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

Neurobiol Aging. 2014 Aug;35(8):1873-82. doi: 10.1016/j.neurobiolaging.2014.02.015. Epub 2014 Feb 20.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging / pathology*
  • Aging / physiology
  • Aging / psychology*
  • Alzheimer Disease / etiology
  • Alzheimer Disease / prevention & control*
  • Amyloid beta-Peptides / metabolism*
  • Brain / metabolism*
  • Brain / pathology*
  • Cognition / physiology*
  • Female
  • Humans
  • Life Style*
  • Magnetic Resonance Imaging
  • Male
  • Motor Activity / physiology*
  • Positron-Emission Tomography
  • Surveys and Questionnaires*


  • Amyloid beta-Peptides