Supplementary Material for: Anterior Temporal Atrophy and Posterior Progression in Patients with Parkinson's Disease

<b><i>Background:</i></b> Parkinson's disease (PD) is characterized by specific motor and nonmotor impairments. This suggests that PD is characterized by disease-specific regional cortical atrophy. Given the change of symptoms over time, a concurrent increase in regional atrophy may further be assumed to reflect the dynamic process of disease progression. <b><i>Methods:</i></b> In this study we retrospectively collected T1-weighted MRI scans from previous studies performed in our center, enabling the comparison of gray matter atrophy in 77 PD patients with 87 controls using voxel-based morphometry (VBM). This large VBM analysis provided the opportunity to investigate cortical atrophy in relation with disease progression. <b><i>Results:</i></b> We found significant PD-related reductions of gray matter density bilaterally in the anterior temporal cortex, the left inferior frontal and left extrastriate visual cortex, independent from normal aging. The anterior temporal cortex did not show major progression, whereas particularly the posterior parts of the lateral temporal cortex and adjacent extrastriate visual cortex occurred at a later stage of disease. <b><i>Conclusions:</i></b> Temporal pole atrophy as an early sign of PD is consistent with the PD pathology classification of Braak. The initial anterior temporal atrophy with spread to occipitotemporal and posterior parietal regions may subserve ‘emotion-based' sensorimotor transformations and deficits in the visual domain, respectively, which may be regarded as premotor symptoms

Supplementary Material for: Hydrocortisone Dose Influences Pain, Depressive Symptoms and Perceived Health in Adrenal Insufficiency: A Randomized Controlled Trial

<br><strong><em>Background:</em></strong> There is a major lack of randomized controlled trials (RCTs) evaluating the effects of hydrocortisone (HC) substitution therapy in patients with secondary adrenal insufficiency. Therefore, we evaluated the effects of two different replacement doses of HC on health-related quality of life (HRQoL) in a RCT. <b><i>Methods:</i></b> This RCT with a double-blind cross-over design was performed at the University Medical Center Groningen. Forty-seven patients (29 men, age 51 ± 14 years, range 19-73 years) with secondary adrenal insufficiency participated. Patients received both a lower and a higher dose of HC (0.2-0.3 and 0.4-0.6 mg/kg body weight/day) for 10 weeks in random order. HRQoL was assessed with a daily mood and symptom checklist (Patient Health Questionnaire-15 [PHQ-15], Generalized Anxiety Disorder-7 [GAD-7], Patient Health Questionnaire-9 [PHQ-9]) and with questionnaires assessing general well-being (RAND 36-Item Health Survey [RAND-36]), mood (Hospital Anxiety and Depression Scale [HADS]) and fatigue (Multidimensional Fatigue Inventory-20 [MFI-20]). ClinicalTrials.gov identifier: NCT01546922. <b><i>Results:</i></b> Patients receiving the higher dose of HC reported significantly fewer symptoms of depression (p = 0.016 and p = 0.045 for HADS and PHQ-9, respectively), less general and mental fatigue (p = 0.004 and p = 0.003, respectively, both MFI-20), increased motivation (p = 0.021, MFI-20), better physical functioning (p = 0.041), better general health (p = 0.013) and more vitality (p = 0.025) (all RAND-36). In addition, while on the higher dose, fewer somatic symptoms (p = 0.022) and less pain (p < 0.001) (both PHQ-15) were experienced. <b><i>Conclusions:</i></b> On the higher dose of HC, patients reported a better HRQoL on various domains as compared to the lower dose of HC. The fact that a higher dose of HC may improve patient well-being should be taken into consideration when individualizing the HC substitution dose