BACKGROUND AND PURPOSE:The visual rating scales for perivascular spaces vary considerably. We sought to develop a new scale for visual assessment of perivascular spaces and to further describe their distribution and association with white matter hyperintensities in old age.

ObjectiveTo explore the differential associations of neurodegeneration and microvascular lesion load with cognitive decline and dementia in older people and the modifying effect of the APOE genotype on these associations.MethodsA sample of 436 participants (age ≥ 60 years) was derived from the population-based Swedish National study on Aging and Care in Kungsholmen, Stockholm, and clinically examined at baseline (2001–2003) and 3 occasions during the 9-year follow-up. At baseline, we assessed microvascular lesion load using a summary score for MRI markers of lacunes, white matter hyperintensities (WMHs), and perivascular spaces and neurodegeneration load for markers of enlarged ventricles, smaller hippocampus, and smaller gray matter. We assessed cognitive function using the Mini-Mental State Examination (MMSE) test and diagnosed dementia following the Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria. We analyzed data using linear mixed-effects, mediation, and random-effects Cox models.ResultsDuring the follow-up, 46 participants were diagnosed with dementia. Per 1-point increase in microvascular lesion and neurodegeneration score (range 0–3) was associated with multiple adjusted β-coefficients of −0.35 (95% confidence interval, −0.51 to −0.20) and −0.44 (−0.56 to −0.32), respectively, for the MMSE score and multiple adjusted hazard ratios of 1.68 (1.12–2.51) and 2.35 (1.58–3.52), respectively, for dementia; carrying APOE ε4 reinforced the associations with MMSE decline. WMH volume changes during the follow-up mediated 66.9% and 12.7% of the total association of MMSE decline with the baseline microvascular score and neurodegeneration score, respectively.ConclusionsBoth cerebral microvascular lesion and neurodegeneration loads are strongly associated with cognitive decline and dementia. The cognitive decline due to microvascular lesions is exacerbated by APOE ε4 and is largely attributed to progression and development of microvascular lesions.

The association of global WMHs with lower GM volume and higher ventricular volume is independent of age, VRFs and APOE-ε4 allele, suggesting that the process of cerebral microvascular disease and neurodegeneration are associated independently of the normal aging process, vascular mechanisms or genetic susceptibility.

Protein levels of APRIL in CSF were increased in NPSLE as compared to OND. Moreover, there was a positive correlation between CSF APRIL levels and fatigue. Our results suggest that APRIL and possibly also BAFF may be involved in the pathogenesis of NPSLE and in SLE-related fatigue.

Background Evidence suggests that enlarged perivascular spaces (PVSs) may represent a marker for cerebral small‐vessel disease. We investigated whether vascular risk factors are correlated with visible PVS in older adults. Methods and Results This population‐based study included 530 participants (age ≥60 years) who were free from dementia and functional dependence, derived from the Swedish National study on Aging and Care in Kungsholmen (2001–2003). We collected data on demographics, vascular risk factors, and health conditions through interviews, clinical examinations, laboratory tests, and patient registers. Cerebral PVSs and white matter hyperintensities on magnetic resonance images were visually assessed with semiquantitative visual rating scales. Data were analyzed using the general linear regression models. After controlling for demographics and cardiovascular disease, very high blood pressure (≥160/100 mm Hg) was significantly associated with global PVS score (β‐coefficient, 1.30; 95% CI, 0.06–2.53) and orthostatic hypotension was associated with PVS score in the basal ganglia (β‐coefficient 0.37; 0.03–0.70), but the associations became non‐significant when adjusting for white matter hyperintensity load. Orthostatic hypotension was significantly associated with global and lobar PVS scores in carriers but not in noncarriers of the APOE ε4 allele. Global or regional PVS score was not significantly associated with other traditional vascular risk factors such as smoking, diabetes mellitus, physical inactivity, and overweight or obesity. Conclusions This study provides limited evidence supporting a correlation of magnetic resonance imaging–visible PVS with traditional vascular risk factors in older adults. The association of orthostatic hypotension with lobar PVS among APOE ε4 carriers suggests that lobar PVS may be a marker for amyloid‐associated small‐vessel disease.

Background The purpose of this study was to examine the associations between combined and individual cerebral small vessel disease (cSVD) markers on future walking speed over 9 years; and to explore whether these associations varied by the presence of cardiovascular risk factors (CRFs). Methods This population-based cohort study included 331 adults, aged ≥60 years, without limitation in walking speed (≥0.8 m/s). At baseline, cSVD markers, including white matter hyperintensities (WMH), lacunes, and perivascular spaces (PVS), were assessed on magnetic resonance imaging. The modifiable CRFs (physical inactivity, heavy alcohol consumption, smoking, hypertension, high total cholesterol, diabetes, and overweight/obese) were combined into a score. The association between baseline cSVD markers and the decline in walking speed was examined using linear mixed-effects models, whereas Cox proportional hazards models were used to estimate the association with walking speed limitation (defined as < 0.8 m/s) over the follow-up. Results Over the follow-up period, 76 (23.0%) persons developed walking speed limitation. Participants in the highest tertile of the combined cSVD marker score had a hazard ratio (HR) of 3.78 (95% confidence interval [CI] 1.70-8.45) for walking speed limitation compared with people in the lowest score tertile, even after adjusting for socio-demographics, CRFs, cognitive function, and chronic conditions. When investigating the cSVD markers individually, having the highest burden of WMH was associated with a significantly faster decline in walking speed (β coefficient − 0.020; 95% CI -0.035-0.004) and a greater HR of walking speed limitation (HR 2.78; 95% CI 1.31-5.89) compared with having the lowest WMH burden. Similar results were obtained for the highest tertile of PVS (HR 2.13; 95% CI 1.04-4.36). Lacunes were associated with walking speed limitation, but only in men. Having ≥4 CRFs and high WMH volume simultaneously, showed a greater risk of walking speed limitation compared with having ≥4 CRFs and low WMH burden. CRFs did not modify the associations between lacunes or PVS and walking speed. Conclusions Combined cSVD markers strongly predict walking speed limitation in healthy older adults, independent of cognitive function, with WMH and PVS being the strongest contributors. Improving cardiovascular health may help to mitigate the negative effects of WMH on future walking speed.

Air enema is a useful diagnostic method in acute colitis, it is easily performed and tolerated well with no observed complications. It is also easy to interpret, as shown by a high level of agreement (kappa = 0.67) among the 3 independent observers with very different levels of experience.

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