Cognitive Function in Adults Aging with Fabry Disease: A Case–Control Feasibility Study Using Telephone-Based Assessments

Abstract

We examined the feasibility of recruiting US adults !45 years old with Fabry disease (FD) for telephone assessments of cognitive functioning. A case-control design matched each FD participant on age, sex, race, and education to four participants from a populationbased study. Fifty-four participants with FD age 46-72 years were matched to 216 controls. Standardized cognitive assessments, quality of life (QOL), and medical histories were obtained by phone, supplemented by objective indices of comorbidities. Normalized scores on six cognitive tasks were calculated. On the individual tasks, scores on list recall and semantic fluency were significantly lower among FD participants (p-values < 0.05), while scores on the other four tasks did not differ. After averaging each participant's normalized scores to form a cognitive composite, we examined group differences in composite scores, before and after adjusting for multiple covariates using generalized estimating equations. The composite scores of FD cases were marginally lower than controls before covariate adjustments (p ¼ 0.08). QOL and mental health variables substantially attenuated this finding (p ¼ 0.75), highlighting the influence of these factors on cognition in FD. Additional adjustment for cardiovascular comorbidities, kidney function, and stroke had negligible impact, despite higher prevalence in the FD sample. Telephonebased cognitive assessment methods are feasible among adults with FD, affording access to a geographically dispersed sample. Although decrements in discrete cognitive domains were observed, the overall cognitive function of older adults with FD was equivalent to that of well-matched controls before and after accounting for multiple confounding variables.

Cognitive Impairments and Subjective Cognitive Complaints in Fabry Disease: A Nationwide Study and Review of the Literature

“…Some studies did not find significant differences between attentional performances in Fabry patients and healthy controls (Low et al 2007;Elstein et al 2012;Sigmundsdottir et al 2014;Lohle et al 2015), but all these studies but the one by Sigmundsdottir et al (2014) used cognitive screening tests and therefore may not have had the adequate diagnostic sensitivity. In accordance with our results, some studies found impairments in executive functions in Fabry disease (Segal et al 2010;Longato et al 2011;Sigmundsdottir et al 2014;Wadley et al 2015), whereas others did not. This may be because that the disease affects only specific executive functions or that different aspects of executive functions are impaired in different patients.…”

“…The majority of previous studies of cognitive functioning in Fabry disease has found that cognitive deficits do occur in this patient group (Low et al 2007;Segal et al 2010; Longato et al 2011;Schermuly et al 2011;Elstein et al 2012;Sigmundsdottir et al 2014;Wadley et al 2015). Only one study found no significant difference in cognitive tests when comparing performances of patients with Fabry disease to performances of healthy controls (Lohle et al 2015).…”

“…The previous studies on cognition in Fabry disease all had several limitations including small cohorts (Bolsover et al 2014) and the applied cognitive tests were screening tests or tapping specific cognitive domains (Lohle et al 2015;Wadley et al 2015). Some studies did not include control groups (Segal et al 2010;Longato et al 2011;Lelieveld et al 2015), whereas others did not include premorbid intellectual level in the evaluation of impairment (Low et al 2007;Segal et al 2010;Schermuly et al 2011;Lohle et al 2015) or mix children and adults in the statistical analyses (Segal et al 2010).…”

“…In Table 1, we have summarised the findings from the previous studies in the field. In general, the studies show cognitive impairment in psychomotor speed, attention and executive functions while the remaining cognitive functions remain preserved (Segal et al 2010;Longato et al 2011;Schermuly et al 2011;Elstein et al 2012;Sigmundsdottir et al 2014;Wadley et al 2015). However, few studies have examined the predictors of cognitive impairment in Fabry disease.…”

“…Postischaemic abnormalities and white matter lesions have been associated with cognitive deficits (Low et al 2007;Schermuly et al 2011;Sigmundsdottir et al 2014;Lelieveld et al 2015), while disease severity and pain have not (Low et al 2007;Schermuly et al 2011;Elstein et al 2012;Sigmundsdottir et al 2014;Wadley et al 2015). Possible gender differences in cognition have only been investigated in few studies, showing mixed results (Elstein et al 2012;Sigmundsdottir et al 2014;Wadley et al 2015). Subjective cognitive complaints in relation to cognitive impairment in Fabry disease have not been investigated.…”