Alzheimer's disease neurodegenerative biomarkers are associated with decreased cognitive function but not β-amyloid in cognitively normal older individuals

J Neurosci. 2013 Mar 27;33(13):5553-63. doi: 10.1523/JNEUROSCI.4409-12.2013.


β-Amyloid (Aβ) plaque deposition and neurodegeneration within temporoparietal and hippocampal regions may indicate increased risk of Alzheimer's disease (AD). This study examined relationships between AD biomarkers of Aβ and neurodegeneration as well as cognitive performance in cognitively normal older individuals. Aβ burden was quantified in 72 normal older human subjects from the Berkeley Aging Cohort (BAC) using [(11)C] Pittsburgh compound B (PIB) positron emission tomography. In the same individuals, we measured hippocampal volume, as well as glucose metabolism and cortical thickness, which were extracted from a template of cortical AD-affected regions. The three functional and structural biomarkers were merged into a highly AD-sensitive multimodality biomarker reflecting neural integrity. In the normal older individuals, there was no association between elevated PIB uptake and either the single-modality or the multimodality neurodegenerative biomarkers. Lower neural integrity within the AD-affected regions and a control area (the visual cortex) was related to lower scores on memory and executive function tests; the same association was not found with PIB retention. The relationship between cognition and the multimodality AD biomarker was stronger in individuals with the highest PIB uptake. The findings indicate that neurodegeneration occurs within AD regions regardless of Aβ deposition and accounts for worse cognition in cognitively normal older people. The impact of neural integrity on cognitive functions is, however, enhanced in the presence of high Aβ burden for brain regions that are most affected in AD.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging
  • Alzheimer Disease / complications*
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / metabolism*
  • Amyloid / metabolism*
  • Analysis of Variance
  • Aniline Compounds
  • Biomarkers / metabolism*
  • Brain Mapping
  • Cognition Disorders / diagnosis*
  • Cognition Disorders / diagnostic imaging
  • Cognition Disorders / etiology*
  • Female
  • Fluorodeoxyglucose F18
  • Humans
  • Linear Models
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Mental Status Schedule
  • Middle Aged
  • Neuropsychological Tests
  • Positron-Emission Tomography
  • Radioisotopes
  • Reproducibility of Results
  • Thiazoles


  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • Amyloid
  • Aniline Compounds
  • Biomarkers
  • Radioisotopes
  • Thiazoles
  • Fluorodeoxyglucose F18