Neuroprotective pathways: lifestyle activity, brain pathology, and cognition in cognitively normal older adults

Abstract

This study used path analysis to examine effects of cognitive activity and physical activity on cognitive functioning in older adults, through pathways involving beta-amyloid (Aβ) burden, cerebrovascular lesions, and neural injury within the brain regions affected in Alzheimer's disease (AD). Ninety-two cognitively normal older adults (75.2 ± 5.6 years) reported lifetime cognitive activity and current physical activity using validated questionnaires. For each participant, we evaluated cortical Aβ burden (using [(11)C] labeled Pittsburgh-Compound-B positron emission tomography), cerebrovascular lesions (using magnetic resonance imaging-defined white matter lesion [WML]), and neural integrity within AD regions (using a multimodal neuroimaging biomarker). Path models (adjusted for age, gender, and education) indicated that higher lifetime cognitive activity and higher current physical activity was associated with fewer WMLs. Lower WML volumes were in turn related to higher neural integrity and higher global cognitive functioning. As shown previously, higher lifetime cognitive activity was associated with lower [(11)C] labeled Pittsburgh-Compound-B retention, which itself moderated the impact of neural integrity on cognitive functioning. Lifestyle activity may thus promote cognitive health in aging by protecting against cerebrovascular pathology and Aβ pathology thought to be relevant to AD development.

Keywords: Beta-amyloid; Cognitive activity; Cognitive aging; PIB-PET; Physical activity; White matter lesion.

Copyright © 2014 Elsevier Inc. All rights reserved.

Figures

Figure 1

The template of cortical AD-vulnerable regions (color coded in red) projected onto a standard surface map. Cortical regions included bilateral middle and medial temporal areas, the angular gyrus, the posterior cingulate region and the precuneus.

Figure 2

Age-, gender, and years of education-adjusted path diagrams for biomarkers and global cognitive functioning. For the cerebrovascular pathway (green), increased WML volumes were confirmed to have a significant negative effect on global cognitive functioning, which was mediated by lower neural integrity within AD regions. For the Aβ pathway (blue), the moderation effect of PIB retention was confirmed by significantly different path coefficients between PIB- and PIB+ groups. Standardized beta coefficients are provided; asterisks specify that beta coefficient is significant at ** p < 0.01, * p < 0.05. Solid black lines indicate significant relationships. Standardized beta coefficients are provided. Abbreviations: WML, White matter lesion; PIB, Pittsburgh-Compound-B

Figure 3

Age-, gender, and years of education-adjusted path diagrams for lifetime cognitive activity and current physical activity, biomarkers and global cognitive functioning. Higher lifetime cognitive activity was confirmed to lower PIB retention and had a beneficial effect on global cognitive functioning, which was mediated by lower WML volumes and greater neural integrity. Likewise current physical activity had a beneficial effect on global cognitive functioning via the mediation of WMLs and neural integrity. Standardized beta coefficients are provided; asterisks specify that beta coefficient is significant at ** p < 0.01, * p < 0.05. Solid black lines indicate significant direct effects, grey lines indicate non-significant relations, and broken lines indicate moderations (examined separately in a multi-group model). Circles denote latent variables; squares represent observed variables. Abbreviations: CA, cognitive activity; PA, physical activity; WML, White matter lesion; PIB, Pittsburgh-Compound-B