Back to Search
Start Over
The C677T Variant in MTHFR Modulates Associations Between Brain Integrity, Mood, and Cognitive Functioning in Old Age
- Source :
- Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. 2:280-288
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- Background The C677T functional variant in the methylenetetrahydrofolate reductase ( MTHFR ) gene leads to reduced enzymatic activity and elevated blood homocysteine levels. Hyperhomocysteinemia has been linked with higher rates of cardiovascular diseases, cognitive decline, and late-life depression. Methods Three-dimensional magnetic resonance imaging data were analyzed from 738 individuals (aged 75.5 ± 6.8 years; 438 men, 300 women), including 173 patients with Alzheimer's disease, 359 subjects with mild cognitive impairment, and 206 healthy older adults, scanned as part of the Alzheimer's Disease Neuroimaging Initiative. Results We found that this variant associates with localized brain atrophy, after controlling for age, sex, and dementia status, in brain regions implicated in both intellectual and emotional functioning, notably the medial orbitofrontal cortices. The medial orbitofrontal cortex is involved in the cognitive modulation of emotional processes, and localized atrophy in this region was previously linked with both cognitive impairment and depressive symptoms. Here, we report that increased plasma homocysteine level mediates the association between MTHFR genotype and lower medial orbitofrontal volumes and that these volumes mediate the association between cognitive decline and depressed mood in this elderly cohort. We additionally show that vitamin B 12 deficiency interacts with the C677T variant in the etiology of hyperhomocysteinemia. Conclusions This study sheds light on important relationships between vascular risk factors, age-related cognitive decline, and late-life depression, and it represents a significant advance in our understanding of clinically relevant associations relating to MTHFR genotype.
- Subjects :
- 0301 basic medicine
Oncology
Brain atrophy
medicine.medical_specialty
Hyperhomocysteinemia
Cognitive Neuroscience
Late-life depression
03 medical and health sciences
0302 clinical medicine
Atrophy
Internal medicine
medicine
Dementia
Radiology, Nuclear Medicine and imaging
Cognitive decline
Psychiatry
Homocysteine
Biological Psychiatry
biology
Late life depression
medicine.disease
3. Good health
030104 developmental biology
Methylenetetrahydrofolate reductase
MTHFR
biology.protein
Orbitofrontal cortex
Age-related cognitive decline
Neurology (clinical)
Psychology
030217 neurology & neurosurgery
MRI
Alzheimer's Disease Neuroimaging Initiative
Subjects
Details
- ISSN :
- 24519022
- Volume :
- 2
- Database :
- OpenAIRE
- Journal :
- Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
- Accession number :
- edsair.doi.dedup.....fc8370a5feff679ca64d203486600f84