessed by clinical tools such as the Wisconsin Card Sorting Test (23) and the Tower of London Test (24). Earlier, we have conducted a review of studies concerned with the executive functions in OSAS (25), focusing on research assessing the tactical and strategic level of information processing. Our focus here is on studies concentrating on the operational level and interested in information processing speed, psychomotor speed, and reaction times in OSAS. The slowing of information processing in OSAS has so far received only

OSAS and information processing speed limited research attention. To the best of our knowledge, there are no earlier reviews of information processing speed per se, but it is always considered in the context of other cognitive processes. Our two main questions are as follows: (i) do patients with OSAS show slowing when compared to control-referenced and norm-referenced data? And (ii) what impact does CPAP treatment have on information processing speed? Materials and methods Data collection

We searched the Medline and PsycINFO databases for articles published between January 1990 and December 2011. Our neuropsychological search terms were as follows: cognition, cognitive ability, mental status, neuropsychology, neuropsychological, memory, attention, vigilance, executive, psychomotor, processing speed, information processing, or cognitive processing. The search terms for OSAS were as follows: sleep apnea, obstructive, disordered breathing, or sleep disorder. Searches were conducted using all possible combinations of these terms. Excluded from consideration were non-English articles, studies of non-human and non-adult subjects (30 events/h). The severity of sleep apnea ranged from moderate to severe (>15 events/h) in 14 study samples (12, 13, 27, 29, 32, 34, 38, 42, 44, 45, 48, 56–58) and from mild to severe (>5 events/h) in 22 study samples (8, 26, 30, 31, 33, 39–41, 43, 46, 47, 49, 50, 52, 59–66). In one study (28), the severity of sleep apnea was reported based on the ODI4 index (4% desaturation events/h). Description of control groups

Sixteen of the studies that compared OSAS patients’ pretreatment performance with healthy controls used polysomnography to ensure that control subjects did not have undiagnosed OSAS (27, 29, 33, 51, 53, 54, 56, 58–66). In one study (13), a subgroup of controls, 10 of 32 healthy 211

Kilpinen et al. controls, underwent a polysomnographic evaluation. In the remaining four studies (31, 42, 47, 48), controls were categorized as healthy if they had no clinical symptoms of sleep disorder. The control group was matched for age, education, and gender in 12 studies (27, 29, 31, 33, 42, 47, 48, 51, 53, 58, 59, 63), for age and education in six studies (13, 54, 57, 62, 65, 66), for age and gender in three studies (27, 56, 61), and for gender and education in one study (64). The mean age of controls ranged from 28 to 57 years (Md, 47) and the mean education time from 11 to 15 years (Md, 13). Five studies (29, 42, 47, 48, 51) did not report mean education years. Patients with OSAS receiving effective CPAP treatment were compared with those receiving placebo treatment (e.g. ineffective CPAP or oral placebo) in nine studies (12, 26, 34, 35, 38–41, 43) and with those receiving conservative treatment (e.g. avoidance of alcohol, weight loss, sleep hygiene) in three studies (28, 32, 46). Two studies (8, 30) compared compliant CPAP users with non-compliant CPAP users. One study (45) focused on the treatment effects between patient groups using either auto-CPAP or constantCPAP. One study (64) used healthy controls as a control group at the post-treatment assessment as well. The remaining 13 studies (36, 37, 42, 44, 47, 50, 52–55, 57–59) did not include a control group at the post-treatment assessment.

Assessment of information processing speed, psychomotor performance, and reaction time

The neuropsychological tests most commonly used for the assessment of information processing speed, psychomotor speed, and reaction time were Trails A in 14 studies (13, 33, 42, 47, 48, 53, 54, 56, 60–65), the Digit Symbol in 12 studies (13, 27, 29, 31, 51, 58–64), the Purdue Pegboard Test (23) in four studies (27, 54, 59, 66), and the Bourdon-Wiersma Test (23) and the Rapid Visual Information Processing Test (23), which were both used in two studies (36, 37, 39, 40). Other methods used were the Grooved Pegboard Test (67), the Sensory-Motor Control Task (23), the Choice Reaction Time Task (23), the Finger Tapping Test (68), the Stroop Neutral Test (18), and the Simple Motor Reaction Time Test (69). Patients’ pretreatment performance compared with controlreferenced and norm-referenced data

Table 1 shows OSAS patients’ pretreatment performance as compared to healthy controls. In 12 of the 21 studies including a total of 261 patients (13, 27, 29, 31, 33, 51, 53, 58, 59, 62, 64, 66), patients with OSAS showed slowed information processing speed in at least one cognitive test. Slowing was detected especially in the Digit Symbol (nine studies), in Trails A (one study), in the

Table 1 Obstructive sleep apnea syndrome (OSAS) patients’ performance as compared to the healthy control group in tests of information processing speed

Bawden et al. (31) Bedard et al. (59) Bedard et al. (27) Canessa et al. (53) Ferini-Strambi et al. (54) Feuerstein et al. (42) Kloepfer et al. (56) Lee et al. (33) Naegele et al. (47) Naegele et al. (48) Neu et al. (29) Quan et al. (60) Redline et al. (61) Rouleau et al. (62) Saunam€aki et al. (63) Saunam€aki et al. (58) Saunam€aki et al. (64) Sharma et al. (51) Twigg et al. (65) Verstraeten et al. (13) Yaouhi et al. (66)

Patients (n)

Controls (n)

Methods

Patients slower than controls

17 10 20 17 23 10 15 17 10 17 15 67 32 28 40 15 20 50 60 36 16

20 10 10 15 23 10 20 16 10 17 16 74 20 18 20 15 17 25 60 32 14

DS DS, PPT DS, PPT TMT-A TMT-A, PPT TMT-A TMT-A TMT-A, S-MCT, CRTT TMT-A TMT-A DS, FTT DS, TMT-A, GPT DS, TMT-A DS, TMT-A DS, TMT-A DS DS, TMT-A DS TMT-A DS, TMT-A, Stroop neutral PPT

DS: P = 0.04 DS: P < 0.05; PPT: P < 0.01 DS: severe OSAS P < 0.05; PPT: moderate OSAS P < 0.01; severe OSAS P < 0.001 TMT-A: P = 0.02 ns ns ns S-MCT: P < 0.01 ns ns DS: P < 0.001; FTT: right P < 0.001, left P = 0.002 ns ns DS: P = 0.029 ns DS: P = 0.038 DS: P = 0.011 DS: P = 0.03 ns DS: P < 0.001 PPT assembly: P = 0.025

‘ns’ indicates no statistically significant difference between the groups. DS, Digit Symbol; PPT, Purdue Pegboard Test; TMT-A, Trails A of the Trail Making Test; S-MCT, Sensory-Motor Control Task; CRTT, Choice Reaction Time Task; FTT, Finger Tapping Test; GPT, Grooved Pegboard Test.

212

OSAS and information processing speed Table 2 Impact of continuous positive airway pressure (CPAP) treatment on information processing speed in placebo-controlled studies

Barbe et al. (35)* Bardwell et al. (12)* Barnes et al. (26)† Engleman et al. (38)† Engleman et al. (39)† Engleman et al. (40)† Engleman et al. (41)† Henke et al. (43)† Lim et al. (34)*

Patients with CPAP (n)

Patients with placebo (n)

Treatment time

29 20 28 34 23 16 32 27 17

25 16 28 34 23 16 32 18 14

6 weeks 7 days 8 weeks 4 weeks 4 weeks 4 weeks 4 weeks 35 days 2 weeks

CPAP compliance h/night (mean  SD) 5 5.5 3.5 2.8 2.8 2.8 3.4 5.8 6.6

        

0.4 0.3 2.1 2.1 2.0 0.6 0.4 2.0 1.2

Methods DS, DS, DS, DS DS, DS, DS DS, DS,

TMT-A TMT-A, Stroop neutral TMT-A RVIPT RVIPT TMT-A TMT-A

Improvement ns ns ns DS: P < 0.01 ns ns DS: P = 0.05 DS: P < 0.03 ns

‘ns’ indicates no statistically significant CPAP treatment effect. DS, Digit Symbol; TMT-A, Trails A of the Trail Making Test; RVIPT, Rapid Visual Information Processing Test. *Parallel study. † Cross-over study.

Purdue Pegboard Test (three studies), and in Finger Tapping (one study). In nine studies with a total of 274 patients (42, 47, 48, 54, 56, 60, 61, 63, 65), patients’ performance did not differ from that of controls. In the eight studies (12, 26, 28, 34–37, 46) where OSAS patients’ pretreatment performance was compared with norm-referenced data, slowing was detected in six studies including a total of 290 patients; five studies (12, 26, 34, 36, 37) showed slowed information processing speed in the Digit Symbol, and three studies (12, 34, 46) in Trails A. Two studies (28, 35) with a total of 104 patients showed performance within the normal range. Impact of CPAP treatment on patients’ information processing speed

The results concerning the impact of CPAP treatment on information processing speed as compared to placebo treatment are shown in Table 2. CPAP treatment time ranged from 1 to 8 weeks and compliance from 2.8 to 6.6 h per night (Md, 3.5 h/night). In three (38, 41, 43) of the nine placebo-controlled studies, CPAP treatment improved information processing speed (in the Digit Symbol), but only two of these studies (38, 41), including a total of 132 patients (66 patients with CPAP and 66 patients with placebo), showed improvement more than placebo treatment. In the three studies (28, 32, 46) that compared CPAP treatment with conservative treatment, CPAP had no significant effect on information processing speed. In two studies (8, 30) comparing the performance of compliant CPAP users with non-compliant users, the information processing speed of compliant users improved as assessed with the Digit Symbol and Trails A. When comparing auto-CPAP use with constant-

CPAP use (45), a significant improvement was seen in both groups at post-treatment assessment on Trails A. The study (64) that compared OSAS patients’ performance with that of healthy controls at both the pre- and post-treatment phases showed no significant improvement in the Digit Symbol or Trails A after CPAP treatment. The results of the 13 studies that had no comparative group regarding the effects of CPAP treatment are shown in Table 3. In these studies, treatment time ranged from two nights to 18 months and compliance from 4.8 to 7.3 h per night (Md, 5.7 h/night). Six studies did not report mean compliance to CPAP treatment. Eight (9, 36, 37, 44, 47, 53, 54, 59) of these 13 studies, including a total of 213 patients, showed an improvement in at least one test assessing the information processing speed. Discussion

According to this systematic review of 44 studies, OSAS patients’ information processing speed was reduced in 50% of the studies when compared to healthy controls. These control-referenced study samples included a total of 535 patients and 462 controls. Slowness was detected more often when the comparisons were made with norm-referenced data. In particular, it seems that psychomotor speed, as assessed with the Digit Symbol, is vulnerable. CPAP treatment improved the processing speed, but only marginally when compared to placebo or conservative treatment. The sample size in the studies reviewed ranged from 10 to 157, and half of the studies had less than 28 patients (Md, 28). This wide variation in sample sizes obviously undermines the comparability of different studies. Most of the studies reviewed consisted of male patients of working 213

Kilpinen et al. Table 3 Impact of continuous positive airway pressure (CPAP) treatment on information processing speed in studies without control group

Bedard et al. (59) Borak et al. (36) Borak et al. (37) Canessa et al. (53) Ferini-Strambi et al. (54) Feuerstein et al. (42) Gale et al. (55) Kingshott et al. (44) Lau et al. (57) Naegele et al. (47) Sanchez et al. (9) Saunam€aki et al. (58) Valencia-Flores et al. (52)

Patients (n)

Treatment time

10 20 20 17 23 10 14 62 37 10 51 15 37

6 and 10 months 3 months 3 and 12 months 3 months 15 days and 4 months 4–6 months 6 months 6 months 18 months 4–6 months 1 and 3 months 6 months 2 nights

CPAP compliance h/night (mean  SD) na na na 5.8 5.2 na na 4.8 7.3 5.3 5.8 6.1 na

 0.6  1.7

 2.4  1.0  0.7

Methods

Result

DS, PPT DS, B-W DS, B-W TMT-A TMT-A, PPT TMT-A DS, TMT-A DS, TMT-A TMT-A, GPT TMT-A SMPRT DS DS

DS: P < 0.01; PPT: dominant hand P < 0.01 B-W: P = 0.01 B-W: P < 0.05 at 12 months TMT-A: P = 0.03 TMT-A: P = 0.002; PPT assembly: P = 0.002 ns ns DS: P < 0.05; TMT-A: P < 0.05 ns P < 0.05 SMPRT: P < 0.01 ns ns

‘ns’ indicates no significant CPAP treatment effect. na, not assessed; DS, Digit Symbol; PPT, Purdue Pegboard Test; B-W, Bourdon-Wiersma Test; Trails A, Trail Making Test A; GPT, Grooved Pegboard Test; SMPRT, Simple Motor Perceptive Reaction Time.

age. This represents an important target group for neuropsychological assessment, but of course, the results cannot be generalized directly to women. It is also worth noting that increasing age may be associated with slowed psychomotor performance, but on the other hand also with slightly better function in processing speed (60). Although educational level is thought to be one of the most important background variables affecting cognitive test performance, education was reported in only 19 of the 44 studies. This obviously complicates comparisons of patients’ and controls’ premorbid cognitive level. Premorbid level of cognitive functioning and other sociodemographic variables must be taken into account when comparing the test results of patients with either healthy controls or norm-referenced data (7). Most of the studies reviewed reported heterogeneous OSAS severity. Comparisons between cognitive slowing and severity of OSAS were rarely reported, but Quan et al. (60) found that motor speed and processing speed performance were significantly impaired in patients with higher oxygen desaturation. Sharma et al. (51) also reported an association between OSAS severity and delayed information processing speed without any independent impairment in other cognitive domains. Bedard et al. (27) showed that increased OSAS severity not only aggravates the neuropsychological deficits already present in moderately affected patients, but also induces new deficits in manual dexterity among the other cognitive changes in more severe patients. Most studies used two or three methods to assess information processing speed. The most commonly used tests were the Digit Symbol and Trails A. We found no congruent recommendations regarding the testing of information 214

processing speed, but according to this review, it seems that the Digit Symbol is quite sensitive. In some studies, the authors failed to specify what particular domain of cognitive function they intended to measure with a single test. For example, the Digit Symbol was used to measure psychomotor speed and attention (29, 30, 61, 64), psychomotor performance, motor persistence, sustained attention, response speed (29, 31), visuospatial coordination (31), visual scanning (29), information processing speed (34, 49, 55, 60), and coding efficiency (speed) (41). Trails A was used to measure psychomotor speed (30, 56), processing speed (34, 55), attention (47, 49), and the visual search process (49). Purdue and Grooved Pegboard were defined as tests of fine-motor speed (30, 60), motor and constructional abilities (54), psychomotor dexterity and speed (57). Half of the studies comparing OSAS patients’ pretreatment performance with that of healthy controls’ showed slowing of information processing (12 of 21 studies). It should be noted that in many of these control-referenced comparisons, study samples were quite low (range, 10–60), and the test performance of the patients and healthy controls was compared with multiple neuropsychological tests. In addition, the significance level was usually set at 0.05. This increases the risk for type I error in the individual studies reviewed. However, the effect sizes have been reported to be large especially when OSAS patients’ psychomotor speed is compared with that of healthy controls’ (5). This supports the finding that the differences detected in the individual studies could be actually significant. Slowness was detected more often when comparisons were made with normative data. This conflicts with earlier reports, according to which patients with

OSAS and information processing speed OSAS mainly perform within the normal normative range (36, 37, 46). However, according to our review, even clinical test methods may show slowed information processing when compared with normative data. It is notable that patients in the studies reviewed were relatively severely affected by OSAS (AHI Md, 50), which may explain the level of slowness seen. Cognitive reserve theory (70) may be one of the explaining factors in those studies showing OSAS patients’ performance within normal range. Lojander et al. (28) discussed in their study that neuropsychological tests might not be sufficiently sensitive to identify mild changes especially among patients with a high premorbid cognitive level. In studies without control groups, CPAP treatment seemed to improve the processing speed. However, the results from controlled studies suggest that the improvement was actually quite minor, and the improvement seen may in fact be explained by other factors than CPAP treatment. Learning effect may be one of the most important explanatory factors in the assessment of information processing speed. It has been reported to have particular significance in executive neuropsychological tests (64). Because these tests are often used in connection with assessing processing speed, familiarity can sometimes contribute to faster performance. Some of the studies reviewed divided the patients into two groups, who were alternately given effective CPAP and placebo treatment (38–41). This order of treatment may have a bearing on the impact of CPAP. According to Barnes et al. (26), improvement was only seen in subjects who received CPAP first, while those who received placebo first (followed by CPAP) showed no significant change with either treatment. Engleman et al. (41) reported the same trend as a potential carry-over effect of CPAP treatment. It is not clear whether the short treatment time might also explain why the improvement remained so marginal. Treatment time varied in placebo-controlled studies from 1 to 8 weeks and in non-controlled studies, where improvement was usually seen, from 1 to 12 months. CPAP adherence may also have an effect on treatment results. In the placebo-controlled studies, average treatment compliance was low (Md, 3.5 h/night), and it is suggested that CPAP use of 4 h per night on 70% of nights could be a clinical and empirical benchmark of CPAP adherence (46, 71). This review shows that psychomotor slowing in particular seems to persist after CPAP treatment. This is in line with the findings of Aloia et al. (6), who reported that impairment in psychomotor

functioning is evident in 80% of the studies and that slowness seems to persist even after CPAP. Therefore, it may represent the more permanent effects of OSAS. However, it is notable that tests of both psychomotor speed and fine-motor coordination were grouped under the psychomotor functioning construct in the study of Aloia et al. (6), and when these two constructs were separated from each other, only psychomotor speed remained intact in OSAS, while fine-motor coordination was consistently impaired. This is consistent with Beebe et al. (5), who reported that fine-motor coordination was markedly affected by OSAS, whereas simple motor speed was less affected. Bedard et al. (59) have also reported that deficits in manual dexterity seem to be irreversible in spite of sleep normalization and respiration with CPAP treatment. According to Decary et al. (4), reduced manual dexterity and motor speed are associated especially with chronic hypoxemia due to OSAS. Tests of finemotor coordination and manual dexterity were rarely used in the studies reviewed here, but when they were used, they showed slowness. To the best of our knowledge this is the first systematic review of research focusing on OSAS patients’ information processing speed as a distinct cognitive domain. This is important in that it has been suggested that higher-level cognitive dysfunction, such as executive dysfunction, can be explained by lower-level cognitive deficits, such as slowed information processing. Our review suggests that slowed information processing, especially psychomotor slowing, is one of the most vulnerable cognitive domains in OSAS, affecting at least half of the patients, and the effect of CPAP treatment on slowness is very limited. It is not clear from the results of this review whether executive dysfunction can be explained by lower-level slowing of information processing, but we can conclude that slowness is easier to detect by clinical neuropsychological assessment methods than executive dysfunction. One limitation of this review is that we did not conduct a meta-analysis. This decision was made because the results of the tests were reported both verbally and numerically based on raw or standard points and because different studies used different versions of the same test methods. We did not want to exclude data from the review because of the heterogeneity of the reported test results. The same problem has been reported earlier as well (7). Another limitation is that reaction times are sometimes assessed as part of vigilance, but we did not include these studies in our review because we wanted to keep these cognitive 215

Kilpinen et al. processes separate. Our focus was on reviewing processing speed in short-term performance without the component of sustaining attention for longer time periods. Vigilance tests cover usually intervals from 10 to 30 min, and subjects are required to maintain alertness to detect rare and subtle stimuli in a boring situation (16, 23). Reaction times in vigilance tests usually become slower, and relapses increase toward the end of the task. According to the earlier studies, untreated OSAS impairs the ability to sustain attention for extended periods affecting driving and occupational functioning (5, 6, 72), but CPAP usually improves vigilance quite effectively (6). A review concerning vigilance in OSAS is highly suggested for future research. Also some other recommendations for further research can be made based on this review. The use of uniform assessment methods and more detailed reporting of test results would make possible a meta-analytic examination. It is recommended that more attention be paid to the number of subjects included in research, to the background variables possibly influencing premorbid cognitive performance, and to the inclusion of large enough control groups. Cognitive changes of female patients with OSAS need more research. Placebo or conservative treatment groups are recommended in treatment efficacy studies to control placebo and learning effects. In addition, the comorbidity of OSAS with other sleep disorders, vascular risk factors, and neurological diseases need further interest to clarify whether cognitive changes are associated with OSAS only or OSAS with other medical risk factors (73, 74). Acknowledgements This study was supported by grants from the Finnish Cultural Foundation.

Conflict of interest The authors report no conflict of interest.

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Information processing speed in obstructive sleep apnea syndrome: a review.

To provide a comprehensive review of studies on information processing speed in patients with obstructive sleep apnea syndrome (OSAS) as compared to h...
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