ASSOCIATION BETWEEN APOE-ε4 CARRIER STATUS AND QUALITATIVE NEUROIMAGING CHARACTERISTICS IN OLDER ADULTS WITH MILD
Alberto J Mimenza-Alvarado1, María J Suing-Ortega1, Teresa Tusie-Luna2,3
1Department of Geriatric Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Background:
The pathogenesis of mild cognitive impairment (MCI) is multifactorial and includes the presence of genetic variants such as the ε4 allele of the apolipoprotein E gene (APOE-ε4). Association between the APOE-ε4 carrier status and deleterious structural and functional changes on magnetic resonance imaging (MRI) has been previously described in individuals with Alzheimer's disease. However, the central nervous system changes may possibly develop in earlier stages of cognitive impairment, as reflected in MCI.
Objective:
The objective of the study was to determine the association between APOE-ε4 carrier status and qualitative changes on MRI (medial temporal and parietal atrophy), as well as the detection of white matter hyperintensities (WMH) in older adults with MCI, in the memory clinic of a tertiary care hospital in Mexico City.
Methods:
A cross-sectional study of 72 adults aged 60 years or above who underwent an exhaustive clinical, neuroimaging, and neuropsychological evaluation. Multivariate logistic regression models were constructed to determine the association between APOE-ε4 carrier status and qualitative/quantitative changes on MRI.
Results:
Mean age was 75.2 years (± 7.2) and 64% were female. Twenty-one participants were cognitively normal and 51 had MCI. Almost 56% were APOE-ε4 carriers and were associated with medial-temporal atrophy according to the Scheltens scale (odds ratio [OR]: 20.0, 95% confidence intervals [CI]: 3.03-131.7), parietal atrophy according to the Koedam's score (OR: 6.3; 95% CI 1.03-39.53), and WMH according to the Fazekas scale (OR: 11.7, 95% CI: 1.26-108.2), even after adjusting for age, educational level, and cardiovascular risk factors.
Conclusion:
The APOE-ε4 carrier status was associated with medial temporal and parietal atrophy, as well as WMH. Our findings support the hypothesis suggesting the contribution of this genotype to neurodegeneration and cerebral vascular pathology.
Insights
The apolipoprotein E ε4 allele (APOE-ε4) is linked to brain changes in mild cognitive impairment (MCI). APOE-ε4 carriers showed increased medial temporal, parietal atrophy, and white matter hyperintensities on MRI scans.
Area of Science:
- Neuroimaging
- Genetics
- Neurology
Background:
- Mild cognitive impairment (MCI) pathogenesis is complex, involving genetic factors like the apolipoprotein E ε4 allele (APOE-ε4).
- APOE-ε4 carrier status is associated with brain changes in Alzheimer's disease, but effects in earlier stages like MCI are less understood.
- Investigating APOE-ε4's role in MCI is crucial for understanding early neurodegeneration.
Purpose of the Study:
- To determine the association between APOE-ε4 carrier status and MRI-detected brain changes in older adults with MCI.
- Specifically examined medial temporal and parietal atrophy, and white matter hyperintensities (WMH).
- Conducted in a memory clinic setting in Mexico City.
Main Methods:
- Cross-sectional study of 72 adults (≥60 years) with comprehensive clinical, neuroimaging, and neuropsychological evaluations.
- Utilized multivariate logistic regression to analyze the association between APOE-ε4 status and MRI findings.
- Assessed medial temporal atrophy (Scheltens scale), parietal atrophy (Koedam's score), and WMH (Fazekas scale).
Main Results:
- APOE-ε4 carriers (56% of participants) showed significantly higher rates of medial temporal atrophy (OR: 20.0), parietal atrophy (OR: 6.3), and WMH (OR: 11.7).
- These associations remained significant after adjusting for age, education, and cardiovascular risk factors.
- The study included 51 individuals with MCI and 21 cognitively normal participants.
Conclusions:
- APOE-ε4 carrier status is significantly associated with medial temporal and parietal atrophy, and white matter hyperintensities in individuals with MCI.
- Findings support APOE-ε4's contribution to neurodegeneration and cerebral vascular pathology in early cognitive decline.
- Highlights the importance of genetic factors in MCI progression.
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