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Eight-Year Follow-Up of Neuropsychiatric Symptoms and Brain Structural Changes in Fabry Disease.

ABSTRACT: Brain structural alterations and neuropsychiatric symptoms have been described repeatedly in Fabry disease, yet cognitive deficits have been shown to be only mild. Here, we aimed to investigate neuropsychiatric symptoms and brain structure longitudinally. We expected no clinically relevant increase of neuropsychiatric symptoms in parallel to increased brain structural alterations. We assessed 14 Fabry patients (46.1 ± 10.8 years) who had participated in our investigation eight years ago. Patients engaged in neuropsychiatric testing, as well as structural magnetic resonance imaging and angiography to determine white matter lesions, hippocampal volume, and the diameter of the larger intracranial arteries. While Fabry patients did not differ on cognitive performance, they showed progressive and significant hippocampal volume loss over the 8-year observation period. White matter lesions were associated with older age and higher white matter lesion load at baseline, but did not reach statistical significance when comparing baseline to follow-up. Likewise, intracranial artery diameters did not increase significantly. None of the imaging parameters were associated with the neuropsychiatric parameters. Depression frequency reduced from 50% at baseline to 21% at follow-up, but it did not reach significance. This investigation demonstrates clinical stability in cognitive function, while pronounced hippocampal atrophy is apparent throughout the 8 years. Our middle-aged Fabry patients appeared to compensate successfully for progressive hippocampal volume loss. The hippocampal volume decline indicates brain regional neuronal involvement in Fabry disease.

SUBMITTER: Lelieveld IM

PROVIDER: S-EPMC4560446 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Eight-Year Follow-Up of Neuropsychiatric Symptoms and Brain Structural Changes in Fabry Disease.

Lelieveld Irene M IM Böttcher Anna A Hennermann Julia B JB Beck Michael M Fellgiebel Andreas A

PloS one 20150904 9

Brain structural alterations and neuropsychiatric symptoms have been described repeatedly in Fabry disease, yet cognitive deficits have been shown to be only mild. Here, we aimed to investigate neuropsychiatric symptoms and brain structure longitudinally. We expected no clinically relevant increase of neuropsychiatric symptoms in parallel to increased brain structural alterations. We assessed 14 Fabry patients (46.1 ± 10.8 years) who had participated in our investigation eight years ago. Patient ...[more]

PMID: 26340726

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Project description:BACKGROUND:Fabry disease, an X-linked genetic condition, results from alpha-galactosidase deficiency and increased accumulation of glycosphingolipids in cardiovascular tissues. Clinical manifestation includes vasculature associated complications. Hyperlipidaemia is one of the cardiovascular risk factors however it has never been well defined in Fabry disease. Enzyme Replacement Therapy (ERT) is available but its effect on serum cholesterol is unknown. The aim of this project was to assess the influence of long-term ERT on lipid profile in a large cohort of adult patients with Fabry disease. METHODS:This was a retrospective analysis of lipid profile results. Patients with Fabry disease were on ERT for 10 years, were not treated with statins and had no severe renal impairment. All patients had lipid profile measured before ERT was commenced and 6, 12, 24, 36, 48, 60, 120 months later. Statistical analysis included ANOVA, Student t-test and descriptive statistics. RESULTS:Among 72 patients, 40 were females (median age 45; range 29-75), 32 males (median age 46; range 20-69). There was no significant difference in total cholesterol or HDL-cholesterol measured at baseline before ERT was commenced and 6, 12, 24, 36, 48, 60 and 120 months after ERT was commenced in 72 patients (ANOVA; P = 0.673 and P = 0.883, respectively). Female patients on ERT had higher mean HDL-cholesterol as compared to female patients with Fabry disease who were asymptomatic and not treated (P ? 0.05). Total cholesterol between treated and non-treated female patients was comparable. Female patients on ERT have higher total cholesterol and HDL-cholesterol when compared to lipid results in male patients on ERT. Total cholesterol/HDL-cholesterol ratio was low in female and male patients on ERT over 10 years. CONCLUSION:Adult patients with Fabry disease have remarkably elevated HDL-cholesterol and as a result, elevated total cholesterol. It is possible that elevated HDL-cholesterol has a cardioprotective effect in patients with this condition. Long term ERT does not have a significant impact on lipid profile in female and male population with Fabry disease.

Project description:Background Health coaching is a patient-centred approach to supporting self-management for the chronic conditions. However, long-term evidence of effectiveness of health coaching remains scarce. The object of this study was to evaluate the long-term effect of telephone health coaching (THC) on mortality and morbidity among people with type 2 diabetes (T2D), coronary artery disease (CAD) and congestive heart failure (CHF).. Methods 1535 T2D, CAD and CHF patients with unmet treatment targets were randomly allocated into an intervention group (n = 1034) and control group (n = 501). Intervention group received monthly individual strength-based, autonomy supportive THC sessions (average 30 min) for behavior change with a specially trained nurse for 12 months additional to usual health care. Control group received usual health care services. The primary outcome was a composite of death from cardiovascular causes or non-fatal stroke or non-fatal myocardial infarction (AMI) or unstable angina pectoris (UAP) during a follow-up of 8 years Three other composite endpoints with distinct combinations of fatal and non-fatal cardiovascular events and death from any cause were used as secondary outcomes. Other outcomes followed were the most relevant components of the composite endpoints. Randomized controlled trial (RCT) data was linked to Finnish national health and social care registries and electronic health records (EHR). Post-trial eight-year evaluation was conducted using intention-to-treat (ITT) and per-protocol (PP) analysis. Results The composite primary outcome event rate per 100 person years was lower in the intervention group (3.45) than in control group (3.88) in ITT -analysis, but the difference was not statistically significant (hazard ratio in the intervention group 0.87; 95% CI, 0.71 to 1.07; P = 0.19). In the subgroup (T2D, CAD/CHF) analysis, there were no statistically significant effects. The secondary PP-analysis showed statistically significant benefits for those who participated in the study. Conclusions No statistically significant effect of health coaching on mortality and morbidity was found in intention to treat analysis. The per protocol results suggest, however, that the intervention may be effective among patients who are willing and able to participate in health coaching. More research is needed to identify patients most likely to benefit from low-intensity health coaching. Trial registration NCT00552903 (registration date: the 1st of November 2007, updated the 3rd of February 2009). Supplementary Information The online version contains supplementary material available at 10.1186/s12913-021-07263-w.

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Dataset Information

Eight-Year Follow-Up of Neuropsychiatric Symptoms and Brain Structural Changes in Fabry Disease.

Publications

Eight-Year Follow-Up of Neuropsychiatric Symptoms and Brain Structural Changes in Fabry Disease.

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