Diabetes, Mild Cognitive Impairment and Dementia

There is a paper by Xu and colleagues titled ‘Accelerated Progression from Mild Cognitive Impairment to Diabetes’ which is freely available here. The work has a Creative Commons 3.0 license. The authors are investigating how diabetes influence the progression of mild cognitive impairment (MCI) to dementia. There have been a large number of studies investigating biomarkers and their relationship to conversion from MCI to various subtypes of dementia. Notable risk factors including Medial Temporal Lobe atrophy have been identified from such analyses. The conversion from MCI to dementia however is difficult to predict even with the use of biomarkers and there will most likely be a refinement of the criteria for MCI. The researchers analyse cohorts from a prospective cohort study in Sweden with 1700 participants. In one cohort the participants had a diagnosis of Mild Cognitive Impairment and in the other they were cognitively intact. There was a lengthy follow-up period of 9 years where the researchers were looking for evidence of conversion to MCI or dementia in the relevant cohorts.

Participants were grouped into amnestic Mild Cognitive Impairment (aMCI), other cognitive impairment non dementia (oCIND) or cognitively intact groups initially. For the aMCI group, the researchers used a delayed recall task and a cut-off point of two standard deviations below the population norm. For the oCIND group performance on the Mini Mental State Examination (MMSE) was used. There are more sensitive tests for assessing these subtle impairments in cognition however and the MMSE is restricted in the cognitive domains that it can be used to assess. This for me was a limitation in the ascertainment of the cognitively impaired groups. There are other types of MCI as well which it would have been interesting to include – for instance executive MCI. The researchers outline their detailed workups for dementia and diabetes.

In the results section, the key finding was that the rate of progression from MCI to dementia was increased by the presence of diabetes. The data shows that the median time from baseline to dementia in the diabetes or pre-diabetes group was 1.83 years and 5.01 years without these conditions. The confidence intervals are quite convincing as well. The graph below shows the cumulative hazard for dementia in the respective groups.

Graph Showing Cumulative Hazard for dementia in subjects with and without diabetes or pre-diabetes (from Xu et al paper)

These are quite significant results and are similarly convincing when the hazards ratio for conversion to Alzheimer’s Disease is considered. These results tally up with other research showing an increased prevalence of Alzheimer’s Disease with diabetes. What is really interesting to consider is the underlying pathogenesis and if we look at Armstrong’s revised ‘Amyloid Cascade Hypothesis‘ it is possible to suggest that the diabetes might be consistent with the primary degeneration discussed in that model which later interacts with the plaques and tangles to produce secondary degeneration. At this stage it is conjecture and there is a lot of testing to be done on Armstrong’s model. However there is a lot of data which would support it already and there is a lot of data supporting the relationship between diabetes and increased prevalence of Alzheimer’s Disease although there are also counterintuitive findings such as a slower rate of disease progression.

These findings pose a serious challenge to the research community – either disprove the acceleration identified in this study or else confirm it and investigate exactly what processes are causing this to occur.

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3 thoughts on “Diabetes, Mild Cognitive Impairment and Dementia

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