Daniel R. Altmann

The global burden of disease attributable to low consumption of fruit and vegetables: implications for the global strategy on diet

OBJECTIVE We estimated the global burden of disease attributable to low consumption of fruit and vegetables, an increasingly recognized risk factor for cardiovascular disease and cancer, and compared its impact with that of other major risk factors for disease. METHODS The burden of disease attributable to suboptimal intake of fruit and vegetables was estimated using information on fruit and vegetable consumption in the population, and on its association with six health outcomes (ischaemic heart disease, stroke, stomach, oesophageal, colorectal and lung cancer). Data from both sources were stratified by sex, age and by 14 geographical regions. FINDINGS The total worldwide mortality currently attributable to inadequate consumption of fruit and vegetables is estimated to be up to 2.635 million deaths per year. Increasing individual fruit and vegetable consumption to up to 600 g per day (the baseline of choice) could reduce the total worldwide burden of disease by 1.8%, and reduce the burden of ischaemic heart disease and ischaemic stroke by 31% and 19% respectively. For stomach, oesophageal, lung and colorectal cancer, the potential reductions were 19%, 20%, 12% and 2%, respectively. CONCLUSION This study shows the potentially large impact that increasing fruit and vegetable intake could have in reducing many noncommunicable diseases. It highlights the need for much greater emphasis on dietary risk factors in public health policy in order to tackle the rise in noncommunicable diseases worldwide, and suggests that the proposed intersectoral WHO/FAO fruit and vegetable promotion initiative is a crucial component in any global diet strategy.

Magnetization transfer ratio and myelin in postmortem multiple sclerosis brain

Several quantitative magnetic resonance (MR) measures are used to investigate multiple sclerosis (MS) in vivo. Precise quantitative investigation of the histopathological correlates of such measures has, to date, been limited. This study investigates the relationship of quantitative measures of myelin content, axonal density, and gliosis with quantitative MR measures in postmortem (PM) MS tissue. MR imaging (MRI) was performed on a 1.5T scanner and T1‐relaxation time (T1‐RT) and magnetization transfer ratio (MTR) maps were acquired in fresh PM brain of 20 MS subjects. Myelin content, axonal counts, and the extent of gliosis all were quantified using morphometric and digital imaging techniques. MRI and pathological data were in most cases coregistered using stereotactic navigation. Using multiple regression analysis, we detected significant correlations between myelin content (Trmyelin) and MTR (r = −0.84, p < 0.001) and myelin content and axonal count (−0.80, p < 0.001); MTR correlated with T1‐RT (r = −0.79, p < 0.001). No association was detected between the extent of gliosis and either MR measure. MTR was significantly higher in remyelinated than demyelinated lesions (means: 30.0 [standard deviation, 2.9] vs 23.8 [standard deviation, 4.3], p = 0.008). In conclusion, MTR is affected by myelin content in MS white matter. Ann Neurol 2004

Retinal nerve fiber layer axonal loss and visual dysfunction in optic neuritis.

Axonal loss is thought to be a likely cause of persistent disability after a multiple sclerosis relapse; therefore, noninvasive in vivo markers specific for axonal loss are needed. We used optic neuritis as a model of multiple sclerosis relapse to quantify axonal loss of the retinal nerve fiber layer (RNFL) and secondary retinal ganglion cell loss in the macula with optical coherence tomography. We studied 25 patients who had a previous single episode of optic neuritis with a recruitment bias to those with incomplete recovery and 15 control subjects. Optical coherence tomography measurement of RNFL thickness and macular volume, quantitative visual testing, and electrophysiological examination were performed. There were highly significant reductions (p < 0.001) of RNFL thickness and macular volume in affected patient eyes compared with control eyes and clinically unaffected fellow eyes. There were significant relationships among RNFL thickness and visual acuity, visual field, color vision, and visual‐evoked potential amplitude. This study has demonstrated functionally relevant changes indicative of axonal loss and retinal ganglion cell loss in the RNFL and macula, respectively, after optic neuritis. This noninvasive RNFL imaging technique could be used in trials of experimental treatments that aim to protect optic nerves from axonal loss. Ann Neurol 2005

Gray matter atrophy is related to long‐term disability in multiple sclerosis

To determine the relation of gray matter (GM) and white matter (WM) brain volumes, and WM lesion load, with clinical outcomes 20 years after first presentation with clinically isolated syndrome suggestive of multiple sclerosis (MS).

MRI criteria for multiple sclerosis in patients presenting with clinically isolated syndromes: a multicentre retrospective study.

BACKGROUND The 2001 and 2005 McDonald criteria allow MRI evidence for dissemination in space (DIS) and dissemination in time (DIT) to be used to diagnose multiple sclerosis in patients who present with clinically isolated syndromes (CIS). In 2006, new criteria were proposed in which DIS requires at least one T2 lesion in at least two of four locations (juxtacortical, periventricular, infratentorial, and spinal-cord) and DIT requires a new T2 lesion on a follow-up scan. We applied all three criteria in a large cohort of CIS patients to assess their performance by use of conversion to clinically definite multiple sclerosis (CDMS) as the outcome. METHODS Patients who had two MRI scans within 12 months of CIS onset were identified in four centres in the Magnims European research network. The specificity and sensitivity of MRI criteria for CDMS after 3 years was assessed in 208 patients. A Cox proportional hazards model was applied in a larger cohort of 282 patients that included all patients irrespective of length of follow-up. FINDINGS The specificity of all criteria for CDMS was high (2001 McDonald, 91%; 2005 McDonald, 88%; new, 87%). Sensitivity of the new (72%) and 2005 McDonald (60%) criteria were higher than the 2001 McDonald criteria (47%). The Cox proportional hazards model showed a higher conversion risk for all three criteria in those with both DIS and DIT than those with either DIS or DIT alone. When all three criteria were included in the model, only the new criteria had an independent significant effect on conversion risk. INTERPRETATION The new criteria are simpler than the McDonald criteria without compromising specificity and accuracy. The presence of both DIS and DIT from two MRI scans has a higher specificity and risk for CDMS than either DIS or DIT alone.

Alcohol consumption and mortality: modelling risks for men and women at different ages

Abstract Objective: To estimate the relation between alcohol consumption and risk of death,the level of alcohol consumption at which risk is least, and how these vary with age and sex Design: Analysis using published systematic reviews and population data Setting: England and Wales in 1997 Main outcome measures: Death from any of the following causes: cancer of lip, oralcavity, pharynx, oesophagus, colon, rectum, liver, larynx, and breast, essential hypertension, coronary heart disease, stroke, cirrhosis, non-cirrhotic chronic liver disease, chronic pancreatitis,and injuries Results: A direct dose-response relation exists between alcohol consumption and risk of death in women aged 16-54 and in men aged 16-34. At older ages the relation is U shaped. Thelevel at which the risk is lowest increases with age, reaching 3 units a week in women aged over 65 and 8 units a week in men aged over 65. The level at which the risk is increased by 5% above this minimum is 8 units a week in women aged 16-24 and 5 units a week in men aged 16-24, increasing to 20 and 34 units a week in women and men aged over 65,respectively Conclusions: Substantially increased risks of all cause mortality can occur even in people drinking lower than recommended limits, and especially among younger people

Lamotrigine for neuroprotection in secondary progressive multiple sclerosis: a randomised, double-blind, placebo-controlled, parallel-group trial

BACKGROUND Partial blockade of voltage-gated sodium channels is neuroprotective in experimental models of inflammatory demyelinating disease. In this phase 2 trial, we aimed to assess whether the sodium-channel blocker lamotrigine is also neuroprotective in patients with secondary progressive multiple sclerosis. METHODS Patients with secondary progressive multiple sclerosis who attended the National Hospital for Neurology and Neurosurgery or the Royal Free Hospital, London, UK, were eligible for inclusion in this double-blind, parallel-group trial. Patients were randomly assigned via a website by minimisation to receive lamotrigine (target dose 400 mg/day) or placebo for 2 years. Treating physicians, evaluating physicians, and patients were masked to treatment allocation. The primary outcome was the rate of change of partial (central) cerebral volume over 24 months. All patients who were randomly assigned were included in the primary analysis. This trial is registered with ClinicalTrials.gov, NCT00257855. FINDINGS 120 patients were randomly assigned to treatment (87 women and 33 men): 61 to lamotrigine and 59 to placebo. 108 patients were analysed for the primary endpoint: 52 in the lamotrigine group and 56 in the placebo group. The mean change in partial (central) cerebral volume per year was -3.18 mL (SD -1.25) in the lamotrigine group and -2.48 mL (-0.97) in the placebo group (difference -0.71 mL, 95% CI -2.56 to 1.15; p=0.40). However, in an exploratory modelling analysis, lamotrigine treatment seemed to be associated with greater partial (central) cerebral volume loss than was placebo in the first year (p=0.04), and volume increased partially after treatment stopped (p=0.04). Lamotrigine treatment reduced the deterioration of the timed 25-foot walk (p=0.02) but did not affect other secondary clinical outcome measures. Rash and dose-related deterioration of gait and balance were experienced more by patients in the lamotrigine group than the placebo group. INTERPRETATION The effect of lamotrigine on cerebral volume of patients with secondary progressive multiple sclerosis did not differ from that of placebo over 24 months, but lamotrigine seemed to cause early volume loss that reversed partially on discontinuation of treatment. Future trials of neuroprotection in multiple sclerosis should include investigation of complex early volume changes in different compartments of the CNS, effects unrelated to neurodegeneration, and targeting of earlier and more inflammatory disease. FUNDING Multiple Sclerosis Society of Great Britain and Northern Ireland.

The experience of dying with dementia: a retrospective study.

Objective. To describe the last year of life of people with dementia, their symptoms, care needs, use of and satisfaction with health services and the bereavement state of the respondent.

Quantitative Magnetization Transfer Imaging in Postmortem Multiple Sclerosis Brain

To investigate the relationship of myelin content, axonal density, and gliosis with the fraction of macromolecular protons (fB) and T2 relaxation of the macromolecular pool (T2B) acquired using quantitative magnetization transfer (qMT) MRI in postmortem brains of subjects with multiple sclerosis (MS).

Gray and white matter volume changes in early RRMS : A 2-year longitudinal study

Background: Brain atrophy, in excess of that seen with normal aging, has been observed early in the clinical course of relapsing-remitting multiple sclerosis (RRMS). Previous work has suggested that at this stage of the disease, gray matter (GM) atrophy progresses more rapidly than the white matter (WM) atrophy. Objectives: To characterize the evolution of GM and WM volumes over 2 years, and their associations with lesion loads in a cohort of patients with clinically early RRMS. Methods: Twenty-one patients with RRMS (mean age 37.5 years, mean disease duration from symptom onset 2.1 years) and 10 healthy control subjects (mean age 37.1 years) were studied. Tissue volumes, as fractions of total intracranial volumes, were estimated at baseline and 1- and 2-year follow-up. Brain parenchymal fractions (BPF), GM fractions (GMF), and WM fractions (WMF) were estimated. In subjects with MS, brain lesion loads were determined on conventional T2-weighted along with pre- and post-gadolinium (Gd) enhanced T1-weighted images at each timepoint. Results: A decrease in GMF was observed in subjects with MS vs normal controls over the 2 years of the study (mean −2.1% vs −1.0%, p = 0.044), while no change was seen in WMF over the same period (mean −0.09% vs +0.09%, p = 0.812). However, when the MS cohort was divided in half, dependent upon change in Gd-enhancing lesion load over 2 years (n = 20), a decrease in WMF was seen in the group (n = 10) with the largest decline in Gd volume, whereas WMF increased in the other half (n = 10) concurrent with a net increase in volume of Gd-enhancing lesions (difference between groups: p = 0.034). Conclusions: Increasing gray matter but not white matter (WM) atrophy was observed early in the clinical course of relapsing-remitting multiple sclerosis. Fluctuations in inflammatory WM lesions appear to be related to volume changes in WM over this time period.