Age and Vascular Burden Determinants of Cortical Hemodynamics Underlying Verbal Fluency

PLoS One. 2015 Sep 22;10(9):e0138863. doi: 10.1371/journal.pone.0138863. eCollection 2015.


Background: Aging processes and several vascular burden factors have been shown to increase the risk of dementia including Alzheimer's disease. While pathological alterations in dementia precede diagnosis by many years, reorganization of brain processing might temporarily delay cognitive decline. We hypothesized that in healthy elderly individuals both age-related neural and vascular factors known to be related to the development of dementia impact functional cortical hemodynamics during increased cognitive demands.

Methods: Vascular burden factors and cortical functional hemodynamics during verbal fluency were assessed in 1052 non-demented elderly individuals (51 to 83 years; cross-sectional data of the longitudinal TREND study) using functional near-infrared spectroscopy (fNIRS). The prediction of functional hemodynamic responses by age in multiple regressions and the impact of single and cumulative vascular burden factors including hypertension, diabetes, obesity, smoking and atherosclerosis were investigated.

Results: Replicating and extending previous findings we could show that increasing age predicted functional hemodynamics to be increased in right prefrontal and bilateral parietal cortex, and decreased in bilateral inferior frontal junction during phonological fluency. Cumulative vascular burden factors, with hypertension in particular, decreased left inferior frontal junction hemodynamic responses during phonological fluency. However, age and vascular burden factors showed no statistical interaction on functional hemodynamics.

Conclusion: Based on these findings, one might hypothesize that increased fronto-parietal processing may represent age-related compensatory reorganization during increased cognitive demands. Vascular burden factors, such as hypertension, may contribute to regional cerebral hypoperfusion. These neural and vascular hemodynamic determinants should be investigated longitudinally and combined with other markers to advance the prediction of future cognitive decline and dementia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging / physiology*
  • Blood Pressure / physiology*
  • Brain / blood supply
  • Brain / physiology*
  • Brain / physiopathology
  • Cerebrovascular Circulation / physiology*
  • Cognition Disorders / diagnosis
  • Cognition Disorders / physiopathology
  • Cross-Sectional Studies
  • Dementia / diagnosis
  • Dementia / physiopathology
  • Female
  • Hemodynamics / physiology*
  • Humans
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Psychomotor Performance / physiology
  • Risk Factors
  • Spectroscopy, Near-Infrared
  • Verbal Behavior / physiology*

Grant support

This work was supported by mixed financing with institutional support by the University Hospital of Tübingen, Hertie-Institute for Clinical Brain Research, German Center for Neurodegenerative Diseases (DZNE), Center for integrative Neurosciences (CIN), Parkinson Fonds and Industry (Teva Pharmaceutical Industries, ucb, Janssen Pharmaceutical Inc.), The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.