Dorien Bangma

FDM IN NEURODEGENERATIVE DISEASES | 75 for the overlap or connections between brain areas. The results indicated that only the volume of the medial frontal cortex was a significant predictor of FDM in people living with mild AD, i.e., predicting 35% of variance of the FCI total score. The association between white matter connectivity (using MRI based diffusion tensor imaging) and FDM was determined in a third study (Gerstenecker, Hoagey, et al., 2017). In people living with MCI, a greater degeneration of the white matter (i.e., a reduction of fractional anisotropy) in areas related to the precuneus, lateral and medial occipital, lateral temporal and lateral prefrontal cortices was related to lower performances on the FCI. In people living with mild AD, a decreased white matter integrity (i.e., increased axial diffusivity λ1 and mean diffusivity of λ1, λ2 and λ3) in similar regions as found in people living with MCI was related to lower FDM performances. In healthy controls, no relation between white matter connectivity and FDM was found. In a fourth study, Pereira, Yassuda et al. (2010) investigated AD biomarkers (i.e., the concentrations of Total Tau, Phospho-Tau 181 and Amyloid ß 1-42 in the cerebrospinal fluid) in nineteen people living with MCI and related these concentrations to performances on a measure of FDM (i.e., the DAFS subscale ‘dealing with finances’). The results showed that higher concentrations of Total Tau and Phopsho-Tau 181 were associated with lower performances on the tests of FDM in people living with MCI, whereas overall functional capacity (i.e., total score on DAFS) was not associated to any of these biomarkers. Finally, Tolbert et al. (2019) investigated FDM performances (i.e., on the FCI-SF) in relation to cortical ß-amyloid deposition. A higher cortical-to-cerebellum standardized uptake value ratio/SUVr indicates greater cortical ß- amyloid deposition which is described as one of the pathological hallmarks of AD and has the utility of predicting cognitive decline in normal aging and MCI (Clark et al., 2011; Doraiswamy et al., 2014). In a pooled sample of people living with MCI and people living with AD, while controlling for age, education and sex, higher ß-amyloid SUVr was significantly negatively correlated with FDM performances. Frontotemporal Dementia (FTD) Three studies, which included a total of 52 participants (weighted age = 67.3 years), investigated FDM in people living with FTD (Table 4.2c). All participants were diagnosed with the behavioral variant of FTD, although one study did not provide information about demographics and disease characteristics of participants (Giannouli et al., 2018). The included studies consistently found lower performances on tests of FDM compared to healthy controls (Giannouli et al., 2018; Gill et al., 2019; Lima-Silva et al., 2015). This is confirmed by the large pooled mean effect size found in the meta-analysis (i.e., g = 2.56 [1.73; 3.39], SE = 0.42, p < .001 based on three studies; Figure 4.2). Significant heterogeneity was found ( Q (2) = 7.4, p = .025, I 2 = 73.0%) and the funnel plot showed significant asymmetry ( p = .010; Figure 4.3). However, only a small number of studies were included so these bias assessments should be interpreted with caution. Gill et al. (2019) reported that people living with FTD showed an intact performance on ‘reading/writing’, ‘rational beliefs about money’ and ‘debt management’ of the FACT and FCAI compared to healthy controls. One study indicated that people living with FTD showed significantly lower FDM performances compared to people living with mild AD (i.e., deviation