Post-mortem brain pathology is related to declining respiratory function in community-dwelling older adults

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Abstract

Damage to brain structures which constitute the distributed neural network that integrates respiratory muscle and pulmonary functions, can impair adequate ventilation and its volitional control. We tested the hypothesis that the level of brain pathology in older adults is associated with declining respiratory function measured during life. 1,409 older adults had annual testing with spirometry (SPI) and respiratory muscle strength (RMS) based on maximal inspiratory and maximal expiratory pressures (MEPs). Those who died underwent structured brain autopsy. On average, during 5 years of follow-up, SPI and RMS showed progressive decline which was moderately correlated (ρ = 0.57, p < 0.001). Among decedents (N = 447), indices of brain neuropathologies showed differential associations with declining SPI and RMS. Nigral neuronal loss was associated with the person-specific decline in SPI (Estimate, -0.016 unit/year, S.E. 0.006, p = 0.009) and reduction of the slope variance was equal to 4%. By contrast, Alzheimer's disease (AD) pathology (Estimate, -0.030 unit/year, S.E. 0.009, p < 0.001) and macroscopic infarcts (-0.033 unit/year, S.E., 0.011, p = 0.003) were associated with the person-specific decline in RMS and reduction of the slope variance was equal to 7%. These results suggest that brain pathology is associated with the rate of declining respiratory function in older adults.

Figures

  • TABLE 1 | Clinical characteristics of participants in these analyses.
  • FIGURE 1 | Change in spirometry (SPI) and respiratory muscle strength (RMS) and the effect of more brain pathology on their rates of change. The left panels show change in SPI (top) and RMS (bottom) during the study. Crude paths of change (gray lines) and mean paths of change predicted by the model (black lines) in SPI (top) and RMS (bottom). To facilitate visualization data from a 25% random sample of decedents is illustrated in the left panels. To display the association of brain pathology on the rate of change in respiration, four hypothetical average participants with their estimated rate of declining respiration based on the model which included all the cases analyzed in this study are illustrated. The right panels show the model derived predicted paths of SPI (top) and RMS (bottom) for four participants with increasing burden of brain pathology: (1) Black line, the predicted path for a participant with No pathology; (2) Red line, the predicted path for a participant with Alzheimer’s disease (AD) pathology; (3) Green line, the predicted path for a participant with AD pathology and macroinfarcts; (4) Blue line, the predicted path for a participant with AD pathology, macroinfarcts and severe nigral neuronal loss.
  • FIGURE 2 | Annual rates of change in SPI and RMS. On the left is a two-dimensional histogram of annual rates of change in SPI and RMS estimated by simultaneous random effects model (Table 2). The figure on the right depicts the density of the number of participants shown in the two dimensional histogram with yellow showing increased density compared to the shades of red. X axis shows change in SPI and Y axis shows the change in RMS. In both portions of the figure, each point illustrates the person-specific change in both aspects of respiratory function. As can be seen on the right, nearly all values are less than zero, for SPI and RMS since both declined in nearly all cases.
  • TABLE 2 | Correlation of baseline and longitudinal changes in spirometry and respiratory muscle strength.
  • TABLE 3 | Linear-mixed effect models showing the effect of demographic variables on the rate of change of spirometric measures, MIPs and MEPs in community-dwelling older adults.
  • TABLE 4 | Associations of individual brain pathologies and the annual rate of change in spirometry and respiratory muscle strength.
  • TABLE 5 | Brain pathologies independently associated with the annual rate of change in spirometry and respiratory muscle strength prior to death.
  • TABLE 6 | Percentage of the variance of rate of change in spirometry and respiratory muscle strength explained by demographics and post-mortem indices.

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CITATION STYLE

APA

Buchman, A. S., Yu, L., Wilson, R. S., Dawe, R. J., VanderHorst, V., Schneider, J. A., & Bennett, D. A. (2015). Post-mortem brain pathology is related to declining respiratory function in community-dwelling older adults. Frontiers in Aging Neuroscience, 7(OCT). https://doi.org/10.3389/fnagi.2015.00197

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