Presumed small vessel disease, imaging and cognition markers in the Alzheimer's Disease Neuroimaging Initiative.

MRI-derived features of presumed cerebral small vessel disease are frequently found in Alzheimer's disease. Influences of such markers on disease-progression measures are poorly understood. We measured markers of presumed small vessel disease (white matter hyperintensity volumes; cerebral microbleeds) on baseline images of newly enrolled individuals in the Alzheimer's Disease Neuroimaging Initiative cohort (GO and 2) and used linear mixed models to relate these to subsequent atrophy and neuropsychological score change. We also assessed heterogeneity in white matter hyperintensity positioning within biomarker abnormality sequences, driven by the data, using the Subtype and Stage Inference algorithm. This study recruited both sexes and included: controls: [n = 159, mean(SD) age = 74(6) years]; early and late mild cognitive impairment [ns = 265 and 139, respectively, mean(SD) ages =71(7) and 72(8) years, respectively]; Alzheimer's disease [n = 103, mean(SD) age = 75(8)] and significant memory concern [n = 72, mean(SD) age = 72(6) years]. Baseline demographic and vascular risk-factor data, and longitudinal cognitive scores (Mini-Mental State Examination; logical memory; and Trails A and B) were collected. Whole-brain and hippocampal volume change metrics were calculated. White matter hyperintensity volumes were associated with greater whole-brain and hippocampal volume changes independently of cerebral microbleeds (a doubling of baseline white matter hyperintensity was associated with an increase in atrophy rate of 0.3 ml/year for brain and 0.013 ml/year for hippocampus). Cerebral microbleeds were found in 15% of individuals and the presence of a microbleed, as opposed to none, was associated with increases in atrophy rate of 1.4 ml/year for whole brain and 0.021 ml/year for hippocampus. White matter hyperintensities were predictive of greater decline in all neuropsychological scores, while cerebral microbleeds were predictive of decline in logical memory (immediate recall) and Mini-Mental State Examination scores. We identified distinct groups with specific sequences of biomarker abnormality using continuous baseline measures and brain volume change. Four clusters were found; Group 1 showed early Alzheimer's pathology; Group 2 showed early neurodegeneration; Group 3 had early mixed Alzheimer's and cerebrovascular pathology; Group 4 had early neuropsychological score abnormalities. White matter hyperintensity volumes becoming abnormal was a late event for Groups 1 and 4 and an early event for 2 and 3. In summary, white matter hyperintensities and microbleeds were independently associated with progressive neurodegeneration (brain atrophy rates) and cognitive decline (change in neuropsychological scores). Mechanisms involving white matter hyperintensities and progression and microbleeds and progression may be partially separate. Distinct sequences of biomarker progression were found. White matter hyperintensity development was an early event in two sequences

A patient with Rothmund-Thomson Syndrome and Tongue Cancer - Experience of radiation toxicity

We describe a male patient with Rothmund-Thomson syndrome (RTS) given postoperative radiotherapy for squamous carcinoma of the tongue. This was well tolerated. This is only the second reported case of oral cancer and radiotherapy in RTS.</p

Effect of gap length and position on results of treatment of cancer of the larynx in Scotland by radiotherapy:a linear quadratic analysis

Purpose: This paper reports on the analysis of the effect of the length and position of unplanned gaps in radiotherapy treatment schedules.Materials and methods: Data from an audit of the treatment of carcinoma of the larynx are used. They represent all newly diagnosed cases of glottic node-negative carcinoma of the larynx between 1986 and 1990, inclusive, in Scotland that were referred to one of the five Scottish Oncology Centres for primary radical radiotherapy treatment. The end-points are local control of cancer of the larynx in 5 years and the length of the disease-free period. The local control rates at greater than or equal to 5 years, P-c, were analyzed by log Linear models and Cox proportional hazard models were used to model the disease-free period.Results: Unplanned gaps in treatment are associated with poorer local control rates and an increased hazard of a local recurrence through their effect on extending the treatment time. A gap of 1 day is potentially damaging but the greatest effect is at treatment extensions of 3 or more days, where the hazard of a failure of local control is increased by a factor of 1.75 (95% confidence interval 1.20-2.55) compared to no gap. The time factor for the actual time was imprecisely estimated at 2.7 Gy/day with a standard error of 13.2 Gy/day. Among those cases who had exactly one gap resulting in a treatment extension of 1 day, there is no evidence that gap position influences local control (P = 0.17). The treatment extension as a result of the gap is more important than the position of the gap in the schedule.Conclusions: Gaps in the treatment schedule have a detrimental effect on the disease-free period. A gap has a slightly greater effect than an increase in the prescribed treatment time. Any gap in treatment is potentially damaging. The position of the gap in the schedule was shown to be not important. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.</p

Effect of Exercise Training on Estimated GFR, Vascular Health, and Cardiorespiratory Fitness in Patients With CKD: A Pilot Randomized Controlled Trial

Background: Exercise capacity, which is predictive of all-cause mortality and cardiovascular disease risk, is reduced significantly in patients with non-dialysis-dependent chronic kidney disease. This pilot study examined the effect of moderate-intensity exercise training on kidney function and indexes of cardiovascular risk in patients with progressive chronic kidney disease stages 3 to4. Study Design: Single-blind, randomized, controlled, parallel trial. Setting & Participants: 20 patients (aged 18-80 years; 17 men) randomly assigned to rehabilitation (n=10) or usual care (n=10). Participants were included if they were 18 years or older and had evidence of rate of decline in creatinine-based estimated glomerular filtration rate (eGFRcr)≥2.9mL/min/1.73m2 per year for 12 months preintervention. Patients were excluded if they had unstable medical conditions or had recently started regular exercise. Intervention: The rehabilitation group received resistance and aerobic training (3 days per week) for a 12-month period. The usual care group received standard care. Outcomes: Kidney function assessed by comparing mean rate of change in eGFRcr (mL/min/1.73m2 per year) from a 12-month preintervention period against the 12-month intervention period. Pulse wave velocity (PWV), peak oxygen uptake (Vo 2peak), and waist circumference assessed at 0, 6, and 12 months. Measurements: eGFR assessed using creatinine, cystatin C (eGFRcys), and a combination of both values (eGFRcr-cys). Results: 18 participants (rehabilitation, 8; usual care, 10) completed the study. A significant mean difference in rate of change in eGFRcr (+7.8±3.0 [95% CI, 1.1-13.5] mL/min/1.73m2 per year; P =0.02) was observed between the rehabilitation and usual care groups, with the rehabilitation group demonstrating a slower decline. No significant between-group mean differences existed in absolute eGFRcr, eGFRcr-cys, or eGFRcys at 12 months of study intervention. Significant between-group mean differences existed in PWV (-2.30 [95% CI,-3.02 to-1.59] m/s), waist circumference (-7.1±12.8 [95% CI,-12.4 to-3.2] cm), and Vo 2peak (5.7 [95% CI, 1.34-10.10] mL/kg/min). Change in eGFRcr was correlated inversely with PWV (r =-0.5; P =0.04) at 12 months. Limitations: Small sample size, inconsistency between primary and secondary measures of kidney function. Conclusions: The effect of a 1-year exercise intervention on progression of kidney disease is inconclusive. A larger study with longer follow-up may be necessary