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Gender-specific impact of personal health parameters on individual brain aging in cognitively unimpaired elderly subjects.

Frontiers in aging neuroscience | 2014

Aging alters brain structure and function. Personal health markers and modifiable lifestyle factors are related to individual brain aging as well as to the risk of developing Alzheimer's disease (AD). This study used a novel magnetic resonance imaging (MRI)-based biomarker to assess the effects of 17 health markers on individual brain aging in cognitively unimpaired elderly subjects. By employing kernel regression methods, the expression of normal brain-aging patterns forms the basis to estimate the brain age of a given new subject. If the estimated age is higher than the chronological age, a positive brain age gap estimation (BrainAGE) score indicates accelerated atrophy and is considered a risk factor for developing AD. Within this cross-sectional, multi-center study 228 cognitively unimpaired elderly subjects (118 males) completed an MRI at 1.5Tesla, physiological and blood parameter assessments. The multivariate regression model combining all measured parameters was capable of explaining 39% of BrainAGE variance in males (p < 0.001) and 32% in females (p < 0.01). Furthermore, markers of the metabolic syndrome as well as markers of liver and kidney functions were profoundly related to BrainAGE scores in males (p < 0.05). In females, markers of liver and kidney functions as well as supply of vitamin B12 were significantly related to BrainAGE (p < 0.05). In conclusion, in cognitively unimpaired elderly subjects several clinical markers of poor health were associated with subtle structural changes in the brain that reflect accelerated aging, whereas protective effects on brain aging were observed for markers of good health. Additionally, the relations between individual brain aging and miscellaneous health markers show gender-specific patterns. The BrainAGE approach may thus serve as a clinically relevant biomarker for the detection of subtly abnormal patterns of brain aging probably preceding cognitive decline and development of AD.

Pubmed ID: 24904408 RIS Download

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Associated grants

  • Agency: NIA NIH HHS, United States
    Id: K01 AG030514
  • Agency: NIA NIH HHS, United States
    Id: P30 AG010129
  • Agency: NIA NIH HHS, United States
    Id: U01 AG024904

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ADNI - Alzheimer's Disease Neuroimaging Initiative (tool)

RRID:SCR_003007

Database of the results of the ADNI study. ADNI is an initiative to develop biomarker-based methods to detect and track the progression of Alzheimer's disease (AD) that provides access to qualified scientists to their database of imaging, clinical, genomic, and biomarker data.

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Foundation for the National Institutes of Health (tool)

RRID:SCR_004493

A public charity whose mission is to support the NIH in its mission to improve health, by forming and facilitating public-private partnerships for biomedical research and training. Its vision is Building Partnerships for Discovery and Innovation to Improve Health. The FNIH draws together the world''s foremost researchers and resources, pressing the frontier to advance critical discoveries. They are recognized as the number-one medical research charity in the countryleveraging support, and convening high level partnerships, for the greatest impact on the most urgent medical challenges we face today. Grants are awarded as part of a public-private partnership with the National Heart, Lung, and Blood Institute (NHLBI) on behalf of The Heart Truth in support of women''s heart health education and research. Funding for the Community Action Program is provided by the FNIH through donations from individuals and corporations including The Heart Truth partners Belk Department Stores, Diet Coke, and Swarovski. Successful biomedical research relies upon the knowledge, training and dedication of those who conduct it. Bringing multiple disciplines to bear on health challenges requires innovation and collaboration on the part of scientists. Foundation for NIH partnerships operate in a variety of ways and formats to recruit, train, empower and retain their next generation of researchers. From lectures and multi-week courses, to scholarships and awards through fellowships and residential training programs, their programs respond to the needs of scientists at every level and stage in their careers.

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brain-development.org (tool)

RRID:SCR_005838

brain-development.org hosts data and resources used in computational analysis of brain development, including MRI data sets of developing human, software tools, atlases, protocols and software. Several different atlas datasets are available including: * Adult * Pediatric * Neonatal (T2 Templates, Probability Maps) * Neonatal (High-definition, T1 and T2 Templates, Probability Maps) * Fetal (High-definition, T2 Templates, Probability Maps) * Atlas software Anatomical segmentation protocols are available, as well as an Image Registration Toolkit.

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Structural Brain Mapping Group (tool)

RRID:SCR_008487

This is the website of the Structural Brain Mapping Group at the Department of Psychiatry, University of Jena. Our principal research focuses on the development of methods for structural brain imaging and their application. Specific areas of interest include the investigation of structural brain plasticity and schizophrenia research. Regional structural brain changes are among the most robust biological findings in schizophrenia, yet the underlying pathophysiological changes remain poorly understood. Recent evidence suggests that abnormal neuronal/dendritic plasticity is related to alterations in membrane lipids. We examined whether serum activity of membrane lipid remodeling/repairing cytosolic phospholipase A2 (PLA2) were related to regional brain structure in magnetic resonance images (MRI). The study involved 24 schizophrenia patients, who were either drug-nave or off antipsychotic medication, and 25 healthy controls. Using voxel-based morphometry (VBM) analysis of T1-high-resolution MRI-images, we correlated both gray matter and white matter changes with serum PLA2-activity. PLA2 activity was increased in patients, consistent with previous findings. VBM group comparison of patients vs. controls showed abnormalities of frontal and medial temporal cortices/hippocampus, and left middle/superior temporal gyrus in first-episode patients. Group comparison of VBM/ PLA2-correlations revealed a distinct pattern of disease-related interactions between gray/white matter changes in patients and PLA2-activity: in first-episode patients (n = 13), PLA2-activity was associated with structural alterations in the left prefrontal cortex and the bilateral thalamus. Recurrent-episode patients (n = 11) showed a wide-spread pattern of associations between PLA2-activity and structural changes in the left (less right) prefrontal and inferior parietal cortex, the left (less right) thalamus and caudate nucleus, the left medial temporal and orbitofrontal cortex and anterior cingulum, and the cerebellum. Our findings demonstrate a potential association between membrane lipid biochemistry and focal brain structural abnormalities in schizophrenia. Differential patterns in first-episode vs. chronic patients might be related to PLA2-increase at disease-onset reflecting localized regenerative activity, whereas correlations in recurrent- episode patients might point to less specific neurodegenerative aspects of disease progression.

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