Quantitative magnetization transfer provides information complementary to grey matter atrophy in Alzheimer's disease brains

Preliminary studies, based on a region-of-interest approach, suggest that quantitative magnetization transfer (qMT), an extension of magnetization transfer imaging, provides complementary information to conventional magnetic resonance imaging (MRI) in the characterisation of Alzheimer's disease (AD).The aim of this study was to extend these findings to the whole brain, using a voxel-wise approach.We recruited 19 AD patients and 11 healthy subjects (HS). All subjects had an MRI acquisition at 3.0 T including a T₁-weighted volume, 12 MT-weighted volumes for qMT, and data for computing T₁ and B₁ maps. The T₁-weighted volumes were processed to yield grey matter (GM) volumetric maps, while the other sequences were used to compute qMT parametric maps of the whole brain. qMT maps were warped to standard space and smoothed, and subsequently compared between groups. Of all the qMT parameters considered, only the forward exchange rate, RM₀^B, showed significant group differences. These images were therefore retained for the multimodal statistical analysis, designed to locate brain regions of RM₀^B differences between AD and HS groups, adjusting for local GM atrophy.Widespread areas of reduced RM₀^B were found in AD patients, mainly located in the hippocampus, in the temporal lobe, in the posterior cingulate and in the parietal cortex.These results indicate that, among qMT parameters, RM₀^B is the most sensitive to AD pathology. This quantity is altered in the hippocampus of patients with AD (as found by previous works) but also in other brain areas, that PET studies have highlighted as involved with both, reduced glucose metabolism and amyloid β deposition. RM₀^B might reflect, through the measurement of the efficiency of MT exchange, some information with a specific pathological counterpart. Given previous evidence of a strict relationship between RM₀^B and intracellular pH, an intriguing speculation is that our findings might reflect metabolic changes related to mitochondrial dysfunction, which has been proposed as a contributor to neurodegeneration in AD.     

Damage to the cingulum contributes to Alzheimer's disease pathophysiology by deafferentation mechanism

This study investigates the differential contribution of gray matter (GM) atrophy and deafferentation through white matter (WM) damage in the clinical progression of Alzheimer's disease (AD). Thirty-one patients with probable AD, 23 with amnestic mild cognitive impairment (a-MCI), and 14 healthy subjects underwent MRI scanning at 3T. Voxel-based morphometry was used to assess regional GM atrophy in AD and a-MCI patients. Diffusion tensor-MRI tractography was used to reconstruct the cingulum bilaterally, and to quantify, voxel-by-voxel, its fractional anisotropy (FA) and mean diffusivity (MD) (measures of microscopic WM integrity). Atrophy of the cinguli was also assessed by means of jacobian determinants (JD) of local transformations. In AD patients, four clusters of reduced GM were found nearby the cinguli, in the posterior (PCC) and anterior cingulate cortex, and in the hippocampal/parahippocampal areas. Widespread areas of reduced FA and increased MD were found in the cinguli of both, AD and a-MCI patients. A region of macroscopic atrophy was detectable in AD patients only. Strong associations were found between local GM densities in the four identified clusters, and measures of micro- and (to a lesser extent) macroscopic damage of patients' cinguli. Linear regression analyses revealed that MD in the cinguli predicts patients' measures of episodic memory in combination with GM density of hippocampal/parahippocampal areas, and measures of global cognition in combination with GM density of the PCC. This study indicates that brain deafferentation though the cingulum is likely to play a remarkable role in progressive development of cognitive impairment in AD.     

Characterization of the functional response in the human spinal cord: Impulse-response function and linearity

Functional magnetic resonance imaging (fMRI) has emerged during the last decade as the main non-invasive technique for the investigation of human brain function. More recently, fMRI was also proposed for functional studies of the human spinal cord, but with controversial results. In fact, the functional contrast is not well-characterized, and even its origin has been challenged. In the present work, we characterized the temporal features of the functional signal evoked in the human spinal cord by a motor task, studied with an approach based on time-locked averaging of functional time series of different durations. Based on the results here reported, we defined an impulse-response function (irf) able to explain the functional response for motor tasks in the interval of 15-42 s of duration, thus suggesting the linearity of the phenomenon in this interval. Conversely, with stimulation durations ranging between 3 and 9 s, the functional signal was not detectable, and was under the level predicted by a linear behavior, suggesting deviation from linearity during short stimulations. The impulse-response function appeared slower than in the brain, peaking at about 9 s after its beginning. The observed contrast was generally larger than in the brain, on the order of about 5.4% of baseline signal at 1.5 T. The findings further suggested that the physiological origin of T(2) weighted functional imaging is similar in the spinal cord and in the brain.     

Ten‐year changes in ambulatory blood pressure: The prognostic value of ambulatory pulse pressure

Blood pressure (BP) changes and risk factors associated with pulse pressure (PP) increase in elderly people have rarely been studied using ambulatory blood pressure monitoring (ABPM). The aim is to evaluate 10‐year ambulatory blood pressure (ABP) changes in older hypertensives, focusing on PP and its associations with mortality. An observational study was conducted on 119 consecutive older treated hypertensives evaluated at baseline (T0) and after 10 years (T1). Treatment adherence was carefully assessed. The authors considered clinical parameters at T1 only in survivors (n = 87). Patients with controlled ABP both at T0 and T1 were considered as having sustained BP control. Change in 24‐hour PP between T0 and T1 (Δ24‐hour PP) was considered for the analyses. Mean age at T0: 69.4 ± 3.7 years. Females: 57.5%. Significant decrease in 24‐hour, daytime, and nighttime diastolic BP (all P < .05) coupled with an increase in 24‐hour, daytime, and nighttime PP (all P < .05) were observed at T1. Sustained daytime BP control was associated with lower 24‐hour PP increase than nonsustained daytime BP control (+2.23 ± 9.36 vs +7.79 ± 8.64 mm Hg; P = .037). The association between sustained daytime BP control and Δ24‐hour PP remained significant even after adjusting for age, sex, and 24‐hour PP at T0 (β=0.39; P = .035). Both 24‐hour systolic BP and 24‐hour PP at T0 predicted mortality (adjusted HR 1.07, P = .001; adjusted HR 1.25, P < .001, respectively). After ROC comparison (P = .001), 24‐hour PP better predicted mortality than 24‐hour systolic BP. The data confirm how ABP control affects vascular aging leading to PP increase. Both ambulatory PP and systolic BP rather than diastolic BP predict mortality in older treated hypertensives.     

Efficacy and safety of Nd. YAG laser for the treatment of bleeding from radiation proctocolitis

BACKGROUND: Bleeding due to radiation proctocolitis is a frequent and severe complication of radiotherapy in cancers of the pelvis. AIM: The aim of this study was to evaluate the efficacy and safety of endoscopic treatment with Nd:YAG laser in this condition. PATIENTS AND METHODS: A series of 9 patients with radiation-induced damage in the rectum and sigma were treated with endoscopic Nd:YAG laser until significant bleeding stopped and endoscopic features of proctocolitis improved. They received a median of 3 laser treatments (range 1-10) over a maximum time period of 11 months. RESULTS: In 4 cases, bleeding ceased and, in 4, it was reduced to occasional spotting. In the remaining patient, laser therapy led to only a transient improvement, but did not modify the requirement of blood transfusion. In the 5 patients also suffering from urgency, incontinence and/or rectal mucoid discharge, the laser therapy course also relieved these symptoms. No significant treatment-related complications were observed. CONCLUSIONS: Endoscopic Nd: YAG laser is a useful and safe treatment for patients with bleeding due to radiation proctocolitis.