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Generalized Psychophysiological Interaction (PPI) Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease
Published on: November 14, 2017
Apolipoprotein E allele 4 is not a sufficient or a necessary predictor of the development of Mild Cognitive
1Department of Psychiatry, Derby City General Hospital, Uttoxeter Road, Derby 22, UK. heun@gmx.com
Abstract:
The presence of Mild Cognitive Impairment (MCI) and of an apolipoprotein E (apoE) varepsilon4 allele both predict the development of Alzheimer's disease. However, the extent to which this allele also predicts the development of MCI is unclear even though MCI is an early transitional stage in the development of Alzheimer's disease. The present study investigates the prevalence of the apoE varepsilon4 allele in incipient MCI. Participants were recruited from the population-based Leipzig Longitudinal Study of the Aged (LEILA75+). All subjects who were initially cognitively healthy, i.e. did not meet MCI criteria described by Petersen [Petersen RC. Mild cognitive impairment. J Intern Med 2004; 256(3): 183-94], and whose apoE status could be determined were followed-up. After 4.5 years, 15.5% of the cognitively healthy target population had developed MCI. The frequencies of the apoE varepsilon4 genotype did not differ between individuals with incipient MCI (12.9%) and individuals who remained cognitively healthy during the study (18.4%, p>0.5). Consequently, the apoE varepsilon4 genotype is not a necessary or sufficient risk factor for MCI. Further studies need to investigate the influence of the whole range of genetic and environmental risk factors on the course of Alzheimer's disease including the initial development of MCI and the later conversion to Alzheimer's disease.
Insights
The apolipoprotein E (apoE) varepsilon4 allele does not predict the development of Mild Cognitive Impairment (MCI). This finding suggests apoE varepsilon4 is not a necessary or sufficient risk factor for MCI.
Area of Science:
- Neuroscience
- Genetics
- Epidemiology
Background:
- Mild Cognitive Impairment (MCI) precedes Alzheimer's disease.
- The apolipoprotein E (apoE) varepsilon4 allele is a known risk factor for Alzheimer's disease.
- The role of apoE varepsilon4 in the development of MCI is not well understood.
Purpose of the Study:
- To investigate the prevalence of the apoE varepsilon4 allele in individuals with incipient Mild Cognitive Impairment (MCI).
Main Methods:
- Population-based cohort study (Leipzig Longitudinal Study of the Aged, LEILA75+).
- Follow-up of initially cognitively healthy individuals for 4.5 years.
- Genotyping for apoE varepsilon4 status and assessment of MCI criteria.
Main Results:
- 15.5% of the initially healthy population developed MCI over 4.5 years.
- The frequency of the apoE varepsilon4 genotype did not differ between individuals who developed MCI (12.9%) and those who remained cognitively healthy (18.4%).
- p-value > 0.5 indicates no statistically significant difference.
Conclusions:
- The apoE varepsilon4 genotype is neither a necessary nor a sufficient risk factor for the development of MCI.
- Further research is needed on combined genetic and environmental factors influencing MCI and Alzheimer's disease progression.
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