Supplemental Table 1 Studies Considered in Our Review Study Sample Follow up assessments Domains and tests Main results

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1 Supplemental Table 1 Studies Considered in Our Review Study Sample Follow up assessments Domains and tests Main results Moorhead 20 BD I Performance IQ: Wechsler et al. (2007) 7 & follow up after 4 Abbreviated Scale of Intelligence 21 HC years Verbal IQ: Wechsler Abbreviated Scale BD: 50% female of Intelligence HC: 50% female Mean age: ~40 years Memory: Extended Rivermead Behavioural Memory Test No main effects of group (BD vs. HC) or time (baseline vs. follow up) on neuropsychological performance Reductions in temporal lobe gray matter were correlated with decline in full scale & performance IQ Reductions in temporal lobe gray matter were correlated with decline in verbal IQ in BD patients only Depp et al. 35 BD community dwelling (2008) 8 outpatients (34 BD I, 1 BD II) 35 HC schizophrenic outpatients BD: 28.6% female HC: 58.8% female Mean age: ~60 years (adults middle aged & older) Mild level of affective symptoms in patients & follow up at 1 3 years Global Composite Neurocognitive Functioning Score calculated from the following: Boston Naming Test Block Design (WAIS R) Digit Span (WAIS R) Trail Making Test Forms A & B FAS Letter Fluency Story memory Figure memory Cognitive functioning impaired in BD patients compared to HC No significant differences between groups in mean change over time (small improvement in all groups) Greater variability across time points in BD compared to HC & schizophrenic group No significant relationship between (mild) psychiatric symptoms (at baseline or follow up) & change in neuropsychological functioning Grooved Pegboard Test Digit Vigilance 1

2 California Verbal Learning Test Wisconsin Card Sorting Test Mur et al. 33 BD outpatients (24 BD I, 9 (2008) 9 BD II) 33 HC BD: 48% female & follow up after 2 years Executive tests: Trail Making Test B; FAS verbal fluency task of the Controlled Oral Word Association Test Categories; WAIS III digit span backward BD patients show deficits relative to HC in executive functioning (executive & inhibition domain) & processing speed; these deficits remain stable over time HC: 48% female Mean age: ~41 years Inhibition: Stroop Test, Wisconsin Card Sorting Test, Conners Continuous Performance Test II Attention: Stroop Test, WAIS III digit span forward, Conners Continuous Performance Test II No main effect of time in any cognitive domain Deficits in processing speed were found to be related to worse work adaptation Processing speed: Trail Making Test A; Conners Continuous Performance Test II Verbal memory: CaliforniaVerbal Learning Test Visual memory: Rey Complex Figure Test Gildengers et al. (2009) BD outpatients (28 BD I, 5 BD II) 36 HC BD: 72.7% female HC: 55.6% female 2 4 assessments: baseline & follow up at 1, 2 & 3 years Dementia Rating Scale: attention, executive function (initiation/ preservation), visuospatial ability (construction), abstraction (conceptualization) & memory BD patients showed worse cognitive functioning than HC & a greater decline in general Dementia Rating Scale score over time Group effects (BD perform worse than HC) for attention & memory subscales Mean age: ~70 years (sample: adults >50 years) Time (improvement), but no group effects for conceptualization & 2

3 executive functioning No time group for single subscales Greater intra individual variability between time points in BD compared to HC Arts et al. 76 BD patients (57 BD I, 17 BD (2011) 11 II, 2 schizoaffective bipolar type) at baseline; 39 patients remaining at final interview 61 HC BD: 54% female HC: 62% female Mean age: ~45 years Mild level of affective symptoms in patients Patients: assessment every 2 months over 2 years (i.e., maximum of 12 assessments) HC: twice at 2 month intervals Verbal learning & memory: Visual Verbal Learning Test Sustained attention: Continuous Performance Test CPT HQ Basic information processing: neutral & congruent condition of Flanker CPT Selective attention & response inhibition: incongruent condition of Flanker CPT Motor speed: Tapping Speed Test Attentional span: Digit Span, forward condition Working memory: Digit Span, backward condition BD patients show small impairments relative to HC in the following domains: sustained attention (largest effect), verbal learning & memory, basic information processing, selective attention, working memory Cognitive function in BD patients varies over time in most domains (exception: sustained attention & motor speed) & covaries with cognitive complaints Cognitive functioning improves over time (practice effects) with the exception of sustained attention & tapping Mood & medication have a modest effect on cognitive performance Global functioning relates to cognitive functioning & cognitive complaints Chaves et al. 29 BD outpatients (22 BD I, 7 (2011) 12 BD II) 30 HC BD: 50% female & follow up after 3 months South Texas Assessment of Neurocognition Speed of processing: Letter & Semantic Fluency, Digit Symbol BD patients show deficits relative to HC on measures of speed of processing & attention Small effects of change in mood symptoms on change in cognitive 3

4 HC: 50% female Mean age: BD, ~40 years; HC, ~32 years Clinically stable patients with mild to moderate affective symptoms Coding, Trail Making Test A Attention: Identical Pairs Continuous Performance Test IP CPT, Digit Span Forward Executive functioning & working memory: Digit Span Backward, Digit Sequencing Task, Penn Conditional Exclusion Test, Trail Making Test B performance in BD group (only worsening of depressive symptoms correlated with poorer verbal fluency) Declarative memory: California Verbal Learning Test, Digit Symbol Recall Delaloye et al. (2011) BD outpatients (BD I & BD II) 15 HC Mean age: ~68 years (older adults) & after 2 years Processing Speed: Reaction Time Test Working memory: Reading Span Test Episodic memory: Cued Recall 48 Items Test Executive functions: Color Trail Making Test, Stroop Color Word Interference Task, Consonant Updating Test Processing speed: BD patients performed worse than HC, but no main effect of time & no time group Working memory: main effect of time, but no main effect of group & no time group Episodic memory: BD patients performed worse than HC, but no main effect of time & no time group Executive functions: no main effects of group or time & no time group Overall: mean trajectory of cognitive changes similar for BD patients & HC No correlation between duration of illness & cognitive performance or change in cognitive performance 4

5 Depp et al. 42 BD (36 BD I, 6 BD II) (2012) HC BD: 40.5% female HC: 57.1% female Mean age: ~42 years Clinically stable patients with mild depressive or manic symptoms 2 4 assessments: baseline & follow up after 6, 12 & 26 weeks Composite score for cognitive ability calculated from the following: Digits Symbol Coding (WAIS III) Letter Number Sequencing (WAIS III) Trail Making Test Verbal Fluency (phonologic, semantic, category switching) Color Word Interference Rey Tangled Lines Test Hopkins Verbal Learning Test Revised Longitudinal gray matter & white matter changes did not differ between BD & HC BD patients performed worse on overall cognitive functioning than HC over each of the four assessments Improvement in cognitive tests over time, but level of practice effects similar for BD patients & HC Course of global cognitive ability in BD was independent from changes in affective symptoms Elevated intra individual variability in BD compared to HC BD, bipolar disorder; HC, healthy controls; WAIS III, Wechsler Adult Intelligence Scale III; WAIS R, Wechsler Adult Intelligence Scale Revised. 5