Study Quality
Two potential indicators of study quality–study size and confirmation of nonT2DM status in the control population–were included as moderators. Study size was split
into tertiles and compared across groups. For confirmation of control status, each study
was coded for whether or not non-T2DM status was confirmed via blood sample and
effect sizes were compared across groups. Between group comparisons for both measures
were conducted using meta-analysis analog to the one-way ANOVA. A conservative
approach to study quality was taken, such that if a study did not report confirmation (via
blood test) of non-T2DM status in the control group, it was assumed that this was not
done. The moderator analysis for study size and confirmation of non-T2DM controls
were conducted using the meta-analysis analog to oneway ANOVA, and were conducted
using the SPSS macros.
Results
Table S1 presents the results of the analog to ANOVA moderator analyses for
sample size and confirmation of control status.
Overall EF Composite
Sample size significantly moderated the association between T2DM status and EF
(QB (2,57)=7.19, p=0.028) such that studies falling within the lowest tertile of study size
had significantly larger effect size (d=-0.421, SE=0.070) than studies in the middle
(p=0.0098; d=-0.227, SE=0.051) or largest tertile (p=0.0099; d=-0.214, SE=0.035);
however, the effect of T2DM status on EF was significant (at p<0.001) for all three
groups. Studies in the middle and largest tertile were not significantly different from
eachother (p=0.84). Confirmation of control status (p=0.98) did not influence effect size.
Verbal Fluency
Sample size also significantly moderated the association between T2DM status
and EF (QB (2,28)=23.30, p<0.001) such that studies falling within the lowest tertile of
study size had significantly larger effect size (d=-0.545, SE=0.088) than studies in the
middle (p=0.0035; d=-0.237, SE=0.059) or largest tertile (p<0.001; d=-0.143,
SE=0.019); however the effect of T2DM status on EF was significant (at p<0.001) for all
three groups. Studies in the middle and largest tertile were not significantly different from
each other (p=0.10). Confirmation of control status (p=0.51) did not moderate the
association between T2DM and EF
Mental Flexibility
Neither confirmation of control status (p=0.63), nor sample size (p=0.45)
moderated the association between T2DM and EF.
Working Memory
Neither confirmation of control status (p=0.76), nor sample size (p=0.12)
moderated the association between T2DM and EF.
Attention
Neither confirmation of T2DM status (p=0.28), nor sample size (p=0.16)
moderated the association between T2DM and EF.
Discussion
With respect to study quality, moderator analysis revealed a significant effect of
sample size for both the overall EF composite and the verbal fluency subcomponent, such
that studies in the smallest tertile of sample size had larger effect sizes than those in the
middle or largest tertiles; however, sample size did not moderate the size of the effect for
mental flexibility, working memory, or attention. Importantly, while study size
significantly moderated the effect size of the association between T2DM and lower EF,
the association was statistically significant for all three tertiles. Study sample size is often
used an indicator of study quality; however, it is important to recognize that other factors
affecting study quality may be of equal importance particularly within the context of the
association between T2DM and EF. For example, matching on relevant characteristics
such as age, sex, and education, as well as, exclusion of potentially confounding
disorders such as hypertension, cerebrovascular disease or other cognitive disorders are
all relevant to the relationship between T2DM and EF and may have played a role in
differences in effect sizes observed. Additionally, it is possible that these methods may
have been employed disproportionately in small-to-moderate sized studies for logistical
reasons. Interestingly, confirmation of non-T2DM control status did not moderate effect
size. This may indicate that self-report methods of ascertaining T2DM status are
sufficient for assessing the relationship between T2DM and EF; however, it is also
possible that between study differences on other important factors (such as those listed
above) may have confounded a potential moderating effect of confirmation of non-T2DM
control status.
Table S1: Moderator Analysis – Analog to ANOVA
Moderator
Sample Size
Control Status
n
79069
79069
k
QB(df)
Overall EF
60 7.19 (2)
60 0.0007(1)
p
QW(df)
p
0.028
0.98
53.93 (57)
58.00(58)
0.59
0.48
25.23 (28)
37.38 (29)
0.62
0.14
20.92 (19)
20.49 (20)
0.34
0.43
29.88 (25)
32.69 (26)
0.23
0.17
34.82 (24)
34.76 (25)
0.071
0.093
Sample Size
Control Status
41467
41467
Sample Size
Control Status
24243
24243
Verbal Fluency
31 23.30 (2) <0.001
31 0.44 (1)
0.51
Mental Flexibility
22 1.58 (2)
0.45
22 0.23 (1)
0.63
Sample Size
Control Status
28118
28118
Working Memory
28 4.30 (2)
0.12
28 0.09 (1)
0.76
Sample Size
Control Status
25669
25669
27
27
Attention
3.62 (2)
1.17 (1)
0.16
0.28