Stuart Neilson

Rising amyotrophic lateral sclerosis mortality in France 1968–1990: Increased life expectancy and inter-disease competition as an explanation

Gompertzian analysis is a statistical technique which has been successfully applied to the analysis of amyotrophic lateral sclerosis (ALS) mortality in England and Wales, Japan and the United States. This paper analyses the consistent trend of rising ALS mortality in France over the years 1968–1990, a period during which crude mortality rose from 400 deaths in 1968 to 950 deaths in 1990. The findings indicate that age-specific mortality rates have risen at ages older than 54 years for men and 53 years for women and decreased slightly at younger ages. The evolving ALS mortality pattern is attributable to changing inter-disease competition resulting from the increased life expectancy of the French population, rather than to changing environmental aetiopathogenic factors or to substantial artefact effects.

Longitudinal analysis of amyotrophic lateral sclerosis mortality in Norway, 1966–1989: evidence for a susceptible subpopulation

Mortality from amyotrophic lateral sclerosis (ALS) in Norway has increased substantially over the last two or three decades, as it has in other Western nations. The reasons for this general increase are not clear, but the rise has been attributed to increasing exposure to a broad range of environmental agents. Our previous research has indicated that another explanation for the substantial rise in ALS mortality is more likely to be valid. In particular, the mortality rate curve for ALS is consistent with deaths being confined to an inherently susceptible subpopulation. The size of susceptible subpopulations and mortality rates within them have been shown to be consistent in England and Wales, Japan and the United States. The same methods have been used to analyse Norwegian mortality data. The analysis demonstrates that the rise in ALS mortality is real and that the cause of the increase is almost entirely attributable to the increasing life expectancy of the Norwegian population. Increased life expectancy, a consequence of decreasing general mortality, allows ALS susceptible individuals to survive to the ages at which ALS is expressed. As in other national populations, it is expected that mortality from the disease will continue to increase with continuing increases in life expectancy.

Rising mortality from motor neurone disease: an explanation.

There is considerable debate about the increasing mortality from motor neurone disease (MND). However, examination of the relationship between increased life expectancy (through decreased general mortality) and increased mortality in both England and Wales and the United States indicates a close association between the two variables. Using a statistical model, defined sub‐populations susceptible to MND can be identified in both countries. The size of such a sub‐population has been estimated from the 1989 mortality data to be approximately 160 000 people in England and Wales. The proportion of this sub‐population dying from MND has increased over the last 30 years, rather than, as previously, dying at an earlier age from other conditions. On this basis, deaths from MND are expected to increase by a further 20% in this sub‐population between 1991‐2021 because of continuing changes in life expectancy. MND is a condition made increasingly visible in mortality statistics through decreased general mortality, rather than one in which the underlying population at risk has substantially changed. Aetiological extrapolations from the data indicate that susceptibility to the disease is acquired early in life, and that it is unlikely, given the relative stability of the underlying sub‐population, that either changed environmental circumstances or artifactual factors can account in themselves for the rise in mortality.

Static and dynamic models of interdisease competition: Past and projected mortality from amyotrophic lateral sclerosis and multiple sclerosis

Longitudinal Gompertzian analysis is an effective method for determining both the pure probability of death for a given condition and the size of inherently susceptible subpopulations [1]. Gompertzian analysis has been used in this study to provide the parameters necessary to construct a stationary population lifetable (static model) of mortality for amyotrophic lateral sclerosis (ALS) and for multiple sclerosis (MS). The static model demonstrates the relative effect of changing general mortality upon the mortality from each specific disease in a situation where interdisease competition is continuously changing. In order to represent mortality in a real population more closely (where age structure is not the result of mortality rates alone) a dynamic model was constructed for both conditions using the age distributions of the population of England and Wales. The quality of the model was verified by comparison of estimated mortality with historical data from the last three decades. The dynamic model has then been used to estimate mortality from each condition over the next three decades on the basis of population projections made by the Central Statistical Office [2], assuming no major change in the factors which lead to either condition. This analysis demonstrates both the theoretical applicability and practical capabilities of Gompertz-derived mortality models for analysing changing mortality patterns.

Mortality from motor neuron disease in Japan, 1950–1990: association with radioactive fallout from atmospheric weapons testing

Motor neuron disease (MND) is a progressive and invariably fatal disease affecting the nuclei of the pyramidal tract and anterior horn cells. Despite intensive research into environmental agents associated with the onset or course of the disease, there is no single factor that can be confidently linked over time with regional, national or international variations in mortality rates. However, unusual variations in MND mortality rate in Japan from 1950-1990 were found to correlate highly significantly with variations in radioactive fallout released by atmospheric weapons testing in the Pacific. This association could be explained by the ingestion of alpha-emitting radionuclides acting upon a pre-existing susceptible subpopulation, a hypothesis which is consistent with recent research on the epidemiology and pathology of MND. However, it is likely that radiation is only one of many factors that act singly or in combination to accelerate the condition in subpopulations susceptible to MND.

A new analysis of mortality from motor neurone disease in Japan, 1950–1990: Rise and fall in the postwar years

Recent studies have demonstrated a worldwide rise in mortality from motor neurone disease (MND). However, in Japan mortality appears to have fallen significantly since the late 1960s, especially amongst women. Studies of the cause of both the worldwide rise, and the unique decline in MND mortality in Japan, have largely failed to substantiate the role of any single factor, or group of factors in these phenomena. Modelling the relationship between age and mortality using gompertzian analysis has already shown that the rise in MND mortality in England and Wales, and the United States, is mainly the result of increased longevity and decreasing competition from other causes of death amongst a susceptible subpopulation. Employing the same techniques on Japanese mortality data from 1950 to 1990 demonstrates that an unusual and accelerated increase of mortality occurred in the 1950s and 1960s, probably caused by an earlier unknown but extremely potent environmental agent or agents. This premature depletion of the susceptible subpopulation resulted subsequently in a lower than expected mortality rate. Mortality is now rising slowly to expected levels as the size of the susceptible subpopulation recovers to reach the ages at which MND is normally expressed. Further substantial rises in mortality are anticipated in future decades.

Reinterpreting mortality statistics: some uses of gompertzian analysis in epidemiological research

Gompertzian analyses of mortality data have recently been undertaken for a number of individual conditions (Riggs JE. Mech Ageing Dev 1990; 55: 207-220 [1]; Neilson S et al. Mech Ageing Dev 1992; 64: 201-216 [2]; Neilson S et al. Acta Neurol Scand 1993; 87: 184-191 [3]). Such analyses are in principle of particular epidemiological value in circumstances where demographic change is occurring and where the balance between mortality from different conditions is subject to change. However, the extent to which a Gompertzian relationship between age and mortality holds for particular conditions has been subject to debate. In this analysis it is demonstrated that even some conditions which do not superficially hold to a Gompertz relationship do in fact do so, if such conditions are considered to be restricted to small, inherently susceptible subpopulations. By analysing mortality from a range of neurological conditions within the context of general mortality in England and Wales, conditions with different aetiologies such as Huntingtons chorea, amyotrophic lateral sclerosis and multiple sclerosis can be shown to have a Gompertzian mortality rate distribution. Such analyses are of substantial value in indicating how demographic change affects the balance of mortality between conditions, as well as directing interest to revised aetiological possibilities.

Cross-sectional Gompertzian analysis: the development of a Gompertz mortality ratio (GMR) and its applicability

Many conventional epidemiological analyses of the distribution and aetiology of disease employ standardised mortality ratios (SMRs) as a basis upon which to evaluate comparative studies of disease in populations. However SMRs, whilst constructed to control for age and sex, are not capable of incorporating other variables such as life expectancy which has been demonstrated to be of crucial importance in understanding the changing relationships between mortality from different causes. The development of a Gompertz mortality ratio (GMR) and its application to recent mortality from amyotrophic lateral sclerosis (ALS) in the Counties of England and Wales illustrates the value of substituting GMRs for SMRs in the analysis of competitive relationships between conditions, especially those associated with enhanced life expectancy.

Ecological correlates of motor neuron disease mortality: a hypothesis concerning an epidemiological association with radon gas and gamma exposure.

This study investigates variations in motor neuron disease (MND) mortality rates between the counties of England and Wales from 1981 to 1989, and their relationship with gamma-ray dose rates, indoor radon gas concentrations and enhanced general life expectancy. A stong correlation was confirmed between age-adjusted rates of MND mortality and life expectancy. Weaker, but statistically significant, associations were observed between indoor radon gas concentrations, terrestrial gamma radiation and marginal variations in MND mortality. Life expectancy and radon gas concentrations were positively associated with MND mortality rates whilst gamma radiation was negatively associated. The negative correlation of gamma radiation with MND mortality may be understood with reference to its negative effects on overall population life expectancy. Radon gas concentrations seemingly account for a small elevation in MND mortality, amounting to at most 4% of total deaths. Further research is required to investigate this association.

Decline and Rise of Mortality from Motor Neuron Disease in Spain, 1960-1989: Demographic, Environmental and Competitive Influences

Mortality rates from motor neuron disease (MND) in Spain were analysed for the years 1960-1989, a period in which 3,530 deaths were recorded from the disease and during which the crude annual mortality rate ranged between 0.35 and 0.95 deaths per 100,000 persons. Whilst the crude mortality rate fell by 54% during the decade 1960-1969, there was a net increase of 26% over the entire period. The influence of three sets of variables-the increasing mean age of the population, changing environmental factors, and changing competition between diseases-upon mortality rates were investigated through Gompertzian analysis of crude and age-adjusted mortality rates. The increased mean age of the population contributed significantly to the overall rise in mortality from MND over the whole period, a feature that has previously been demonstrated to occur in the majority of industrialised countries. The unusual pattern of a decline and subsequent rise in mortality appears to be due to the influence of changing environmental factors on a sub-population susceptible to the disease.