Dorien Bangma

FDM IN NEURODEGENERATIVE DISEASES | 69 Results Alzheimer’s Disease (AD) Twenty-five studies investigated FDM in people living with AD (Table 4.2a), evaluating 1086 people living with AD in total. Participants’ average age ranged from 66.9 to 83.0 years (weighted average = 74.8 years). Most studies included people living with AD who were in a mild and/or moderate stage of the disease, two studies also included a group of people in a severe stage of AD (Giannouli et al., 2018; Giannouli & Tsolaki, 2014). Seven studies, however, did not specify the stage of the disease (Gill et al., 2019; Kershaw & Webber, 2008; Lima-Silva et al., 2015; Loewenstein et al., 1989, 1995; Mahurin et al., 1991; Pereira, Yassuda, et al., 2010). All cross-sectional studies on AD reported significantly lower performances on performance-based tests of FDM in people living with AD compared to healthy controls (Table 4.2a). This corresponds to the overall large pooled mean effect size for the difference between people living with AD and healthy controls that was found in the meta-analysis ( g = 2.69 [2.15; 3.23], SE = 0.27, p < .001 based on 17 studies; Figure 4.2). Significant heterogeneity was found ( Q (16) = 246.6, p < .001, I 2 = 93.5%). More than half of the studies that were included in the meta-analysis used the FCI (n = 9). Studies using the FCI reported a significantly lower overall effect size ( g = 2.17 [1.40; 2.94], SE = 0.39, p < .001) compared to the studies using FDM tests other than the FCI ( g = 3.33 [2.49; 4.16], SE = 0.43, p < .001; Q(1) = 4.00, p = .045). The effect size of three studies using FDM tests other than the FCI are, compared to the other studies, relatively high ( g = 9.63 (Giannouli et al., 2018), g = 5.02 (Kershaw & Webber, 2008) and g = 4.03 (Lima-Silva et al., 2015); Figure 4.2). Nevertheless, the overall effect size remained large and significant when these studies are excluded ( g = 2.05 [1.77; 2.33], SE = 0.14, p < .001 based on 14 studies). The difference between studies using the FCI compared to the remaining studies is, however, no longer significant after excluding these studies (n = 5, g = 1.80 [1.35; 2.25], SE = 0.23, p < .001; Q(1) = 1.86, p = .173). The funnel plot showed significant asymmetry ( p = .015; Figure 4.3) with a slight right skewed distribution. After removal of the three studies with relatively high effect sizes, the funnel plot asymmetry was no longer significant ( p = .476). The content analysis of the included studies that described the stage of the disease of included participants indicates that relatively simple aspects of FDM (e.g., ‘identifying currency’ and ‘naming coins’) seem to be intact in people living with mild AD, since no differences between people living with mild AD and healthy controls were found regarding these specific domains in some of the studies (Griffith et al., 2003; Loewenstein et al., 1989; Marson et al., 2000, 2009). However, other studies did find significantly lower performances in people living with mild AD, compared to healthy controls, on similar domains of FDM (Gerstenecker et al., 2019; Gerstenecker, Hoagey, et al., 2017; Martin, Griffith, et al., 2008). Furthermore, overall FDM performance (reflected by total scores) was significantly lower in people living with mild AD compared to healthy controls in all studies that included people living with mild AD. Four studies (Giannouli et al., 2018; Giannouli & Tsolaki, 2014; Marson et al., 2000, 2009) divided the included participants in multiple subgroups based on disease severity which enabled the comparison of people living with AD in different disease stages.