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. 2013 Dec 31;8(12):e85460.
doi: 10.1371/journal.pone.0085460. eCollection 2013.

Imaging-based biomarkers of cognitive performance in older adults constructed via high-dimensional pattern regression applied to MRI and PET

Ying Wang  1 , Joshua O Goh  2 , Susan M Resnick  3 , Christos Davatzikos  1
Affiliations

Imaging-based biomarkers of cognitive performance in older adults constructed via high-dimensional pattern regression applied to MRI and PET

Ying Wang et al. PLoS One. .

Abstract

In this study, we used high-dimensional pattern regression methods based on structural (gray and white matter; GM and WM) and functional (positron emission tomography of regional cerebral blood flow; PET) brain data to identify cross-sectional imaging biomarkers of cognitive performance in cognitively normal older adults from the Baltimore Longitudinal Study of Aging (BLSA). We focused on specific components of executive and memory domains known to decline with aging, including manipulation, semantic retrieval, long-term memory (LTM), and short-term memory (STM). For each imaging modality, brain regions associated with each cognitive domain were generated by adaptive regional clustering. A relevance vector machine was adopted to model the nonlinear continuous relationship between brain regions and cognitive performance, with cross-validation to select the most informative brain regions (using recursive feature elimination) as imaging biomarkers and optimize model parameters. Predicted cognitive scores using our regression algorithm based on the resulting brain regions correlated well with actual performance. Also, regression models obtained using combined GM, WM, and PET imaging modalities outperformed models based on single modalities. Imaging biomarkers related to memory performance included the orbito-frontal and medial temporal cortical regions with LTM showing stronger correlation with the temporal lobe than STM. Brain regions predicting executive performance included orbito-frontal, and occipito-temporal areas. The PET modality had higher contribution to most cognitive domains except manipulation, which had higher WM contribution from the superior longitudinal fasciculus and the genu of the corpus callosum. These findings based on machine-learning methods demonstrate the importance of combining structural and functional imaging data in understanding complex cognitive mechanisms and also their potential usage as biomarkers that predict cognitive status.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Regression results for LTM, STM, semantic retrieval and manipulation performance.
The vertical axis indicates the predicted cognitive scores based on MRI and PET data, and the horizontal axis refers to the measured cognitive scores.
Figure 2
Figure 2. Identified brain regions related to memory functions overlaid on the template image.
Contribution maps are displayed in radiological convention. A) LTM; B) STM.
Figure 3
Figure 3. Identified brain regions related to executive processes overlaid on the template image.
Contribution maps are displayed in radiological convention. A) Semantic Retrieval; B) Manipulation.
Figure 4
Figure 4. Examples of brain regions correlating with performance in the memory measures by GLM.
Contribution maps are displayed in radiological convention. A) LTM; B) STM.
Figure 5
Figure 5. Examples of brain regions correlating with performance in the executive measures by GLM.
Semantic retrieval and manipulation (left/right).
See this image and copyright information in PMC

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