online supplementary materials for siegert et...

Online supplementary materials for Siegert et al.: A Meta-Analysis of Performance on Simple Span and More Complex Working Memory Tasks in Parkinson’s Disease.

Online Supplementary Appendix 1 - Reference list of all the studies included in the four meta-analyses.

Amador, S. C., Hood, A. J., Schiess, M. C., Izor, R., & Sereno, A. B. (2006). Dissociating cognitive deficits involved in voluntary eye movement dysfunctions in Parkinson’s disease patients. Neuropsychologia, 44(8), 1475-1482.

Blanchet, S., Marie, R. M., Dauvillier, F., Landeau, B., Benali, K., Eustache, F., et al. (2000). Cognitive processes involved in delayed non-matching-to-sample performance in Parkinson’s disease. European Journal of Neurology, 7(5), 473-483.

Boller, F., Marcie, P., Starkstein, S., & Traykov, L. (1998). Memory and depression in Parkinson’s disease. European Journal of Neurology, 5(3), 291-295.

Bradley, V. A., Welch, J. L., & Dick, D. J. (1989). Visuospatial working memory in Parkinson’s disease. Journal of Neurology, Neurosurgery & Psychiatry, 52(11), 1228-1235.

Breitenstein, C., Van Lancker, D., Daum, I., & Waters, C. H. (2001). Impaired perception of vocal emotions in Parkinson’s disease: Influence of speech time processing and executive functioning. Brain & Cognition, 45(2), 277-314.

Bublak, P., Muller, U., Gron, G., Reuter, M., & von Cramon, D. (2002). Manipulation of working memory information is impaired in Parkinson’s disease and related to working memory capacity. Neuropsychology, 16(4), 577-590.

Chan, F., Armstrong, I. T., Pari, G., Riopelle, R. J., & Munoz, D. P. (2005). Deficits in saccadic eye-movement control in Parkinson’s disease. Neuropsychologia, 43(5), 784-796.

Channon, S. (1997). Impairments in deductive reasoning and working memory in Parkinson’s disease. Behavioural Neurology, 10(1), 1-8.

Cooper, J. A., Sagar, H. J., Doherty, S. M., Jordan, N., Tidswell, P., & Sullivan, E. V. (1992). Different effects of dopaminergic and anticholinergic therapies on cognitive and motor function in Parkinson’s disease. Brain, 115, 1701-1725.

Cooper, J. A., Sagar, H. J., Jordan, N., Harvey, N. S., & Sullivan, E. V. (1991). Cognitive impairment in early, untreated Parkinson’s disease and its relationship to motor disability. Brain, 114(5), 2095-2122.

Costa, A., Peppe, A., Dell'Agnello, G., Carlesimo, G. A., Murri, L., Bonuccelli, U., et al. (2003). Dopaminergic modulation of visual-spatial working memory in Parkinson’s disease. Dementia & Geriatric Cognitive Disorders, 15(2), 55-66.

Dalrymple-Alford, J. C., Kalders, A. S., Jones, R. D., & Watson, R. W. (1994). A central executive deficit in patients with Parkinson’s disease. Journal of Neurology, Neurosurgery & Psychiatry, 57(3), 360-367.

Dujardin, K., Degreef, J. F., Rogelet, P., Defebvre, L., & Destee, A. (1999). Impairment of the supervisory attentional system in early untreated patients with Parkinson’s disease. Journal of Neurology, 246(9), 783-788.

Fern-Pollak, L., Whone, A. L., Brooks, D. J., & Mehta, M. A. (2004). Cognitive and motor effects of dopaminergic medication withdrawal in Parkinson’s disease. Neuropsychologia, 42(14), 1917-1926.

Fournet, N., Moreaud, O., Roulin, J. L., Naegele, B., & Pellat, J. (1996). Working memory in medicated patients with Parkinson’s disease: The central executive seems to work. Journal of Neurology, Neurosurgery & Psychiatry, 60(3), 313-317.

Gabrieli, J. D., Singh, J., Stebbins, G. T., & Goetz, C. G. (1996). Reduced working memory span in Parkinson’s disease: Evidence for the role of frontostriatal system in working and strategic memory. Neuropsychology, 10(3), 321-332.

Gilbert, B., Belleville, S., Bherer, L., & Chouinard, S. (2005). Study of verbal working memory in patients with Parkinson’s disease. Neuropsychology, 19(1), 106-114.

Gnanalingham, K. K., Byrne, E. J., Thornton, A., Sambrook, M. A., & Bannister, P. (1997). Motor and cognitive function in lewy body dementia: Comparison with alzheimer's and Parkinson’s diseases. Journal of Neurology, Neurosurgery & Psychiatry, 62(3), 243-252.

Gotzsche, P. C., Hrobjartsson, A., Maric, K., Tendal, B. (2007). Data extraction errors in meta-analyses that use standardized mean differences. Journal of the American Medical Association, 298(4), 430-437.

Graceffa, A. M., Carlesimo, G. A., Peppe, A., & Caltagirone, C. (1999). Verbal working memory deficit in Parkinson’s disease subjects. European Neurology, 42(2), 90-94.

Hart, R. P., Wade, J. B., Calabrese, V. P., & Colenda, C. C. (1998). Vigilance performance in Parkinson’s disease and depression. Neuropsychology Development & Cognition Section a Journal of Clinical & Experimental Neuropsychology, 20(1), 111-117.

Hodgson, T. L., Dittrich, W. H., Henderson, L., & Kennard, C. (1999). Eye movements and spatial working memory in Parkinson’s disease. Neuropsychologia, 37(8), 927-938.

Hoppe, C., Muller, U., Werheid, K., Thone, A., & von Cramon, D. (2000). Digit ordering test: Clinical, psychometric, and experimental evaluation of a verbal working memory test. Clinical Neuropsychologist, 14(1), 38-55.

Howard, L. A., Binks, M. G., Moore, A. P., & Playfer, J. R. (2000). The contribution of apraxic speech to working memory deficits in Parkinson’s disease. Brain and Language, 74(2), 269-288.

Jahanshahi, M., Rowe, J., Saleem, T., Brown, R., Limousin-Dowsey, P., Rothwell, J., et al. (2002). Striatal contribution to cognition: Working

memory and executive function in Parkinson’s disease before and after unilateral posteroventral pallidotomy. Journal of Cognitive Neuroscience, 14(2), 298-310.

Katsarou, Z., Bostantjopoulou, S., Kimiskidis, V., Rossopoulos, E., & Kazis, A. (2004). Auditory event-related potentials in Parkinson’s disease in relation to cognitive ability. Perceptual & Motor Skills, 98(3 Pt 2), 1441-1448.

Kemps, E., Szmalec, A., Vandierendonck, A., & Crevits, L. (2005). Visuo-spatial processing in Parkinson’s disease: Evidence for diminished visuo-spatial sketch pad and central executive resources. Parkinsonism & Related Disorders, 11(3), 181-186.

Kensinger, E. A., Shearer, D. K., Locascio, J. J., Growdon, J. H., & Corkin, S. (2003). Working memory in mild alzheimer's disease and early Parkinson’s disease. Neuropsychology, 17(2), 230-239.

Kliegel, M., Phillips, L., Lemke, U., & Kopp, U. (2005). Planning and realisation of complex intentions in patients with Parkinson’s disease. Journal of Neurology, Neurosurgery & Psychiatry, 76(11), 1501-1505.

Lange, K., Robbins, T., Marsden, C., James, M., & et al. (1992). L-dopa withdrawal in Parkinson’s disease selectively impairs cognitive performance in tests sensitive to frontal lobe dysfunction. Psychopharmacology, 107(2-3), 394-404.

Lange, K. W., Tucha, O., Alders, G. L., Preier, M., Csoti, I., Merz, B., et al. (2003). Differentiation of parkinsonian syndromes according to differences in executive functions. Journal of Neural Transmission, 110(9), 983-995.

Le Heron, C. J., MacAskill, M. R., & Anderson, T. J. (2005). Memory-guided saccades in Parkinson’s disease: Long delays can improve performance. Experimental Brain Research, 161(3), 293-298.

Moreaud, O., Fournet, N., Roulin, J. L., Naegele, B., & Pellat, J. (1997). The phonological loop in medicated patients with Parkinson’s disease: Presence of phonological similarity and word length effects. Journal of Neurology, Neurosurgery & Psychiatry, 62(6), 609-611.

Morris, R. G., Downes, J. J., Sahakian, B. J., Evenden, J. L., & et al. (1988). Planning and spatial working memory in Parkinson’s disease. Journal of Neurology, Neurosurgery & Psychiatry, 51(6), 757-766.

Muller, U., Wachter, T., Barthel, H., Reuter, M., & Von Cramon, D. Y. (2000). Striatal [123i]beta-cit spect and prefrontal cognitive functions in Parkinson’s disease. Journal of Neural Transmission, 107(3), 303-319.

Owen, A. M., Beksinska, M., James, M., Leigh, P., & et al. (1993). Visuospatial memory deficits at different stages of Parkinson’s disease. Neuropsychologia, 31(7), 627-644.

Owen, A. M., Iddon, J. L., Hodges, J. R., Summers, B. A., & et al. (1997). Spatial and non-spatial working memory at different stages of Parkinson’s disease. Neuropsychologia, 35(4), 519-532.

Owen, A. M., James, M., Leigh, P. N., Summers, B. A., Marsden, C. D., Quinn, N. P., et al. (1992). Fronto-striatal cognitive deficits at different stages of Parkinson’s disease. Brain, 115(6), 1727-1751.

Owen, A. M., Sahakian, B. J., Hodges, J. R., Summers, B. A., & et al. (1995). Dopamine-dependent frontostriatal planning deficits in early Parkinson’s disease. Neuropsychology, 9(1), 126-140.

Pantelis, C., Barnes, T. R. E., Nelson, H. E., Tanner, S., Weatherley, L., Owen, A. M., et al. (1997). Frontal-striatal cognitive deficits in patients with chronic schizophrenia. Brain, 120(10), 1823-1843.

Perbal, S., Deweer, B., Pillon, B., Vidailhet, M., Dubois, B., & Pouthas, V. (2005). Effects of internal clock and memory disorders on duration reproductions and duration productions in patients with Parkinson’s disease. Brain and Cognition, 58(1), 35-48.

Pollux, P. M. (2004). Advance preparation of set-switches in Parkinson’s disease. Neuropsychologia, 42(7), 912-919.

Postle, B. R., Jonides, J., Smith, E. E., Corkin, S., & Growdon, J. H. (1997). Spatial, but not object, delayed response is impaired in early Parkinson’s disease. Neuropsychology, 11(2), 171-179.

Press, D., Mechanic, D., Tarsy, D., & Manoach, D. (2002). Cognitive slowing in Parkinson’s disease resolves after practice. Journal of Neurology, Neurosurgery & Psychiatry, 73(5), 524-528.

Pulvermuller, F., Lutzenberger, W., Muller, V., Mohr, B., Dichgans, J., & Birbaumer, N. (1996). P3 and contingent negative variation in Parkinson’s disease. Electroencephalography & Clinical Neurophysiology, 98(6), 456-467.

Robbins, T. W., James, M., Owen, A., Lange, K., & et al. (1994). Cognitive deficits in progressive supranuclear palsy, Parkinson’s disease, and multiple system atrophy in tests sensitive to frontal lobe dysfunction. Journal of Neurology, Neurosurgery & Psychiatry, 57(1), 79-88.

Rogers, R. D., Sahakian, B. J., Hodges, J. R., Polkey, C. E., Kennard, C., & Robbins, T. W. (1998). Dissociating executive mechanisms of task control following frontal lobe damage and Parkinson’s disease. Brain, 121(5), 815-842.

Shaunak, S., O'Sullivan, E., Blunt, S., Lawden, M., Crawford, T., Henderson, L., et al. (1999). Remembered saccades with variable delay in Parkinson’s disease. Movement Disorders, 14(1), 80-86.

Skeel, R. L., Crosson, B., Nadeau, S. E., Algina, J., Bauer, R. M., & Fennell, E. B. (2001). Basal ganglia dysfunction, working memory, and sentence comprehension in patients with Parkinson’s disease. Neuropsychologia, 39(9), 962-971.

Stebbins, G. T., Gabrieli, J. D., Shannon, K. M., Penn, R. D., & Goetz, C. G. (2000). Impaired frontostriatal cognitive functioning following posteroventral pallidotomy in advanced Parkinson’s disease. Brain & Cognition, 42(3), 348-363.

Stepankova, K., & Ruzicka, E. (1998). Object location learning and non-spatial working memory of patients with Parkinson’s disease may be

preserved in 'real life' situations. Physiological Research, 47(5), 377-384.

Stern, E. R., Horvitz, J. C., Cote, L. J., & Mangels, J. A. (2005). Maintenance of response readiness in patients with Parkinson’s disease: Evidence from a simple reaction time task. Neuropsychology, 19(1), 54-65.

Tamura, I., Kikuchi, S., Otsuki, M., Kitagawa, M., & Tashiro, K. (2003). Deficits of working memory during mental calculation in patients with Parkinson’s disease. Journal of the Neurological Sciences, 209(1-2), 19-23.

Uekermann, J., Daum, I., Bielawski, M., Muhlack, S., Peters, S., Przuntek, H., et al. (2004). Differential executive control impairments in early Parkinson’s disease. Journal of Neural Transmission. Supplement, 68, 39-51.

Uekermann, J., Daum, I., Peters, S., Wiebel, B., Przuntek, H., & Muller, T. (2003). Depressed mood and executive dysfunction in early Parkinson’s disease. Acta Neurologica Scandinavica, 107(5), 341-348.

Werheid, K., Hoppe, C., Thone, A., Muller, U., Mungersdorf, M., & von Cramon, D. (2002). The adaptive digit ordering test. Clinical application, reliability, and validity of a verbal working memory test. Archives of Clinical Neuropsychology, 17(6), 547-565.

Yokoyama, T., Imamura, Y., Sugiyama, K., Nishizawa, S., Yokota, N., Ohta, S., et al. (1999). Prefrontal dysfunction following unilateral posteroventral pallidotomy in Parkinson’s disease. Journal of Neurosurgery, 90(6), 1005-1010.

Online Supplementary Appendix 2 - Studies that yielded data for meta-analyses grouped by task with brief descriptions of the unique or ‘other’ tasks

VERBAL SPAN TASKSDigit Span Studies (n=23): (Blanchet et al., 2000), (Boller et al., 1998), (Bradley et al., 1989), (Breitenstein et al., 2001), (Bublak et al., 2002), (Cooper et al., 1991), (Dalrymple-Alford et al., 1994), (Gilbert et al., 2005), (Gnanalingham et al., 1997), (Hoppe et al., 2000), (Katsarou et al., 2004), (Kensinger et al., 2003), (Kliegel et al., 2005), (K. W. Lange et al., 2003), (Muller et al., 2000), (Perbal et al., 2005), (Pollux, 2004), (Stern et al., 2005), (Tamura et al., 2003), (Uekermann et al., 2004), (Uekermann et al., 2003), (Werheid et al., 2002), (Yokoyama et al., 1999)Word Span Studies (n=5): (Fournet et al., 1996), (Graceffa et al., 1999), (Howard et al., 2000), (Moreaud et al., 1997), (Skeel et al., 2001)Other Verbal Span Task Studies (n=1): (Dujardin et al., 1999) – Three consonants presented visually to participant who has to verbally recall after a variable time delay.

SPATIAL SPAN TASKSCorsi’s Blocks Studies (n=9): (Boller et al., 1998; Hodgson et al., 1999), (Kemps et al., 2005), (K. Lange et al., 1992), (Morris et al., 1988; A. M. Owen et al., 1992), (Pantelis et al., 1997), (Perbal et al., 2005), (Robbins et al., 1994)Other spatial span tasks (n=10): (Blanchet et al., 2000) – Experimenter points to varying number of nine squares in array on paper and participant must reproduce the sequence.(Bradley et al., 1989) – Filled and unfilled boxes presented on screen for 100 msec and then filled boxes are cleared. Participant must then touch the boxes that were full but in any order. (Chan et al., 2005) – Participants focused on a central location and a peripheral stimulus was briefly presented. After a variable delay they had to look at the spot where the light had appeared (remembered saccade). (Fern-Pollak et al., 2004) – Participants fixated on a central X on a white screen. A black circle appeared on screen for 150msecs. After a delay a tone prompted participants to point to where they recalled the circle had been presented. (Fournet et al., 1996) – A 5 x 5 matrix of boxes was presented on screen. Each box was filled and then emptied one at a time. Participants had to recall the sequence in which boxes had been filled. (K. W. Lange et al., 2003) – From Baddeley (1997). A geometric figure is presented at the fixation point for 200 msecs. After a masked delay the participant must recall how many right angles the figure had.

(Le Heron et al., 2005) – Participants fixated on a central stimulus and a peripheral stimulus was presented for 400msecs. After a delay a tone cued participants to look at the spot where they remembered the light flashing (remembered saccade). (Adrian M. Owen et al., 1993) – Five white squares presented sequentially on screen in different locations. After a brief delay two squares are presented and participant must indicate which one is in the same location as one of the initial five. (Postle et al., 1997) – Two irregular shapes presented on screen. After a delay a single shape is presented and participant must decide if it is in the same position as either one of the earlier two stimuli. (Shaunak et al., 1999) – Remembered saccade (see above).

COMPLEX VERBAL TASKSDigit Span Backwards (n=14): (Breitenstein et al., 2001), (Bublak et al., 2002), (Gnanalingham et al., 1997), (Hoppe et al., 2000), (K. W. Lange et al., 2003), (Muller et al., 2000), (Perbal et al., 2005), (Pollux, 2004), (Stern et al., 2005), (Tamura et al., 2003), (Uekermann et al., 2004), (Uekermann et al., 2003), (Werheid et al., 2002), (Yokoyama et al., 1999). Digit Ordering Test (n=3): (Cooper et al., 1991), (Cooper et al., 1992), (Stebbins et al., 2000)Other Complex Verbal WM Tasks (n=8): (Channon, 1997) – Participants were given strings of consonants of varying length and asked to recall the last 4 or 6 letters in the string (after Morris & Jones, 1990). (Gabrieli et al., 1996) – Participants were read a sentence and had to answer a multiple choice question about the sentence content. Then they were asked to recall the last word of the sentence.(Gilbert et al., 2005) – Participants were presented a string of consonants and had to recall the last x number of letters in the same order. Where x was based upon that individual’s simple span (based on Morris & Jones, 1990. (Hart et al., 1998) – used the Continuous Performance Test. (Jahanshahi et al., 2002) – Participants required to generate random sequences of numbers. (Kensinger et al., 2003) – The 2-back task from Cohen et al. (1997).(Press et al., 2002) – Participants visually presented a set of 1-5 digits to remember and then had to say if a subsequently presented digit was in the original set (Sternberg’s Item Recognition Paradigm)(Pulvermuller et al., 1996) – Used an alphabetical go/no-go task.

COMPLEX SPATIAL WM TASKSOwens’ WM Task (n=8): (K. Lange et al., 1992), (Morris et al., 1988), (Adrian M. Owen et al., 1993), (Adrian M. Owen et al., 1997), (A. M. Owen et al., 1992), (Pantelis et al., 1997), (Robbins et al., 1994), (Rogers et al., 1998)Other Complex Spatial WM Tasks (n=6):

(Amador et al., 2006) – Participants fixated on a central stimuli and a second stimulus was presented briefly to the left or right. After a variable delay the participants had to look to a point opposite where the peripheral stimulus had flashed (i.e. delayed anti-saccade task).(Costa et al., 2003) – Used a visuospatial 1-back task. (Hodgson et al., 1999) – Used the CANTAB spatial WM task(Adrian M. Owen et al., 1995) – Participants had to touch four large red squares on a screen in as many different sequences as possible. (Perbal et al., 2005) – Backward spatial span(Stepankova & Ruzicka, 1998) – Participants had to open 8 differently shaped cards to read a number inside. Cards position on table shuffled after each opening. Participants had to avoid opening any single card twice.

Online Supplementary Appendix 3 - Summary tables of included studies with basic data and study differences with confidence intervals for all studies in four meta-analyses

Simple verbal basic data

Study Parkinson’s Disease Non-PD ParticipantsN Mean SD N Mean SD

Digit span forwardBlanchet (2000) 13 12.50 3.40 12 13.30 2.40Boller (1998) 22 5.32 1.25 11 5.82 0.87Bradley (1989) 16 6.50 1.20 16 6.80 1.30Breitenstein (2001)

20 6.70 1.00 16 6.60 1.20

Bublak (2002) 14 6.60 0.90 14 6.40 1.30Cooper (1991) 60 6.50 1.40 37 6.70 1.50Dalrymple-Alfrod (1994)

8 5.30 1.41 8 5.50 1.41

Gilbert (2005) 14 6.86 1.51 14 7.00 1.11Gnanalingham (1997)

13 6.10 1.40 22 6.20 1.40

Hoppe (2000) 22 6.30 0.90 22 6.30 1.10Katsarou (2004) 45 5.50 0.80 40 5.90 0.70Kensinger (2003)

20 6.70 1.00 112 7.00 1.20

Kliegel (2005) 16 7.30 1.80 16 7.30 2.10Lange (2003) 42 6.80 1.90 32 7.40 1.70Muller (2000) 20 6.20 1.00 20 6.30 1.30Perbal (2005) 18 6.00 1.00 18 5.30 1.00Pollux (2004) 18 6.60 1.03 18 7.06 0.78Stern (2005) 10 7.40 1.58 14 7.10 1.50Tamura (2003) 24 6.44 0.90 24 6.65 1.08Uekermann (2004)

20 6.80 2.04 20 6.65 1.31

Uekermann (2003)

16 5.94 1.06 15 6.27 0.96

Werheid (2002) 20 7.90 1.70 20 8.20 1.60Yokoyama (1999)

25 9.42 2.28 36 10.80 1.80

Word spanFournet (1996) 15 3.70 0.90 15 4.40 0.90Graceffa (1999) 12 3.20 0.80 12 3.60 1.00

Howard (2000) 36 3.45 0.77 43 3.80 0.75Moreaud (1997) 15 3.10 0.90 15 3.60 0.60Skeel (2001) 14 4.40 0.51 14 4.57 0.51Other taskDujardin (1999) 17 14.88 0.33 17 14.71 0.77

Simple verbal study differences

Study Difference (PD minus Non-PD)

Lower 95% confidence limit

Upper 95% confidence limit

Simple verbalBlanchet (2000)

-0.27 -1.05 0.51

Boller (1998) -0.44 -1.16 0.29Bradley (1989) -0.24 -0.93 0.45Breitenstein (2001)

0.09 -0.57 0.75

Bublak (2002) 0.18 -0.56 0.92Cooper (1991) -0.14 -0.55 0.27Dalrymple-Alfrod (1994)

-0.14 -1.12 0.84

Gilbert (2005) -0.11 -0.85 0.64Gnanalingham (1997)

-0.07 -0.76 0.61

Hoppe (2000) 0.00 -0.59 0.59Katsarou (2004)

-0.53 -0.96 -0.10

Kensinger (2003)

-0.26 -0.73 0.22

Kliegel (2005) 0.00 -0.69 0.69Lange (2003) -0.33 -0.79 0.13Muller (2000) -0.09 -0.71 0.53Perbal (2005) 0.70 0.05 1.35Pollux (2004) -0.50 -1.16 0.15Stern (2005) 0.20 -0.62 1.01Tamura (2003) -0.21 -0.78 0.35Uekermann (2004)

0.09 -0.53 0.71

Uekermann (2003)

-0.33 -1.03 0.38

Werheid (2002) -0.18 -0.80 0.44

Yokoyama (1999)

-0.69 -1.20 -0.18

Word spanFournet (1996) -0.78 -1.49 -0.06Graceffa (1999) -0.44 -1.24 0.36Howard (2000) -0.46 -0.90 -0.02Moreaud (1997)

-0.65 -1.37 0.06

Skeel (2001) -0.33 -1.07 0.41Other taskDujardin (1999) 0.29 -0.39 0.96

Complex verbal basic data


Digit span backwardBreitenstein (2001)

20 4.40 1.30 11 4.80 1.10

Bublak (2002) 14 4.30 0.60 14 4.90 1.20Gnanalingham (1997)

13 4.20 1.80 22 4.00 1.40

Hoppe (2000) 22 4.40 0.80 22 4.90 1.00Lange (2003) 42 5.20 1.60 32 6.60 1.70Muller (2000) 20 4.40 0.90 20 4.80 1.10Perbal (2005) 18 4.40 1.00 18 4.80 0.80Pollux (2004) 18 4.83 0.93 18 5.55 1.24Stern (2005) 10 5.80 1.26 14 5.40 1.50Tamura (2003) 24 3.96 0.69 24 4.60 0.92Uekermann (2004)

20 6.25 1.33 20 5.90 1.65

Uekermann (2003)

16 4.25 1.00 15 4.87 1.36

Werheid (2002) 20 6.10 1.50 20 7.00 1.50Yokoyama (1999)

25 8.82 3.45 36 10.00 2.10

Digit orderingCooper (1992) 82 62.40 20.30 22 80.00 11.20Cooper (1991) 60 4.60 1.40 37 5.10 1.50Stebbins (2000) 16 74.19 10.29 16 85.56 8.14Other taskChannon (1997) 20 22.25 6.81 20 27.05 9.20Gabrieli (1996) 10 2.40 1.00 10 4.20 1.00Gilbert (2005) 14 60.00 15.60 14 71.70 6.20Hart (1998) 11 2.40 3.80 11 3.10 2.30Jahanshahi (2002)

13 25.80 19.50 12 45.00 25.70

Kensinger (2003)

20 63.00 19.70 112 80.00 18.30

Press (2002) 10 94.17 5.07 10 96.45 2.37Pulvermuller (1996)

14 2.50 7.08 18 5.40 7.08

Complex verbal study differences




Digit span backwardBreitenstein (2001)

-0.32 -1.06 0.41

Bublak (2002) -0.63 -1.37 0.11Gnanalingham (1997)

0.13 -0.56 0.81

Hoppe (2000) -0.55 -1.14 0.04Lange (2003) -0.85 -1.31 -0.39Muller (2000) -0.40 -1.02 0.22Perbal (2005) -0.44 -1.10 0.21Pollux (2004) -0.66 -1.31 -0.00Stern (2005) 0.28 -0.53 1.10Tamura (2003) -0.79 -1.35 -0.22Uekermann (2004)

0.23 -0.39 0.85

Uekermann (2003)

-0.52 -1.23 0.18

Werheid (2002) -0.60 -1.22 0.02Yokoyama (1999)

-0.43 -0.94 0.08

Digit orderingCooper (1992) -0.94 -1.41 -0.47Cooper (1991) -0.35 -0.76 0.06Stebbins (2000)

-1.23 -1.92 -0.53

Other taskChannon (1997)

-0.59 -1.21 0.03

Gabrieli (1996) -1.80 -2.68 -0.92Gilbert (2005) -0.99 -1.73 -0.24Hart (1998) -0.22 -1.06 0.61Jahanshahi (2002)

-0.85 -1.63 -0.06

Kensinger (2003)

-0.92 -1.39 -0.44

Press (2002) -0.58 -1.45 0.30Pulvermuller (1996)

-0.41 -1.11 0.29

Simple spatial basic data


Corsi BlocksBoller (1998) 22 3.87 0.95 11 5.27 0.65Hodgson (1999) 7 19.10 5.00 5 27.00 6.30Kemps (2005) 15 13.95 2.20 15 15.05 2.20Lange (1992) 10 4.40 0.95 55 5.30 0.74Morris (1988) 12 4.58 0.66 18 5.00 1.10Owen (1992) 44 4.61 0.62 44 5.07 0.78Pantelis (1997) 29 4.38 0.92 29 4.72 0.97Perbal (2005) 18 5.30 1.00 18 5.80 0.90Robbins (1994) 24 4.04 0.84 24 5.05 0.72Other taskBlanchet (2000) 13 7.70 2.40 12 9.20 1.90Bradley (1989) 16 6.50 1.20 16 7.10 1.10Chan (2005) 18 25.00 21.20 18 40.00 21.20Fern-Pollak (2004)

15 10.18 2.48 14 12.10 5.10

Fournet (1996) 15 9.10 2.60 15 11.20 1.20Le Heron (2005)

15 1.01 0.14 15 1.03 0.26

Owen (1993) 42 70.00 22.40 42 76.60 19.40Postle (1997) 15 78.30 7.40 15 86.00 2.70Shaunak (1999) 10 1.08 0.21 9 1.02 0.21Outlying studyLange (2003) 32 1.70 1.50 42 8.20 3.70

Simple spatial study differences




Corsi BlocksBoller (1998) -1.62 -2.34 -0.90Hodgson (1999)

-1.42 -2.57 -0.27

Kemps (2005) -0.50 -1.22 0.22Lange (1992) -1.16 -1.84 -0.49Morris (1988) -0.44 -1.17 0.29Owen (1992) -0.65 -1.07 -0.24Pantelis (1997) -0.36 -0.87 0.16Perbal (2005) -0.53 -1.18 0.13Robbins (1994) -1.30 -1.86 -0.73Other taskBlanchet (2000)

-0.69 -1.47 0.10

Bradley (1989) -0.52 -1.21 0.17Chan (2005) -0.71 -1.36 -0.05Fern-Pollak (2004)

-0.48 -1.21 0.24

Fournet (1996) -1.04 -1.75 -0.32Le Heron (2005)

-0.10 -0.81 0.62

Owen (1993) -0.31 -0.74 0.11Postle (1997) -1.38 -2.10 -0.67Shaunak (1999)

0.29 -0.61 1.19

Outlying studyLange (2003) -2.20 -2.66 -1.74

Complex spatial basic data


Owen memory taskLange (1992) 10 18.70 12.80 55 27.40 12.60Morris (1998) 12 3.75 4.12 18 5.06 8.65Owen (1993) 42 36.30 18.50 42 54.00 24.90Owen (1997) 21 1.00 1.33 21 1.38 2.28Owen (1992) 44 25.00 10.80 44 33.77 10.80Pantelis (1997) 29 53.10 19.44 29 58.31 22.46Robbins (1994) 24 33.16 15.04 24 50.35 24.07Rogers (1998) 12 20.00 4.20 12 27.00 15.60Other memory taskAmador (2006) 14 82.40 23.60 11 104.7 18.50Costa (2003) 15 18.10 1.80 12 18.90 1.80Hodgson (1999) 7 33.90 15.90 5 43.60 7.60Owen (1995) 56 63.00 12.31 56 71.30 10.60Perbal (2005) 18 4.80 0.90 18 4.90 0.70Stepankova (1998)

19 4.80 3.10 16 5.00 3.20

Complex Spatial study differences




Owen memory taskLange (1992) -0.69 -1.36 -0.02Morris (1998) -0.18 -0.91 0.55Owen (1993) -0.81 -1.23 -0.38Owen (1997) -0.20 -0.81 0.40Owen (1992) -0.81 -1.23 -0.39Pantelis (1997) -0.25 -0.76 0.27Robbins (1994) -0.86 -1.42 -0.29Rogers (1998) -0.61 -1.41 0.19Other memory taskAmador (2006) -1.04 -1.83 -0.25Costa (2003) -0.44 -1.20 0.31Hodgson (1999)

-0.73 -1.88 0.41

Owen (1995) -0.72 -1.09 -0.35Perbal (2005) -0.12 -0.78 0.53Stepankova (1998)

-0.06 -0.73 0.60

Online Supplementary Appendix 4. Screening for Dementia in the Parkinson’s Disease Groups - Exclusion Criteria.

Study Test and criteriaAmador (2006) MMSE <25Blanchet (2000) MDRS cut off = 120/144, Excluded clinically DSM-III-RBoller (1998) MMSE >21, DSM-III-R and IV criteria

Bradley (1989)Mental test score >30/37, WAIS or RPM > 15pts below predicted by NART

Breitenstein (2001) MMSE >26Bublak (2002) MMSE >26Chan (2005) Nothing describedChannon (1997) MMSE >26Cooper (1991) Excluded clinically DSM-III-RCooper (1992) BDS, Excluded clinically DSM-III-RCosta (2003) MMSE>23, Excluded clinicallyDalrymple-Alford (1994) Excluded clinicallyDujardin (1999) MDRS >133Fern-Pollak (2004) MMSE-PD >24, Excluded clinicallyFournet (1996) Excluded clinicallyGabrieli (1996) MMSE all >27Gilbert (2005) MMSE >24, MDRSGnanalingham (1997)

Not excluded MMSE mean 24.1 range 16-30, CDR 0-1 where 1 mild dementia

Graceffa (1999) MMSE >24Hart (1998) Nothing describedHodgson (1999) MMSE >27Hoppe (2000) MMSE >26Howard (2000) MMSE >24Jahanshani (2002) Nothing describedKatsarou (2004) MMSE >25, Excluded clinically DSM-IVKemps (2005) Excluded clinically DSM-IVKensinger (2003) BDSKliegel (2005) MMSE >24Lange (1992) Excluded clinicallyLange (2003) MMSE >24Le Heron (2005) MMSE >25Moreaud (1997) Excluded clinicallyMorris (1988) Excluded clinicallyMuller (2000) MMSE >24Owen (1992) MMSE >23, KOLT >22Owen (1993) MMSE >24, KOLT >23Owen (1995) MMSE >24, KOLT >23 (medicated patients only tested)Owen (1997) MMSE >24, KOLT >23Pantelis (1997) MMSE >23Perbal (2005) MDRSPollux (2004) MMSEPostle (1997) BDS, Excluded clinically

Press (2002) MDRS > 136Pulvermuller (1996) “No other disease”Robbins (1994) MMSE >24, KOLT >23Rogers (1998) Nothing describedShaunak (1999) MMSESkeel (2001) MMSE >25Stebbins (1999) MMSE >25Stepankova (1998) MMSE >23Stern (2005) mMMSE >50/57Tamura (2003) MMSE >24, RCPM, HasegawaUekermann (2004) MMSE >25Uekermann (2003) MMSEWerheid (2002) MMSE >24, Excluded clinically DSM-IVYokoyama (1999) Not excluded, MMSE performed

BDS Blessed Dementia ScaleKOLT Kendrick Object Learning TestMDRS Mattis Dementia Rating ScalemMMSE modified Mini Mental Status ExaminationMMSE Mini Mental Status ExaminationMMSE-PD Mini Mental Status Examination for Parkinson’s DiseaseRPM Raven’s Progressive MatricesRCPM Raven’s Coloured Progressive MatricesWAIS Wechsler Adult Intelligence Scale

Online Supplementary Appendix 5 – Sample size, demographics, disease and treatment characteristics of the PD and non-PD

participants from the included studies

Study

N (non PD)

M/F (non PD)

Age (non PD, Mean)

N (PD)

M/F (PD)

Age (PD)

Duration (yrs, Mean)

Severity† Drug Treatment‡

Simple verbalPerbal (2005) 18 8:10 60.3 18 11:7NR 8.9 2.218 Dc

Stern (2005) 14 NR 69.29 10 NR 70.3 7.95 3.24 LD + DA + MB, 2 LD + DA, 4 LD + MB

Bublak (2002) 14 5:9 55.2 14 5:9 55.1 NR 2.310 LD + DA or MB or CT, 1 NABreitenstein (2001) NA NR NR 20 13:7 68.3 NR 2.1

7 LD + DA +/or MB, 7 LD, 6 randomised MB study

Uekermann (2004) 20 9:11 53.2 20 8:12 55.9 4.6 1.75 20 LD and/or DAHoppe (2000) 22 8:14 55.4 22 8:14 55.6 NR 2.222 NR

Kliegel (2005) 16 11:5 62.6 16 11:5 61.1 4.81 1.31 DA, 1 LD + DA + CT, 14 LD + DA

Gnanalingham (1997) 22 13:9 73.3 15 10:5 72.6 9.2NR 15 NR

Muller (2000) 20 7:13 55.7 20 7:13 55.3 3.54 2.34 CT, 9 DA, 11 LD, 4 MB, 5 NA, 7 None

Gilbert (2005) 14 5:9 65.79 14 5:9 66.29 7.29 2.12 AC, 11 LD + AP, 1 NoneDalrymple-Alford (1994) 8 NR 62.4 8 NR 65.6 4.4 2.1

1 DA + MB, 1 LD + AC, 2 LD + NA, 3 LD, 1 MB

Cooper (1991) 37 20:17 59.7 60 31:29 59.8 NR K 22.7 60 NoneWerheid (2002) 20 9:11 58.8 20 9:11 58.2 NR 2 9 DA, 9 LD + DA, 2 NATamura (2003) 24 11:13 61.7 24 15:9 60.9 6 2.21 24 AP

Bradley (1989) 16 12:4 66 16 12:4 66 NR

W Mild-Mod 16 Dc, Many LD + AC

Kensinger (2003) 112 64:48 70.6 20 15:5 68.7 4.7

H&Y 0-2 20 DA

Blanchet (2000) 12 5:7 57.8 13 6:7 63.4 10.2 2.1Unknown proportion LDUekermann (2003) 15 NR NR 16 9:7 NR 1.55 1.44 1 AC, 10 DA, 7 LD, 5 MB, 4 NA

Lange (2003) 32 19:13 63.2 42 24:18 63.7 8 2.54 Dc + CT, 9 Dc + MB, 7 Dc + NA

Boller (1998) 11 5:6 70.2 22 13:9 71 8.4 2.86 22 DcPollux (2004) 18 NR 58 18 9:9 60 8.6 2.16 1 DA alone, 10 LD + DA, 7 LD

Katsarou (2004) 40 29:11 NR 45 31:14 59.3 6.1H&Y 2 or 3 45 LD + DA

Yokoyama (1999) 36 NR 65.5 25 13:12 65.1 NR 2.525 LD (implied)Skeel (2001) 14 11:3 70.7 14 11:3 69.9 8.14 NR 14 LDGraceffa (1999) 12 NR 65.6 12 NR 65.2 NR 1.912 LD + AP

Howard (2000) 43 19:24 66.4 36 18:18 66.5 7.7 22.334 LD MB alone or combined, 2 None

Moreaud (1997) 15 NR 66.6 15 9:6 66.06 8 1.93 11 LD + DA, 1 LD + MB, 2 LD

Fournet (1996) 15 NR 66.6 15 9:6 66.1 8Um21.8 11 LD + DA, 1 LD + MB, 3 LD

Dujardin (1999) 17 5:12 62.8 17 11:6 63.3 NR U 17 None

21.24Complex Verbal Tests

Stern (2005) 14 NR 69.29 10 NR 70.3 7.95 3.24 LD + DA + MB, 2 LD + DA, 4 LD + MB

Uekermann (2004) 20 9:11 53.2 20 8:12 55.9 4.6 1.75 20 LD and/or DAGnanalingham (1997) 22 13:9 73.3 15 10:5 72.6 9.2NR 15 NRBreitenstein (2001) NA NR NR 20 13:7 68.3 NR 2.1

7 LD + DA +/or MB, 7 LD, 6 randomised MB study

Muller (2000) 20 7:13 55.7 20 7:13 55.3 3.54 2.34 CT, 9 DA, 11 LD, 4 MB, 5 NA, 7 None

Yokoyama (1999) 36 NR 65.5 25 13:12 65.1 NR 2.525 LD (implied)Perbal (2005) 18 8:10 60.3 18 11:7NR 8.9 2.218 DcUekermann (2003) 15 NR NR 16 9:7 NR 1.55 1.44 1 AC, 10 DA, 7 LD, 5 MB, 4 NAHoppe (2000) 22 8:14 55.4 22 8:14 55.6 NR 2.222 NRWerheid (2002) 20 9:11 58.8 20 9:11 58.2 NR 2 9 DA, 9 LD + DA, 2 NABublak (2002) 14 5:9 55.2 14 5:9 55.1 NR 2.310 LD + DA or MB or CT, 1 NAPollux (2004) 18 NR 58 18 9:9 60 8.6 2.16 1 DA alone, 10 LD + DA, 7 LDTamura (2003) 24 11:13 61.7 24 15:9 60.9 6 2.21 24 AP


Cooper (1991) 37 20:17 59.7 60 31:29 59.8 NR K 22.7 60 NoneCooper (1992) 22 10:12 60.6 82 42:40 59 1.7NR 57 LD, 15 NoneStebbins (1999) 16 NR 69.19 16 NR 68.56 NR 2.75 16 LD + MBHart (1998) 11 4:7 70.2 11 7:4 65.3 10.2 2.511 NRPulvermuller (1996) 14 4:10 59.5 18 9:9 60.6 8.34 2.17 9 LD + DA, 9 LD + MB

Press (2002) 10 5:5 61.6 10 8:2 63 8H&Y 2-3

1 DA, 3 LD + AC, 1 LD + CT, 2 LD + DA, 1 LD + NA, 2 LD

Channon (1997) 20 11:9 63.9 20 10:10 66 NR NR3 LD + DA, 9 LD + MB, 7 LD, 1 MB

Jahanshani (2002) 12 03:9 55.1 13 10:3 57 14.5 2.912 LDKensinger (2003) 112 64:48 70.6 20 15:5 68.7 4.7

H&Y 0-2 20 DA

Gilbert (2005) 14 05:9 65.79 14 5:9 66.29 7.29 2.12 AC, 11 LD + AP, 1 NoneGabrieli (1996) 10 2:8 55.5 10 6:4 60.1 2.9 2 10 NoneSimple Visual Pantelis (1997) 29 15:14 66.41 29 19:10 62.24 8.64 2.62 22 L Dopa Alone, 7 LD + ACMorris (1988) 18 NR 63.72 12 NR 64.58 NR 2.17 4 LD + AC, 8 LDKemps (2005) 15 7:8 67.8 15 7:8 67.2 11.93 2.25 LD + DA + NA, 10 LD + DAPerbal (2005) 18 8:10 60.3 18 11:7NR 8.9 2.218 DcOwen (1992) 44 NR 60.8 44 NR 60 6.17 2.36 7 Dc + AC, 22 DcLange (1992) 55 NR 55.6 10 8:2 58.7 NR 3.510 LDRobbins (1994) 24 7:17 61.5 24 16:8NR 10.2 3.46 24 LD +?

Hodgson (1999) 12 NR 68 8 NR 67 3.8 1.71 LD + AC, 1 LD + DA, 1 LD + MB, 2 LD, 3 MB

Boller (1998) 11 5:6 70.2 22 13:9 71 8.4 2.86 22 Dc

Shaunak (1999) 9 NR 61 10 NR 62.5 1.21H&Y 2-3 4 MB, 6 None

Le Heron (2005) 15 8:7 65.9 15 8:7 65.3 6.5 2.515 APOwen (1993) 42 21:21 65.47 42 26:16 63.48 6.58 2.24 5 LD + AC, 19 LD, 18 NoneFern-Pollak (2004) 15 NR NR 14 6:8 66.6 6.7 2.07

1 DA + MB, 6 DA, 3 LD + DA, 2 LD + MB, 2 LD

Bradley (1989) 16 12:4 66 16 12:4 66 NR

W Mild-Mod 16 Dc, Many LD + AC

Blanchet (2000) 12 5:7 57.8 13 6:7 63.4 10.2 2.1Unknown proportion LD

Chan (2005) 18 5:13 65.7 18 11:7 67 NRH&Y 1-3

2 AC + AP, 9 DA + AP, 12 LD + AP, 4 MB + AP

Fournet (1996) 15 NR 66.6 15 9:6 66.1 8Um21.8 11 LD + DA, 1 LD + MB, 3 LD

Postle (1997) 15 9:6 66.1 15 12:3 62.7 NRH&Y 0-2 3 None, 12 PD medication


Complex visual Morris (1988) 18 NR 63.72 12 NR 64.58 NR 2.17 4 LD + AC, 8 LDOwen (1997) 21 9:12 56.47 21 16:5 59.07 NR 2.29 4 LD + AC, 10 LD, 7 NonePantelis (1997) 29 15:14 66.41 29 19:10 62.24 8.64 2.62 22 L Dopa Alone, 7 LD + ACRogers (1998) 12 5:7 58.8 12 6:6 59.2 2.4 1.17 1 LD + AC, 11 LDLange (1992) 55 NR 55.6 10 8:2 58.7 NR 3.510 LDOwen (1993) 42 21:21 65.47 42 26:16 63.48 6.58 2.24 5 LD + AC, 19 LD, 18 NoneOwen (1992) 44 NR 60.8 44 NR 60 6.17 2.36 7 Dc + AC, 22 DcRobbins (1994) 24 7:17 61.5 24 16:8NR 10.2 3.46 24 LD +?Stepankova (1998) 16 NR NR 19 13:6 61.4 7.9

H&Y 1-3 5 AP non LD, 14 LD

Perbal (2005) 18 8:10 60.3 18 11:7NR 8.9 2.218 DcCosta (2003) 12 10:2 61.1 15 10:5 58.8 NR 2.210 LD + DA, 5 LD

Hodgson (1999) 12 NR 68 8 NR 67 3.8 1.71 LD + AC, 1 LD + DA, 1 LD + MB, 2 LD, 3 MB

Owen (1995) 56 17:39 54.96 56 36:20 60.98 NR 2.02 7 Dc + AC, 27 Dc, 22 NoneAmador (2006) 11 4:7 55 14 8:6 60 NR 3.65 14 NR

†Mean Hoehn and Yahr score unless otherwise statedH&Y Hoehn and YahrK Mean King’s College Rating ScaleW WebsterU Unified Parkinson's Disease Rating Scale Um Unified Parkinson's Disease Rating Scale

‡Key to Drug treatmentAP unspecified anti-Parkinson Drugs (any of those listed below, alone or in combination)CT COMT inhibitorDA Dopamine agonistDc Unspecified Dopaminergic drugsLD l-Dopa with Carbidopa or BenserazideMB Monoamine oxidase B InhibitorNA NMDA antagonist, Amantadine or Budipine

Key to Abbreviations NA Not applicableNR Not reported

online supplementary materials for siegert et...

Documents