Clinical evidence shows vascular factors may co-occur and complicate the expression of Alzheimer’s disease (AD); yet, the pathologic mechanisms and involvement of different compartments of the vascular network are not well understood. Diseases such as arteriosclerosis diminish vascular compliance and will lead to arterial stiffness, a well-established risk factor for cardiovascular morbidity. Arterial stiffness can be assessed using pulse wave velocity (PWV); however, this is usually done from carotid-to-femoral artery ratios. To probe the brain vasculature, intracranial PWV measures would be ideal. In this study, high temporal resolution 4D flow MRI was used to assess transcranial PWV in 160 subjects including AD, mild cognitive impairment (MCI), healthy controls, and healthy subjects with apolipoprotein ɛ4 positivity (APOE4+) and parental history of AD dementia (FH+). High temporal resolution imaging was achieved by high temporal binning of retrospectively gated data using a local-low rank approach. Significantly higher transcranial PWV in AD dementia and MCI subjects was found when compared to old-age-matched controls (AD vs. old-age-matched controls: P <0.001, AD vs. MCI: P = 0.029, MCI vs. old-age-matched controls P = 0.013). Furthermore, vascular changes were found in clinically healthy middle-age adults with APOE4+ and FH+ indicating significantly higher transcranial PWV compared to controls ( P <0.001).

Importance Prion diseases represent the archetype of brain diseases caused by protein misfolding, the commonest subtype being sporadic Creutzfeldt-Jakob disease (sCJD), a rapidly progressive dementia. Diffusion weighted iimaging (DWI) has emerged as the most sensitive MRI sequence for the diagnosis of sCJD but few studies have assessed the evolution of these signal abnormalities as the disease progresses. Objective The purpose of this study is to assess the natural history of the MRI signal abnormalities on DWI in sCJD in order to improve our understanding of the pathophysiology and to investigate the potential of DWI as a biomarker of disease progression with histopathological correlation. Design Grey matter involvement on DWI was assessed in 37 sCJD patients in 26 cortical and 5 subcortical subdivisions per hemisphere using a semi-quantitative scoring system: 0 – 2 at baseline (BL) and follow-up (FU). A total brain score was calculated as a sum of the score in each individual region. In 7 patients serial mean diffusivity (MD) measurements were obtained. Atrophy, age, disease duration, codon 129 and MRC Rating Scale were documented. Setting National Referral Centre. Participants All participants had a probable or definite diagnosis of sCJD and had at least two MRI studies during the course of the illness. Exposure for Observational Studies Not applicable. Main Outcome Measure Correlation of regional and total brain score with disease duration. Results Significant increase in number of regions demonstrating signal abnormality was seen: 28.0±12.6 at FU versus 21.8±10.76 at BL, p=0.001. 59 of the 62 regions showed increase in signal intensity (SI) on FU, most significantly in the caudate and putamen, p<0.001. Increase in average total brain score from 30.2±7.3 BL to 40.5±20.6 FU, p=0.001 correlated with disease duration and left frontal SI correlated with degree of spongiosis. Decreased MD in the left caudate and putamen on FU was seen, p<0.001. 8 patients showed decreased SI in cortical regions: left inferior temporal and right lingual gyrus. Conclusion and Relevance MRIs in sCJD show increased extent and degree of SI on DWI that correlates with disease duration and degree of spongiosis. Although cortical SI may fluctuate, increased basal ganglia SI is a consistent finding and is due to restricted diffusion. DWI in the basal ganglia may provide a non-invasive biomarker in future therapeutic trials.

BACKGROUND AND PURPOSE:Carotid intraplaque hemorrhage is associated with stroke, plaque thickness, stenosis, ulceration, and adventitial inflammation. Conflicting data exist on whether calcification is a marker of plaque instability, and no data exist on adventitial calcification. Our goal was to determine whether adventitial calcification and soft plaque (a rim sign) help predict carotid intraplaque hemorrhage.

SM + DBT reduces false positives compared to FFDM, while maintaining the CDR and other desirable audit outcome data. SM + DBT is more accurate than FFDM alone, and is a desirable alternative to FFDM + DBT, given the added benefit of radiation reduction.

Cerebral hypoperfusion is thought to contribute to cognitive decline in Alzheimer’s disease, but the natural trajectory of cerebral perfusion in cognitively healthy adults has not been well-studied. This longitudinal study is consisted of 950 participants (40—89 years), who were cognitively unimpaired at their first visit. We investigated the age-related changes in cerebral perfusion, and their associations with APOE-genotype, biological sex, and cardiometabolic measurements. During the follow-up period (range 0.13—8.24 years), increasing age was significantly associated with decreasing cerebral perfusion, in total gray-matter (β=−1.43), hippocampus (−1.25), superior frontal gyrus (−1.70), middle frontal gyrus (−1.99), posterior cingulate (−2.46), and precuneus (−2.14), with all P-values < 0.01. Compared with male-ɛ4 carriers, female-ɛ4 carriers showed a faster decline in global and regional cerebral perfusion with increasing age, whereas the age-related decline in cerebral perfusion was similar between male- and female-ɛ4 non-carriers. Worse cardiometabolic profile (i.e., increased blood pressure, body mass index, total cholesterol, and blood glucose) was associated with lower cerebral perfusion at all the visits. When time-varying cardiometabolic measurements were adjusted in the model, the synergistic effect of sex and APOE-ɛ4 on age-related cerebral perfusion-trajectories became largely attenuated. Our findings demonstrate that APOE-genotype and sex interactively impact cerebral perfusion-trajectories in mid- to late-life. This effect may be partially explained by cardiometabolic alterations.