The findings confirm previous reports of a high prevalence of disease co-morbidity in the older population [22
]. In all groups, fewer than 50% reported no medical conditions with a large number of individuals reporting between one and three conditions. Specific disease prevalence, however, differed between the demented and non-demented groups. Generally there was no association between single-risk factors and incident dementia in MCI. Disease status was predictive of 2-year incident dementia in the MCI group only when co-morbidity was associated with anaemia.
While the pattern of disease prevalence was similar in the NCI, MCI and OCIND groups, individuals with dementia were more likely to have medical co-morbidity related to stroke and PD. This is not unexpected as each of these conditions is known to increase in incidence with age (i.e. the dementia group was older than all other groups), and each is a risk factor for incident dementia [23
]. It is possible, given that medical conditions were acquired using self-report, that prevalence estimates may reflect bias in self-reporting or selective survival across groups. However, self-report and objective disease status have been found to be in high agreement for most of the diseases included here [25
With regard to co-morbidity, the results confirm that medical co-morbidity commonly occurs in both cognitively preserved and cognitively impaired older individuals [27
]. As the specific pattern of disease prevalence was similar in all non-demented groups, the results suggest that the selected conditions and their pattern of co-morbidity alone do not strongly influence the impairment captured in the MCI and OCIND states. This is in contrast to findings from clinical and observational studies that suggest that disease co-morbidity associated with, for example, stroke, hypertension, heart attack, diabetes and their co-occurrence, increase risk for major adverse outcomes associated with health and cognition in older adults. The individuals studied here, however, are representative of the general population and are not a selected group of patients. Published research on progression from secondary and tertiary level health-care systems is likely to vary due to differences in participant's profile and reason for referral.
Most published MCI case definitions do not explicitly state medical exclusion criteria although these are routinely employed in the diagnosis of MCI and tend to relate to psychiatric and vascular co-morbidity [3
]. In clinical trials, strict eligibility criteria are typically necessary when the isolated effect of an agent is to be tested and for safety reasons. However, the results suggest that strict eligibility criteria could result in insufficient or biased case identification as less than 50% of individuals across any group report no medical co-morbidities. As such clinical trial samples will not reflect the population for whom the treatment is being sought. Trials must be designed with careful consideration and general agreement of inclusion/exclusion criteria for MCI, and should only be restricted to those individuals who are most likely to be affected favourably by the treatment [3
An important focus of MCI research is the identification of improved methods of classification to differentiate MCI cases at risk of dementia progression from those who are not [29
]. Medical co-morbidity may affect dementia progression in MCI cohorts. It has been hypothesised that heterogeneity in the outcome of MCI may be linked to the presence of co-morbid disease [30
]. Previous studies have, however, been inconclusive in identifying medical risk factors for incident dementia in MCI groups. Only atrial fibrillation and low folate levels have been associated with an increased risk of dementia progression in MCI [31
]. Disparate results are possibly due to differences in MCI case selection criteria, sample age (young-old versus oldest-old), disease severity levels, measurement of risk factors and study populations (clinic samples with ranging emphasis versus population based). In this study, only anaemia increased risk of dementia in individuals with MCI. Anaemia has not, however, been consistently associated with cognitive decline and dementia risk [32
]: not all studies find an association, including a previous study using the CFAS cohort. One possible reason for a lack of an association in otherwise non-demented samples may be due to a wash-out effect on the relationship when the different cognitive groups (i.e. normal, MCI and OCIND) are combined for analysis. Given that the prevalence of anaemia was similar across all groups, the results suggest that one mechanism by which anaemia impacts dementia risk in MCI could be due to compromised compensatory processes in the MCI state. Indeed, in MCI the pathology underlying cognitive symptoms (e.g. AD or vascular pathology) may make it difficult for the brain to compensate for the additional insult (i.e. low-oxygen supply) caused by the anaemia. In contrast, in the NCI and OCIND states neuropathology would be unlikely to be as great and, therefore, compensatory mechanisms would be expected to be more efficient. This needs to be tested.