Neuropsychiatric symptoms and brain structural alterations in Fabry disease

Schermuly, Ingrid; Müller, Matthias J.; Müller, Kay-Maria; Albrecht, Juliane; Keller, Isabel; Yakushev, Igor; Beck, Michael; Fellgiebel, Andreas

doi:10.1111/j.1468-1331.2010.03155.x

Cited by 49 publications

(87 citation statements)

References 36 publications

(50 reference statements)

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“…Also in line with the literature, cognitive function of the present young to middle-aged study group has been shown to be largely unimpaired. Only a small subgroup of patients with more severe WML displayed slight learning and memory deficits (Schermuly et al 2010). Additionally and also consistent with previous observations we found a high rate of depression (about 60% of the patients) in our FD cohort which was not associated with the brain structural changes and was interpreted to be mainly related to the chronic disease burden (Schermuly et al 2010).…”

Section: Introductionsupporting

confidence: 84%

Hippocampal atrophy as a surrogate of neuronal involvement in Fabry disease

Fellgiebel

Wolf

Kolodny

et al. 2011

J of Inher Metab Disea

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Cerebral micro- and macro-vasculopathy have been described in Fabry disease (FD). Neuronal globotriaosylceramide accumulation in selective cortical and brain stem areas including the hippocampus has been reported by autopsy studies in FD, but clinical surrogates as well as the clinical relevance of these findings have not been investigated so far. We measured the hippocampus volumes in a group of clinically affected patients with FD and correlated the findings with the cognitive performance of the patients. Hippocampal volumes were determined manually on T1-weighted MR-images of 25 FD patients (age 36.5 ± 11.0 years) and 20 age-matched controls. Additionally, individual white matter (WM) and gray matter (GM) volumes were measured using brain segmentation analyses. After controlling for age, white matter lesion (WML) volume, and WM/GM-volumes hippocampal volumes were significantly decreased in FD. These findings were substantially more pronounced in a subgroup of men with FD. WM and WM/GM volumes, and memory function did not significantly differ between patients and controls. In patients with FD hippocampal volumes were neither significantly correlated to WML volume nor to WM or WM/GM volumes. Hippocampus atrophy was not driven by the WML or other brain tissue atrophy and seems to correlate with the neuronal involvement in FD. In this young to middle-aged Fabry cohort the hippocampus degeneration was functionally compensated without memory impairment. Longitudinal studies are needed to determine whether this degenerative component in FD will progress and, in concert with the individual WML-load, predict subsequent cognitive decline.

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Section: Introductionsupporting

confidence: 84%

Hippocampal atrophy as a surrogate of neuronal involvement in Fabry disease

Fellgiebel

Wolf

Kolodny

et al. 2011

J of Inher Metab Disea

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“…Likewise, lower QOL in both mental and physical domains is consistent with previous reports (Low et al 2007). Prior research found that mild deficits in executive function among 25 patients with FD compared to 20 controls were no longer significant after controlling for depression (Schermuly et al 2011). In our study, controlling for depressive symptoms, perceived stress, and QOL variables substantially attenuated the trend for lower composite cognitive scores among FD participants.…”

Section: Discussionmentioning

confidence: 97%

“…Hearing loss also can affect cognitive processing and correlates with neuropathic and vascular damage in FD (Ries et al 2007). White matter changes also are important findings; however, to date, the relation of brain abnormalities to described minor changes in cognitive function in FD is not compelling (Moore et al 2007;Muller et al 2005;Schermuly et al 2011;Fellgiebel et al 2012). Chronic distress associated with FD may have more influence on cognitive function than do pathologic alterations in the central nervous system (Segal et al 2010;Schermuly et al 2011).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

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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.

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“…17 One case of prolonged transient global amnesia has been reported in a Fabry patient. 18 Dementia, cognitive impairment, and depression occur in patients with FD 19 although additional studies are needed to establish a direct link to FD.…”

Section: Cerebral Manifestations Of Fdmentioning

confidence: 99%