Cerebral hemodynamics in aging: the interplay between blood pressure, cerebral perfusion, and dementia.

Bespreking proefschrift Jurgen A.H.R. Claassen. Cerebral hemodynamics in aging: the interplay between blood pressure, cerebral perfusion, and dementia

The effect of raloxifene on bone marrow adipose tissue and bone turnover in postmenopausal women with osteoporosis

In patients with postmenopausal osteoporosis low bone volume is associated with high bone marrow adipose tissue (MAT). Moreover, high MAT is associated with increased fracture risk. This suggests an interaction between MAT and bone turnover, however literature remains equivocal. Estrogen treatment decreases MAT, but the effect of raloxifene, a selective estrogen receptor modulator (SERM) registered for treatment of postmenopausal osteoporosis, on MAT is not known. The aim of this study is 1] to determine the effect of raloxifene on MAT and 2] to determine the relationship between MAT and bone turnover in patients with osteoporosis. Bone biopsies from the MORE trial were analyzed. The MORE trial investigated the effects of raloxifene 60 or 120 mg per day versus placebo on bone metabolism and fracture incidence in patients with postmenopausal osteoporosis. We quantified MAT in iliac crest biopsies obtained at baseline and after 2 years of treatment (n = 53; age 68.2 ± 6.2 years). Raloxifene did not affect the change in MAT volume after 2 years compared to baseline (placebo: 1.89 ± 10.84%, raloxifene 60 mg: 6.31 ± 7.22%, raloxifene 120 mg: − 0.77 ± 10.72%), nor affected change in mean adipocyte size (placebo: 1.45 (4.45) μm, raloxifene 60 mg: 1.45 (4.35) μm, raloxifene 120 mg: 0.81 (5.21) μm). Adipocyte number tended to decrease after placebo treatment (− 9.92 (42.88) cells/mm2) and tended to increase during raloxifene 60 mg treatment (13.27 (66.14) cells/mm2) while adipocyte number remained unchanged in the raloxifene 120 mg group, compared to placebo (3.06 (39.80) cells/mm2, Kruskal-Wallis p = 0.055, post hoc: placebo vs raloxifene 60 mg p = 0.017). MAT volume and adipocyte size were negatively associated with osteoclast number at baseline (R2 = 0.123, p = 0.006 and R2 = 0.098, p = 0.016 respectively). Furthermore adipocyte size was negatively associated with osteoid surface (R2 = 0.067, p = 0.049). Finally, patients with vertebral fractures had higher MAT volume (50.82 (8.80)%) and larger adipocytes (55.75 (3.14) μm) compared to patients without fractures (45.58 (12.72)% p = 0.032, 52.77 (3.73) μm p = 0.004 respectively). In conclusion, raloxifene did not affect marrow adipose tissue, but tended to increase adipocyte number compared to placebo. At baseline MAT volume and adipocyte size were associated with bone resorption, and adipocyte size was associated with osteoid surface, suggesting an interaction between bone marrow adipocytes and bone turnover. In addition, we found that high MAT volume and larger adipocyte size are associated with prevalent vertebral fractures in postmenopausal women with osteoporosis, indicating that adipocyte size affects bone quality independent of bone volume

Cortical phase changes in Alzheimer's disease at 7T MRI:a novel imaging marker

AbstractBackgroundPostmortem studies have indicated the potential of high-field magnetic resonance imaging (MRI) to visualize amyloid depositions in the cerebral cortex. The aim of this study is to test this hypothesis in patients with Alzheimer's disease (AD).MethodsT2*-weighted MRI was performed in 16 AD patients and 15 control subjects. All magnetic resonance images were scored qualitatively by visual assessment, and quantitatively by measuring phase shifts in the cortical gray matter and hippocampus. Statistical analysis was performed to assess differences between groups.ResultsPatients with AD demonstrated an increased phase shift in the cortex in the temporoparietal, frontal, and parietal regions (P < .005), and this was associated with individual Mini-Mental State Examination scores (r = −0.54, P < .05).ConclusionIncreased cortical phase shift in AD patients demonstrated on 7-tesla T2*-weighted MRI is a potential new biomarker for AD, which may reflect amyloid pathology in the early stages

The Diagnostic and Prognostic Value of Neuropsychological Assessment in Memory Clinic Patients

Background: Neuropsychological testing has long been embedded in daily clinical practice at memory clinics but the added value of a complete neuropsychological assessment (NPA) to standard clinical evaluation is unknown. Objective: To evaluate the added diagnostic and prognostic value of NPA to clinical evaluation only in memory clinic patients. Methods: In 221 memory clinic patients of a prospective cohort study, clinical experts diagnosed clinical syndrome (subjective cognitive impairment (SCI), mild cognitive impairment (MCI), or dementia) and etiology (Alzheimer's disease (AD) or no AD), and provided a prognosis of disease course (decline or no decline) before and after results of NPA were made available. The reference standard was a panel consensus based on all clinical information at baseline and up to 2 follow-up assessments. Results: With NPA data available, clinicians changed their initial syndromal diagnosis in 22 of patients, and the etiological diagnosis as well as the prognosis in 15. This led to an increase in correctly classified cases of 18 for syndromal diagnosis, 5 for etiological diagnosis, and 1 for prognosis. NPA data resulted in the largest improvement in patients initially classified as SCI (syndrome: 93.3 (n = 14) correctly reclassified, etiology: net reclassification improvement [NRI] = 0.61, prognosis: NRI = 0.13) or MCI (syndrome: 89.3 (n = 23) correctly reclassified, etiology: NRI = 0.17, prognosis: NRI = 0.14), while there was no improvement in patients with dementia (syndrome: 100 (n = 1) correctly reclassified, etiology: NRI = -0.05, prognosis: NRI = -0.06). Overall, inclusion of NPA in the diagnostic process increased confidence in all diagnoses with 6-7. Conclusion: Administration of a complete NPA after standard clinical evaluation has added value for diagnosing cognitive syndrome and its underlying etiology in patients regarded as non-demented based on the first clinical impression

Correction to: Cerebrovascular and amyloid pathology in predementia stages: The relationship with neurodegeneration and cognitive decline (Alzheimer's Research and Therapy (2017) 9 (101) DOI: 10.1186/s13195-017-0328-9)

Upon publication of this article [1], it was noticed that there were some inconsistencies in Tables 1, 2 and 3. Some of the superscript letters were incorrectly assigned. Please see below the correct tables: (Table Presented)

Correction to: Cerebrovascular and amyloid pathology in predementia stages: the relationship with neurodegeneration and cognitive decline (vol 9, 101, 2017)

Upon publication of this article [1], it was noticed that there were some inconsistencies in Tables?1, 2 and 3. Some of the superscript letters were incorrectly assigned. Please see below the correct tables

Cortical phase changes measured using 7-T MRI in subjects with subjective cognitive impairment, and their association with cognitive function

Studies have suggested that, in subjects with subjective cognitive impairment (SCI), Alzheimer's disease (AD)-like changes may occur in the brain. Recently, an in vivo study has indicated the potential of ultra-high-field MRI to visualize amyloid-beta (Aβ)-associated changes in the cortex in patients with AD, manifested by a phase shift on T2*-weighted MRI scans. The main aim of this study was to investigate whether cortical phase shifts on T2*-weighted images at 7 T in subjects with SCI can be detected, possibly implicating the deposition of Aβ plaques and associated iron. Cognitive tests and T2*-weighted scans using a 7-T MRI system were performed in 28 patients with AD, 18 subjects with SCI and 27 healthy controls (HCs). Cortical phase shifts were measured. Univariate general linear modeling and linear regression analysis were used to assess the association between diagnosis and cortical phase shift, and between cortical phase shift and the different neuropsychological tests, adjusted for age and gender. The phase shift (mean, 1.19; range, 1.00–1.35) of the entire cortex in AD was higher than in both SCI (mean, 0.85; range, 0.73–0.99; p <0.001) and HC (mean, 0.94; range, 0.79–1.10; p <0.001). No AD-like changes, e.g. increased cortical phase shifts, were found in subjects with SCI compared with HCs. In SCI, a significant association was found between memory function (Wechsler Memory Scale, WMS) and cortical phase shift (β = –0.544, p = 0.007). The major finding of this study is that, in subjects with SCI, an increased cortical phase shift measured at high field is associated with a poorer memory performance, although, as a group, subjects with SCI do not show an increased phase shift compared with HCs. This increased cortical phase shift related to memory performance may contribute to the understanding of SCI as it is still unclear whether SCI is a sign of pre-clinical AD. </p